Theodore P. Abraham, Luigi P. Badano, Thor Edvardsen, John Gorcsan III, Nobuyuki Kagiyama, Allan L. Klein, Wojciech Kosmala, Kenya Kusunose, Thomas H. Marwich, Denisa Muraru, Kazuaki Negishi, Dermot Phelan, Zoran B. Popovic, Marielle Scherrer-Crosbie, Partho P. Sengupta, Amil Shah, Sirish Shrestha, Paaladinesh Thavendiranathan, James Thomas and Jens-Uwe Voigt : ASE's Comprehensive Strain Imaging, Elsevier, Jul. 2021.
4.
Kenya Kusunose : 映像情報メディカル 超音波診断2021BOOK, Sangyo Kaihatsukiko Inc., Tokyo, May 2021.
5.
Kenya Kusunose : 心エコー図檢査における肺高血圧症の評価, 株式会社 インナービジョン, Tokyo, Apr. 2021.
6.
Kenya Kusunose : Echo-omics : Future directions of artificial intelligence in echocardiography, Ishiyaku Publishers,Inc., Tokyo, Nov. 2020.
Hirotsugu Yamada and Kenya Kusunose : 1. 循環器領域 (心エコー) のトピックス - Onco-cardiology, point-of-care ultrasound, そして人工知能 (AI), 株式会社 インナービジョン, Tokyo, Jun. 2020.
11.
Kenya Kusunose : 心エコーへのAIの応用 - ついに心エコーにまでやってきた, 文光堂, Tokyo, May 2020.
12.
鳥居 裕太 and Kenya Kusunose : 心房細動例のHFpEFではここを診る, 文光堂, Tokyo, Feb. 2020.
13.
西條 良仁 and Kenya Kusunose : LVEFでどのように予測するか, 文光堂, Tokyo, Aug. 2019.
14.
山田 なお and Kenya Kusunose : 大動脈弁逆流の予後を知る, 文光堂, Tokyo, Jul. 2019.
15.
Kenya Kusunose : 最新のエルゴメーター装置を使ってみる! - どれだけやりやすくなったか?, 文光堂, Tokyo, Apr. 2019.
16.
Hirotsugu Yamada, 西尾 進 and Kenya Kusunose : 徳大超音波センターのオキテ100, 文光堂, Tokyo, Mar. 2019.
17.
Kenya Kusunose : 知っておきたい次世代のストレイン指標, 文光堂, Tokyo, Mar. 2019.
18.
Kenya Kusunose : 心エコー 20/3, 文光堂, Tokyo, Mar. 2019.
19.
Kenya Kusunose : ASEガイドラインを意識した左室拡張能評価の基本, 文光堂, Tokyo, Jan. 2019.
20.
Kenya Kusunose : 心エコー 20/1, 文光堂, Tokyo, Jan. 2019.
21.
Kenya Kusunose : 無症候性重症AR - 日常生活に困らないのに⋯, 文光堂, Tokyo, Sep. 2018.
22.
平田 有紀奈 and Kenya Kusunose : 胸部症状のため紹介されたS字状中隔を有する高齢男性の1例, 文光堂, Tokyo, Sep. 2018.
23.
Kenya Kusunose : 循環器内科, 科学評論社, Tokyo, Aug. 2018.
24.
Kenya Kusunose and Hirotsugu Yamada : 心エコーハンドブック 心不全: 竹中 克，戸出 浩之 編, KINPODO, INC., Tokyo, May 2017.
25.
Kenya Kusunose and Hirotsugu Yamada : 労作時と夜間にも息切れを訴える55歳男性, 文光堂, Tokyo, 2012.
26.
Kenya Kusunose and Hirotsugu Yamada : 心嚢液貯留がどのくらいで心タンポナーデと診断すればいいですか?, MEDICAL VIEW CO., LTD., 2011.
27.
Kenya Kusunose and Hirotsugu Yamada : Pre-capillary PH, post capillary PHの診断はどうすればいいですか?, MEDICAL VIEW CO., LTD., 2011.
28.
Kenya Kusunose and Hirotsugu Yamada : 心房細動の患者さんではどのように計測すればいいですか?(EF，左室径，拡張能，弁膜症評価), MEDICAL VIEW CO., LTD., 2011.
29.
Kenya Kusunose and Hirotsugu Yamada : 左室拡張不全をきたす疾患，心膜疾患, 文光堂, Sep. 2010.
30.
Kenya Kusunose and Hirotsugu Yamada : 心筋梗塞後に下腿浮腫を認めた70歳男性, Jul. 2010.
31.
Hirotsugu Yamada and Kenya Kusunose : 弁置換術後にむくみを自覚した72歳女性, Jul. 2010.
32.
Kenya Kusunose and Hirotsugu Yamada : 循環器臨床サピア1, 2009.
Academic Paper (Judged Full Paper):
1.
Kenya Kusunose, T Imai, A Tanaka, M Doi, Y Koide, K Fukumoto, T Kadokami, M Ohishi, H Teragawa, N Ohte, Hirotsugu Yamada, Masataka Sata and K Node : Effects of ipragliflozin on left ventricular diastolic function in patients with type 2 diabetes: A sub-analysis of the PROTECT trial, Journal of Cardiology, Vol.84, No.4, 246-252, 2024.
(Summary)
We hypothesized that the beneficial effects of sodium-glucose cotransporter-2 (SGLT2) inhibitors on diastolic function might depend on baseline left ventricular (LV) systolic function. To investigate the effects of SGLT2 inhibitors on LV diastolic function in patients with type 2 diabetes mellitus (T2DM), we conducted a post-hoc sub-study of the PROTECT trial, stratifying the data according to LV ejection fraction (LVEF) at baseline. After excluding patients without echocardiographic data at baseline or 24 months into the PROTECT trial, 31 and 38 patients with T2DM from the full analysis dataset of the PROTECT trial who received ipragliflozin or no SGLT2 inhibitor (control), respectively, were included. The primary endpoint was a comparison of the changes in echocardiographic parameters and N-terminal pro-brain natriuretic peptide levels from baseline to 24 months between the two groups stratified according to baseline LVEF. Differences in diastolic functional parameters (e' and E/e') were noted between the two groups. Among the subgroups defined according to median LVEF values, those with higher LVEF (≥60 %) who received ipragliflozin appeared to have a higher e' and lower E/e' than did those who received the standard of care with no SGLT2 inhibitor, indicating longitudinal improvements between baseline and follow up (p = 0.001 and 0.016, respectively). Ipragliflozin generally improved LV diastolic function in patients with type 2 diabetes, the extent of this improvement might appear to vary with LV systolic function.
Shusuke Yagi, Ryosuke Miyamoto, Masayoshi Tasaki, Hiroyuki Morino, Ryuji Otani, Muneyuki Kadota, Takayuki Ise, Hiroki Yamazaki, Kenya Kusunose, Koji Yamaguchi, Hirotsugu Yamada, Takeshi Soeki, Tetsuzo Wakatsuki, Daiju Fukuda, Mitsuharu Ueda and Masataka Sata : The APOA1 p.Leu202Arg variant potentially causes autosomal recessive cardiac amyloidosis., Human Genome Variation, Vol.11, No.1, 2024.
(Summary)
ApoA-I amyloidosis is an extremely rare form of systemic amyloidosis that commonly involves the heart, kidneys, and liver. ApoA-I amyloidosis is caused by amyloidogenic variants of APOA1 that are inherited in an autosomal dominant manner. Here, we report a 69-year-old man with sporadic cardiac amyloidosis who was born to consanguineous parents and carried a homozygous variant of p.Leu202Arg in APOA1.
Shusuke Yagi, Muneyuki Kadota, Ryo Bando, Ryosuke Miyamoto, Hiroyuki Morino, Akiyoshi Kakutani, Yoshiaki Kubo, Takayuki Ise, Rie Ueno, Tomoya Hara, Kenya Kusunose, Koji Yamaguchi, Hirotsugu Yamada, Takeshi Soeki, Tetsuzo Wakatsuki, Daiju Fukuda and Masataka Sata : Pulmonary Arterial Hypertension in Neurofibromatosis Type 1: A Case with a Novel NF1 Gene Mutation, Internal Medicine, 2024.
(Summary)
Neurofibromatosis type 1 (NF1) is an autosomal dominant multi-organ disease. The clinical manifestations include not only skin lesions and malignant tumors but also lung complications, including pulmonary arterial hypertension (PAH). However, the association between gene mutations in NF1 and the occurrence of PAH has not yet been elucidated. We herein report a case of isolated PAH in a 67-year-old woman with NF1, presumably caused by a novel heterozygous mutation, c.4485_4486delinsAT (p.Lys1496Ter), in the NF1 gene.
Yoshihito Saijyo, Kenya Kusunose, TOMONORI Takahashi, Hirotsugu Yamada, Masataka Sata, Kimi Sato, Noor Albakaa, Tomoko Ishizu, Yoshihiro Seo and JSE TAVI investigators : Impact of Transcatheter Aortic Valve Replacement on Cardiac Reverse Remodeling and Prognosis in Mixed Aortic Valve Disease, Journal of the American Heart Association, Vol.13, No.4, e033289, 2024.
(Summary)
The management of mixed aortic valve disease (MAVD), defined as the concomitant presence of aortic stenosis (AS) and aortic regurgitation, remains a clinical challenging. The present study assessed the impact of transcatheter aortic valve replacement (TAVR) on cardiac geometry and prognosis in patients with MAVD. A retrospective multicenter TAVR registry was conducted, including patients who underwent TAVR for severe symptomatic AS between January 2015 and March 2019. Patients were subdivided into 2 groups according to concomitant presence of moderate or more severe aortic regurgitation as the MAVD group, and with mild or less severe aortic regurgitation as the isolated AS group. The primary outcome was a composite of cardiovascular death and rehospitalization due to cardiovascular causes. A total of 1742 patients (isolated AS, 1522 patients; MAVD, 220 patients) were included (84.0±5.2 years). Although MAVD exhibited significantly larger left ventricular volumes and higher left ventricular mass index at the TAVR procedure than isolated AS (respectively, <0.001), MAVD showed a greater improvement of left ventricular volumes and left ventricular mass index after TAVR (respectively, ≤0.001). During a median follow-up of 747 days, 301 patients achieved the primary event. The prognosis post-TAVR was comparable between the 2 groups (log-rank =0.65). Even after adjustment using propensity score matching to reduce the potential bias between the 2 groups, similar results were obtained for the entire cohort. Despite more advanced cardiac remodeling in MAVD at the time of TAVR compared with isolated AS, a greater improvement of cardiac reverse remodeling was found in MAVD, and the prognosis following TAVR was comparable between the 2 groups.
Yukina Hirata, Yuka Nomura, Yoshihito Saijyo, Masataka Sata and Kenya Kusunose : Reducing echocardiographic examination time through routine use of fully automated software: a comparative study of measurement and report creation time, Journal of Echocardiography, 2024.
(Summary)
Manual interpretation of echocardiographic data is time-consuming and operator-dependent. With the advent of artificial intelligence (AI), there is a growing interest in its potential to streamline echocardiographic interpretation and reduce variability. This study aimed to compare the time taken for measurements by AI to that by human experts after converting the acquired dynamic images into DICOM data. Twenty-three consecutive patients were examined by a single operator, with varying image quality and different medical conditions. Echocardiographic parameters were independently evaluated by human expert using the manual method and the fully automated US2.ai software. The automated processes facilitated by the US2.ai software encompass real-time processing of 2D and Doppler data, measurement of clinically important variables (such as LV function and geometry), automated parameter assessment, and report generation with findings and comments aligned with guidelines. We assessed the duration required for echocardiographic measurements and report creation. The AI significantly reduced the measurement time compared to the manual method (159 ± 66 vs. 325 ± 94 s, p < 0.01). In the report creation step, AI was also significantly faster compared to the manual method (71 ± 39 vs. 429 ± 128 s, p < 0.01). The incorporation of AI into echocardiographic analysis led to a 70% reduction in measurement and report creation time compared to manual methods. In cases with fair or poor image quality, AI required more corrections and extended measurement time than in cases of good image quality. Report creation time was longer in cases with increased report complexity due to human confirmation of AI-generated findings. This fully automated software has the potential to serve as an efficient tool for echocardiographic analysis, offering results that enhance clinical workflow by providing rapid, zero-click reports, thereby adding significant value.
Yukina Hirata, Takumasa Tsuji, Jun'ichi Kotoku, Masataka Sata and Kenya Kusunose : Echocardiographic artificial intelligence for pulmonary hypertension classification, Heart, Vol.110, No.8, 586-593, 2024.
(Summary)
The classification of pulmonary hypertension (PH) is crucial for determining the appropriate therapeutic strategy. We investigated whether machine learning (ML) algorithms may assist in echocardiographic PH prediction, where current guidelines recommend integrating several different parameters. We obtained physical and echocardiographic data from 885 patients who underwent right heart catheterisation (RHC). Patients were classified into three groups: non-PH, precapillary PH and postcapillary PH, based on values obtained from RHC. Using 24 parameters, we created predictive models employing four different classifiers and selected the one with the highest area under the curve. We then calculated the macro-average classification accuracy for PH on the derivation cohort (n=720) and prospective validation data set (n=165), comparing the results with guideline-based echocardiographic assessment obtained from each cohort. Logistic regression with elastic net regularisation had the highest classification accuracy, with areas under the curves of 0.789, 0.766 and 0.742 for normal, precapillary PH and postcapillary PH, respectively. The ML model demonstrated significantly better predictive accuracy than the guideline-based echocardiographic assessment in the derivation cohort (59.4% vs 51.6%, p<0.01). In the independent validation data set, the ML model's accuracy was comparable to the guideline-based PH classification (59.4% vs 57.8%, p=0.638). This preliminary study suggests promising potential for our ML model in predicting echocardiographic PH. Further research and validation are needed to fully assess its clinical utility in PH diagnosis and treatment decision-making.
N Yamaguchi, Yukina Hirata, Susumu Nishio, TOMONORI Takahashi, Yoshihito Saijo, Muneyuki Kadota, Takayuki Ise, Koji Yamaguchi, Shusuke Yagi, Hirotsugu Yamada, Takeshi Soeki, Tetsuzo Wakatsuki, Masataka Sata and Kenya Kusunose : Pulmonary Pressure-flow responses to exercise in heart failure treated with angiotensin receptor neprilysin inhibitor., International Journal of Cardiology, Vol.400, 131789, 2024.
(Summary)
The role of the angiotensin receptor neprilysin inhibitor (ARNI) in cardiac function, particularly its impact on pulmonary circulation, remains underexplored. Recent studies have described abnormal mean pulmonary artery pressure (mPAP)-cardiac output (CO) responses as having the potential to assess the disease state. The aim of this study was to assess the effects of ARNI on pulmonary circulation in heart failure. We measured echocardiographic parameters post 6-min walk (6 MW) and compared the changes with baseline and follow-up. Our hypothesis was that pulmonary pressure-flow relationship of the pulmonary circulation obtained by 6 MW stress echocardiography would be improved with treatment. We prospectively enrolled 39 heart failure patients and conducted the 6 MW test indoors. Post-6 MW echocardiography measured echocardiographic variables, and CO was derived from electric cardiometry. Individualized ARNI doses were optimized, with follow-up echocardiographic evaluations after 1 year. Left ventricular (LV) volume were significantly reduced (160.7 ± 49.6 ml vs 136.0 ± 54.3 ml, P < 0.001), and LV ejection fraction was significantly improved (37.6 ± 11.3% vs 44.9 ± 11.5%, P < 0.001). Among the 31 patients who underwent 6 MW stress echocardiographic study at baseline and 1 year later, 6 MW distance increased after treatment (380 m vs 430 m, P = 0.003). The ΔmPAP/ΔCO by 6 MW stress decreased with treatment (6.9 mmHg/L/min vs 2.8 mmHg/L/min, P = 0.002). The left atrial volume index was associated with the response group receiving ARNI treatment for pulmonary circulation. Initiation of ARNI was associated with improvement of left ventricular size and LVEF. Additionally, the 6 MW distance increased and the ΔmPAP/ΔCO was improved to within normal range with treatment.
S Yamaguchi, M Maeda, K Oba, G Maimaituxun, O Arasaki, Shusuke Yagi, Kenya Kusunose, Takeshi Soeki, Hirotsugu Yamada, Daiju Fukuda, H Masuzaki, Masataka Sata and Michio Shimabukuro : Sex differences in the association between epicardial adipose tissue volume and left atrial volume index, BMC Cardiovascular Disorders, Vol.24, No.1, 46, 2024.
(Summary)
Sex disparities in the association between epicardial adipose tissue volume (EATV) and cardiovascular disease have been reported. The sex-dependent effects of EATV on left atrial (LA) size have not been elucidated. Consecutive 247 subjects (median 65 [interquartile range 57, 75] years; 67% of men) who underwent multi-detector computed tomography without significant coronary artery disease or moderate to severe valvular disease were divided into two groups: patients with sinus rhythm (SR) or atrial fibrillation (AF). Sex differences in the association between the EATV index (EATVI) (mL/m) and LA volume index (LAVI) in 63 SR (28 men and 35 women) and 184 AF (137 men and 47 women) patients were evaluated using univariate and multivariate regression analyses. In overall that includes both men and women, the relationship between EATVI and LAVI was not significantly correlated for patients with SR and AF. The relationship between EATVI and LAVI differed between men and women in both SR and AF groups. In SR patients, there was a positive relationship between EATVI and LAVI in men, but not in women. In contrast, in patients with AF, a negative relationship was found between EATVI and LAVI in women, whereas no association was found in men. We evaluated sex differences in the association between EATVI and LAVI in patients with either SR or AF, and found a positive relationship in men with SR and a negative relationship in women with AF. This is the first report to evaluate sex differences in the relationship between EATVI and LAVI, suggesting that EAT may play a role, at least in part, in sex differences in the etiology of AF.
Kenya Kusunose, T Tsuji, Yukina Hirata, TOMONORI Takahashi, Masataka Sata, K Sato, N Albakaa, T Ishizu, J Kotoku and Y Seo : Unsupervised cluster analysis reveals different phenotypes in patients after transcatheter aortic valve replacement, European Heart Journal Open, Vol.4, No.1, oead136, 2023.
(Summary)
The aim of this study was to identify phenotypes with potential prognostic significance in aortic stenosis (AS) patients after transcatheter aortic valve replacement (TAVR) through a clustering approach. This multi-centre retrospective study included 1365 patients with severe AS who underwent TAVR between January 2015 and March 2019. Among demographics, laboratory, and echocardiography parameters, 20 variables were selected through dimension reduction and used for unsupervised clustering. Phenotypes and outcomes were compared between clusters. Patients were randomly divided into a derivation cohort ( = 1092: 80%) and a validation cohort ( = 273: 20%). Three clusters with markedly different features were identified. Cluster 1 was associated predominantly with elderly age, a high aortic valve gradient, and left ventricular (LV) hypertrophy; Cluster 2 consisted of preserved LV ejection fraction, larger aortic valve area, and high blood pressure; and Cluster 3 demonstrated tachycardia and low flow/low gradient AS. Adverse outcomes differed significantly among clusters during a median of 2.2 years of follow-up ( < 0.001). After adjustment for clinical and echocardiographic data in a Cox proportional hazards model, Cluster 3 (hazard ratio, 4.18; 95% confidence interval, 1.76-9.94; = 0.001) was associated with increased risk of adverse outcomes. In sequential Cox models, a model based on clinical data and echocardiographic variables ( = 18.4) was improved by Cluster 3 ( = 31.5; = 0.001) in the validation cohort. Unsupervised cluster analysis of patients after TAVR revealed three different groups for assessment of prognosis. This provides a new perspective in the categorization of patients after TAVR that considers comorbidities and extravalvular cardiac dysfunction.
Munkhtsetseg Tserensonom, Shusuke Yagi, Takayuki Ise, Yutaka Kawabata, Muneyuki Kadota, Tomoya Hara, Kenya Kusunose, Koji Yamaguchi, Hirotsugu Yamada, Takeshi Soeki, Tetsuzo Wakatsuki and Masataka Sata : Lipoprotein (a) is a risk factor of aortic valve calcification in patients with a risk of atherosclerosis, The Journal of Medical Investigation : JMI, Vol.70, No.3.4, 450-456, 2023.
(Summary)
Aortic valve calcification (AVC), which causes aortic stenosis (AS), is more common in elderly persons. Controlling for conventional risk variables did not, however, reduce the incidence of AS. Thus, residual risk factors of AS should be identified. We enrolled 513 patients who underwent coronary angiography with computed tomography because of suspicion of coronary artery disease (CAD) or ruling out of CAD before aortic valve replacement. Calcium volume was calculated with a commercially available application. Conventional and lipid-related risk factors including serum levels of Lp(a) were evaluated for all patients. Calcium volume and Lp(a) levels were significantly higher in patients who underwent aortic valve replacement than in those who did not. A single regression analysis showed that the calcium volume was positively associated with age and the Lp(a) levels and negatively associated with the estimated glomerular filtration rate. No statistical significance was observed for other risk factors, including oxidized low-density lipoprotein, omega-3 fatty acids levels. The multiple regression analysis revealed that age (P<0.001), female sex (P<0.05), Lp(a) (P<0.01), and hemoglobin A1c (P<0.01) were determinants of the calcium volume. The area under the curve in receiver operating characteristic analysis of Lp(a) for implementation of AVR was 0.65 at an Lp(a) cut-off level of 16 mg/dL. In conclusion, the serum Lp(a) level is a potent risk factor of AVC in patients with high risk of atherosclerosis. J. Med. Invest. 70 : 450-456, August, 2023.
PT Pham, Oyunbileg Bavuu, JR Kim-Kaneyama, XF Lei, T Yamamoto, K Otsuka, Kumiko Suto, Kenya Kusunose, Shusuke Yagi, Hirotsugu Yamada, Takeshi Soeki, Michio Shimabukuro, GN Barber, Masataka Sata and Daiju Fukuda : Innate Immune System Regulated by Stimulator of Interferon Genes, a Cytosolic DNA Sensor, Regulates Endothelial Function, Journal of the American Heart Association, Vol.12, No.22, e030084, 2023.
(Summary)
Background Sterile inflammation caused by metabolic disorders impairs endothelial function; however, the underlying mechanism by which hyperglycemia induces inflammation remains obscure. Recent studies have suggested that stimulator of interferon genes (STING), a key cytosolic DNA sensor in the innate immune system, contributes to the pathogenesis of inflammatory diseases. This study examines the role of the STING in endothelial dysfunction in streptozotocin-induced diabetic mice. Methods and Results Injection of streptozotocin promoted the expression of STING and DNA damage markers in the aorta of wild-type mice. Streptozotocin elevated blood glucose and lipid levels in both wild-type and STING-deficient mice, which showed no statistical differences. Genetic deletion of STING ameliorated endothelial dysfunction as determined by the vascular relaxation in response to acetylcholine (<0.001) and increased endothelial nitric oxide synthase phosphorylation in the aorta (<0.05) in STZ-injected mice. Endothelium-independent vascular response to sodium nitroprusside did not differ. Treatment with a direct STING agonist, cyclic GMP-AMP, or mitochondrial DNA increased inflammatory molecule expression (eg, and ) and decreased endothelial nitric oxide synthase phosphorylation in human umbilical vein endothelial cells, partially through the STING pathway. Cyclic GMP-AMP significantly impaired endothelial function of aortic segments obtained from wild-type mice, which was ameliorated in the presence of C-176, a STING inhibitor, or a neutralizing interferon-β antibody. Furthermore, the administration of C-176 ameliorated endothelial dysfunction in STZ-induced diabetic mice (<0.01). Conclusions The DNA damage response regulated by STING impairs endothelial function. STING signaling may be a potential therapeutic target of endothelial dysfunction caused by hyperglycemia.
TOMONORI Takahashi, H Iwano, K Shibayama, T Kitai, H Tanaka, Hirotsugu Yamada, Masataka Sata and Kenya Kusunose : The Clinical Utility of Noninvasive Forrester Classification in Acute Heart Failure from PREDICT Study, The American Journal of Cardiology, Vol.207, 75-81, 2023.
(Summary)
The Forrester classification plays a crucial role in comprehending the underlying pathophysiology of heart failure (HF) and is employed to categorize the severity and predict the outcomes of patients with acute HF. Our objective was to assess the predictive value of the Forrester classification, based on noninvasive hemodynamic measurements obtained through Doppler echocardiography at admission, in forecasting the short-term prognosis posthospitalization of patients with acute HF. Patients were recruited for the Prospect trial to elucidate the utility of EchocarDIography-based Cardiac ouTput in acute heart failure (PREDICT) study, a multicenter, prospective study conducted in Japan. Participants were stratified into 4 profiles using cardiac index (CI) and early mitral filling velocity (E)/early-diastolic mitral annular velocity (e') ratio obtained from Doppler echocardiography upon admission (profile I: CI >2.2, E/e' ≤15, profile II: CI >2.2, E/e' >15, profile III: CI ≤2.2, E/e' ≤15, profile IV: CI ≤2.2, E/e' >15). The primary composite outcome of the study was all-cause mortality or worsening HF during the 14 days of hospitalization. Cox proportional hazards model analysis was employed to identify prognostic factors during the observation period. A total of 270 subjects, with a mean age of 74 ± 14 years and a male proportion of 60%, were enrolled in the study. During the 14-day period of hospitalization, 58 participants (22%) had a composite outcome. Patients with low CI (i.e., profiles III and IV) demonstrated an elevated risk of composite outcome after adjusting for confounding variables, as evidenced by the adjusted hazard ratios of 5.85 (95% confidence interval 1.17 to 29.09, p <0.01, vs profile III) and 6.50 (95% confidence interval 1.53 to 27.68, p <0.01, vs profile IV) in comparison with profile I, respectively. In conclusion, the Forrester classification, derived from noninvasive Doppler echocardiography at admission, may predict early deterioration in patients hospitalized with acute HF.
Sanae Morita, Yukina Hirata, Susumu Nishio, TOMONORI Takahashi, Yoshihito Saijo, Hirotsugu Yamada, Masataka Sata and Kenya Kusunose : Correlation between energy loss index and B-type natriuretic peptide: a vector flow mapping study, Journal of Echocardiography, Vol.22, No.1, 25-33, 2023.
(Summary)
Vector Flow Mapping (VFM) and Energy Loss (EL) evaluation are emerging echocardiographic techniques that offer detailed insights into cardiac function. This study aimed to explore the relationship between EL parameters and B-type natriuretic peptide (BNP) levels, a well-established marker of heart failure severity. Our study prospectively enrolled 62 patients experiencing shortness of breath and suspected heart failure, who underwent echocardiography and had BNP levels measured between January 2018 and August 2020. Patients were stratified based on BNP levels, and their clinical and echocardiographic characteristics were evaluated. Univariate and multivariate regression analyses were performed to assess the correlation between BNP levels and various echocardiographic variables, including VFM parameters. Patients were stratified into two groups based on their BNP levels: BNP < 200 pg/ml (n = 53) and BNP 200 pg/ml (n = 9). Patients with BNP 200 pg/ml presented significantly different clinical and echocardiographic characteristics, such as older age, larger left ventricular mass and volume indices, higher pulmonary artery systolic pressure, higher E/e' ratio, and larger EL parameters. Multivariate regression analysis demonstrated the E/e' ratio and ELA (EL during Atrial contraction phase/A wave ratio as significant determinants of logBNP. Receiver operating characteristic curve analysis showed ELA/A > 36.0 J/m as a significant predictor of high BNP with 89% sensitivity and 85% specificity. ELA/A demonstrated an incremental diagnostic value over elevated left atrial pressure for predicting high BNP (C statistic = 0.98 vs 0.74, P = 0.006). This study provides novel insights into the potential utility of EL parameters as auxiliary indicators of cardiac load, thereby enhancing our understanding of heart failure.
Yuichiro Okushi, Yoshihito Saijyo, Hirotsugu Yamada, Hiroaki Toba, Robert Zheng, Hiromitsu Seno, TOMONORI Takahashi, Takayuki Ise, Koji Yamaguchi, Shusuke Yagi, Takeshi Soeki, Tetsuzo Wakatsuki, Masataka Sata and Kenya Kusunose : Effectiveness of surveillance by echocardiography for Cancer therapeutics-related cardiac dysfunction of patients with breast Cancer, Journal of Cardiology, Vol.82, No.6, 467-472, 2023.
(Summary)
Cancer therapeutics-related cardiac dysfunction (CTRCD) affect the prognosis of patients with breast cancer. Echocardiographic surveillance of patients treated with anti-human epidermal growth factor receptor type 2 (HER2) antibodies has been recommended, but few reports have provided evidence on patients with breast cancer only. We aimed to evaluate the effectiveness of echocardiographic surveillance for breast cancer patients. We identified 250 patients with breast cancer who were treated with anti-HER2 antibodies from July 2007 to September 2021. We divided 48 patients with echocardiographic surveillance every 3 months into the surveillance group and 202 patients without echocardiographic surveillance into the non-surveillance group. In the surveillance group, patients with a considerable reduction in global longitudinal strain of 15 % were considered for the initiation of cardioprotective drugs. The composite outcome of CTRCD and acute heart failure was the study endpoint. The mean age was 59 ± 12 years. During the follow-up period of 15 months (12-17 months), 12 patients reached the endpoint. The surveillance group had significantly lower incidence of the composite outcome (2.1 % vs. 5.5 %, adjusted odds ratio: 0.28, 95 % confidential intervals: 0.09-0.94; p = 0.039) and higher rates of prescriptions of cardioprotective drugs than the non-surveillance group. The incidence of cardiac complications was significantly lower in the surveillance group than the non-surveillance group, which supports the effectiveness of echocardiographic surveillance in patients with breast cancer.
Tomoya Hara, Daiju Fukuda, Byambasuren Ganbaatar, Phuong Tran Pham, Kunduziayi Aini, Arief Rahadian, Kumiko Suto, Shusuke Yagi, Kenya Kusunose, Hirotsugu Yamada, Takeshi Soeki and Masataka Sata : Olive mill wastewater and hydroxytyrosol inhibits atherogenesis in apolipoprotein E-deficient mice, Heart and Vessels, Vol.38, No.11, 1386-1394, 2023.
(Summary)
The Mediterranean diet, which is characterized by high consumption of olive oil, prevents cardiovascular disease. Meanwhile, olive mill wastewater (OMWW), which is obtained as a byproduct during olive oil production, contains various promising bioactive components such as water-soluble polyphenols. Hydroxytyrosol (HT), the major polyphenol in OMWW, has anti-oxidative and anti-inflammatory properties; however, the atheroprotective effects of OMWW and HT remain to be fully understood. Here, we investigated the effect of OMWW and HT on atherogenesis. Male 8-week-old apolipoprotein E-deficient mice were fed a western-type diet supplemented with OMWW (0.30%w/w) or HT (0.02%w/w) for 20 weeks. The control group was fed a non-supplemented diet. OMWW and HT attenuated the development of atherosclerosis in the aortic arch as determined by Sudan IV staining (P < 0.01, respectively) without alteration of body weight, plasma lipid levels, and blood pressure. OMWW and HT also decreased the production of oxidative stress (P < 0.01, respectively) and the expression of NADPH oxidase subunits (e.g., NOX2 and p22phox) and inflammatory molecules (e.g. IL-1β and MCP-1) in the aorta. The results of in vitro experiments demonstrated that HT inhibited the expression of these molecules that were stimulated with LPS in RAW264.7 cells, murine macrophage-like cells. OMWW and HT similarly attenuated atherogenesis. HT is a major component of water-soluble polyphenols in OMWW, and it inhibited inflammatory activation of macrophages. Therefore, our results suggest that the atheroprotective effects of OMWW are at least partially attributable to the anti-inflammatory effects of HT.
Kenya Kusunose, Shuichiro Kashima and Masataka Sata : Evaluation of the Accuracy of ChatGPT in Answering Clinical Questions on the Japanese Society of Hypertension Guidelines, Circulation Journal, Vol.87, No.7, 1030-1033, 2023.
(Summary)
To assist healthcare providers in interpreting guidelines, clinical questions (CQ) are often included, but not always, which can make interpretation difficult for non-expert clinicians. We evaluated the ability of ChatGPT to accurately answer CQs on the Japanese Society of Hypertension Guidelines for the Management of Hypertension (JSH 2019).Methods and Results: We conducted an observational study using data from JSH 2019. The accuracy rate for CQs and limited evidence-based questions of the guidelines (Qs) were evaluated. ChatGPT demonstrated a higher accuracy rate for CQs than for Qs (80% vs. 36%, P value: 0.005). ChatGPT has the potential to be a valuable tool for clinicians in the management of hypertension.
Natsumi Yamaguchi, Yoshitaka Kosaka, Akihiro Haga, Masataka Sata and Kenya Kusunose : Artificial intelligence-assisted interpretation of systolic function by echocardiogram, Open Heart, Vol.10, No.2, e002287., 2023.
(Summary)
Precise and reliable echocardiographic assessment of left ventricular ejection fraction (LVEF) is needed for clinical decision-making. Recently, artificial intelligence (AI) models have been developed to estimate LVEF accurately. The aim of this study was to evaluate whether an AI model could estimate an expert read of LVEF and reduce the interinstitutional variability of level 1 readers with the AI-LVEF displayed on the echocardiographic screen. This prospective, multicentre echocardiographic study was conducted by five cardiologists of level 1 echocardiographic skill (minimum level of competency to interpret images) from different hospitals. Protocol 1: Visual LVEFs for the 48 cases were measured without input from the AI-LVEF. Protocol 2: the 48 cases were again shown to all readers with inclusion of AI-LVEF data. To assess the concordance and accuracy with or without AI-LVEF, each visual LVEF measurement was compared with an average of the estimates by five expert readers as a reference. A good correlation was found between AI-LVEF and reference LVEF (r=0.90, p<0.001) from the expert readers. For the classification LVEF, the area under the curve was 0.95 on heart failure with preserved EF and 0.96 on heart failure reduced EF. For the precision, the SD was reduced from 6.1±2.3 to 2.5±0.9 (p<0.001) with AI-LVEF. For the accuracy, the root-mean squared error was improved from 7.5±3.1 to 5.6±3.2 (p=0.004) with AI-LVEF. AI can assist with the interpretation of systolic function on an echocardiogram for level 1 readers from different institutions.
Shusuke Yagi, Tomoya Hara, Hirotsugu Yamada, Kenya Kusunose, Takayuki Ise and Masataka Sata : Intimal Sarcoma of the Pulmonary Artery as an Embolic Cause of Sudden Death, Circulation Journal, Vol.87, No.7, 1036, 2023.
Kenya Kusunose, Yukina Hirata, Natsumi Yamaguchi, Y Kosaka, T Tsuji, J Kotoku and Masataka Sata : Deep learning approach for analyzing chest x-rays to predict cardiac events in heart failure, Frontiers in Cardiovascular Medicine, Vol.10, 1081628, 2023.
(Summary)
A deep learning (DL) model based on a chest x-ray was reported to predict elevated pulmonary artery wedge pressure (PAWP) as heart failure (HF). The aim of this study was to (1) investigate the role of probability of elevated PAWP for the prediction of clinical outcomes in association with other parameters, and (2) to evaluate whether probability of elevated PAWP based on DL added prognostic information to other conventional clinical prognostic factors in HF. We evaluated 192 patients hospitalized with HF. We used a previously developed AI model to predict HF and calculated probability of elevated PAWP. Readmission following HF and cardiac mortality were the primary endpoints. Probability of elevated PAWP was associated with diastolic function by echocardiography. During a median follow-up period of 58 months, 57 individuals either died or were readmitted. Probability of elevated PAWP appeared to be associated with worse clinical outcomes. After adjustment for readmission score and laboratory data in a Cox proportional-hazards model, probability of elevated PAWP at pre-discharge was associated with event free survival, independent of elevated left atrial pressure (LAP) based on echocardiographic guidelines ( < 0.001). In sequential Cox models, a model based on clinical data was improved by elevated LAP (= 0.005), and increased further by probability of elevated PAWP (< 0.001). In contrast, the addition of pulmonary congestion interpreted by a doctor did not statistically improve the ability of a model containing clinical variables (compared = 0.086). This study showed the potential of using a DL model on a chest x-ray to predict PAWP and its ability to add prognostic information to other conventional clinical prognostic factors in HF. The results may help to enhance the accuracy of prediction models used to evaluate the risk of clinical outcomes in HF, potentially resulting in more informed clinical decision-making and better care for patients.
T Tsuji, Yukina Hirata, Kenya Kusunose, Masataka Sata, S Kumagai, K Shiraishi and J Kotoku : Classification of chest X-ray images by incorporation of medical domain knowledge into operation branch networks., BMC Medical Imaging, Vol.23, No.1, 62, 2023.
(Summary)
This study was conducted to alleviate a common difficulty in chest X-ray image diagnosis: The attention region in a convolutional neural network (CNN) does not often match the doctor's point of focus. The method presented herein, which guides the area of attention in CNN to a medically plausible region, can thereby improve diagnostic capabilities. The model is based on an attention branch network, which has excellent interpretability of the classification model. This model has an additional new operation branch that guides the attention region to the lung field and heart in chest X-ray images. We also used three chest X-ray image datasets (Teikyo, Tokushima, and ChestX-ray14) to evaluate the CNN attention area of interest in these fields. Additionally, after devising a quantitative method of evaluating improvement of a CNN's region of interest, we applied it to evaluation of the proposed model. Operation branch networks maintain or improve the area under the curve to a greater degree than conventional CNNs do. Furthermore, the network better emphasizes reasonable anatomical parts in chest X-ray images. The proposed network better emphasizes the reasonable anatomical parts in chest X-ray images. This method can enhance capabilities for image interpretation based on judgment.
U Munkhjargal, Daiju Fukuda, B Ganbaatar, Kumiko Suto, Tomomi Matsuura, Takayuki Ise, Kenya Kusunose, Koji Yamaguchi, Shusuke Yagi, Hirotsugu Yamada, Takeshi Soeki, Tetsuzo Wakatsuki and Masataka Sata : A Selective Mineralocorticoid Receptor Blocker, Esaxerenone, Attenuates Vascular Dysfunction in Diabetic C57BL/6 Mice, Journal of Atherosclerosis and Thrombosis, Vol.30, No.4, 326-334, 2023.
(Summary)
Pharmacological blockade of mineralocorticoid receptors (MRs) is a potential therapeutic approach to reduce cardiovascular complications since MRs play a crucial role in cardiovascular regulation. Recent studies suggest that MR antagonists affect several extrarenal tissues, including vessel function. We investigated the effect of a novel nonsteroidal selective MR blocker, esaxerenone, on diabetes-induced vascular dysfunction. Diabetes was induced by a single dose of streptozotocin in 8-week-old male C57BL/6 mice. Esaxerenone (3 mg/kg/day) or a vehicle was administered by gavage to diabetic mice for 3 weeks. Metabolic parameters, plasma aldosterone levels, and parameters related to renal function were measured. Endothelium-dependent or -independent vascular responses of the aortic segments were analyzed with acetylcholine or sodium nitroprusside, respectively. Human umbilical vein endothelial cells (HUVECs) were used for the in vitro study. Induction of diabetes elevated plasma aldosterone level (P<0.05) and impaired endothelium-dependent vascular relaxation (P<0.05). The administration of esaxerenone ameliorated the endothelial dysfunction (P<0.01) without the alteration of metabolic parameters, blood pressure, and renal function. Esaxerenone improved the eNOS phosphorylation in the aorta obtained from diabetic mice (P<0.05) compared with that in the vehicle-treated group. Furthermore, a major MR agonist, aldosterone, decreased eNOS phosphorylation and increased eNOS phosphorylation in HUVECs, which recovered with esaxerenone. Esaxerenone ameliorated the endothelium-dependent vascular relaxation caused by aldosterone in the aortic segments obtained from C57BL/6 mice (P<0.001). Esaxerenone attenuates the development of diabetes-induced endothelial dysfunction in mice. These results suggest that esaxerenone has potential vascular protective effects in individuals with diabetes.
TOMONORI Takahashi, Kenya Kusunose, S Hayashi, Robert Zheng, Natsumi Yamaguchi, Sae Morita, Yukina Hirata, Susumu Nishio, Yoshihito Saijyo, Takayuki Ise, Koji Yamaguchi, Shusuke Yagi, Hirotsugu Yamada, Takeshi Soeki, Tetsuzo Wakatsuki and Masataka Sata : Isoproterenol loading transesophageal echocardiography in atrial fibrillation, The International Journal of Cardiovascular Imaging, Vol.39, No.3, 511-518, 2023.
(Summary)
In patients with sludge or severe spontaneous echo contrast (SEC) in the left atrial appendage (LAA), cases with isoproterenol loading transesophageal echocardiography (ISP-TEE) have been reported to identify the presence of thrombus in the LAA. This study aimed to assess the validity and hemodynamic changes of ISP-TEE in the LAA. We prospectively enrolled patients with atrial fibrillation (AF) who underwent ISP-TEE. The degree of sludge/SEC was categorized as being either absent (grade 0), mild SEC (grade 1), moderate SEC (grade 2), severe SEC or sludge (grade 3). The hemodynamic evaluation was performed by measuring LAA flow velocity, LAA tissue Doppler imaging (LAA-TDI) velocity, and pulmonary vein systolic forward flow velocity (PVS). In total, 35 patients (mean age 71 ± 7 years; 71% male) underwent ISP-TEE. Among 35 patients, 30 patients had grade 3 or 2 SEC, 5 patients had grade 1 SEC. After ISP loading, 23 patients (66% of all patients) showed improved sludge/SEC and one patient was diagnosed with thrombus in the LAA. There were 25 patients with grade 1 SEC, or no SEC (classified as Group1), 10 patients had residual sludge or grade 2 to 3 SEC (classified as Group2) after ISP administration. LAA flow, LAA-TDI, and PVS velocities were significantly higher in group 1 than in group 2 after ISP administration. There was no complication during the examination and after 24 h and 3 months. ISP infusion may be a potential tool to recognize LAA thrombus under the sludge/SEC during TEE in AF.
(Keyword)
Humans / Male / Middle Aged / Aged / Female / Atrial Fibrillation / Echocardiography, Transesophageal / Isoproterenol / Sewage / Atrial Appendage / Predictive Value of Tests / Thrombosis
Kenya Kusunose, Yuichiro Okushi, Y Okayama, Robert Zheng, M Nakai, Y Sumita, Takayuki Ise, Koji Yamaguchi, Shusuke Yagi, Hirotsugu Yamada, Takeshi Soeki, Tetsuzo Wakatsuki and Masataka Sata : Benefits of guideline-directed medical therapy to loop diuretics in management of heart failure, The Journal of Medical Investigation : JMI, Vol.70, No.1.2, 41-53, 2023.
Yutaka Kawabata, Tetsuzo Wakatsuki, Koji Yamaguchi, Daiju Fukuda, Hiroyuki Ito, Tomomi Matsuura, Kenya Kusunose, Takayuki Ise, Shusuke Yagi, Hirotsugu Yamada, Takeshi Soeki, Y Tsuruo and Masataka Sata : Association of Microluminal Structures Assessed by Optical Coherence Tomography With Local Inflammation in Adjacent Epicardial Adipose Tissue and Coronary Plaque Characteristics in Fresh Cadavers, Circulation Journal, Vol.87, No.2, 329-335, 2023.
(Summary)
Coronary intraplaque microluminal structures (MS) are associated with plaque vulnerability, and the inward progression of vascular inflammation from the adventitia towards the media and intima has also been demonstrated. Therefore, in the present study we investigated the relationships among MS, local inflammation in adjacent epicardial adipose tissue (EAT), and coronary plaque characteristics.Methods and Results: Optical coherence tomography (OCT) revealed MS in the left anterior descending coronary artery in 10 fresh cadaveric hearts. We sampled 30 lesions and subdivided them based on the presence of MS: MS (+) group (n=19) and MS (-) group (n=11). We measured inflammatory molecule levels in the adjacent EAT and percentage lipid volume assessed by integrated backscatter intravascular ultrasound in each lesion. The expression levels of vascular endothelial growth factor B and C-C motif chemokine ligand 2 were significantly higher in the MS (+) group than in the MS (-) group (0.9±0.7 vs. 0.2±0.2 arbitrary units (AU), P=0.04 and 1.5±0.5 vs. 0.6±0.7 AU, P=0.02, respectively). Percentage lipid volume was significantly higher in the MS (+) group than in the MS (-) group (38.7±16.5 vs. 23.7±10.9%, P=0.03). Intraplaque MS observed on OCT were associated with lipid-rich plaques and local inflammation in the adjacent EAT. Collectively, these results suggest that local inflammation in the EAT is associated with coronary plaque vulnerability via MS.
Tomonori Takahashi, Kenya Kusunose, Robert Zheng, Natsumi Yamaguchi, Yukina Hirata, Susumu Nishio, Yoshihito Saijyo, Takayuki Ise, Koji Yamaguchi, Shusuke Yagi, Hirotsugu Yamada, Takeshi Soeki, Tetsuzo Wakatsuki and Masataka Sata : Association between cardiovascular risk factors and left ventricular strain distribution in patients without previous cardiovascular disease, Journal of Echocardiography, Vol.20, No.4, 208-215, 2022.
(Summary)
Some cardiovascular (CV) risk factors, such as hypertension and diabetes mellitus, have been reported to reduce left ventricular (LV) longitudinal strain (LS) even in patients with preserved LV ejection fraction. We hypothesized that multiple CV risk factors might cause changes in myocardial strain. Our study aimed to assess the association between multiple CV risk factors and strain in patients without previous CV disease (CVD). We retrospectively evaluated 137 patients without CVD, who underwent echocardiography at our institution between May 2017 and February 2020. They were divided into four groups based on the number of risk factors (group 0: no risk factor, group 1: one risk factor, group 2: two risk factors, and groups 3: three or four risk factors). Risk factors were hypertension, dyslipidemia, diabetes mellitus, and chronic kidney disease. Absolute values of global LS (GLS) and relative apical LS ratio (RALSR) defined using the equation: average apical LS/(average basal LS + average mid LS) and was used as a marker of strain distribution. Out of 137 patients, group 0 had 35 patients, group 1 had 35 patients, group 2 had 32 patients, and group 3 had 35 patients. GLS was 22.4 ± 2.0%, 21.7 ± 2.1%, 21.3 ± 1.8%, 20.7 ± 2.2%, and RALSR was 0.64 ± 0.06, 0.66 ± 0.06, 0.68 ± 0.08, 0.69 ± 0.07 in groups 0-3, respectively. The one-way ANOVA detected significant differences between groups in GLS (p = 0.005) and RALSR (p = 0.037), respectively. Group 3 had a significantly lower GLS and higher RALSR than group 0 (p < 0.05). In patients without previous CVD, LS decreased especially from the basal segment as the number of cardiovascular risks increased. The segmental LS may be markers of occult LV dysfunction in patients with CV risk factors.
O Bavuu, Daiju Fukuda, B Ganbaatar, Tomomi Matsuura, Takayuki Ise, Kenya Kusunose, Koji Yamaguchi, Shusuke Yagi, Hirotsugu Yamada, Takeshi Soeki, Tetsuzo Wakatsuki and Masataka Sata : Esaxerenone, a selective mineralocorticoid receptor blocker, improves insulin sensitivity in mice consuming high-fat diet., European Journal of Pharmacology, 175190, 2022.
(Summary)
Esaxerenone is a novel, non-steroidal selective mineralocorticoid receptor (Csige et al.) blocker. MR activation plays a crucial role in the development of cardiovascular and metabolic diseases. In this study, we investigated the effects of esaxerenone on various metabolic parameters in mice. Esaxerenone (3 mg/kg/day) was orally administered to high-fat diet (HFD)-fed male C57BL/6 mice. Mice fed a normal diet (ND) served as controls. Glucose and insulin tolerance, plasma lipid levels, and transaminase levels were assessed as metabolic parameters. Macrophage accumulation in the adipose tissue was evaluated using histological analysis. 3T3-L1 adipocytes, HepG2 cells, and C2C12 myotubes were used for in vitro experiments. Gene expression and insulin signaling were examined using quantitative RT-PCR and western blotting, respectively. HFD successfully induced insulin resistance compared with that in ND. Esaxerenone ameliorated insulin resistance (P < 0.05) without altering other metabolic parameters, such as the lipid profile. Esaxerenone administration tended to decrease plasma transaminase levels compared with those in the non-treated group. In the adipose tissue, esaxerenone decreased macrophage accumulation (P < 0.05) and increased the expression levels of adiponectin and PPARγ. Aldosterone significantly decreased the expression levels of PPARγ and adiponectin in 3T3-L1 adipocytes. Furthermore, aldosterone attenuated insulin-induced Akt phosphorylation in 3T3-L1 adipocytes, HepG2 cells, and C2C12 myotubes in a dose-dependent manner (P < 0.01). These effects were ameliorated by pretreatment with esaxerenone. Esaxerenone ameliorated insulin resistance in HFD-fed mice. Reduction of inflammation and improvement in insulin signaling may underlie the beneficial effects of esaxerenone.
Kenya Kusunose, Hirotsugu Yamada, Y Saijo, Susumu Nishio, Yukina Hirata, Takayuki Ise, Koji Yamaguchi, Daiju Fukuda, Shusuke Yagi, Takeshi Soeki, Tetsuzo Wakatsuki and Masataka Sata : Clinical course and decision-making in heart failure by preload stress echocardiography: a preliminary study, ESC Heart Failure, Vol.9, No.6, 4020-4029, 2022.
(Summary)
Abnormal left ventricular diastolic response to preload stress can be an early marker of heart failure (HF). The aim of this study was to assess clinical course in patients with HF with preserved ejection fraction (HFpEF) who underwent preload stress echocardiography. In the subgroup analysis, we assessed the prognosis of patients with unstable signs during preload stress classified by treatment strategies. We prospectively conducted preload stress echocardiographic studies between January 2006 and December 2013 in 211 patients with HFpEF. Fifty-eight patients had abnormal diastolic reserve during preload stress (unstable impaired relaxation: unstable IR). Of 58 patients with unstable IR, 19 patients were assigned to additional therapy by increased or additional therapy and 39 patients were assigned to standard therapy. Composite outcomes were prespecified as the primary endpoint of death and hospitalization for deteriorating HF. During a median period of 6.9 years, 19 patients (33%) reached the composite outcome. Unstable group with standard therapy had significantly shorter event-free survival than stable group. Patients with uptitration of therapy had longer event-free survival than those with standard therapy group after adjustment of laboratory data (hazard ratio, 0.20, 95% confidence interval, 0.05-0.90; P = 0.036); the 10 year event-free survival in patients with and without uptitration of therapy was 93% and 51%, respectively (P = 0.023). Patients with unstable sign had significantly shorter event-free survival than patients with stable sign. After additional therapy, the prognosis of patients with unstable signs improved. This technique may impact decision-making for improving their prognosis.
Koji Yamaguchi, Tetsuzo Wakatsuki, Tomomi Matsuura, Kazuhisa Matsumoto, Yutaka Kawabata, Muneyuki Kadota, Kenya Kusunose, Takayuki Ise, Shusuke Yagi, Daiju Fukuda, Hirotsugu Yamada, Takeshi Soeki and Masataka Sata : Drug-coated balloon angioplasty for severe pulmonary vein stenosis resulting from cryoballoon ablation for atrial fibrillation, Journal of Cardiology Cases, Vol.26, 35-38, 2022.
Y Okushi, Kenya Kusunose, M Nakai, Y Sumita, Takayuki Ise, Koji Yamaguchi, Shusuke Yagi, Daiju Fukuda, Hirotsugu Yamada, Takeshi Soeki, Tetsuzo Wakatsuki and Masataka Sata : Comparison of Direct Oral Anticoagulants for Acute Hospital Mortality in Venous Thromboembolism, American Journal of Cardiovascular Drugs, Vol.22, No.4, 407-416, 2022.
(Summary)
The choice of direct oral anticoagulants (DOACs) for venous thromboembolism (VTE) is at the physician's discretion; however, it is useful to know the differences in the clinical data of DOACs to help physicians choose. We aimed to compare the mortality associated with the use of rivaroxaban, edoxaban, and apixaban in clinical practice. We identified 38,245 patients with first hospitalization for VTE from the Diagnosis Procedure Combination database in the Japanese Registry of All Cardiac and Vascular Datasets (JROAD-DPC). We classified patients into three groups by DOAC (rivaroxaban and edoxaban group, rivaroxaban and apixaban group, and edoxaban and apixaban group) and compared the in-hospital mortality and bleeding risk by propensity score (PS) matching in each group. After PS matching, patients with rivaroxaban use had significantly lower total in-hospital mortality (1.2% vs. 2.1%; odds ratio [OR] 0.55, p = 0.012) and in-hospital mortality within 21 days (0.4% vs. 1.0%; OR 0.41, p = 0.020) and 28 days (0.7% vs. 1.3%; OR 0.53, p = 0.042) than patients with apixaban use. In the subanalysis, significant differences were only observed in patients younger than 80 years of age, patients with pulmonary embolism, and patients without heart failure. There was no significant difference in in-hospital mortality in the other groups and in the rate of bleeding events among the three groups. On PS-matched analysis, there was a difference in in-hospital mortality, especially in the rivaroxaban and apixaban group. Identifying the clinical characteristics of patients associated with each DOAC, as well as prognosis, will be useful in determining treatment strategies for VTE.
Kenya Kusunose, Yukina Hirata, Natsumi Yamaguchi, Y Kosaka, T Tsuji, J Kotoku and Masataka Sata : Deep Learning for Detection of Exercise-Induced Pulmonary Hypertension Using Chest X-Ray Images, Frontiers in Cardiovascular Medicine, Vol.9, 891703, 2022.
(Summary)
Stress echocardiography is an emerging tool used to detect exercise-induced pulmonary hypertension (EIPH). However, facilities that can perform stress echocardiography are limited by issues such as cost and equipment. We evaluated the usefulness of a deep learning (DL) approach based on a chest X-ray (CXR) to predict EIPH in 6-min walk stress echocardiography. The study enrolled 142 patients with scleroderma or mixed connective tissue disease with scleroderma features who performed a 6-min walk stress echocardiographic test. EIPH was defined by abnormal cardiac output (CO) responses that involved an increase in mean pulmonary artery pressure (mPAP). We used the previously developed AI model to predict PH and calculated PH probability in this cohort. EIPH defined as ΔmPAP/ΔCO >3.3 and exercise mPAP >25 mmHg was observed in 52 patients, while non-EIPH was observed in 90 patients. The patients with EIPH had a higher mPAP at rest than those without EIPH. The probability of PH based on the DL model was significantly higher in patients with EIPH than in those without EIPH. Multivariate analysis showed that gender, mean PAP at rest, and the probability of PH based on the DL model were independent predictors of EIPH. A model based on baseline parameters (age, gender, and mPAP at rest) was improved by adding the probability of PH predicted by the DL model (AUC: from 0.65 to 0.74; = 0.046). Applying the DL model based on a CXR may have a potential for detection of EIPH in the clinical setting.
Hiroyuki Iwano, Hiroto Utsunomiya, Kentaro Shibayama, Hidekazu Tanaka, Akihiro Isotani, Toshinari Onishi, Masaru Obokata, Masaki Izumo, Kenya Kusunose, Atsuko Furukawa, Masahiro Yamada, Takeshi Kitai, Tetsuari Onishi, Masayoshi Yamamoto, Shunsuke Sasaki, Kotaro Nochioka, Yoichi M. Ito and Toshihisa Anzai : Results of PRospect trial to Elucidate the utility of EchocarDiography-based Cardiac ouTput in acute heart failure (PREDICT)., Journal of Cardiology, 2022.
(Summary)
The predictive value of echocardiographic parameters for early worsening heart failure (WHF), worsening of symptoms of heart failure requiring intensification of therapy during an admission for acute decompensated heart failure (ADHF), has not been elucidated. Sixteen centers in Japan prospectively enrolled 303 ADHF hospitalized patients who did not receive positive inotropic agents as an initial therapy. Physical and Doppler echocardiographic examinations were performed before the initial therapy and the association of low output findings and occurrence of early WHF were tested. Early WHF occurred in 63 patients with a median duration of 6 (IQR: 2-23) hours from the administration of the initial therapy. In patients with left ventricular (LV) ejection fraction <40% (N = 153), echocardiographic stroke volume index, and cardiac index showed greater c-index [95% confidence interval, 0.71 (0.61-0.79) and 0.72 (0.63-0.80), respectively] compared to single low perfusion finding (symptomatic hypotension, reduced pulse pressure, and impaired mentation) other than cool extremities. When physical findings were combined (low perfusion score), the predictive ability improved to the similar levels of echocardiographic LV output parameters [c-index: 0.69 (0.60-0.76)]. However, addition of cardiac index significantly improved the prognostic ability when added to low perfusion score [0.82 (0.74-0.87), p < 0.001]. In contrast, in patients with LV ejection fraction ≥40% (N = 150), low perfusion score, rather than LV output parameters, was predictive of early WHF [c-index: 0.73 (0.56-0.85)]. We demonstrated the predictive value of echocardiographic LV output indices for early WHF in ADHF patients with LV systolic dysfunction. These data support the motivation for routine use of echocardiography for initial assessment of ADHF.
A Mizuno, Kenya Kusunose, T Kishi, J Rewley, C Matsumoto, Y Sahashi, M Ishida, S Sanada, M Fukuda, T Sugimoto, M Hirano, D Yoneoka, Masataka Sata, T Anzai and K Node : Impact of Tweeting Summaries by the Japanese Circulation Society Official Account on Article Viewership - Pilot Trial, Circulation Journal, Vol.86, No.4, 715-720, 2022.
(Summary)
The impact of promotional tweets from the official journal account (forCirculation JournalandCirculation Reports) on article viewership has not been thoroughly evaluated.Methods and Results:We retrospectively collected journal viewership data forCirculation JournalandCirculation Reportsfrom March 2021 to August 2021. We compared viewership between articles with (n=15) and without (n=250) tweets. After 1 : 4 propensity score matching (15 tweeted articles and 60 non-tweeted matched controls), journal viewership metrics within 7 days of the tweeting date (and the hypothetical tweeting date), was larger in tweeted articles than non-tweeted articles (median [interquartile range] Abstract page views 89 [60-104] vs. 18 [8-41]). This pilot study suggests a positive relationship between journal-posted promotional tweets and article viewership.
(Keyword)
Benchmarking / Humans / Japan / Pilot Projects / Retrospective Studies / Social Media
Kazuhisa Matsumoto, Takeshi Tobiume, Tomomi Matsuura, Takayuki Ise, Kenya Kusunose, Koji Yamaguchi, Shusuke Yagi, Daiju Fukuda, Tetsuzo Wakatsuki, Hirotsugu Yamada, Takeshi Soeki and Masataka Sata : Evaluation of the input site and characteristics of the antegrade fast pathway based on three-dimensional bi-atrial stimulus-ventricle mapping, Journal of Interventional Cardiac Electrophysiology, Vol.63, No.2, 417-424, 2022.
(Summary)
Previous studies examined the right atrial (RA) input site of the antegrade fast pathway (AFp) (AFpI). However, the left atrial (LA) input to the atrioventricular (AV) node has not been extensively evaluated. In this study, we created three-dimensional (3-D) bi-atrial stimulus-ventricle (St-V) maps and analyzed the input site and characteristics of the AFp in both the RA and LA. Forty-four patients diagnosed with atrial fibrillation or WPW syndrome were included in this study. Three-dimensional bi-atrial St-V mapping was performed using an electroanatomical mapping system. Sites exhibiting the minimal St-V interval (MinSt-V) were defined as AFpIs and were classified into seven segments, four in the RA (F, S, M, and I) and three in the LA (M1, M2, and M3). By combining the MinSt-V in the RA and LA, the AFpIs were classified into three types: RA, LA, and bi-atrial (BA) types. The clinical and electrophysiological characteristics were compared. AFpIs were most frequently observed at site S in the RA (34%) and M2 in the LA (50%), and the BA type was the most common (57%). AFpIs in the LA were recognized in 75% of the patients. There were no clinical or electrophysiological indicators for predicting AFpI sites. Three-dimensional bi-atrial St-V maps could classify AFpIs in both the RA and LA. AFpIs in the LA were frequently recognized. There were no significant clinical or electrophysiological indicators for predicting AFpI sites, and 3-D bi-atrial St-V mapping was the only method to reveal the precise AFp input site.
Kenya Kusunose, Robert Zheng, Hirotsugu Yamada and Masataka Sata : How to standardize the measurement of left ventricular ejection fraction, Journal of Medical Ultrasonics, Vol.49, No.1, 35-43, 2022.
Shusuke Yagi, Daiju Fukuda, Takayuki Ise, Koji Yamaguchi, Kenya Kusunose, Muneyuki Kadota, Yutaka Kawabata, Tomomi Matsuura, Tomohiro Soga, Hirotsugu Yamada, Takeshi Soeki, Tetsuzo Wakatsuki, Shinji Kawahito and Masataka Sata : Clinical clerkship students' preferences and satisfaction regarding online lectures during the COVID-19 pandemic, BMC Medical Education, Vol.22, No.1, 43, 2022.
(Summary)
The COVID-19 pandemic has caused an unprecedented disruption in medical education. Students and lecturers had to adapt to online education. The current study aimed to investigate the level of satisfaction and future preference for online lectures among clinical clerkship students and elucidated the factors that affect these outcomes. We selected a sample of 114 medical students undergoing clinical clerkship during the COVID-19 pandemic. We conducted onsite lectures before the pandemic and online lectures after the outbreak. A survey was conducted, and the sample included students and 17 lecturers. The average scores of total satisfaction and future preference related to online lectures were computed. Students' scores on total satisfaction with online lectures and their future preference were higher than those for onsite lectures. Scores on the ease of debating dimension were low and those on accessibility of lectures in online lectures were higher than those in onsite lectures. There was no difference between the two groups in the scores on the comprehensibility and ease of asking questions dimensions. Results of the multiple regression analysis revealed that accessibility determined total satisfaction, and future preference was determined by comprehensibility as well as accessibility. Contrary to students' future preferences, lecturers favored onsite lectures to online ones. Online lectures are an acceptable mode of teaching during the COVID-19 pandemic for students undergoing clinical clerkship. Online lectures are expected to become more pervasive to avoid the spread of COVID-19.
(Keyword)
COVID-19 / Clinical Clerkship / Humans / Pandemics / Personal Satisfaction / SARS-CoV-2 / Students, Medical
Nao Ishii, Kenya Kusunose, A Shono, K Matsumoto, Susumu Nishio, Natsumi Yamaguchi, Yukina Hirata, Tomomi Matsuura, Takayuki Ise, Koji Yamaguchi, Shusuke Yagi, Daiju Fukuda, Hirotsugu Yamada, Takeshi Soeki, Tetsuzo Wakatsuki and Masataka Sata : Effects of Radiofrequency Catheter Ablation on Cardiac Reserve Using Preload Stress Echocardiography in Paroxysmal and Persistent Atrial Fibrillation, The American Journal of Cardiology, Vol.168, 71-77, 2022.
(Summary)
The effects of catheter ablation on exercise tolerance and quality of life in patients with atrial fibrillation (AF) have been reported. We assessed cardiac function in more detail using the leg positive pressure (LPP) technique and found that contractile reserve is particularly important in relation to exercise tolerance and prognosis. In this study, we used the LPP technique to examine changes in contractile reserve immediately after ablation and 6 months later. We prospectively enrolled patients who underwent catheter ablation for AF at 2 institutes. We performed LPP stress echocardiography 2 to 3 days after (FU-1) and 6 months after (FU-2) ablation to examine changes in cardiac function indexes. The primary end point was improvement in contractile reserve. Ultimately, 109 patients (mean age 67.4 ± 9.6 years; 70% men) underwent 2 sessions of LPP stress echocardiography. The median CHADS-VAS score was 2 (interquartile range 13). From FU-1 to FU-2, the change in the stroke volume index after the LPP maneuver increased in patients with paroxysmal and persistent AF with low CHADS-VAS scores (both p <0.05). Regardless of AF subtype, contractile reserve at FU-2 improved in patients with low CHADS-VAS scores compared with that at FU-1. In contrast, patients with high CHADS-VAS scores had no change. In conclusion, patients with AF with a low CHADS-VAS score had improved contractile reserve after ablation, whereas patients with high scores did not show any improvement. Aggressive interventions in patients with high scores may lead to better management after catheter ablation.
(Keyword)
Aged / Atrial Fibrillation / Catheter Ablation / Echocardiography, Stress / Female / Humans / Male / Middle Aged / Predictive Value of Tests / Quality of Life / Risk Assessment / Risk Factors / Treatment Outcome
Kenya Kusunose, H Yoshida, A Tanaka, H Teragawa, Y Akasaki, Y Fukumoto, K Eguchi, H Kamiya, K Kario, Hirotsugu Yamada, Masataka Sata, K Node and Munehide Matsuhisa : Effect of febuxostat on left ventricular diastolic function in patients with asymptomatic hyperuricemia: a sub analysis of the PRIZE Study, Hypertension Research, Vol.45, No.1, 106-115, 2022.
Kumiko Suto, Daiju Fukuda, Masakazu Shinohara, Byambasuren Ganbaatar, Shusuke Yagi, Kenya Kusunose, Hirotsugu Yamada, Takeshi Soeki, Ken-Ichi Hirata and Masataka Sata : Pemafibrate, A Novel Selective Peroxisome Proliferator-Activated Receptor α Modulator, Reduces Plasma Eicosanoid Levels and Ameliorates Endothelial Dysfunction in Diabetic Mice., Journal of Atherosclerosis and Thrombosis, Vol.28, No.12, 1349-1360, 2021.
(Summary)
Various pathological processes related to diabetes cause endothelial dysfunction. Eicosanoids derived from arachidonic acid (AA) have roles in vascular regulation. Fibrates have recently been shown to attenuate vascular complications in diabetics. Here we examined the effects of pemafibrate, a selective peroxisome proliferator-activated receptor α modulator, on plasma eicosanoid levels and endothelial function in diabetic mice. Diabetes was induced in 7-week-old male wild-type mice by a single injection of streptozotocin (150 mg/kg). Pemafibrate (0.3 mg/kg/day) was administered orally for 3 weeks. Untreated mice received vehicle. Circulating levels of eicosanoids and free fatty acids were measured using both gas and liquid chromatography-mass spectrometry. Endothelium-dependent and endothelium-independent vascular responses to acetylcholine and sodium nitroprusside, respectively, were analyzed. Pemafibrate reduced both triglyceride and non-high-density lipoprotein -cholesterol levels (P<0.01), without affecting body weight. It also decreased circulating levels of AA (P<0.001), thromboxane B (P<0.001), prostaglandin E, leukotriene B (P<0.05), and 5-hydroxyeicosatetraenoic acid (P<0.001), all of which were elevated by the induction of diabetes. In contrast, the plasma levels of 15-deoxy-Δ-prostaglandin J, which declined following diabetes induction, remained unaffected by pemafibrate treatment. In diabetic mice, pemafibrate decreased palmitic acid (PA) and stearic acid concentrations (P<0.05). Diabetes induction impaired endothelial function, whereas pemafibrate ameliorated it (P<0.001). The results of ex vivo experiments indicated that eicosanoids or PA impaired endothelial function. Pemafibrate diminished the levels of vasoconstrictive eicosanoids and free fatty acids accompanied by a reduction of triglyceride. These effects may be associated with the improvement of endothelial function by pemafibrate in diabetic mice.
Kenya Kusunose, Miharu Arase, Robert Zheng, Yukina Hirata, Susumu Nishio, Takayuki Ise, Koji Yamaguchi, Daiju Fukuda, Shusuke Yagi, Hirotsugu Yamada, Takeshi Soeki, Tetsuzo Wakatsuki and Masataka Sata : Clinical Utility of Overlap Time for Incomplete Relaxation to Predict Cardiac Events in Heart Failure: Incomplete relaxation in heart failure, Journal of Cardiac Failure, Vol.27, No.11, 1222-1230, 2021.
(Summary)
The overlap time of transmitral flow can be a novel marker of subclinical left ventricular (LV) dysfunction for predicting adverse events in heart failure (HF). We aimed to 1) investigate the role of overlap time of E-A wave in association with clinical parameters, and 2) evaluate whether the overlap time could add prognostic information with respect to other conventional clinical prognosticators in HF. We prospectively evaluated 153 patients hospitalized with HF (mean age 68±15 years; 63% male). The primary endpoint was readmission following HF and cardiac death. During a median period of 25 months, 43 patients were either readmitted or died. Overlap time appeared to be associated with worse outcomes. After adjustment for readmission score and ratio of diastolic filling period and cardiac cycle length in a Cox proportional-hazards model, overlap time was associated with event free survival, independent of elevated left atrial pressure (LAP) based on guidelines. When overlap time was added to the model based on clinical variables and elevated LAP, the C-statistic significantly improves from 0.70 (95% CI: 0.63-0.77) to 0.77 (95% CI: 0.69-0.83, compared P=0.035). This preliminary study suggested that prolonged overlap time may have potential for predicting readmission and cardiac mortality risk assessment in HF.
Robert Zheng, Kenya Kusunose, Y Okushi, Y Okayama, M Nakai, Y Sumita, Takayuki Ise, Koji Yamaguchi, Shusuke Yagi, Daiju Fukuda, Hirotsugu Yamada, Takeshi Soeki, Tetsuzo Wakatsuki and Masataka Sata : Impact of cancer on short-term in-hospital mortality after primary acute myocardial infarction, Open Heart, Vol.8, No.2, e00186, 2021.
Kenya Kusunose, Hironori Takahashi, Susumu Nishio, Yukina Hirata, Robert Zheng, Takayuki Ise, Koji Yamaguchi, Shusuke Yagi, Daiju Fukuda, Hirotsugu Yamada, Takeshi Soeki, Tetsuzo Wakatsuki, Kenji Shimada, Yasuhisa Kanematsu, Yasushi Takagi and Masataka Sata : Predictive value of left atrial function for latent paroxysmal atrial fibrillation as the cause of embolic stroke of undetermined source, Journal of Cardiology, Vol.78, No.5, 355-361, 2021.
(Summary)
In patients with embolic stroke of undetermined source (ESUS), paroxysmal atrial fibrillation (AF) is often diagnosed, however, the risk of paroxysmal AF in ESUS has not been well described. Several studies have suggested a linkage between left atrial (LA) functional parameters and risk of AF in stroke patients. The aim of this study was to assess the role of LA functional parameters as predictors of latent paroxysmal AF in ESUS on admission. Between January 2015 and December 2019, consecutive stroke patients with suspected ESUS at admission were prospectively included in this study. They were under hospital electrocardiographic monitoring for detection of new-onset AF. Various echocardiographic parameters including left atrial strain were assessed for association with new-onset AF. We gathered 1082 consecutive patients with ischemic stroke. After exclusions, 121 patients with suspected ESUS at admission formed the study cohort. New-onset AF was detected in 46 (38%) patients during hospital electrocardiographic monitoring (median follow-up: 18 days). LA pump and reservoir strains were significantly and independently associated with new-onset AF. Receiver operating characteristic analysis for the association with new-onset AF showed that the areas under the curve (AUCs) of clinical parameters plus one of each strain (LA pump strain: AUC: 0.86±0.04 and LA reservoir strain: AUC: 0.76±0.05) models were significantly better than plus LA volume index (AUC: 0.68±0.04, compared p-values <0.05). LA strain was significantly associated with new development of AF. Patients with impaired LA function at admission should be carefully monitored to find AF.
Kenya Kusunose, Yuichiro Okushi, Yoshihiro Okayama, Robert Zheng, Michikazu Nakai, Yoko Sumita, Takayuki Ise, Koji Yamaguchi, Shusuke Yagi, Daiju Fukuda, Hirotsugu Yamada, Takeshi Soeki, Tetsuzo Wakatsuki and Masataka Sata : Use of Echocardiography and Heart Failure In-Hospital Mortality from Registry Data in Japan., Journal of Cardiovascular Development and Disease, Vol.8, No.10, 124, 2021.
(Summary)
Echocardiography requires a high degree of skill on the part of the examiner, and the skill may be more improved in larger volume centers. This study investigated trends and outcomes associated with the use and volume of echocardiographic exams from a real-world registry database of heart failure (HF) hospitalizations. This study was based on the Diagnosis Procedure Combination database in the Japanese Registry of All Cardiac and Vascular Datasets (JROAD-DPC). A first analysis was performed to assess the trend of echocardiographic examinations between 2012 and 2016. A secondary analysis was performed to assess whether echocardiographic use was associated with in-hospital mortality in 2015. During this period, the use of echocardiography grew at an average annual rate of 6%. Patients with echocardiography had declining rates of hospital mortality, and these trends were associated with high hospitalization costs. In the 2015 sample, a total of 52,832 echocardiograms were examined, corresponding to 65.6% of all HF hospital admissions for that year. We found that the use and volume of echocardiography exams were associated with significantly lower odds of all-cause hospital mortality in heart failure (adjusted odds ratio (OR): 0.48 for use of echocardiography and 0.78 for the third tertile; both < 0.001). The use of echocardiography was associated with decreased odds of hospital mortality in HF. The volumes of echocardiographic examinations were also associated with hospital mortality.
Shusuke Yagi, T Takahashi, K Murakami, M Azuma, M Sugano, R Miyamoto, M Niki, Hirotsugu Yamada, Yutaka Kawabata, Tani Akihiro, Daiju Fukuda, Muneyuki Kadota, Takayuki Ise, Kenya Kusunose, Takeshi Tobiume, Tomomi Matsuura, Koji Yamaguchi, Takeshi Soeki, Tetsuzo Wakatsuki, H Hata and Masataka Sata : Infective Endocarditis from Furuncle with Meningitis Complication Caused by Methicillin-resistant Staphylococcus aureus, Internal Medicine, Vol.60, No.20, 3251-3255, 2021.
Satoshi Jujo, Jannet J. Lee-Jayaram, Brandan I. Sakka, Atsushi Nakahira, Akihisa Kataoka, Masaki Izumo, Kenya Kusunose, Natsinee Athinartrattanapong, Sayaka Oikawa and Benjamin W. Berg : Pre-clinical medical student cardiac point-of-care ultrasound curriculum based on the American Society of Echocardiography recommendations: a pilot and feasibility study., Pilot and Feasibility Studies, Vol.7, No.1, 175, 2021.
(Summary)
Cardiac point-of-care ultrasound (POCUS) training has been integrated into medical school curricula. However, there is no standardized cardiac POCUS training method for medical students. To address this issue, the American Society of Echocardiography (ASE) proposed a framework for medical student cardiac POCUS training. The objective of this pilot study was to develop a medical student cardiac POCUS curriculum with test scoring systems and test the curriculum feasibility for a future definitive study. Based on the ASE-recommended framework, we developed a cardiac POCUS curriculum consisting of a pre-training online module and hands-on training with a hand-held ultrasound (Butterfly iQ, Butterfly Network Inc., Guilford, CT, USA). The curriculum learning effects were assessed with a 10-point maximum skill test and a 40-point maximum knowledge test at pre-, immediate post-, and 8-week post-training. To determine the curriculum feasibility, we planned to recruit 6 pre-clinical medical students. We semi-quantitatively evaluated the curriculum feasibility in terms of recruitment rate, follow-up rate 8 weeks after training, instructional design of the curriculum, the effect size (ES) of the test score improvements, and participant satisfaction. To gather validity evidence of the skill test, interrater and test-retest reliability of 3 blinded raters were assessed. Six pre-clinical medical students participated in the curriculum. The recruitment rate was 100% (6/6 students) and the follow-up rate 8 weeks after training was 100% (6/6). ESs of skill and knowledge test score differences between pre- and immediate post-, and between pre- and 8-week post-training were large. The students reported high satisfaction with the curriculum. Both interrater and test-retest reliability of the skill test were excellent. This pilot study confirmed the curriculum design as feasible with instructional design modifications including the hands-on training group size, content of the cardiac POCUS lecture, hands-on teaching instructions, and hand-held ultrasound usage. Based on the pilot study findings, we plan to conduct the definitive study with the primary outcome of long-term skill retention 8 weeks after initial training. The definitive study has been registered in ClinicalTrials.gov (Identifier: NCT04083924).
Kenya Kusunose, T Imai, A Tanaka, K Dohi, K Shiina, T Yamada, K Kida, K Eguchi, H Teragawa, Y Takeishi, N Ohte, Hirotsugu Yamada, Masataka Sata and K Node : Effects of canagliflozin on NT-proBNP stratified by left ventricular diastolic function in patients with type 2 diabetes and chronic heart failure: a sub analysis of the CANDLE trial, Cardiovascular Diabetology, Vol.20, No.1, 186, 2021.
(Summary)
Identification of the effective subtypes of treatment for heart failure (HF) is an essential topic for optimizing treatment of the disorder. We hypothesized that the beneficial effect of SGLT2 inhibitors (SGLT2i) on the levels of N-terminal pro-brain natriuretic peptide (NT-proBNP) might depend on baseline diastolic function. To elucidate the effects of SGLT2i in type 2 diabetes mellitus (T2DM) and chronic HF we investigated, as a post-hoc sub-study of the CANDLE trial, the effects of canagliflozin on NT-proBNP levels from baseline to 24 weeks, with the data stratified by left ventricular (LV) diastolic function at baseline. Patients (n = 233) in the CANDLE trial were assigned randomly to either an add-on canagliflozin (n = 113) or glimepiride treatment groups (n = 120). The primary endpoint was a comparison between the two groups of the changes from baseline to 24 weeks in NT-pro BNP levels, stratified according to baseline ventricular diastolic function. The change in the geometric mean of NT-proBNP level from baseline to 24 weeks was 0.98 (95% CI 0.89-1.08) in the canagliflozin group and 1.07 (95% CI 0.97-1.18) in the glimepiride group. The ratio of change with canagliflozin/glimepiride was 0.93 (95% CI 0.82-1.05). Responder analyses were used to investigate the response of an improvement in NT-proBNP levels. Although the subgroup analyses for septal annular velocity (SEP-e') showed no marked heterogeneity in treatment effect, the subgroup with an SEP-e' < 4.7 cm/s indicated there was an association with lower NT-proBNP levels in the canagliflozin group compared with that in the glimepiride group (ratio of change with canagliflozin/glimepiride (0.83, 95% CI 0.66-1.04). In the subgroup with a lower LV diastolic function, canagliflozin showed a trend of reduced NT-pro BNP levels compared to that observed with glimepiride. This study suggests that the beneficial effects of canagliflozin treatment may be different in subgroups classified by the severity of LV diastolic dysfunction.
Yuta Torii, Kenya Kusunose, Yukina Hirata, Susumu Nishio, Takayuki Ise, Koji Yamaguchi, Daiju Fukuda, Shusuke Yagi, Hirotsugu Yamada, Takeshi Soeki, Tetsuzo Wakatsuki and Masataka Sata : Left Atrial Strain Associated with Functional Recovery in Patients Receiving Optimal Treatment for Heart Failure, Journal of the American Society of Echocardiography, Vol.34, No.9, 966-975, 2021.
(Summary)
Heart failure with recovered ejection fraction (HFrecEF) has been reported in several previous studies to have a better prognosis than heart failure with reduced ejection fraction (HFrEF). However, the factors associated with HFrecEF have not been identified. The aim of this study was to test the hypothesis that left atrial (LA) strain could help identify patients with recovered ejection fraction (EF) among those with heart failure (HF) with low EF on admission. One hundred consecutive patients hospitalized for the first time for new-onset HF were enrolled. Patients were clinically diagnosed with HFrEF on admission (left ventricular EF < 40%) and received optimal treatment for HF. Twenty-eight patients improved to HFrecEF during 6 months of follow-up. Regarding clinical background, there were significantly more women and a lower rate of atrial fibrillation in the HFrecEF group than in the HFrEF group. In a multivariate logistic regression analysis, LA strain was an independent predictor of HFrecEF, even after adjustment for gender and left ventricular EF (odds ratio: 4.06; 95% CI: 2.04-8.07; P < .001). A cutoff value of 10.8% for LA strain showed high sensitivity (96%) and specificity (82%) in identifying HFrecEF in patients with HF presenting with low EF on admission. During a follow-up period of 24 ± 13 months, 31 patients (31%) had cardiovascular death or readmission for HF. Patients with reduced LA strain (<10.8%) had significantly shorter event-free survival than those with preserved LA strain (P = .02). LA strain is a useful indicator for predicting HFrecEF and should be considered as a routine measurement in patients with HFrEF on admission.
Sae X. Morita, Kenya Kusunose, Akihiro Haga, Masataka Sata, Kohei Hasegawa, Yoshihiko Raita, Muredach P. Reilly, Michael A. Fifer, Mathew S. Maurer and Yuichi J. Shimada : Deep Learning Analysis of Echocardiographic Images to Predict Positive Genotype in Patients With Hypertrophic Cardiomyopathy., Frontiers in Cardiovascular Medicine, Vol.8, 669860, 2021.
(Summary)
Genetic testing provides valuable insights into family screening strategies, diagnosis, and prognosis in patients with hypertrophic cardiomyopathy (HCM). On the other hand, genetic testing carries socio-economical and psychological burdens. It is therefore important to identify patients with HCM who are more likely to have positive genotype. However, conventional prediction models based on clinical and echocardiographic parameters offer only modest accuracy and are subject to intra- and inter-observer variability. We therefore hypothesized that deep convolutional neural network (DCNN, a type of deep learning) analysis of echocardiographic images improves the predictive accuracy of positive genotype in patients with HCM. In each case, we obtained parasternal short- and long-axis as well as apical 2-, 3-, 4-, and 5-chamber views. We employed DCNN algorithm to predict positive genotype based on the input echocardiographic images. We performed 5-fold cross-validations. We used 2 reference models-the Mayo HCM Genotype Predictor score (Mayo score) and the Toronto HCM Genotype score (Toronto score). We compared the area under the receiver-operating-characteristic curve (AUC) between a combined model using the reference model plus DCNN-derived probability and the reference model. We calculated the -value by performing 1,000 bootstrapping. We calculated sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV). In addition, we examined the net reclassification improvement. We included 99 adults with HCM who underwent genetic testing. Overall, 45 patients (45%) had positive genotype. The new model combining Mayo score and DCNN-derived probability significantly outperformed Mayo score (AUC 0.86 [95% CI 0.79-0.93] vs. 0.72 [0.61-0.82]; < 0.001). Similarly, the new model combining Toronto score and DCNN-derived probability exhibited a higher AUC compared to Toronto score alone (AUC 0.84 [0.76-0.92] vs. 0.75 [0.65-0.85]; = 0.03). An improvement in the sensitivity, specificity, PPV, and NPV was also achieved, along with significant net reclassification improvement. In conclusion, compared to the conventional models, our new model combining the conventional and DCNN-derived models demonstrated superior accuracy to predict positive genotype in patients with HCM.
Tomomi Matsuura, Takeshi Soeki, Daiju Fukuda, Etsuko Uematsu, Takeshi Tobiume, Tomoya Hara, Kenya Kusunose, Takayuki Ise, Koji Yamaguchi, Shusuke Yagi, Hirotsugu Yamada, Tetsuzo Wakatsuki and Masataka Sata : Activated Factor X Signaling Pathway via Protease-Activated Receptor 2 Is a Novel Therapeutic Target for Preventing Atrial Fibrillation, Circulation Journal, Vol.85, No.8, 1383-1391, 2021.
(Summary)
Activated factor X (FXa), which contributes to chronic inflammation via protease-activated receptor 2 (PAR2), might play an important role in atrial fibrillation (AF) arrhythmogenesis. This study aimed to assess whether PAR2 signaling contributes to AF arrhythmogenesis and whether rivaroxaban ameliorates atrial inflammation and prevents AF.Methods and Results:In Study 1, PAR2 deficient (PAR2-/-) and wild-type mice were infused with angiotensin II (Ang II) or a vehicle via an osmotic minipump for 2 weeks. In Study 2, spontaneously hypertensive rats (SHRs) were treated with rivaroxaban, warfarin, or vehicle for 2 weeks after 8 h of right atrial rapid pacing. The AF inducibility and atrial remodeling in both studies were examined. Ang II-treated PAR2-/- mice had a lower incidence of AF and less mRNA expression of collagen1 and collagen3 in the atrium compared to wild-type mice treated with Ang II. Rivaroxaban significantly reduced AF inducibility compared with warfarin or vehicle. In SHRs treated with a vehicle, rapid atrial pacing promoted gene expression of inflammatory and fibrosis-related biomarkers in the atrium. Rivaroxaban, but not warfarin, significantly reduced expression levels of these genes. The FXa-PAR2 signaling pathway might contribute to AF arrhythmogenesis associated with atrial inflammation. A direct FXa inhibitor, rivaroxaban, could prevent atrial inflammation and reduce AF inducibility, probably by inhibiting the pro-inflammatory activation.
Pham Tran Phuong, Daiju Fukuda, Sachiko Nishimoto, JR Kim-Kaneyama, XF Lei, Yutaka Takahashi, Tomohito Sato, Kimie Tanaka, Kumiko Suto, Yutaka Kawabata, Koji Yamaguchi, Shusuke Yagi, Kenya Kusunose, Hirotsugu Yamada, Takeshi Soeki, Tetsuzo Wakatsuki, Kenji Shimada, Yasuhisa Kanematsu, Yasushi Takagi, Michio Shimabukuro, Mitsutoshi Setou, Glen N Barber and Masataka Sata : STING, a cytosolic DNA sensor, plays a critical role in atherogenesis: a link between innate immunity and chronic inflammation caused by lifestyle-related diseases, European Heart Journal, Vol.42, No.42, 4336-4348, 2021.
(Summary)
Lifestyle-related diseases promote atherosclerosis, a chronic inflammatory disease; however, the molecular mechanism remains largely unknown. Endogenous DNA fragments released under over-nutrient condition provoke sterile inflammation through the recognition by DNA sensors. Here, we investigated the role of stimulator of interferon genes (STING), a cytosolic DNA sensor, in atherogenesis. Apolipoprotein E-deficient (Apoe-/-) mice fed a western-type diet (WTD), a hypercholesterolaemic mouse model, showed higher STING expression and markers for DNA damage such as γH2AX, p53, and single-stranded DNA (ssDNA) accumulation in macrophages in the aorta compared with wild-type (WT) mice. The level of cGAMP, a STING agonist, in the aorta was higher in Apoe-/- mice. Genetic deletion of Sting in Apoe-/- mice reduced atherosclerotic lesions in the aortic arch, lipid, and macrophage accumulation in plaques, and inflammatory molecule expression in the aorta compared with the control. Pharmacological blockade of STING using a specific inhibitor, C-176, ameliorated atherogenesis in Apoe-/- mice. In contrast, bone marrow-specific STING expression in Apoe-/- mice stimulated atherogenesis. Expression or deletion of STING did not affect metabolic parameters and blood pressure. In vitro studies revealed that STING activation by cGAMP or mitochondrial DNA accelerated inflammatory molecule expression (e.g. TNF-α or IFN-β) in mouse and human macrophages. Activation of nuclear factor-κB and TANK binding kinase 1 was involved in STING-associated vascular inflammation and macrophage activation. Furthermore, human atherosclerotic lesions in the carotid arteries expressed STING and cGAMP. Stimulator of interferon genes stimulates pro-inflammatory activation of macrophages, leading to the development of atherosclerosis. Stimulator of interferon genes signalling may serve as a potential therapeutic target for atherosclerosis.
B Ganbaatar, Daiju Fukuda, M Shinohara, Shusuke Yagi, Kenya Kusunose, Hirotsugu Yamada, Takeshi Soeki, KI Hirata and Masataka Sata : Inhibition of S1P Receptor 2 Attenuates Endothelial Dysfunction and Inhibits Atherogenesis in Apolipoprotein E-Deficient Mice, Journal of Atherosclerosis and Thrombosis, Vol.28, No.6, 630-642, 2021.
(Summary)
The bioactive lipid, sphingosine-1-phosphate (S1P), has various roles in the physiology and pathophysiology of many diseases. There are five S1P receptors; however, the role of each S1P receptor in atherogenesis is still obscure. Here we investigated the contribution of S1P receptor 2 (S1P2) to atherogenesis by using a specific S1P2 antagonist, ONO-5430514, in apolipoprotein E-deficient (Apoe) mice. Apoe mice fed with a western-type diet (WTD) received ONO-5430514 (30 mg/kg/day) or vehicle. To examine the effect on atherogenesis, Sudan IV staining, histological analysis, qPCR, and vascular reactivity assay was performed. Human umbilical vein endothelial cells (HUVEC) were used for in vitro experiments. WTD-fed Apoe mice had significantly higher S1P2 expression in the aorta compared with wild-type mice. S1P2 antagonist treatment for 20 weeks reduced atherosclerotic lesion development (p<0.05). S1P2 antagonist treatment for 8 weeks ameliorated endothelial dysfunction (p<0.05) accompanied with significant reduction of lipid deposition, macrophage accumulation, and inflammatory molecule expression in the aorta compared with vehicle. S1P2 antagonist attenuated the phosphorylation of JNK in the abdominal aorta compared with vehicle (p<0.05). In HUVEC, S1P promoted inflammatory molecule expression such as MCP-1 and VCAM-1 p<0.001), which was attenuated by S1P2 antagonist or a JNK inhibitor (p<0.01). S1P2 antagonist also inhibited S1P-induced JNK phosphorylation in HUVEC (p<0.05). Our results suggested that an S1P2 antagonist attenuates endothelial dysfunction and prevents atherogenesis. S1P2, which promotes inflammatory activation of endothelial cells, might be a therapeutic target for atherosclerosis.
Robert Zheng and Kenya Kusunose : Review: application of current imaging modalities in the management of left-sided valvular heart disease., Cardiovascular Diagnosis and Therapy, Vol.11, No.3, 793-803, 2021.
(Summary)
In terms of valvular heart disease (VHD) imaging, transthoracic echocardiography (TTE) is the preferred first choice because of its widespread availability. Other modalities, such as transesophageal echocardiography, computed tomography and magnetic resonance imaging, have played a supplementary role in diagnosis for severity, deciding the timing/type of treatment, detection of post procedural complications, and prognostic predictions. However, there are few consensuses on how to employ these modalities, as the evidence is not extensive as that for TTE. On the other hand, these imaging modalities also have their own unique strengths. If employed properly, these modalities have the potential to play a more prominent role in clinical decision making. In this review, we focus on the potential, limitations and application of current imaging modalities in the management of left-sided VHD.
Y Okushi, Kenya Kusunose, Y Okayama, Robert Zheng, M Nakai, Y Sumita, Takayuki Ise, Takeshi Tobiume, Koji Yamaguchi, Shusuke Yagi, Daiju Fukuda, Hirotsugu Yamada, Takeshi Soeki, Tetsuzo Wakatsuki and Masataka Sata : Acute Hospital Mortality of Venous Thromboembolism in Patients With Cancer From Registry Data, Journal of the American Heart Association, Vol.10, No.11, e019373, 2021.
(Summary)
Background The prognosis of patients with cancer-venous thromboembolism (VTE) is not well known because of a lack of registry data. Moreover, there is also no knowledge on how specific types are related to prognosis. We sought to evaluate the clinical characteristics and outcomes of patients with cancer-associated VTE, compared with a matched cohort without cancer using real-world registry data of VTE. Methods and Results This study was based on the Diagnosis Procedure Combination database in the JROAD-DPC (Japanese Registry of All Cardiac and Vascular Diseases and the Diagnosis Procedure Combination). Of 5 106 151 total patients included in JROAD-DPC, we identified 49 580 patients who were first hospitalized with VTE from April 2012 to March 2017. Propensity score was estimated with a logistic regression model, with cancer as the dependent variable and 18 clinically relevant covariates. After propensity matching, there were 25 148 patients with VTE with or without cancer. On propensity score-matched analysis with 25 148 patients with VTE, patients with cancer had higher total in-hospital mortality within 7 days (1.3% versus 1.1%, odds ratio [OR], 1.66; 95% CI, 1.31-2.11; <0.0001), 14 days (2.5% versus 1.5%, OR, 2.07; 95% CI, 1.72-2.49; <0.0001), and 30 days (4.8% versus 2.0%, OR, 2.85; 95% CI, 2.45-3.31; <0.0001). On analysis for each type of cancer, in-hospital mortality in 11 types of cancer was significantly high, especially pancreas (OR, 12.96; 95% CI, 6.41-26.20), biliary tract (OR, 8.67; 95% CI, 3.00-25.03), and liver (OR, 7.31; 95% CI, 3.05-17.50). Conclusions Patients with cancer had a higher in-hospital acute mortality for VTE than those without cancer, especially in pancreatic, biliary tract, and liver cancers.
Ayu Shono, Kensuke Matsumoto, Nao Yamada, Kenya Kusunose, Makiko Suzuki, Keiko Sumimoto, Yusuke Tanaka, Kentaro Yamashita, Nao Shibata, Shun Yokota, Makiko Suto, Kumiko Dokuni, Hidekazu Tanaka and Ken-Ichi Hirata : "Accelerated aging" of the heart as heart failure with preserved ejection fraction-analysis using leg-positive pressure stress echocardiography., The International Journal of Cardiovascular Imaging, Vol.37, No.8, 2473-2482, 2021.
(Summary)
The aging process is a significant risk factor for heart failure. The incidence of heart failure with preserved ejection fraction (HFpEF) dramatically increases with age. Although HFpEF occurs along a continuum of aging of the cardiovascular system, the pathophysiology that differentiates overt HFpEF from physiological aging is not fully understood. A total of 102 subjects were prospectively recruited: 25 patients with HFpEF and 77 healthy controls. Controls were stratified into three age-groups: young (n = 27, 20-40 years), middle aged (n = 25, 40-65 years), and elderly (n = 25, > 65 years). All participants underwent preload stress echocardiography using a leg-positive pressure (LPP) maneuver. With an increase in age, progressive concentric left ventricular (LV) remodeling was observed in healthy controls, resulting in the hemodynamic consequences of an age-dependent increase in the E/e' ratio (ANOVA, P < 0.001). During LPP stress, the E/e' ratio significantly increased in the middle-aged and elderly groups (from 8 ± 2 to 9 ± 3, from 10 ± 2 to 12 ± 3, P < 0.05, respectively), and this was more pronounced in patients with HFpEF (from 16 ± 5 to 17 ± 7, P < 0.05). Forward stroke volume (SV) significantly increased in each healthy group during LPP stress (all P < 0.001) but failed to increase in the HFpEF group (from 43 ± 13 to 44 ± 14 mL/m, P = 0.65). In a multivariate analysis, LV mass index (odds ratio [OR] 1.051, P < 0.05), E/e' ratio (OR 1.480; P < 0.05), and change in SV (OR 0.780; P < 0.05) were independent parameters that differentiated HFpEF from physiological aging. Structural remodeling and impaired preload reserve may both be critical features that characterize the pathophysiology of HFpEF.
Yukina Hirata, Kenya Kusunose, Takumasa Tsuji, Kohei Fujimori, Jun'ichi Kotoku and Masataka Sata : Deep Learning for Detection of Elevated Pulmonary Artery Wedge Pressure using Standard Chest X-Ray, The Canadian Journal of Cardiology, Vol.37, No.8, 1198-1206, 2021.
(Summary)
To accurately diagnose and control heart failure (HF), it is important to carry out a simple assessment of elevated pulmonary arterial wedge pressure (PAWP). The aim of this study was to develop and validate an objective method for detecting elevated PAWP by applying deep learning (DL) to a chest x-ray (CXR). We enrolled 1013 consecutive patients with a right-heart catheter between October 2009 and February 2020. We developed a convolutional neural network to identify patients with elevated PAWP (> 18 mm Hg) as the actual value of PAWP to be used in the dataset for training. In the prospective validation dataset used to detect elevated PAWP, the area under the receiver operating characteristic curve (AUC) was calculated using the DL model that evaluated the CXR. In the prospective validation dataset, the AUC of the DL model with CXR was not significantly different from the AUC produced by brain natriuretic peptide (BNP) and the echocardiographic left-ventricular diastolic dysfunction (DD) algorithm (DL model: 0.77 vs BNP: 0.77 vs DD algorithm: 0.70; respectively; P = NS for all comparisons); it was, however, significantly higher than the AUC of the cardiothoracic ratio (DL model vs cardiothoracic ratio [CTR]: 0.66, P = 0.044). The model based on 3 parameters (BNP, DD algorithm, and CTR) was improved by adding the DL model (AUC: from 0.80 to 0.86; P = 0.041). Applying the DL model based on a CXR (a classical, universal, and low-cost test) is useful for screening for elevated PAWP.
Miharu Arase, Kenya Kusunose, N Yamaguchi, Yukina Hirata, Susumu Nishio, Y Okushi, Takayuki Ise, Takeshi Tobiume, Koji Yamaguchi, Daiju Fukuda, Shusuke Yagi, Hirotsugu Yamada, Takeshi Soeki, Tetsuzo Wakatsuki and Masataka Sata : Cardiac reserve by 6-minute walk stress echocardiography in systemic sclerosis., Open Heart, Vol.8, No.1, e001559, 2021.
Kenya Kusunose, Y Okushi, Y Okayama, Robert Zheng, M Abe, M Nakai, Y Sumita, Takayuki Ise, Takeshi Tobiume, Koji Yamaguchi, Shusuke Yagi, Daiju Fukuda, Hirotsugu Yamada, Takeshi Soeki, Tetsuzo Wakatsuki and Masataka Sata : Association between Vitamin D and Heart Failure Mortality in 10,974 Hospitalized Individuals., Nutrients, Vol.13, No.2, 335, 2021.
(Summary)
A broad range of chronic conditions, including heart failure (HF), have been associated with vitamin D deficiency. Existing clinical trials involving vitamin D supplementation in chronic HF patients have been inconclusive. We sought to evaluate the outcomes of patients with vitamin D supplementation, compared with a matched cohort using real-world big data of HF hospitalization. This study was based on the Diagnosis Procedure Combination database in the Japanese Registry of All Cardiac and Vascular Datasets (JROAD-DPC). After exclusion criteria, we identified 93,692 patients who were first hospitalized with HF between April 2012 and March 2017 (mean age was 79 ± 12 years, and 52.2% were male). Propensity score (PS) was estimated with logistic regression model, with vitamin D supplementation as the dependent variable and clinically relevant covariates. On PS-matched analysis with 10,974 patients, patients with vitamin D supplementation had lower total in-hospital mortality (6.5 vs. 9.4%, odds ratio: 0.67, < 0.001) and in-hospital mortality within 7 days and 30 days (0.9 vs. 2.5%, OR, 0.34, and 3.8 vs. 6.5%, OR: 0.56, both < 0.001). In the sub-group analysis, mortalities in patients with age < 75, diabetes, dyslipidemia, atrial arrhythmia, cancer, renin-angiotensin system blocker, and β-blocker were not affected by vitamin D supplementation. Patients with vitamin D supplementation had a lower in-hospital mortality for HF than patients without vitamin D supplementation in the propensity matched cohort. The identification of specific clinical characteristics in patients benefitting from vitamin D may be useful for determining targets of future randomized control trials.
Gulinu Maimaituxun, Kenya Kusunose, Hirotsugu Yamada, Daiju Fukuda, Shusuke Yagi, Yuta Torii, Nao Yamada, Takeshi Soeki, H Masuzaki, Masataka Sata and Michio Shimabukuro : Deleterious Effects of Epicardial Adipose Tissue Volume on Global Longitudinal Strain in Patients With Preserved Left Ventricular Ejection Fraction, Frontiers in Cardiovascular Medicine, Vol.7, 607825, 2021.
Akira Takashima, Shusuke Yagi, Koji Yamaguchi, Kiyoe Kurahashi, Yuko Kojima, Robert Zheng, Takayuki Ise, Kenya Kusunose, Sumiko Yoshida, Hirotsugu Yamada, Takeshi Soeki, Tetsuzo Wakatsuki, Ken-ichi Aihara, Masashi Akaike and Masataka Sata : Congenital Hypogonadotropic Hypogonadism with Early-Onset Coronary Artery Disease., The Journal of Medical Investigation : JMI, Vol.68, No.1.2, 189-191, 2021.
(Summary)
The patient with congenital hypogonadotropic hypogonadism (HH) shows low serum levels of androgen, which is a group of sex hormones including testosterone, caused by the decreased gonadotropin release in the hypothalamus. Recent reports showed androgens exert protective effects against insulin resistance or atherosclerotic diseases, such as diabetes mellitus or coronary artery disease. However, whether the juvenile hypogonadism affects the diabetes or cardiovascular disease is unclear. We report a case of a middle-aged man with congenital HH who had severe coronary artery disease complicated with metabolic disorders. J. Med. Invest. 68 : 189-191, February, 2021.
Yutaka Kawabata, Takeshi Soeki, Hiroyuki Ito, Tomomi Matsuura, Kenya Kusunose, Takayuki Ise, Koji Yamaguchi, Takeshi Tobiume, Shusuke Yagi, Daiju Fukuda, Hirotsugu Yamada, Tetsuzo Wakatsuki, M Kitani, K Kawano, Y Taketani and Masataka Sata : Effects of L-/N-Type Calcium Channel Blockers on Angiotensin II-Renin Feedback in Hypertensive Patients, International Journal of Hypertension, 6653851, 2020.
Takeshi Tobiume, R Kato, Tomomi Matsuura, Kazuhisa Matsumoto, M Hara, N Takamori, Y Taketani, K Okwa, Takayuki Ise, Kenya Kusunose, Koji Yamaguchi, Shusuke Yagi, Daiju Fukuda, Hirotsugu Yamada, Tetsuzo Wakatsuki, Takeshi Soeki, Masataka Sata and K Matsumoto : Antegrade slow pathway mapping of typical atrioventricular nodal reentrant tachycardia based on direct slow pathway capture, Journal of Arrhythmia, Vol.37, No.1, 128-139, 2020.
Kenya Kusunose, Yukina Hirata, T Tsuji, J Kotoku and Masataka Sata : Deep learning to predict elevated pulmonary artery pressure in patients with suspected pulmonary hypertension using standard chest X ray, Scientific Reports, Vol.10, No.1, 19311, 2020.
(Summary)
Accurate diagnosis of pulmonary hypertension (PH) is crucial to ensure that patients receive timely treatment. We hypothesized that application of artificial intelligence (AI) to the chest X-ray (CXR) could identify elevated pulmonary artery pressure (PAP) and stratify the risk of heart failure hospitalization with PH. We retrospectively enrolled a total of 900 consecutive patients with suspected PH. We trained a convolutional neural network to identify patients with elevated PAP (> 20 mmHg) as the actual value of PAP. The endpoints in this study were admission or occurrence of heart failure with elevated PAP. In an independent evaluation set for detection of elevated PAP, the area under curve (AUC) by the AI algorithm was significantly higher than the AUC by measurements of CXR images and human observers (0.71 vs. 0.60 and vs. 0.63, all p < 0.05). In patients with AI predicted PH had 2-times the risk of heart failure with PH compared with those without AI predicted PH. This preliminary work suggests that applying AI to the CXR in high risk groups has limited performance when used alone in identifying elevated PAP. We believe that this report can serve as an impetus for a future large study.
Yoshihito Saijyo, Kenya Kusunose, Y Okushi, Hirotsugu Yamada, Hiroaki Toba and Masataka Sata : Relationship between regional left ventricular dysfunction and cancer-therapy-related cardiac dysfunction, Heart, Vol.106, No.22, 1752-1758, 2020.
(Summary)
The aim of our study was to assess the association between risk of cancer-therapy-related cardiac dysfunction (CTRCD) after first follow-up and the difference in echocardiographic measures from baseline to follow-up. We retrospectively enrolled 87 consecutive patients (58±14 years, 55 women) who received anthracycline and underwent echocardiographic examinations both before (baseline) and after initial anthracycline administration (first follow-up). We measured absolute values of global longitudinal strain (GLS), apical longitudinal strain (LS), mid-LS and basal-LS at baseline and first follow-up, and per cent changes (Δ) of these parameters were calculated. Among 61 patients who underwent further echocardiographic examinations (second follow-up, third follow-up, etc), we assessed the association between regional left ventricular (LV) systolic dysfunction from baseline to follow-up and development of CTRCD, defined as LV ejection fraction (LVEF) under 53% and more absolute decrease of 10% from baseline, after first follow-up. LVEF (65%±4% vs 63±4%, p=0.004), GLS (23.2%±2.6% vs 22.2±2.4%, p=0.005) and basal-LS (21.9%±2.5% vs 19.9±2.4%, p<0.001) at first follow-up significantly decreased compared with baseline. Among the 61 patients who had further follow-up echocardiographic examinations, 13% developed CTRCD. In the Cox-hazard model, worse Δbasal-LS was significantly associated with CTRCD. By Kaplan-Meier analysis, patients with Δbasal-LS decrease of more than the median value (-9.7%) had significantly worse event-free survival than those with a smaller decrease (p=0.015). Basal-LS significantly decreased prior to development of CTRCD, and worse basal-LS was associated with development of CTRCD in patients receiving anthracycline chemotherapy.
Kenya Kusunose : Steps to use artificial intelligence in echocardiography., Journal of Echocardiography, Vol.19, No.1, 21-27, 2020.
(Summary)
Artificial intelligence (AI) has influenced every field of cardiovascular imaging in all phases from acquisition to reporting. Compared with computed tomography and magnetic resonance imaging, there is an issue of high observer variation in the interpretation of echocardiograms. Therefore, AI can help minimize the observer variation and provide accurate diagnosis in the field of echocardiography. In this review, we summarize the necessity for automated diagnosis in the echocardiographic field, and discuss the results of AI application to echocardiography and future perspectives. Currently, there are two roles for AI in cardiovascular imaging. One is the automation of tasks performed by humans, such as image segmentation, measurement of cardiac structural and functional parameters. The other is the discovery of clinically important insights. Most reported applications were focused on the automation of tasks. Moreover, algorithms that can obtain cardiac measurements are also being reported. In the next stage, AI can be expected to expand and enrich existing knowledge. With the continual evolution of technology, cardiologists should become well versed in this new knowledge of AI and be able to harness it as a tool. AI can be incorporated into everyday clinical practice and become a valuable aid for many healthcare professionals dealing with cardiovascular diseases.
Kenya Kusunose, nao Yamada, Hirotsugu Yamada, Susumu Nishio, Yoshihito Saijoh, Yukina Hirata, Yuta Torii, Takayuki Ise, Koji Yamaguchi, Daiju Fukuda, Shusuke Yagi, Takeshi Soeki, Tetsuzo Wakatsuki and Masataka Sata : Association between Right Ventricular Contractile Function and Cardiac Events in Isolated Post-capillary and Combined Pre- and Post-capillary Pulmonary Hypertension, Journal of Cardiac Failure, Vol.26, No.1, 43-51, 2020.
(Summary)
Recent studies have shown that patients with combined pre- and postcapillary pulmonary hypertension (CpcPH) had worse outcomes than those with isolated postcapillary pulmonary hypertension (IpcPH). However, the prognostic factors including right ventricular (RV) function have not been well documented. The aim of this study was to assess the differentiation of PH phenotypes, using echocardiography, and the association between RV longitudinal strain and cardiac events. We prospectively recruited consecutive patients who had undergone right heart catheterization. The primary endpoint was cardiovascular death or readmission due to heart failure. We included 137 patients with Group 2 PH. A RV longitudinal strain of 17% was sensitive (85%) and specific (70%) to determine the CpcPH. During a median period of 31 months, 43 patients experienced the primary endpoint during follow-up. In a multivariate analysis, RV longitudinal strain was associated with the primary endpoint in both CpcPH and IpcPH (HR: 0.84, P = 0.003; HR: 0.86, P = 0.001). Lower RV longitudinal strain was independently associated with worse outcomes in CpcPH and IpcPH. RV longitudinal strain may play a prognostic role in PH phenotypes.
Yukina Hirata, Susumu Nishio, Kenya Kusunose, Yukina Fujita, Miharu Arase, Hirotsugu Yamada and Masataka Sata : Comparison of Global Longitudinal Strain Measurement Among Recent Version Echocardiographic Machines and Vendor Independent Strain Analysis Software, Japanese Journal of Medical Ultrasound Technology, Vol.45, No.4, 405-413, 2020.
(Summary)
<p><b>Purpose</b>: Global longitudinal strain (GLS) assessed using the two-dimensional (2D) speckle tracking method is considered to be an accurate and reproducible measurement method for assessing the LV contractility. However, the measurement variability across different ultrasonography machines has been discussed. This study aimed to determine whether the measurement variability among newer echocardiographic machines is lower than that reported in previous studies.</p><p><b>Subjects and Methods</b>: We enrolled 34 healthy volunteers. Apical images were acquired using three types of latest ultrasonography machines at the Tokushima University Hospital. The GLS values were assessed and compared using the latest version of the vendor-specific software and one vendor-independent software packages (EchoInsight ver. 2.2.6.2230, Epsilon).</p><p><b>Results and Discussion</b>: The upgraded vendor-specific software showed good correlation in GLS [GE vs. Philips (r=0.678, p<0.001, Bias 1.1%, 2SD ±2.9%), GE vs. Canon (r=0.690, p<0.001, Bias 0.4%, 2SD ±2.5%), Philips vs. Canon (r=0.551, p<0.001, Bias 1.5%, 2SD ±3.2%)]. The GLS measured using vendor-independent software provided greater degree of correlation than that with each software alone.</p><p><b>Conclusion</b>: The measurement variability of GLS between devices was superior than that reported previously. Moreover, the GLS measured using the images acquired using each device with EchoInsight showed good inter-device correlation.</p>
Yuta Torii, Kenya Kusunose, Robert Zheng, Hirotsugu Yamada, Rie Amano, Rikizo Matsumoto, Yukina Hirata, Susumu Nishio, Nao Yamada, Takayuki Ise, Koji Yamaguchi, Takeshi Tobiume, Daiju Fukuda, Shusuke Yagi, Takeshi Soeki, Tetsuzo Wakatsuki, Yoshihiro Okayama and Masataka Sata : Association between Sarcopenia/Lower Muscle Mass and Short-Term Regression of Deep Vein Thrombosis Using Direct Oral Anticoagulants, International Heart Journal, Vol.61, No.4, 787-794, 2020.
(Summary)
Advanced age, obesity, and muscle weakness are independent factors in the onset of deep vein thrombosis (DVT). Recently, an association between sarcopenia and DVT has been reported. We hypothesized that sarcopenia related factors, observed by ultrasonography, are associated with the regression effect on the thrombus following anticoagulation therapy. The present study focused on gastrocnemius muscle (GCM) thickness and the GCM's internal echogenic brightness. We examined the association with DVT regression following direct oral anticoagulants (DOACs) treatment.The prospective cohort study period was between October 2017 and August 2018. We enrolled 46 patients diagnosed with DVT by ultrasonography, who were aged >60 years old and treated with DOACs. Sarcopenia was evaluated using the Asian Working Group for Sarcopenia flowchart. The average DOACs treatment period was 94 days, and 29 patients exhibited thrombus regression. On univariate logistic regression analysis, sarcopenia, average GCM diameter index, and gastrocnemius integrated backscatter index were significantly associated with thrombus regression. In a multivariate model, only the average GCM diameter index correlated with thrombus regression.The average GCM diameter index is associated with DVT regression treated with DOACs. Considering the GCM diameter during DVT treatment can be a marker to make a decision for the treatment of DVT.
(Keyword)
Aged / Aged, 80 and over / Factor Xa Inhibitors / female / Humans / male / Middle Aged / Muscle, Skeletal / Prospective Studies / Sarcopenia / Ultrasonography / Venous Thrombosis
Kenya Kusunose : Radiomics in Echocardiography: Deep Learning and Echocardiographic Analysis., Current Cardiology Reports, Vol.22, No.9, 89, 2020.
(Summary)
Recent development in artificial intelligence (AI) for cardiovascular imaging analysis, involving deep learning, is the start of a new phase in the research field. We review the current state of AI in cardiovascular field and discuss about its potential to improve clinical workflows and accuracy of diagnosis. In the AI cardiovascular imaging field, there are many applications involving efficient image reconstruction, patient triage, and support for clinical decisions. These tools have a role to support repetitive clinical tasks. Although they will be powerful in some situations, these applications may have new potential in the hands of echo cardiologists, assisting but not replacing the human observer. We believe AI has the potential to improve the quality of echocardiography. Someday AI may be incorporated into the daily clinical setting, being an instrumental tool for cardiologists dealing with cardiovascular diseases.
Kenya Kusunose, M Fujiwara, Hirotsugu Yamada, Susumu Nishio, Y Saijo, N Yamada, Yukina Hirata, Yuta Torii, Takayuki Ise, Koji Yamaguchi, Daiju Fukuda, Shusuke Yagi, Takeshi Soeki, Tetsuzo Wakatsuki and Masataka Sata : Deterioration of Biventricular Strain Is an Early Marker of Cardiac Involvement in Confirmed Sarcoidosis, European Heart Journal Cardiovascular Imaging, Vol.21, No.7, 796-804, 2020.
(Summary)
Risk assessment of developing cardiac involvement in systemic sarcoidosis can be challenging because of limited data. Recently, attention has been given to left ventricular and right ventricular (LV and RV) involvement in cardiac sarcoidosis (CS) and its prevalence, relevance, and prognostic value. The aim of this study was to assess the role of biventricular strain to predict prognosis in confirmed sarcoidosis patients. LV and RV longitudinal strains (LSs) were evaluated by 2D speckle tracking in 139 consecutive confirmed sarcoidosis patients without other pre-existing structural heart diseases, and 52 age- and gender-matched control subjects. The primary endpoint was CS-related events (cardiac death or development of cardiac involvement). Sarcoidosis without cardiac involvement had significantly lower LV and RV free wall LS compared with control subjects. Basal LS had a higher area under the curve for differentiation of sarcoidosis in patients without cardiac involvement compared to control (cut-off value: -18% with 89% sensitivity and 69% specificity). During a median period of 50 months, the occurrence of CS-related events was observed in 20 patients. In a multivariate analysis, basal LV LS and RV free wall LS were associated with the events [hazard ratio (HR) 0.72, P < 0.001 and HR: 0.83, P = 0.006, respectively]. Patients with impaired biventricular function had significantly shorter event-free survival than those with preserved biventricular function (P < 0.001). Deterioration of biventricular strain was associated with CS-related events. This information might be useful for clinical evaluation and follow-up in sarcoidosis.
Kenya Kusunose : Clinical Application of Stress Echocardiography in Management of Heart Failure., Heart Failure Clinics, Vol.16, No.3, 347-355, 2020.
(Summary)
The key to understanding hemodynamics in heart failure (HF) is the relation between elevated left ventricular (LV) filling pressure and cardiac output. Some patients show abnormal response to stress in the relationship between LV filling pressure and cardiac output. In patients with preserved diastolic function, cardiac output can be increased without significantly elevated filling pressure during stress. In patients with HF, as long as the Frank-Starling mechanism operates effectively, cardiac output can increase while acquiring elevated filling pressure. In patients with decompensated HF, hemodynamic stress will lead to a much greater elevation in filling pressure and pulmonary venous hypertension.
Kenya Kusunose, Takashi Abe, Akihiro Haga, Daiju Fukuda, Hirotsugu Yamada, Masafumi Harada and Masataka Sata : A Deep Learning Approach for Assessment of Regional Wall Motion Abnormality From Echocardiographic Images, JACC. Cardiovascular Imaging, Vol.13, No.2, 374-381, 2020.
(Summary)
This study investigated whether a deep convolutional neural network (DCNN) could provide improved detection of regional wall motion abnormalities (RWMAs) and differentiate among groups of coronary infarction territories from conventional 2-dimensional echocardiographic images compared with that of cardiologists, sonographers, and resident readers. An effective intervention for reduction of misreading of RWMAs is needed. The hypothesis was that a DCNN trained using echocardiographic images would provide improved detection of RWMAs in the clinical setting. A total of 300 patients with a history of myocardial infarction were enrolled. From this cohort, 3 groups of 100 patients each had infarctions of the left anterior descending (LAD) artery, the left circumflex (LCX) branch, and the right coronary artery (RCA). A total of 100 age-matched control patients with normal wall motion were selected from a database. Each case contained cardiac ultrasonographs from short-axis views at end-diastolic, mid-systolic, and end-systolic phases. After the DCNN underwent 100 steps of training, diagnostic accuracies were calculated from the test set. Independently, 10 versions of the same model were trained, and ensemble predictions were performed using those versions. For detection of the presence of WMAs, the area under the receiver-operating characteristic curve (AUC) produced by the deep learning algorithm was similar to that produced by the cardiologists and sonographer readers (0.99 vs. 0.98, respectively; p = 0.15) and significantly higher than the AUC result of the resident readers (0.99 vs. 0.90, respectively; p = 0.002). For detection of territories of WMAs, the AUC by the deep learning algorithm was similar to the AUC by the cardiologist and sonographer readers (0.97 vs. 0.95, respectively; p = 0.61) and significantly higher than the AUC by resident readers (0.97 vs. 0.83, respectively; p = 0.003). From a validation group at an independent site (n = 40), the AUC by the deep learning algorithm was 0.90. The present results support the possibility of using DCNN for automated diagnosis of RWMAs in the field of echocardiography.
Kenya Kusunose : What is a better measure of regurgitant severity in secondary mitral regurgitation by echocardiography?, Heart, Vol.106, No.12, 874-875, 2020.
Kenya Kusunose, Akihiro Haga, Mizuki Inoue, Daiju Fukuda, Hirotsugu Yamada and Masataka Sata : Clinically Feasible and Accurate View Classification of Echocardiographic Images Using Deep Learning, Biomolecules, Vol.10, No.5, E665, 2020.
(Summary)
A proper echocardiographic study requires several video clips recorded from different acquisition angles for observation of the complex cardiac anatomy. However, these video clips are not necessarily labeled in a database. Identification of the acquired view becomes the first step of analyzing an echocardiogram. Currently, there is no consensus whether the mislabeled samples can be used to create a feasible clinical prediction model of ejection fraction (EF). The aim of this study was to test two types of input methods for the classification of images, and to test the accuracy of the prediction model for EF in a learning database containing mislabeled images that were not checked by observers. We enrolled 340 patients with five standard views (long axis, short axis, 3-chamber view, 4-chamber view and 2-chamber view) and 10 images in a cycle, used for training a convolutional neural network to classify views (total 17,000 labeled images). All DICOM images were rigidly registered and rescaled into a reference image to fit the size of echocardiographic images. We employed 5-fold cross validation to examine model performance. We tested models trained by two types of data, averaged images and 10 selected images. Our best model (from 10 selected images) classified video views with 98.1% overall test accuracy in the independent cohort. In our view classification model, 1.9% of the images were mislabeled. To determine if this 98.1% accuracy was acceptable for creating the clinical prediction model using echocardiographic data, we tested the prediction model for EF using learning data with a 1.9% error rate. The accuracy of the prediction model for EF was warranted, even with training data containing 1.9% mislabeled images. The CNN algorithm can classify images into five standard views in a clinical setting. Our results suggest that this approach may provide a clinically feasible accuracy level of view classification for the analysis of echocardiographic data.
Hiroyuki Iwano, Kentaro Shibayama, Takeshi Kitai, Kenya Kusunose, Tetsuari Onishi, Hidekazu Tanaka and Toshihisa Anzai : Study protocol for prospect trial to elucidate the utility of echocardiography-based cardiac output in acute heart failure (PREDICT)., Journal of Echocardiography, Vol.18, No.4, 235-239, 2020.
(Summary)
Early worsening heart failure (WHF), defined as worsening of symptoms and signs of heart failure requiring intensification of medical or mechanical therapy during an admission for acute decompensated heart failure (ADHF), has recently been recognized as a risk of morbidity or mortality after the discharge. Although echocardiographic parameters of left ventricular (LV) output has been shown to be associated with long-term outcome in heart failure patients, its predictive value for early WHF has not been elucidated. Prospect trial to Elucidate the utility of EchocarDiography-based Cardiac output in acute heart failure (PREDICT) is a multicenter, nonrandomized, prospective observational study to test the predictive value of echocardiographic LV output parameters for early WHF in ADHF patients. We will enroll patients admitted to 16 participating hospitals due to ADHF who did not receive positive inotropic agents as an initial therapy. Primary outcome will be set at early WHF defined as need for initiation of positive inotropic agents within 7 days after the admission. Predictive accuracy will be compared between Doppler echocardiographic LV output (stroke distance, stroke volume index, and cardiac index) and low perfusion findings assessed by physical examination. N/A. The PREDICT is expected to provide large data set to test the predictive value of echocardiographic LV output for early WHF in ADHF patients.
B Ganbaatar, Daiju Fukuda, M Shinohara, Shusuke Yagi, Kenya Kusunose, Hirotsugu Yamada, Takeshi Soeki, KI Hirata and Masataka Sata : Empagliflozin Ameliorates Endothelial Dysfunction and Suppresses Atherogenesis in Diabetic Apolipoprotein E-deficient Mice, European Journal of Pharmacology, Vol.15, No.875, 173040, 2020.
(Summary)
Recent studies reported cardioprotective effects of sodium glucose co-transporter 2 (SGLT2) inhibitors; however, the underlying mechanisms are still obscure. Here, we investigated whether empagliflozin attenuates atherogenesis and endothelial dysfunction in diabetic apolipoprotein E-deficient (ApoE) mice. Male streptozotocin (STZ) - induced diabetic ApoE mice were treated with empagliflozin for 12 or 8 weeks. Empagliflozin lowered blood glucose (P < 0.001) and lipid levels in diabetic ApoE mice. Empagliflozin treatment for 12 weeks significantly decreased atherosclerotic lesion size in the aortic arch (P < 0.01) along with reduction of lipid deposition (P < 0.05), macrophage accumulation (P < 0.001), and inflammatory molecule expression in plaques compared with the untreated group. Empagliflozin treatment for 8 weeks significantly ameliorated diabetes-induced endothelial dysfunction as determined by the vascular response to acetylcholine (P < 0.001). Empagliflozin reduced RNA expression of a macrophage marker, CD68, and inflammatory molecules such as MCP-1 (P < 0.05) and NADPH oxidase subunits in the aorta compared with the untreated group. Empagliflozin also reduced plasma levels of vasoconstrictive eicosanoids, prostaglandin E and thromboxane B (P < 0.001), which were elevated in diabetic condition. Furthermore, empagliflozin attenuated RNA expression of inflammatory molecules in perivascular adipose tissue (PVAT), suggesting the reduction of inflammation in PVAT. In in vitro studies, methylglyoxal (MGO), a precursor of AGEs, significantly increased the expression of inflammatory molecules such as MCP-1 and TNF-α in a murine macrophage cell line, RAW264.7. Our results indicated that empagliflozin attenuated endothelial dysfunction and atherogenesis in diabetic ApoE mice. Reduction of vasoconstrictive eicosanoids and inflammation in the vasculature and PVAT may have a role as underlying mechanisms at least partially.
Yoshihito Saijo, Kenya Kusunose, Nao Yamada, Hirotsugu Yamada, Susumu Nishio, Yukina Hirata and Masataka Sata : Sequential speckle tracking imaging to detect early stage of cancer therapeutics-related cardiac dysfunction in a patient with breast cancer, Journal of Echocardiography, Vol.18, No.2, 134-135, 2020.
Arief Rahadian, Daiju Fukuda, HM Salim, Shusuke Yagi, Kenya Kusunose, Hirotsugu Yamada, Takeshi Soeki and Masataka Sata : Canagliflozin Prevents Diabetes-Induced Vascular Dysfunction in ApoE-Deficient Mice, Journal of Atherosclerosis and Thrombosis, Vol.27, No.11, 1141-1151, 2020.
(Summary)
Recent studies have demonstrated that selective sodium-glucose cotransporter 2 inhibitors (SGLT2is) reduce cardiovascular events, although their mechanism remains obscure. We examined the effect of canagliflozin, an SGLT2i, on atherogenesis and investigated its underlying mechanism. Canagliflozin (30 mg/kg/day) was administered by gavage to streptozotocin-induced diabetic apolipoprotein E-deficient (ApoE) mice. Sudan IV staining was performed at the aortic arch. Immunostaining, quantitative RT-PCR, and vascular reactivity assay were performed using the aorta. In vitro experiments using human umbilical vein endothelial cells (HUVECs) were also performed. Canagliflozin decreased blood glucose (P<0.001) and total cholesterol (P<0.05) levels. Sudan IV staining showed that 12-week canagliflozin treatment decreased atherosclerotic lesions (P<0.05). Further, 8-week canagliflozin treatment ameliorated endothelial dysfunction, as determined by acetylcholine-induced vasodilation (P<0.05), and significantly reduced the expressions of inflammatory molecules such as ICAM-1 and VCAM-1 in the aorta at the RNA and protein levels. Canagliflozin also reduced the expressions of NADPH oxidase subunits such as NOX2 and p22phox in the aorta and reduced urinary excretion of 8-OHdG, suggesting a reduction in oxidative stress. Methylglyoxal, a precursor of advanced glycation end products, increased the expressions of ICAM-1 and p22phox in HUVECs (P<0.05, both). Methylglyoxal also decreased the phosphorylation of eNOS and Akt but increased the phosphorylation of eNOS and p38 MAPK in HUVECs. Canagliflozin prevents endothelial dysfunction and atherogenesis in diabetic ApoE mice. Anti-inflammatory and antioxidative potential due to reduced glucose toxicity to endothelial cells might be its underlying mechanisms.
Kenya Kusunose, Akihiro Haga, Natsumi Yamaguchi, Takashi Abe, Daiju Fukuda, Hirotsugu Yamada, Masafumi Harada and Masataka Sata : Deep Learning for Assessment of Left Ventricular Ejection Fraction from Echocardiographic Images, Journal of the American Society of Echocardiography, Vol.33, No.5, 632-635, 2020.
Akihiro Tani, Kenya Kusunose, Kazuhisa Mastumoto, Hirotsugu Yamada and Masataka Sata : Diastolic Mitral Regurgitation on Color M-Mode Echocardiography in a Patient With Complete Atrioventricular Block., Circulation Reports, Vol.2, No.3, 207-208, 2020.
平田 有紀奈, 西尾 進, 原田 修, 宮里 尚美, 原國 督, Kenya Kusunose, 伊藤 敦彦, Hirotsugu Yamada and Masataka Sata : Validation of Epicardial Adipose Tissue Thickness by Echocardiography for Predicting Coronary Artery Disease: a Multicenter Study, Japanese Journal of Medical Ultrasound Technology, Vol.45, No.1, 11-20, 2020.
Akihiro Haga and Kenya Kusunose : Echo radiomics, Medical Imaging Technology, Vol.38, No.1, 21-26, 2020.
(Summary)
<p>Recent progress in image analysis methods including a deep learning open a new phase in the analysis using echo-cardiographic images. Indeed, a disease-existence diagnosis, disease-difference diagnosis, and functional diagnosis via the computational analysis with echocardiographic images are nowadays the active research field. In this paper, we introduce the research of cardiac conditions using two-dimensional echo imaging, especially, a quantitative evaluation of left ventricular ejection fraction (LVEF). Although the previous LVEF evaluation is needed through an observer dependent process that requires manual tracing, we show here that the direct evaluation from echocardiographic images using deep neural network with various view modes gives precise prediction in LVEF. In addition, the pre-processing used in our research, including automated classification of imaging plane, is introduced.</p>
(Keyword)
Ultra-sound image / Echocardiographic analysis / Left ventricular ejection fraction / Deep learning
Maimaituxun Gulinu, Hirotsugu Yamada, Daiju Fukuda, Shusuke Yagi, Kenya Kusunose, Hirata Yukina, Nishio Susumu, Takeshi Soeki, Masuzaki Hiroaki, Masataka Sata and Michio Shimabukuro : Association of Local Epicardial Adipose Tissue Depots and Left Ventricular Diastolic Performance in Patients With Preserved Left Ventricular Ejection Fraction, Circulation Journal, Vol.84, No.2, 203-216, 2020.
Arief Rahadian, Daiju Fukuda, HM Salim, Shusuke Yagi, Kenya Kusunose, Hirotsugu Yamada, Takeshi Soeki, Michio Shimabukuro and Masataka Sata : Thrombin inhibition by dabigatran attenuates endothelial dysfunction in diabetic mice, Vascular Pharmacology, Vol.124, 106632, 2020.
(Summary)
Diabetic patients have coagulation abnormalities, in which thrombin plays a key role. Whereas accumulating evidence suggests that it also contributes to the development of vascular dysfunction through the activation of protease-activated receptors (PARs). Here we investigated whether the blockade of thrombin attenuates endothelial dysfunction in diabetic mice. Induction of diabetes by streptozotocin (STZ) increased the expression of PAR1, PAR3, and PAR4 in the aorta. STZ-induced diabetic mice showed impairment of endothelial function, while the administration of dabigatran etexilate, a direct thrombin inhibitor, significantly attenuated endothelial dysfunction in diabetic mice with no alteration of metabolic parameters including blood glucose level. Dabigatran did not affect endothelium-independent vasodilation. Dabigatran decreased the expression of inflammatory molecules (e.g., MCP-1 and ICAM-1) in the aorta of diabetic mice. Thrombin increased the expression of these inflammatory molecules and the phosphorylation of IκBα, and decreased the phosphorylation of eNOS in human umbilical endothelial cells (HUVEC). Thrombin significantly impaired the endothelium-dependent vascular response of aortic rings obtained from wild-type mice. Inhibition of NF-κB attenuated thrombin-induced inflammatory molecule expression in HUVEC and ameliorated thrombin-induced endothelial dysfunction in aortic rings. Dabigatran attenuated the development of diabetes-induced endothelial dysfunction. Thrombin signaling may serve as a potential therapeutic target in diabetic condition.
João L. Cavalcante, Kenya Kusunose, Nancy A. Obuchowski, Christine Jellis, Brian P. Griffin, Scott D. Flamm and Deborah H. Kwon : Prognostic Impact of Ischemic Mitral Regurgitation Severity and Myocardial Infarct Quantification by Cardiovascular Magnetic Resonance., JACC. Cardiovascular Imaging, Vol.13, No.7, 1489-1501, 2019.
(Summary)
This study sought to evaluate the role of cardiac magnetic resonance (CMR) for the quantification of ischemic mitral regurgitation (IMR) and myocardial infarct size (MIS) in patients with ischemic cardiomyopathy (ICM). This study also sought to explore the interaction between IMR severity and MIS and its association with outcomes in patients with ICM. IMR occurs secondary to a disease of the left ventricle and is associated with poor outcomes. The role of CMR for the evaluation and risk stratification of patients with ICM and IMR remains uncertain. Consecutive patients with ICM who underwent baseline CMR were included. MIS was quantified on late gadolinium enhancement imaging as the proportion of left ventricular mass. IMR was quantified with CMR by calculating the mitral regurgitant fraction (MRFraction). Cox proportional hazards models were built to assess the association of IMR and MIS quantification with the combined endpoint of all-cause death or heart transplant. We evaluated 578 patients (mean age: 62 ± 11 years, 76% males). The mean left ventricular ejection fraction was 25 ± 11%, with an MIS of 24 ± 16% and MRFraction of 18 ± 17%. Over a median follow-up time of 4.9 years, 198 (34%) patients experienced death or cardiac transplant. On multivariable analysis, after comprehensive medical risk score, subsequent revascularization, implantable cardioverter-defibrillator insertion, and surgical mitral valve intervention were controlled for, the interaction of IMR severity and MIS emerged as a powerful predictor of adverse outcomes (p = 0.008). For patients with significant IMR (MRFraction: ≥35%), the hazard ratio comparing moderate MIS (15% to 29%) versus small MIS (<15%) was 1.51 (0.57 to 3.98), and the hazard ratio comparing large MIS (≥30%) versus small MIS was 5.41 (2.34 to 12.7). Risk associated with IMR is more comprehensively described as an interaction between IMR severity and MIS. Further studies in patients IMR using comprehensive CMR evaluation are needed to verify whether this approach can improve patient selection and procedural outcomes to address IMR.
Yukina Hirata, Kenya Kusunose, Hirokazu Miki and Hirotsugu Yamada : Improvement of global longitudinal strain following high-dose chemotherapy and autologous peripheral blood stem cell transplantation in patients with amyloid light-chain cardiac amyloidosis: a case report., European Heart Journal. Case Reports, Vol.3, No.4, 1-6, 2019.
(Summary)
Cardiac amyloidosis (CA) is a secondary form of cardiomyopathy where abnormal accumulation of amyloid protein in the myocardial interstitium causes cardiac hypertrophy and myocardial fibrosis. If primary CA advances to heart failure, most patients do not survive for very long after the diagnosis. A 40-year-old man was admitted to our hospital for dyspnoea, progressive anaemia, and decreased appetite. He has diagnosed with amyloid light-chain (AL) amyloidosis. Although BD treatment (bortezomib + dexamethasone) and medical treatment were started, there was no sign of improvement. Then, high-dose chemotherapy followed by autologous peripheral blood stem cell transplantation (auto-PBSCT) was initiated. Pretreatment echocardiography revealed typical findings of CA, such as ventricular wall thickening, valvular thickening, diastolic dysfunction, and pericardial effusion. Global longitudinal strain (GLS) was significantly reduced, and bull's-eye mapping showed typical apical sparing. After auto-PBSCT, GLS gradually improved and was almost normal after 2 years. Other echocardiographic parameters, functional status, and laboratory data also showed that there was significant regression of CA. Although the prognosis in primary CA is extremely poor, we achieved long-term survival in a patient with effective high-dose chemotherapy and auto-PBSCT. Global longitudinal strain may be a useful marker of prognosis, regression, and recovery.
K Aini, Daiju Fukuda, K Tanaka, Y Higashikuni, Yukina Hirata, Shusuke Yagi, Kenya Kusunose, Hirotsugu Yamada, Takeshi Soeki and Masataka Sata : Vildagliptin, a DPP-4 Inhibitor, Attenuates Endothelial Dysfunction and Atherogenesis in Nondiabetic Apolipoprotein E-Deficient Mice, International Heart Journal, Vol.60, No.6, 1421-1429, 2019.
(Summary)
Dipeptidyl peptidase-4 (DPP-4) inhibitors are novel antidiabetic agents with possible vascular protection effects. Endothelial dysfunction is an initiation step in atherogenesis. The purpose of this study was to investigate whether vildagliptin (Vilda) attenuates the development of endothelial dysfunction and atherosclerotic lesions in nondiabetic apolipoprotein E-deficient (ApoE) mice. Eight-week-old nondiabetic ApoE mice fed a Western-type diet received Vilda (50 mg/kg/day) for 20 weeks or 8 weeks. After 20 weeks of treatment, Vilda administration reduced atherogenesis in the aortic arch as determined by en face Sudan IV staining compared with the vehicle group (P < 0.05). Vilda also reduced lipid accumulation (P < 0.05) and vascular cell adhesion molecule-1 (VCAM-1) expression (P < 0.05) and tended to decrease macrophage infiltration (P = 0.05) into atherosclerotic plaques compared with vehicle. After 8 weeks of treatment, endothelium-dependent vascular reactivity was examined. Vilda administration significantly attenuated the impairment of endothelial function in nondiabetic ApoE mice compared with the vehicle group (P < 0.05). Vilda treatment did not alter metabolic parameters, including blood glucose level, in both study protocols. To investigate the mechanism, aortic segments obtained from wild-type mice were incubated with exendin-4 (Ex-4), a glucagon-like peptide-1 (GLP-1) analog, in the presence or absence of lipopolysaccharide (LPS). Ex-4 attenuated the impairment of endothelium-dependent vasodilation induced by LPS (P < 0.01). Furthermore, Ex-4 promoted phosphorylation of eNOS at Ser1177 which was decreased by LPS in human umbilical endothelial cells (P < 0.05). Vilda inhibited the development of endothelial dysfunction and prevented atherogenesis in nondiabetic ApoE mice. Our results suggested that GLP-1-dependent amelioration of endothelial dysfunction is associated with the atheroprotective effects of Vilda.
Kenya Kusunose, Yuta Torii, Hirotsugu Yamada, Susumu Nishio, Yukina Hirata, Yoshihito Saijoh, Takayuki Ise, Koji Yamaguchi, Daiju Fukuda, Shusuke Yagi, Takeshi Soeki, Tetsuzo Wakatsuki and Masataka Sata : Association of Echocardiography Before Major Elective Non-Cardiac Surgery With Improved Postoperative Outcomes - Possible Implications for Patient Care., Circulation Journal, Vol.83, No.12, 2512-2519, 2019.
(Summary)
Whether preoperative echocardiography improves postoperative outcomes is not well established, so we examined the value of echocardiographic assessment on the onset of postoperative heart failure (HF), and determining which patients benefitted most from undergoing echocardiography prior to major elective non-cardiac surgery.Methods and Results:We identified all patients aged 50 years and older who had major elective non-cardiac surgery, and excluded patients with previously identified severe cardiovascular disease. The primary endpoint was the onset of HF during hospitalization. A total of 806 patients were included in the analysis. During hospitalization, 49 patients (6%) reached the primary endpoint. Within the matched cohort, preoperative echocardiography was associated with a statistically significant decrease in postoperative HF (hazard ratio: 0.46, P=0.01). In subgroup analyses, age, sex, body surface area, hypertension, diabetes mellitus, prior HF, surgical type, chronic kidney disease, pulmonary disease, and malignancy influenced the association of echocardiography with postoperative HF. The use of echocardiography in elderly patients with certain risk factors was associated with improved postoperative outcomes. The basis for this finding remains to be determined; particularly whether echocardiography is simply a marker of a population with better outcomes or whether it leads to better management that improves outcomes.
(Keyword)
Aged / Echocardiography / Female / Heart Failure / Humans / Incidence / Japan / Male / Middle Aged / Predictive Value of Tests / Preoperative Care / Retrospective Studies / Risk Assessment / Risk Factors / Surgical Procedures, Operative / Time Factors / Treatment Outcome
PT Pham, Daiju Fukuda, Shusuke Yagi, Kenya Kusunose, Hirotsugu Yamada, Takeshi Soeki, Michio Shimabukuro and Masataka Sata : Rivaroxaban, a specific FXa inhibitor, improved endothelium-dependent relaxation of aortic segments in diabetic mice, Scientific Reports, Vol.9, No.1, 11206, 2019.
(Summary)
Activated factor X (FXa) plays a central role in the coagulation cascade, while it also mediates vascular function through activation of protease-activated receptors (PARs). Here, we examined whether inhibition of FXa by rivaroxaban, a direct FXa inhibitor, attenuates endothelial dysfunction in streptozotocin (STZ)-induced diabetic mice. Induction of diabetes increased the expression of a major FXa receptor, PAR2, in the aorta (P < 0.05). Administration of rivaroxaban (10 mg/kg/day) to diabetic wild-type (WT) mice for 3 weeks attenuated endothelial dysfunction as determined by acetylcholine-dependent vasodilation compared with the control (P < 0.001), without alteration of blood glucose level. Rivaroxaban promoted eNOS phosphorylation in the aorta (P < 0.001). Induction of diabetes to PAR2-deficient (PAR2) mice did not affect endothelial function and eNOS phosphorylation in the aorta compared with non-diabetic PAR2 mice. FXa or a PAR2 agonist significantly impaired endothelial function in aortic rings obtained from WT mice, but not in those from PAR2 mice. FXa promoted JNK phosphorylation (P < 0.01) and reduced eNOS phosphorylation (P < 0.05) in human coronary artery endothelial cells (HCAEC). FXa-induced endothelial dysfunction in aortic rings (P < 0.001) and eNOS phosphorylation (P < 0.05) in HCAEC were partially ameliorated by a JNK inhibitor. Rivaroxaban ameliorated diabetes-induced endothelial dysfunction. Our results suggest that FXa or PAR2 is a potential therapeutic target.
Yuta Torii, Kenya Kusunose, Hirotsugu Yamada, Susumu Nishio, Yukina Hirata, Amano Rie, Yamao Masami, Zheng Robert, Yoshihito Saijoh, nao Yamada, Takayuki Ise, Koji Yamaguchi, Shusuke Yagi, Takeshi Soeki, Tetsuzo Wakatsuki and Masataka Sata : Updated Left Ventricular Diastolic Function Recommendations and Cardiovascular Events in Patients with Heart Failure Hospitalization, Journal of the American Society of Echocardiography, Vol.32, No.10, 1286-1297, 2019.
(Summary)
Evaluation of diastolic dysfunction is crucial in determining elevated left atrial pressure. However, a validation of the long-term prognostic value of the newly proposed algorithm updated in 2016 has not been performed. The aim of the present study was to investigate the relative value of the updated 2016 diastolic dysfunction grading system for the incidence of readmission in patients with heart failure (HF) with reduced ejection fraction (HFrEF) and HF with preserved ejection fraction (HFpEF). Two hundred thirty-two patients hospitalized with HF were retrospectively evaluated. Subjects were divided into two subgroups: those with HFrEF (n = 127) and those with HFpEF (n = 105). Readmission risk scores were calculated using the Yale Center for Outcomes Research and Evaluation HF, LACE index, and HOSPITAL scores. The primary end point was readmission following HF and cardiac death. Over a period of 24 months, 86 patients were either readmitted or died. Multivariate Cox analysis was performed on both the HFrEF and HFpEF groups. In the HFrEF group, both the 2009 and 2016 algorithms had superior incremental value for the association of the primary end point to several readmission risk scores. In the HFpEF group, only the 2016 algorithm led to significant improvement in association with the primary end point. The 2016 algorithm had incremental value over several readmission risk scores alone. The recommendations of the 2016 algorithm can be useful for readmission and cardiac mortality risk assessment in patients with HFrEF and HFpEF. The use of echocardiography to estimate elevated left atrial pressure appears to identify a higher risk group and may allow a more tailored approach to therapy.
Kenya Kusunose : Clinical application of stress echocardiography for valvular heart disease., Journal of Medical Ultrasonics, Vol.47, No.1, 81-89, 2019.
(Summary)
Stress echocardiography is widely used to assess several cardiovascular diseases, including ischemic heart disease, valvular heart disease (VHD), heart failure, congenital heart disease, and pulmonary hypertension. In valvular heart disease with asymptomatic severe or symptomatic non-severe status, stress echocardiography plays a central role in the management. As of 2017, the updated American College of Cardiology/American Heart Association and European Society of Cardiology/European Association for Cardio-Thoracic Surgery VHD guidelines recommended stress testing to (1) confirm symptoms and (2) evaluate the hemodynamic response to exercise. In patients with undetermined VHD severity in the presence of low-flow status, it can also be helpful to determine whether the VHD is severe based on flow-dependent changes in response to stress. The clinical indications of stress echocardiography in VHD have expanded with growing evidence for prognosis and being an early marker for interventions. As a result, demand has increased in major cardiology societies for the standardization of stress echocardiography in VHD. Echocardiographic centers should be aware of the clinical potential of stress echocardiography to ensure its optimal application and performance in VHD. This article reviews the clinical application of stress echocardiography, including dobutamine, semisupine bicycle, treadmill, and leg-positive pressure for VHD patient management, and focuses on the current consensus regarding the use of stress echocardiography in VHD. Stress echocardiography is safe and should be encouraged, especially in heart valve clinics, to understand the complex mechanism in asymptomatic patients.
Kenya Kusunose, Akihiro Haga, Takashi Abe and Masataka Sata : Utilization of Artificial Intelligence in Echocardiography, Circulation Journal, Vol.83, No.8, 1623-1629, 2019.
(Summary)
Echocardiography has a central role in the diagnosis and management of cardiovascular disease. Precise and reliable echocardiographic assessment is required for clinical decision-making. Even if the development of new technologies (3-dimentional echocardiography, speckle-tracking, semi-automated analysis, etc.), the final decision on analysis is strongly dependent on operator experience. Diagnostic errors are a major unresolved problem. Moreover, not only can cardiologists differ from one another in image interpretation, but also the same observer may come to different findings when a reading is repeated. Daily high workloads in clinical practice may lead to this error, and all cardiologists require precise perception in this field. Artificial intelligence (AI) has the potential to improve analysis and interpretation of medical images to a new stage compared with previous algorithms. From our comprehensive review, we believe AI has the potential to improve accuracy of diagnosis, clinical management, and patient care. Although there are several concerns about the required large dataset and "black box" algorithm, AI can provide satisfactory results in this field. In the future, it will be necessary for cardiologists to adapt their daily practice to incorporate AI in this new stage of echocardiography.
Daiju Fukuda, Sachiko Nishimoto, Kunduziayi Aini, Atsushi Tanaka, Tsuyoshi Nishiguchi, Joo-Ri Kim-Kaneyama, Xiao-Feng Lei, Kiyoshi Masuda, Takuya Naruto, Kimie Tanaka, Yasutomi Higashikuni, Yoichiro Hirata, Shusuke Yagi, Kenya Kusunose, Hirotsugu Yamada, Takeshi Soeki, Issei Imoto, Takashi Akasaka, Michio Shimabukuro and Masataka Sata : Toll-Like Receptor 9 Plays a Pivotal Role in Angiotensin II-Induced Atherosclerosis, Journal of the American Heart Association, Vol.8, No.7, e010860, 2019.
(Summary)
Background Toll-like receptor ( TLR ) 9 recognizes bacterial DNA , activating innate immunity, whereas it also provokes inflammation in response to fragmented DNA released from mammalian cells. We investigated whether TLR 9 contributes to the development of vascular inflammation and atherogenesis using apolipoprotein E-deficient ( Apoe ) mice. Methods and Results Tlr9-deficient Apoe ( Tlr9 Apoe ) mice and Apoe mice on a Western-type diet received subcutaneous angiotensin II infusion (1000 ng/kg per minute) for 28 days. Angiotensin II increased the plasma level of double-stranded DNA, an endogenous ligand of TLR 9, in these mice. Genetic deletion or pharmacologic blockade of TLR 9 in angiotensin II-infused Apoe mice attenuated atherogenesis in the aortic arch ( P<0.05), reduced the accumulation of lipid and macrophages in atherosclerotic plaques, and decreased RNA expression of inflammatory molecules in the aorta with no alteration of metabolic parameters. On the other hand, restoration of TLR 9 in bone marrow in Tlr9 Apoe mice promoted atherogenesis in the aortic arch ( P<0.05). A TLR 9 agonist markedly promoted proinflammatory activation of Apoe macrophages, partially through p38 mitogen-activated protein kinase signaling. In addition, genomic DNA extracted from macrophages promoted inflammatory molecule expression more effectively in Apoe macrophages than in Tlr9 Apoe macrophages. Furthermore, in humans, circulating double-stranded DNA in the coronary artery positively correlated with inflammatory features of coronary plaques determined by optical coherence tomography in patients with acute myocardial infarction ( P<0.05). Conclusions TLR 9 plays a pivotal role in the development of vascular inflammation and atherogenesis through proinflammatory activation of macrophages. TLR 9 may serve as a potential therapeutic target for atherosclerosis.
Yukina Hirata, Kenya Kusunose, Hirotsugu Yamada, Sae Morita, Yuta Torii, Susumu Nishio, Robert Zheng, Yoshihito Saijo, Daiju Fukuda, Shusuke Yagi, Takeshi Soeki and Masataka Sata : Left atrial functional response after a marathon in healthy amateur volunteers, The International Journal of Cardiovascular Imaging, Vol.35, No.4, 633-643, 2019.
(Summary)
Middle-aged marathon runners have an increased risk of developing atrial fibrillation (AF). A previous study described that repetitive marathon running was associated with left atrial (LA) dysfunction. However, whether this change is common in marathon runners and which runners are at risk of LA dysfunction remain unknown. The purpose of this study was to determine which factors could predict LA dysfunction. We prospectively examined 12 healthy amateur volunteers (9 males, 31 ± 8 years old) who participated in a full marathon. All echocardiographic measurements and speckle-tracking echocardiography were performed before and after the marathon. The endpoint was defined as reduced LA reservoir strain 1 day after the marathon (non-responder group). Seven participants were in the non-responder group. Age (35 ± 9 vs. 26 ± 2 years, p = 0.020), augmentation index (76 ± 12 vs. 55 ± 8, p = 0.002), and diastolic blood pressures (83 ± 11 vs. 70 ± 7 mmHg, p = 0.021) in the non-responder group were significantly higher compared with the responder group. In multivariate linear regression analysis, only the augmentation index was an independent predictor of reduced LA reservoir function after the marathon (β = - 0.646, p = 0.023). The augmentation index was a predictive marker for reduction in LA reservoir function after a marathon in healthy amateur volunteers.
Shusuke Yagi, Daisuke Kondo, Takayuki Ise, Daiju Fukuda, Koji Yamaguchi, Tetsuzo Wakatsuki, Yutaka Kawabata, Hiroyuki Ito, Yoshihito Saijo, Hiromitsu Seno, Kumiko Sutou, Rie Ueno, Takafumi Todoroki, Kenya Kusunose, Tomomi Matsuura, Takeshi Tobiume, Hirotsugu Yamada, Takeshi Soeki, Michio Shimabukuro, Ken-ichi Aihara, Masashi Akaike and Masataka Sata : Association of Decreased Docosahexaenoic Acid Level After Statin Therapy and Low Eicosapentaenoic Acid Level with In-Stent Restenosis in Patients with Acute Coronary Syndrome, Journal of Atherosclerosis and Thrombosis, Vol.26, No.3, 272-281, 2019.
(Summary)
It is speculated that statin therapy modulates the synthesis of polyunsaturated fatty acids (PUFA), including eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). However, the data available on the effects of statin therapy on the serum levels of PUFA and the subsequent impact on in-stent restenosis (ISR) in patients with acute coronary syndrome (ACS) are limited. A total of 120 ACS patients who received emergent coronary stent implantation, follow-up coronary angiography to evaluate ISR, and new statin therapy were enrolled. We measured the serum levels of the PUFA and lipids at the onset of ACS and at the follow-up coronary angiography. The follow-up coronary angiography revealed 38 ISR cases. New statin therapy significantly reduced the serum levels of DHA and low-density lipoprotein cholesterol (LDL-C), while it did not affect EPA level. Single regression analysis revealed that a decreased serum level of LDL-C was associated with decreased DHA level. The multiple logistic regression analysis revealed that the decreased DHA level after statin therapy and low serum level of EPA on admission were determinants of prevalence of ISR. Statin therapy decreased the serum level of DHA with a parallel reduction in LDL-C level in patients with ACS. Decreased DHA level after statin therapy and low EPA level on admission are risk factors for ISR, indicating that in patients with ACS, decreased serum levels of DHA may be a residual target for the prevention of ISR.
Yuko Saito, Hirotsugu Yamada, Kenya Kusunose, Ken Saito and Masataka Sata : Noninvasive assessment of left-ventricular diastolic electromechanical coupling in hypertensive heart disease,, Journal of Echocardiography, Vol.17, No.4, 206-212, 2019.
(Summary)
There is a need to stratify patients who may develop heart failure because of the current "heart failure pandemic". We hypothesized that noninvasive assessment of diastolic electromechanical coupling by electrocardiography and Doppler echocardiography may be clinically useful for risk stratification of hypertensive patients who may develop heart failure. We measured the time from the peak to end of the T wave (TpTe) as an electrophysiological parameter, and peak early diastolic mitral flow (E) and lateral annular (e') velocities as mechanical parameters in 109 patients with hypertension. Relationships between these parameters and their association with the prognosis were evaluated. The e' was inversely correlated with TpTe (p < 0.001) and QTc (p < 0.014), whereas E/e' was positively correlated with TpTe (p < 0.001) and QTc (p < 0.001). The TpTe predicted patients with E/e' > 12. There were 24 cardiovascular events during follow-up (57 ± 20 months), and Kaplan-Meier analysis showed that outcome was worse (p = 0.003) in patients with higher E/e' than lower E/e'; however, there was no difference between patients with longer TpTe (≧72 ms) and shorter TpTe (< 72 ms). The correlation of TpTe with e' and E/e' in hypertensive patients suggests that these parameters reflect diastolic ventricular electromechanical coupling. The E/e' predicted outcome, and an elevated E/e' should be suspected when TpTe is prolonged (> 72 ms). Noninvasive evaluation of diastolic electromechanical coupling is clinically useful in patients with hypertension for predicting their outcome.
Mina Takahashi, Takeshi Tobiume, Kazuhisa Matsumoto, Tomomi Matsuura, Takeshi Soeki, 藤本 裕太, 原田 貴文, Zengu Robahto, 數藤 久美子, 西條 良仁, 上野 理絵, Yutaka Kawabata, Mika Bando, nao Yamada, Hiroyuki Ito, 轟 貴史, Takayuki Ise, Kenya Kusunose, Koji Yamaguchi, Shusuke Yagi, Daiju Fukuda, Hirotsugu Yamada, Tetsuzo Wakatsuki and Masataka Sata : A successful case of catheter ablation against ventricular tachycardia storm due to old myocardial infarction in a patient with aortic valve replacement, Shikoku Acta Medica, Vol.74, No.56, 201-208, 2019.
(Summary)
A 68-year-old woman with VT storm and frequent appropriate ICD therapy was referred for catheter ablation. Her past history was notable for aortic valve replacement by mechanical valve due to infectious endocarditis 17 years prior to presentation and left ventricular apical old myocardial infarction with unknown onset. At 67 years old, She admitted to the prior hospital due to ventricular tachycardia with LBBB and superior axis at heart rate of 210 per minutes. Administration of amiodarone and magnesium sulfate was ineffective and cardioversion of 200J was successfully terminated the tachycardia. Intra-cardiac defibrillator was implanted and the administration of amiodarone and mexiletine was started. 5 months after, she admitted to the hospital due to the frequent appropriate shock against the same ventricular tachycardia. Administration of lidocaine, sotalol, pilsicainide, and magnesium sulfate could not control the tachycardia and she was referred to our hospital for catheter ablation. During the first session, ventricular tachycardia was easily induced and electroanatomical mapping was performed both during tachycardia and during sinus rhythm. Late diastolic potential preceding the onset of QRS wave by 45ms was detected at the infero-septal side of the apical aneurysm. 7 5s of the RF energy application at this site could terminate the tachycardia and thereafter no ventricular tachycardia was induced. But after dose-reduction or cessation of some anti-arrhythmic drugs, ventricular tachycardia was recurred and second session was performed. This time, no ventricular tachycardia was induced, then we performed isthmus transection and core isolation against the apical aneurysm. Thereafter no ventricular tachycardia was occurred in spite of dose-reduction or cessation of some anti-arrhythmic drugs.
松本 力三, 西尾 進, 平田 有紀奈, 湯浅 麻美, Yuta Torii, 天野 里江, 山尾 雅美, Miharu Arase, Kenya Kusunose, Hirotsugu Yamada and Masataka Sata : 糖尿病性腎症の各病期における超音波指標の比較, Japanese Journal of Medical Ultrasound Technology, Vol.44, No.4, 447-455, 2019.
Shusuke Yagi, Robert Zheng, Seiichi Nishiyama, Yutaka Kawabata, Takayuki Ise, Kosuke Sugiura, Haruhiko Yoshinari, Toshihiko Nishisho, Yoshimi Bando, Kumiko Kagawa, Daiju Fukuda, Tomohiro Soga, Yoshihito Saijoh, Kenya Kusunose, Koji Yamaguchi, Hirotsugu Yamada, Takeshi Soeki, Tetsuzo Wakatsuki, Shinji Kawahito, Masashi Akaike and Masataka Sata : Osteolytic primary bone lymphoma in the multiple bones, The Journal of Medical Investigation : JMI, Vol.66, No.3,4, 347-350, 2019.
(Summary)
Primary non-Hodgkin bone lymphoma (PBL) can involve solitary or multiple destructive bone lesions such as those of the femur or pelvis humerus, and some cases have osteolytic lesions. PBL is a rare disease in adults. Thus, PBL is rarely considered a differential diagnosis of the osteolytic tumor. In addition, PBL can be underdiagnosed because patients do not experience symptoms or show objective abnormalities in the early stage. Here, we reported an elderly patient with PBL in multiple bones, including the cranial and femoral bones that were fractured due to falling. J. Med. Invest. 66 : 347-350, August, 2019.
Shusuke Yagi, Itsuro Endo, Taichi Murakami, Tetsuya Hida, Yousuke Yamamoto, Tomohiro Soga, Takayuki Ise, Kenya Kusunose, Koji Yamaguchi, Daiju Fukuda, Hirotsugu Yamada, Takeshi Soeki, Tetsuzo Wakatsuki, Shinji Kawahito and Masataka Sata : Adult onset of Immunoglobulin A vasculitis - A case report,, The Journal of Medical Investigation : JMI, Vol.66, No.3,4, 344-346, 2019.
(Summary)
Immunoglobulin A vasculitis (IgAV), formerly known as Henoch-Schönlein purpura, primarily occurs during childhood between the ages of 3 and 15 years and is the most common form of systemic vasculitis in children ; its occurrence in adults has been rarely reported. Such low incidence could be attributable to either under-diagnosis or misdiagnosis. Thus, not only pediatricians but also physicians should be able to diagnose IgAV accurately to manage the patients appropriately and avoid its associated complications. In addition, treatment of adult onset IgAV with renal involvement has not been fully established yet. We describe here a case of adult onset IgAV complicated by proteinuria and pharyngitis, which was cured by no specific treatment. J. Med. Invest. 66 : 344-346, August, 2019.
(Keyword)
Acetaminophen / Adult / Factor XIII / Humans / Immunoglobulin A / Male / Pharyngitis / Proteinuria / Purpura, Schoenlein-Henoch
Shusuke Yagi, Rie Ueno, Kumiko Sutou, Tetsuzo Wakatsuki, Koji Yamaguchi, Yoshihito Saijo, Tomoya Hara, Takayuki Ise, Kenya Kusunose, Mika Bando, Tomomi Matsuura, Takeshi Tobiume, Hirotsugu Yamada, Daiju Fukuda, Takeshi Soeki, Masashi Akaike and Masataka Sata : Lambda-like J wave due to acute myocardial infarction of the diagonal branch, The Journal of Medical Investigation : JMI, Vol.66, No.1,2, 185-187, 2019.
(Summary)
The culprit lesion of acute myocardial infarction could be predicted by electrocardiogram findings. However, we experienced some cases with coronary angiographic finding in the area of ST-T elevation that was different from that predicted. The lambda-like J wave could be caused by ischemia although the mechanism has not been fully elucidated. We report a case of acute myocardial infarction that showed discrepancy between ST-T elevation with lambda-like ischemic J wave in a broad area and coronary angiographical finding of diagonal branch occlusion. J. Med. Invest. 66 : 185-187, February, 2019.
Sachiko Nishimoto, Kunduziayi Aini, Daiju Fukuda, Yasutomi Higashikuni, Kimie Tanaka, Yoichiro Hirata, Shusuke Yagi, Kenya Kusunose, Hirotsugu Yamada, Takeshi Soeki, Michio Shimabukuro and Masataka Sata : Activation of Toll-Like Receptor 9 Impairs Blood Flow Recovery After Hind-Limb Ischemia, Frontiers in Cardiovascular Medicine, Vol.5, 144, 2018.
(Summary)
Peripheral artery disease causes significant functional disability and results in impaired quality of life. Ischemic tissue injury releases various endogenous ligands for Toll-like receptors (TLRs), suggesting the involvement of TLRs in blood flow recovery. However, the role of TLR9, which was originally known as a sensor for bacterial DNA, remains unknown. This study investigated the role of TLR9 in blood flow recovery in the ischemic limb using a mouse hind-limb ischemia model. Unilateral femoral artery ligation was performed in TLR9-deficient () mice and wild-type mice. In wild-type mice, femoral artery ligation significantly increased mRNA expression of TLR9 in the ischemic limb ( < 0.001) and plasma levels of cell-free DNA (cfDNA) as determined by single-stranded DNA (ssDNA) ( < 0.05) and double-stranded DNA (dsDNA) ( < 0.01), which are endogenous ligands for TLR9, compared with the sham-operated group. Laser Doppler perfusion imaging demonstrated significantly improved ratio of blood flow in the ischemic to non-ischemic limb in mice compared with wild-type mice at 2 weeks after ligation ( < 0.05). mice showed increased capillary density and reduced macrophage infiltration in ischemic limb. Genetic deletion of TLR9 reduced the expression of TNF-α, and attenuated NF-κB activation in ischemic muscle compared with wild-type mice ( < 0.05, respectively) at 3 days after the surgery. ODN1826, a synthetic agonistic oligonucleotide for TLR9, or plasma obtained from mice with ischemic muscle promoted the expression of TNF-α in wild-type macrophages ( < 0.05), but not in macrophages. ODN1826 also activated NF-κB signaling as determined by the degradation of IκBα in wild-type macrophages ( < 0.05), but not in macrophages. In vitro experiments using human umbilical vein endothelial cells demonstrated that TNF-α, or conditioned medium obtained from wild-type macrophages treated with ODN1826 accelerated cell death as determined by MTS assay ( < 0.05 and < 0.01, respectively). Our results suggest that ischemic muscle releases cfDNA, which activates TLR9 and enhances inflammation, leading to impairment of blood flow recovery in the ischemic limb. cfDNA-TLR9 signaling may serve as a potential therapeutic target in ischemic limb disease.
Patrick Collier, Bo Xu, Kenya Kusunose, Dermot Phelan, Andrew Grant, Paaladinesh Thavendiranathan, Brian P. Griffin, Richard A. Grimm, Thomas H. Marwick and Zoran B. Popović : Impact of abnormal longitudinal rotation on the assessment of right ventricular systolic function in patients with severe pulmonary hypertension., Journal of Thoracic Disease, Vol.10, No.8, 4694-4704, 2018.
(Summary)
Assessment of right ventricular (RV) function plays an important role in patients with cardiopulmonary disease, and current guidelines recommend parameters including tricuspid annular plane systolic excursion (TAPSE) and right ventricular systolic excursion velocity (RVS') to assess RV longitudinal function. We assessed the hypothesis that the previously undescribed motion of RV longitudinal rotation (RVLR) is an independent predictor of both TAPSE and RVS'. We assessed a series of 100 consecutive patients with pulmonary hypertension (PH) undergoing echocardiography. Patients with left ventricular (LV) dilation and dysfunction were excluded. Standard RV parameters were determined using established guidelines, while RVLR and right ventricular global longitudinal strain (RVGLS) measurements were performed using 2-dimensional (2D) speckle tracking technique. Mean peak RVLR measured -4.2±3.7 degrees. By convention, negative values implied clockwise motion. In a multiple linear regression model, TAPSE could be predicted from a combination of RVLR and RVGLS (R=0.56, P<0.001). A similar relationship was found for RVS' which could also be predicted from a combination of RVLR and RVGLS (R=0.52, P<0.001). While no association was found between RVLR and RV size, estimated RV systolic pressure (RVSP) or the presence of a pericardial effusion, a mild correlation was noted between RVLR and QRS duration (R=0.25, P=0.01). RVLR is an independent predictor of TAPSE and RVS'. Awareness of this motion should be considered in the interpretation of TAPSE and RVS' values as markers of RV systolic function, as abnormal RVLR may account for exaggerated values, particularly in patients with PH and RV dysfunction.
Yoshihito Saijo, Hirotsugu Yamada, Kenya Kusunose, Mika Bando, Susumu Nishio, Yuta Torii, Yukina Hirata, Hiromitsu Seno, Tomomi Matsuura, Takayuki Ise, Takeshi Tobiume, Koji Yamaguchi, Shusuke Yagi, Takeshi Soeki, Tetsuzo Wakatsuki and Masataka Sata : A clinical application of preload stress echocardiography for predicting future hemodynamic worsening in patients with early-stage heart failure., Echocardiography, Vol.35, No.10, 1587-1595, 2018.
(Summary)
To improve the prognosis of patients with heart failure, risk stratification in their early stage is important. We assessed whether the change in transmitral flow (TMF) velocity pattern during preload augmentation can predict future hemodynamic worsening in early-stage heart failure patients with impaired relaxation TMF pattern. We designed a prospective cohort study that included 155 consecutive patients with impaired relaxation (IR) pattern at rest. Preload stress echocardiography was achieved using leg-positive pressure (LPP), and changes in TMF pattern during the LPP was observed during baseline echocardiographic examination. The patients whose TMF pattern developed to pseudonormal (PN) pattern throughout the study period were classified into the change to PN group, and patients whose TMF pattern stayed in IR pattern were classified into the stay in IR group. The median follow-up period was 17 months. The average age was 68 ± 11 years old, and 97 patients (63%) were male. Among 155 patients, 27 were classified into the change to PN group. A Cox proportional hazard analysis confirmed that the change in the peak atrial systolic TMF velocity during the LPP (ΔA, hazard ratio = 0.58 per 1SD; 95% CI = 0.39-0.88, P = 0.010) was the powerful independent predictor of change into PN pattern. Kaplan-Meier analysis revealed that the patients with ΔA -7 cm/s had more likely to develop into PN pattern than patients with ΔA > -7 cm/s (P = 0.001). Evaluation of a response in TMF during the LPP might provide an incremental diagnostic value to detect future overt heart failure in patients with early-stage heart failure.
Kenya Kusunose, Hiromitsu Seno, Hirotsugu Yamada, Susumu Nishio, Yuta Torii, Yukina Hirata, Y Saijo, Takayuki Ise, Koji Yamaguchi, Daiju Fukuda, Shusuke Yagi, Takeshi Soeki, Tetsuzo Wakatsuki and Masataka Sata : Right Ventricular Function and Beneficial Effects of Cardiac Rehabilitation in Patients With Systolic Chronic Heart Failure., The Canadian Journal of Cardiology, Vol.34, No.10, 1307-1315, 2018.
(Summary)
It has been recognized that a comprehensive cardiac rehabilitation (CR) program improves mortality in patients with chronic heart failure. On the other hand, the magnitude of the improvement in exercise capacity after CR differs among individuals. The aim of this study was to assess the echocardiographic determinants of responders to CR using preload stress echocardiography. We prospectively enrolled 58 chronic heart failure patients with reduced left ventricular ejection fraction (aged 62 ± 11 years; 69% male; left ventricular ejection fraction 43% ± 7%) who had received optimized medical treatment in a CR program for 5 months. We performed preload echocardiographic studies using leg positive pressure (LPP) to assess the echocardiographic parameters during preload augmentation. We defined 41 patients as a development cohort to assess the predictive value of echocardiographic variables. Next, we validated results in the remaining 17 patients as a validation cohort. In the development cohort, significant improvement in peak oxygen uptake (VO) (>10%) after CR was observed in 58% patients. In a multivariable logistic regression model, the significant predictor of improvement in exercise capacity was right ventricular (RV) strain during LPP (odds ratio: 3.96 per 1 standard deviation; P = 0.01). An RV strain value of -16% during LPP had a good sensitivity of 0.79 and a specificity of 0.71 to identify patients with improvement in peak VO. In the validation cohort, an optimal cutoff value of RV strain value was the same (area under the curve: 0.77, sensitivity: 0.78, specificity: 0.65). RV strain during LPP may be an echocardiographic parameter for assessing beneficial effects of CR.
Takeshi Soeki, Tomomi Matsuura, Takeshi Tobiume, Sachiko Bando, Matsumoto Kazuhisa, Hiromi Nagano, Etsuko Uematsu, Kenya Kusunose, Takayuki Ise, Koji Yamaguchi, Shusuke Yagi, Daiju Fukuda, Hirotsugu Yamada, Tetsuzo Wakatsuki, Michio Shimabukuro and Masataka Sata : Clinical, Electrocardiographic, and Echocardiographic Parameter Combination Predicts the Onset of Atrial Fibrillation., Circulation Journal, Vol.82, No.9, 2253-2258, 2018.
(Summary)
The ability to identify risk markers for new-onset atrial fibrillation (AF) is critical to the development of preventive strategies, but it remains unknown whether a combination of clinical, electrocardiographic, and echocardiographic parameters predicts the onset of AF. In the present study, we evaluated the predictive value of a combined score that includes these parameters.Methods and Results:We retrospectively studied 1,040 patients without AF who underwent both echocardiography and 24-h Holter electrocardiography between May 2005 and December 2010. During a median follow-up period of 68.4 months (IQR, 49.9-93.3 months), we investigated the incidence of new-onset AF. Of the 1,040 patients, 103 (9.9%) developed AF. Patients who developed AF were older than patients who did not. Total heart beats, premature atrial contraction (PAC) count, maximum RR interval, and frequency of sinus pause quantified on 24-h electrocardiography were associated with new-onset AF. LA diameter (LAD) on echocardiography was also associated with the development of AF. On multivariate Cox analysis, age 58 years, PAC count 80 beats/day, maximum RR interval 1.64 s, and LAD 4.5 cm were independently associated with the development of AF. The incidence rate of new-onset AF significantly increased as the combined score (i.e., the sum of the risk score determined using hazard ratios) increased. A combined score that includes age, PAC count, maximum RR interval, and LAD could help characterize the risk of new-onset AF.
Kageyuki Oba, Minetaka Maeda, Gulinu Maimaituxun, Satoshi Yamaguchi, Osamu Arasaki, Daiju Fukuda, Shusuke Yagi, Hirata Yukina, Susumu Nishio, Takashi Iwase, Shoichiro Takao, Kenya Kusunose, Hirotsugu Yamada, Takeshi Soeki, Tetsuzo Wakatsuki, Masafumi Harada, Hiroaki Masuzaki, Masataka Sata and Michio Shimabukuro : Effect of the Epicardial Adipose Tissue Volume on the Prevalence of Paroxysmal and Persistent Atrial Fibrillation., Circulation Journal, Vol.82, No.7, 1778-1787, 2018.
(Summary)
Although increasing evidence suggests that epicardial adipose tissue volume (EATV) is associated with atrial fibrillation (AF), it is controversial whether there is a dose-response relationship of increasing EATV along the continuum of AF. We evaluated the effect of the EATV on the prevalence of paroxysmal AF (PAF) and persistent AF (PeAF) and the relationships with cardiac structure and functional remodeling.Methods and Results:Subjects who underwent multidetector computed tomography (MDCT) coronary angiography because of symptoms suggestive of coronary artery disease were divided into sinus rhythm (SR) (n=112), PAF (n=133), and PeAF (n=71) groups. The EATV index (EATV/body surface area, mL/m) was strongly associated with the prevalence of PAF and PeAF on the model adjusted for known AF risk factors. The effect of the EATV index on the prevalence of PeAF, but not on that of PAF, was modified by the left atrial (LA) dimension, suggesting that extension of the LA dimension is related to EATV expansion in PeAF. The cutoff value of the EATV index for the prevalence was higher in PeAF than in PAF (64 vs. 55 mL/m, P<0.01). The EATV index is associated with the prevalence of PAF and PeAF, and its cutoff values are predictive for PAF and PeAF development independently of other AF risk factors.
Kensuke Matsumoto, Akira Onishi, Hirotsugu Yamada, Kenya Kusunose, Makiko Suto, Yutaka Hatani, Hiroki Matsuzoe, Kazuhiro Tatsumi, Hidekazu Tanaka and Ken-Ichi Hirata : Noninvasive Assessment of Preload Reserve Enhances Risk Stratification of Patients With Heart Failure With Reduced Ejection Fraction, Circulation. Cardiovascular Imaging, Vol.11, No.5, e007160, 2018.
(Summary)
BACKGROUND: The leg-positive pressure maneuver can safely and noninvasively apply preload stress without increase in total body fluid volume. The purpose of this study was to determine whether preload stress could be useful for risk stratification of patients with heart failure with reduced ejection fraction. METHODS AND RESULTS: For this study, 120 consecutive patients with heart failure with reduced ejection fraction were prospectively recruited. The stroke work index was estimated as product of stroke volume index and mean blood pressure, and the E/e' ratio was calculated to estimate ventricular filling pressure. The echocardiographic parameters were obtained both at rest and during leg-positive pressure stress. During the median follow-up period of 20 months, 30 patients developed adverse cardiovascular events. During preload stress, stroke work index increased significantly (from 3280+/-1371 to 3857+/-1581 mm Hg.mL/m(2); P<0.001) along with minimal changes in ventricular filling pressure (E/e', from 16+/-10 to 17+/-9; P<0.05) in patients without cardiovascular events. However, patients with cardiovascular events showed impairment of Frank-Starling mechanism (stroke work index, from 2863+/-969 to 2903+/-1084 mm Hg.mL/m(2); P=0.70) and a serious increase in E/e' ratio (from 19+/-11 to 25+/-14; P<0.001). Both the patients without contractile reserve and those without diastolic reserve exhibited worse event-free survival than the others (P<0.001). In a Cox proportional-hazards analysis, the changes in stroke work index (hazard ratio: 0.44 per 500 mm Hg.mL/m(2) increase; P=0.001) and in E/e' (hazard ratio: 2.58 per 5-U increase; P<0.001) were predictors of cardiovascular events. CONCLUSION: Contractile reserve and diastolic reserve during leg-positive pressure stress are important determinants of cardiovascular outcomes for patients with heart failure with reduced ejection fraction.
Kenya Kusunose, Y Okushi, Hirotsugu Yamada, Susumu Nishio, Yuta Torii, Yukina Hirata, Y Saijo, Takayuki Ise, Koji Yamaguchi, Shusuke Yagi, Takeshi Soeki, Tetsuzo Wakatsuki and Masataka Sata : Prognostic Value of Frailty and Diastolic Dysfunction in Elderly Patients., Circulation Journal, Vol.82, No.8, 2103-2110, 2018.
(Summary)
High prevalence of frailty and of diastolic dysfunction (DD) in heart failure and high mortality in frail adults have been noted. We characterized frailty by quantifying differences on echocardiography, and assessed the added prognostic utility of frailty and DD grade in an elderly population. One hundred and ninety-one patients 65 years who had at least 1 cardiovascular risk factor were prospectively recruited for clinically indicated echocardiography at the present institute. Weight loss, exhaustion, and deficits in physical activity, gait speed, and handgrip strength were used to categorize patients as frail (3 features), intermediately frail (1 or 2 features), or non-frail (0 features). DD grade 2 was defined as severe. Frailty was associated with larger left atrial volume, smaller stroke volume, and worse DD grade after adjustment for age. In a period of 14 months, 29 patients (15%) had cardiovascular events. The addition of frailty score and severe DD significantly improved the prognostic power of a model containing male gender (model 1, male gender, χ=6.4; model 2, model 1 plus frailty score, χ=16.7, P=0.004; model 3, model 2 plus severe DD, χ=25.5, P=0.015). Both frailty and DD grade were significantly associated with future cardiovascular events in an elderly population with preserved ejection fraction and 1 risk factor of cardiovascular disease.
Tomoya Hara, Pham Tran Phuong, Daiju Fukuda, Koji Yamaguchi, Chie Murata, Sachiko Nishimoto, Shusuke Yagi, Kenya Kusunose, Hirotsugu Yamada, Soeki Takeshi, Tetsuzo Wakatsuki, Issei Imoto, Michio Shimabukuro and Masataka Sata : Protease-Activated Receptor-2 Plays a Critical Role in Vascular Inflammation and Atherosclerosis in Apolipoprotein E-Deficient Mice., Circulation, Vol.138, No.16, 1706-1719, 2018.
(Summary)
-The coagulation system is closely linked with vascular inflammation, although the underlying mechanisms are still obscure. Recent studies show that protease-activated receptor (PAR)-2, a major receptor of activated factor X (FXa), are expressed in both vascular cells and leukocytes, suggesting that PAR-2 may contribute to the pathogenesis of inflammatory diseases. Here we investigated the role of PAR-2 in vascular inflammation and atherogenesis. -We generated apolipoprotein E-deficient ( ) mice lacking systemic PAR-2 expression ( ). mice which lack or express PAR-2 only in bone-marrow (BM) cells were also generated by BM transplantation. Atherosclerotic lesions were investigated after 20 weeks on a western-type diet (WTD) by histological analyses, quantitative RT-PCR, and western blotting. In vitro experiments using BM-derived macrophages were performed to confirm pro-inflammatory roles of PAR-2. The association between plasma FXa level and the severity of coronary atherosclerosis was also examined in humans who underwent coronary intervention. - mice showed reduced atherosclerotic lesions in the aortic arch (<0.05) along with features of stabilized atherosclerotic plaques such as less lipid deposition (<0.05), collagen loss (<0.01), macrophage accumulation (<0.05), and inflammatory molecule expression (<0.05) compared with mice. Systemic PAR2 deletion in mice significantly decreased the expression of inflammatory molecules in the aorta. The results of BM transplantation experiments demonstrated that PAR-2 in hematopoietic cells contributed to atherogenesis in mice. PAR-2 deletion did not alter metabolic parameters. In vitro experiments demonstrated that FXa or a specific peptide agonist of PAR-2 significantly increased expression of inflammatory molecules and lipid uptake in BM-derived macrophages from wild-type mice compared with those from PAR-2-deficient mice. Activation of NF- κB signaling was involved in PAR-2-associated vascular inflammation and macrophage activation. In humans who underwent coronary intervention, plasma FXa level independently correlated with the severity of coronary atherosclerosis as determined by Gensini score (<0.05) and plaque volume (<0.01). -PAR-2 signaling activates macrophages and promotes vascular inflammation, increasing atherosclerosis in mice. This signaling pathway may also participate in atherogenesis in humans.
Gulinu Maimaituxun, Michio Shimabukuro, Daiju Fukuda, Shusuke Yagi, Yukina Hirata, Takashi Iwase, Shoichiro Takao, Tomomi Matsuura, Takayuki Ise, Kenya Kusunose, Takeshi Tobiume, Koji Yamaguchi, Hirotsugu Yamada, Takeshi Soeki, Tetsuzo Wakatsuki, Masafumi Harada and Masataka Sata : Local Thickness of Epicardial Adipose Tissue Surrounding the Left Anterior Descending Artery Is a Simple Predictor of Coronary Artery Disease - New Prediction Model in Combination With Framingham Risk Score., Circulation Journal, Vol.82, No.5, 1369-1378, 2018.
(Summary)
Compared with global cardiac adiposity, the local accumulation of fat surrounding coronary arteries might have a more direct impact on coronary artery disease (CAD). Here, we compared the local epicardial adipose tissue (EAT) thickness and global cardiac adiposity volumes for predicting CAD.Methods and Results:A total of 197 consecutive subjects underwent 320-slice multi-detector computed tomography coronary angiography and were segregated into CAD (1 coronary artery branch stenosis 50%) and non-CAD groups. EAT thickness was measured at the right coronary artery (EAT), the left anterior descending artery (EAT), and the left circumflex artery (EAT). Although EATand EATwere similar between the 2 groups, EATwas larger in the CAD group than in the non-CAD group (5.45±2.16 mm vs. 6.86±2.19 mm, P<0.001). EAT, after correcting for confounding factors, was strongly associated with CAD (r=0.276, P<0.001) and Gensini score (r=0.239, P<0.001). On multiple regression analysis, Framingham risk score combined with EATwas a strong predictor of CAD (adjusted R=0.121; P<0.001). The local fat thickness surrounding the LAD is a simple and useful surrogate marker for estimating the presence, severity, and extent of CAD, independent of classical cardiovascular risk factors.
Chetan P. Huded, Kenya Kusunose, Fatima Shahid, Andrew L. Goodman, Alaa Alashi, Richard A. Grimm, A Marc Gillinov, Douglas R. Johnston, L Leonardo Rodriguez, Zoran B. Popovic, Kimi Sato, Lars G. Svensson, Brian P. Griffin and Milind Y. Desai : Novel Echocardiographic Parameters in Patients With Aortic Stenosis and Preserved Left Ventricular Systolic Function Undergoing Surgical Aortic Valve Replacement., The American Journal of Cardiology, Vol.122, No.2, 284-293, 2018.
(Summary)
We sought to study the incremental prognostic impact of baseline valvuloarterial impedance (Zva) and left ventricular global longitudinal strain (LV-GLS) in patients with severe aortic stenosis and preserved left ventricular ejection fraction (LVEF) treated with surgical aortic valve replacement (AVR). We included 961 consecutive patients (68 ± 13 years; 63% men) with severe aortic stenosis (indexed aortic valve area <0.6 cm) and LVEF >50% who underwent surgical AVR at our institution between January 2007 and December 2008. The analysis is based on derivation (n = 637) and validation (n = 324) subgroups. Society of Thoracic Surgeons (STS) score was calculated. Zva (systolic arterial pressure + mean aortic valve gradient)/left ventricular stroke volume index and LV-GLS (measured offline using Velocity Vector Imaging; Siemens Medical Solutions, Mountain View, California) were calculated. The primary outcome was death. Median Zva and LV-GLS were 4.5 mm Hg × ml× m and -14.5%, respectively. AVR was performed at a median of 34 days from initial evaluation (isolated AVR in 46%, bioprosthetic AVR in 93%). At 7.5 ± 3 years, 320 patients died (33%; 30 days/in-hospital death in 0.5%). In the derivation subgroup, on multivariate Cox survival analysis, higher STS score (hazard ratio [HR] 1.06), higher Zva (HR 1.13), and worse LV-GLS (HR 1.07) were independently associated with long-term survival (all p <0.01). When Zva and LV-GLS were sequentially added to STS score, the c-statistic improved from 0.63 [0.55 to 0.77] to 0.70 [0.60 to 0.81] and 0.78 [0.69 to 0.83], respectively, all p <0.001). Findings were confirmed in the validation subgroup. In conclusion, in patients with severe aortic stenosis and preserved LVEF treated with surgical AVR, baseline Zva and LV-GLS provide improved risk stratification with synergistic prognostic value.
Chetan P. Huded, Ahmad Masri, Kenya Kusunose, Andrew L. Goodman, Richard A. Grimm, A Marc Gillinov, Douglas R. Johnston, L Leonardo Rodriguez, Zoran B. Popovic, Lars G. Svensson, Brian P. Griffin and Milind Y. Desai : Outcomes in Asymptomatic Severe Aortic Stenosis With Preserved Ejection Fraction Undergoing Rest and Treadmill Stress Echocardiography., Journal of the American Heart Association, Vol.7, No.8, e007880, 2018.
(Summary)
In asymptomatic patients with severe aortic stenosis and preserved left ventricular ejection fraction, we sought to assess the incremental prognostic value of resting valvuloarterial impedence (Zva) and left ventricular global longitudinal strain (LV-GLS) to treadmill stress echocardiography. We studied 504 such patients (66±12 years, 78% men, 32% with coronary artery disease who underwent treadmill stress echocardiography between 2001 and 2012. Clinical and exercise variables (% of age-sex predicted metabolic equivalents [%AGP-METs]) were recorded. Resting Zva ([systolic arterial pressure+mean aortic valve gradient]/[LV-stroke volume index]) and LV-GLS (measured offline using Velocity Vector Imaging, Siemens) were obtained from the baseline resting echocardiogram. Death was the primary outcome. There were no major adverse cardiac events during treadmill stress echocardiography. Indexed aortic valve area, Zva, and LV-GLS were 0.46±0.1 cm/m, 4.5±0.9 mm Hg/mL per m and -16±4%, respectively; only 50% achieved >100% AGP-METs. Sixty-four percent underwent aortic valve replacement. Death occurred in 164 (33%) patients over 8.9±3.6 years (2 within 30 days of aortic valve replacement). On multivariable Cox survival analysis, higher Society of Thoracic Surgeons score (hazard ratio or HR 1.06), lower % AGP-METS (HR 1.16), higher Zva (HR 1.25) and lower LV-GLS (HR 1.12) were associated with higher longer-term mortality, while aortic valve replacement (HR 0.45) was associated with improved survival (all <0.01). Sequential addition of ZVa and LV-GLS to clinical model (Society of Thoracic Surgeons score and %AGP-METs) increased the c-statistic from 0.65 to 0.69 and 0.75, respectively, both <0.001); findings were similar in the subgroup of patients who underwent aortic valve replacement. In asymptomatic patients with severe aortic stenosis undergoing treadmill stress echocardiography, LV-GLS and ZVa offer incremental prognostic value.
Kenya Kusunose, Kentaro Shibayama, Hiroyuki Iwano, Masaki Izumo, Nobuyuki Kagiyama, Koji Kurosawa, Hirotsugu Mihara, Hiroki Oe, Tetsuari Onishi, Toshinari Onishi, Mitsuhiko Ota, Shunsuke Sasaki, Yumi Shiina, Hikaru Tsuruta and Hidekazu Tanaka : Reduced variability of visual left ventricular ejection fraction assessment with reference images: The Japanese Association of Young Echocardiography Fellows multicenter study., Journal of Cardiology, Vol.72, No.1, 74-80, 2018.
(Summary)
Visual estimation of left ventricular ejection fraction (LVEF) is widely applied to confirm quantitative EF. However, visual assessment is subjective, and variability may be influenced by observer experience. We hypothesized that a learning session might reduce the misclassification rate. Protocol 1: Visual LVEFs for 30 cases were measured by 79 readers from 13 cardiovascular tertiary care centers. Readers were divided into 3 groups by their experience: limited (1-5 years, n=28), intermediate (6-11 years, n=26), and highly experienced (12-years, n=25). Protocol 2: All readers were randomized to assess the effect of a learning session with reference images only or feedback plus reference images. After the session, 20 new cases were shown to all readers following the same methodology. To assess the concordance and accuracy pre- and post-intervention, each visual LVEF measurement was compared to overall average values as a reference. Experience affected the concordance in visual EF values among the readers. Groups with intermediate and high experience showed significantly better mean difference (MD), standard deviation (SD), and coefficient of variation (CV) than those with limited experience at baseline. The learning session with reference image reduced the MD, SD, and CV in readers with limited experience. The learning session with reference images plus feedback also reduced proportional bias. Importantly, the misclassification rate for mid-range EF cases was reduced regardless of experience. This large multicenter study suggested that a simple learning session with reference images can successfully reduce the misclassification rate for LVEF assessment.
Masahiro Nakabachi, Satoshi Yamada, Hiroyuki Iwano, Taichi Hayashi, Kazunori Okada, Kenya Kusunose, Kiyotaka Watanabe, Tomoko Ishizu, Kazuaki Wakami, Hirotsugu Yamada, Kaoru Dohi, Yoshihiro Seo, Nobuyuki Ohte, Chikara Shimizu and Taisei Mikami : Left Ventricular Mass Influences Relationship Between Filling Pressure and Early-Diastolic Ratio of Inflow Velocity to Mitral Annular Velocity (E/e')., Circulation Journal, Vol.82, No.3, 732-738, 2018.
(Summary)
Early-diastolic mitral annular velocity (e') and the ratio of early-diastolic left ventricular (LV) inflow velocity (E) to e' (E/e') have been widely used as indexes of LV relaxation and filling pressure, respectively. However, many recent studies have demonstrated that they are not reliable in various clinical settings. We thus investigated the factors influencing these echocardiographic parameters in a multicenter study.Methods and esults:The study group comprised 69 patients, referred for cardiac catheterization, and enrolled in 5 university hospitals. Time constant ( ) and LV mean diastolic pressure (LVMDP) were measured using a micromanometer-tipped catheter. Although e' only weakly correlated with (r=-0.35, P<0.01), E/e' modestly correlated with LVMDP (r=0.48, P<0.001). Multivariable analysis revealed that hypertension ( =-0.33, P<0.01) and LV ejection fraction (LVEF) ( =0.44, P<0.001) were the independent determinants of e', and LV mass index (LVMI) ( =0.37, P<0.001) and LVMDP ( =0.47, P<0.001) were those of E/e'. Additionally, E/e' significantly correlated with LVMDP in patients with normal LVMI (r=0.74, P<0.001) but not in those with increased LVMI. The coincidence of hypertension and LVEF affected the relationship between LV relaxation and e', whereas LVMI altered the relationship between LV filling pressure and E/e'. Thus, clinical conditions associated with an increase in LVMI, such as LV hypertrophy and LV dilatation, should be considered when estimating the filling pressure from E/e'.
Yukina Hirata, Hirotsugu Yamada, Kenya Kusunose, Susumu Nishio, Yuta Torii, Yuki Horike and Masataka Sata : Provocation of clinically significant left ventricular outflow tract obstruction by postural change in patients with sigmoid septum., Journal of Echocardiography, Vol.16, No.4, 173-174, 2018.
Christine L. Jellis, Teerapat Yingchoncharoen, Neville Gai, Kenya Kusunose, Zoran B. Popović, Scott Flamm and Deborah Kwon : Correlation between right ventricular T mapping and right ventricular dysfunction in non-ischemic cardiomyopathy., The International Journal of Cardiovascular Imaging, Vol.34, No.1, 55-65, 2018.
(Summary)
Right ventricular (RV) fibrosis is increasingly recognized as the underlying pathological substrate in a variety of clinical conditions. We sought to employ cardiac magnetic resonance (CMR) techniques of strain imaging and longitudinal relaxation time (T) mapping to better examine the relationship between RV function and structure. Our aim was to initially evaluate the feasibility of these techniques to evaluate the right ventricle. We then sought to explore the relationship between RV function and underlying fibrosis, along with examining the evolution of RV remodeling according to the amount of baseline fibrosis. Echocardiography was performed in 102 subjects with non-ischemic cardiomyopathy. Right ventricular parameters were assessed including: fractional area change (FAC) and longitudinal strain. The same cohort underwent CMR. Post-contrast T mapping was performed as a marker of fibrosis with a Look-Locker technique using inversion recovery imaging. Mid-ventricular post-contrast T values of the RV free wall, RV septum and lateral LV were calculated using prototype analysis software. Biventricular volumetric data including ejection fraction was measured by CMR using a cine short axis stack. CMR strain analysis was also performed to assess 2D RV longitudinal and radial strain. Simultaneous biochemical and anthropometric data were recorded. Subjects were followed over a median time of 29 months (IQR 20-37 months) with echocardiography to evaluate temporal change in RV FAC according to baseline post-contrast T values. Longitudinal data analysis was performed to adjust for patient loss during follow-up. Subjects (62% men, 51 ± 15 years) had mild to moderately impaired global RV systolic function (RVEF = 39 ± 15%; RVEDV = 187 ± 69 ml; RVESV = 119 ± 68 ml) and moderate left ventricular dysfunction at baseline (LVEF 30 ± 17%). Good correlation was observed between mean LV and RV post-contrast T values (r = 0.652, p < 0.001), with similar post-contrast T values maintained in both the RV free wall and septum (r = 0.761, p < 0.001). CMR RVEF demonstrated a proportional correlation with echocardiographic measures of RV longitudinal function and CMR RV strain (longitudinal r = -0.449, p = 0.001; radial r = -0.549, p < 0.001). RVEF was related to RV post-contrast T values, particularly in those with RV dysfunction (free wall T r = 0.259 p = 0.027; septal T r = 0.421 p < 0.001). RV strain was also related to RV post-contrast T values (r = -0.417, p = 0.002). Linear regression analysis demonstrated strain and post-contrast T1 values to be independently associated with RVEF. Subjects with severe RV dysfunction (CMR RVEF <25%) demonstrated lower RV CMR strain (longitudinal p = 0.018; radial p < 0.001), RV T values (free wall p = 0.013; septum <0.001) and RV longitudinal echocardiography parameters despite no difference in afterload. During follow-up, those with RV free wall post-contrast T values ≥ 350 ms demonstrated ongoing improvement in FAC (Δ6%), whilst values <350 ms were associated with deterioration in RV function (ΔFAC = -5%) (p = 0.026). CMR provides a comprehensive method by which to evaluate right ventricular function. Post-contrast T mapping and CMR strain imaging are technically feasible and provide incremental information regarding global RV function and structure. The proportional relationship between RV function and post-contrast T values supports that myocardial fibrosis is a causative factor of RV dysfunction in NICM, irrespective of RV afterload. This same structural milieu also appears integral to the propensity for both positive and negative RV remodeling long-term, suggestive that this is also determined by the degree of underlying RV fibrosis.
(Keyword)
Adult / Aged / Biomechanical Phenomena / Cardiomyopathies / Echocardiography, Doppler / Feasibility Studies / Female / Fibrosis / Humans / Image Interpretation, Computer-Assisted / Linear Models / Logistic Models / Magnetic Resonance Imaging, Cine / Male / Middle Aged / Myocardial Contraction / myocardium / Predictive Value of Tests / Prognosis / Retrospective Studies / Risk Factors / Ventricular Dysfunction, Right / Ventricular Function, Right / Ventricular Remodeling
Akira Hirono, Kenya Kusunose, Norihito Kageyama, Masayuki Sumitomo, Masahiro Abe, Hiroyuki Fujinaga and Masataka Sata : Development and validation of optimal cut-off value in inter-arm systolic blood pressure difference for prediction of cardiovascular events, Journal of Cardiology, Vol.71, No.20, 24-30, 2018.
(Summary)
An inter-arm systolic blood pressure difference (IAD) is associated with cardiovascular disease. The aim of this study was to develop and validate the optimal cut-off value of IAD as a predictor of major adverse cardiac events in patients with arteriosclerosis risk factors. From 2009 to 2014, 1076 patients who had at least one cardiovascular risk factor were included in the analysis. We defined 700 randomly selected patients as a development cohort to confirm that IAD was the predictor of cardiovascular events and to determine optimal cut-off value of IAD. Next, we validated outcomes in the remaining 376 patients as a validation cohort. The blood pressure (BP) of both arms measurements were done simultaneously using the ankle-brachial blood pressure index (ABI) form of automatic device. The primary endpoint was the cardiovascular event and secondary endpoint was the all-cause mortality. During a median period of 2.8 years, 143 patients reached the primary endpoint in the development cohort. In the multivariate Cox proportional hazards analysis, IAD was the strong predictor of cardiovascular events (hazard ratio: 1.03, 95% confidence interval: 1.01-1.05, p=0.005). The receiver operating characteristic curve revealed that 5mmHg was the optimal cut-off point of IAD to predict cardiovascular events (p<0.001). In the validation cohort, the presence of a large IAD (IAD ≥5mmHg) was significantly associated with the primary endpoint (p=0.021). IAD is significantly associated with future cardiovascular events in patients with arteriosclerosis risk factors. The optimal cut-off value of IAD is 5mmHg.
(Keyword)
Aged / Aged, 80 and over / Arm / blood pressure / Blood Pressure Determination / Cardiovascular Diseases / Female / Humans / Male / Middle Aged / Risk Factors / Systole
Kenya Kusunose, Nancy A. Obuchowski, Marc Gillinov, Zoran B. Popovic, Scott D. Flamm, Brian P. Griffin and Deborah H. Kwon : Predictors of Mortality in Patients With Severe Ischemic Cardiomyopathy Undergoing Surgical Mitral Valve Intervention., Journal of the American Heart Association, Vol.6, No.11, e007163, 2017.
(Summary)
Ischemic mitral regurgitation is associated with substantial risk of death. Although surgical mitral valve intervention (MVi) may improve symptoms, it has not been shown to improve survival. The aim of this study was to identify predictors of mortality in patients with ischemic mitral regurgitation and MVi. We evaluated 117 consecutive patients (age, 65±10 years) with advanced ischemic cardiomyopathy who underwent cardiac magnetic resonance and subsequent MVi between January 1, 2002 and January 1, 2012. Cardiac magnetic resonance was used to assess left ventricular remodeling and myocardial scarring. The effective regurgitant orifice area was calculated from the proximal isovelocity surface area by echocardiography. There were 43 deaths (37%) during follow-up (median, 62 months). On multivariable analysis, age ≥70 years (=0.013), diabetes mellitus (=0.001), dyslipidemia (=0.012), papillary muscle scar (=0.010), incomplete revascularization (=0.001), and total scar %×effective regurgitant orifice area ≥0.20 cm (=0.005) were each independently associated with all-cause mortality. Although patients with effective regurgitant orifice area <0.2 cm at baseline demonstrated an increased hazard ratio of 3.3 for every 10% increase in scar, the hazard ratio increased to 9 for every 10% increase in scar in those with baseline effective regurgitant orifice area ≥0.20 cm. Mortality also was significantly higher in patients with incomplete revascularization compared with those with vascularized viable myocardium (61% versus 28%; <0.001). Increased total scar burden and the presence of incomplete revascularization are powerful predictors of mortality in patients with advanced ischemic cardiomyopathy undergoing MVi. Viability assessment with cardiac magnetic resonance imaging can identify which patients with ischemic mitral regurgitation are at highest risk for mortality after surgical MVi.
(Keyword)
Aged / Cardiomyopathies / Cause of Death / Echocardiography / Female / Follow-Up Studies / Heart Valve Prosthesis Implantation / Humans / Magnetic Resonance Imaging, Cine / Male / Middle Aged / Mitral Valve / Mitral Valve Insufficiency / myocardial ischemia / Retrospective Studies / Risk Assessment / Risk Factors / Severity of Illness Index / Survival Rate / United States
Hiromu Yamazaki, Shusuke Yagi, Yuta Torii, Rie Amano, Yasuyuki Oomichi, Teruaki Sangawa, Daiju Fukuda, Muneyuki Kadota, Takayuki Ise, Rie Ueno, Tomoya Hara, Kenya Kusunose, Tomomi Matsuura, Takeshi Tobiume, Koji Yamaguchi, Hirotsugu Yamada, Takeshi Soeki, Tetsuzo Wakatsuki, Masashi Akaike and Masataka Sata : Edoxaban improves acute venous thromboembolism while preserving protein C and protein S levels, Journal of Cardiology, Vol.71, No.3, 305-309, 2017.
(Summary)
It is well known that warfarin inhibits the synthesis of vitamin K-dependent anticoagulants, including thrombin, protein C and S, and factor Xa, leading, paradoxically, to an initial hypercoagulable state. Edoxaban, a direct inhibitor of activated factor X is widely used for the treatment of acute venous thromboembolism (VTE). However, the effect of edoxaban on circulating coagulation factors, in patients with acute VTE, remains unknown. We enrolled 57 patients with acute VTE with/without pulmonary embolism treated with edoxaban (n=37) or warfarin (n=20) in a clinical setting. Before treatment and 2 weeks after treatment, we evaluated thrombotic burden using ultrasound or computed tomography angiography. We also evaluated thrombin generation, represented by prothrombin fragment F1+2; thrombus degradation, represented by D-dimer; and levels of anticoagulants, including protein C, protein S, and antithrombin III. Both edoxaban and warfarin treatment improved thrombotic burden and decreased prothrombin fragment F1+2, and D-dimer. Edoxaban treatment preserved protein C and protein S levels. In contrast, warfarin decreased protein C and protein S levels. Neither treatment affected antithrombin III. Edoxaban improves VTE while preserving protein C and protein S levels, thereby indicating that edoxaban improves thrombotic burden while maintaining levels of anticoagulants.
Shusuke Yagi, Ken-ichi Aihara, Takeshi Kondo, Kiyoe Kurahashi, Sumiko Yoshida, Itsuro Endo, Daiju Fukuda, Yutaka Nakaya, Kin-Ichiro Suwaki, Takashi Takeji, Toshihiro Wada, Masdan Hotimah Salim, Saori Hama, Tomomi Matsuura, Takayuki Ise, Kenya Kusunose, Koji Yamaguchi, Takeshi Tobiume, Hirotsugu Yamada, Takeshi Soeki, Tetsuzo Wakatsuki, Munehide Matsuhisa, Michio Shimabukuro, Masashi Akaike and Masataka Sata : Predictors for the Treatment Effect of Sodium Glucose Co-transporter 2 Inhibitors in Patients with Type 2 Diabetes Mellitus., Advances in Therapy, Vol.35, No.1, 124-134, 2017.
(Summary)
Predictors for the effect of sodium glucose co-transporter 2 (SGLT2) inhibitors at lowering hemoglobin A1c (HbA1c) levels in type 2 diabetes mellitus patients remain unclear. We therefore aimed to elucidate these predictors in type 2 diabetes patients after 3 months of SGLT2 treatment. A total of 302 consecutive type 2 diabetes patients who had been treated with SGLT2 inhibitors as monotherapy or add-on therapy to existing antidiabetic treatments were enrolled retrospectively. After excluding 27 patients whose HbA1c levels could not be evaluated 3 months after treatment, the glucose-lowering effects of SGLT2 inhibitors were assessed in 275 patients by measuring HbA1c levels before and 3 months after treatment. The predictors for changes in HbA1c levels after 3 months of treatment were evaluated. SGLT2 inhibitor treatment for 3 months decreased HbA1c levels from 7.8 ± 1.2% to 7.4 ± 1.0% (p < 0.0001). A multiple regression analysis showed that the independent determinants for SGLT2 inhibitor treatment effect included decreased HbA1c levels after 1 month of treatment, high baseline HbA1c levels, and a high estimated glomerular filtration rate (eGFR). We show that type 2 diabetes patients who received the greatest glucose-lowering effect with SGLT2 inhibitor treatment were those with preserved renal function (high baseline eGFR) and high baseline HbA1c levels. Moreover, SGLT2 inhibitor treatment efficacy could be predicted by the patients' initial response to treatment.
Shusuke Yagi, Takeshi Soeki, Ken-Ichi Aihara, Daiju Fukuda, Takayuki Ise, Muneyuki Kadota, Sachiko Bando, Tomomi Matsuura, Takeshi Tobiume, Koji Yamaguchi, Kenya Kusunose, Hirotsugu Yamada, Tetsuzo Wakatsuki, Michio Shimabukuro, Masashi Akaike and Masataka Sata : Low Serum Levels of Eicosapentaenoic Acid and Docosahexaenoic Acid are Risk Factors for Cardiogenic Syncope in Patients with Brugada Syndrome, International Heart Journal, Vol.58, No.5, 720-723, 2017.
(Summary)
The n-3 polyunsaturated fatty acids (PUFAs), including eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), have antiarrhythmic effects, possibly via modulation of the cardiac ion channels. Nevertheless, it is unknown whether low serum levels of n-3 PUFAs are risk factors for ventricular fibrillation in patients with Brugada syndrome (BrS). We retrospectively reviewed data from 62 men with BrS and evaluated their serum levels of EPA and DHA, and the risk factors for sudden cardiac death, including a history of cardiogenic syncope. Nineteen patients had a history of cardiogenic syncope, and their EPA and DHA levels were significantly lower than those of the patients without syncope. Multivariate logistic regression analysis revealed that low EPA and DHA levels were associated with the incidence of syncope. The receiver-operator characteristic curve showed the area under the curves of EPA and DHA for history of syncope were 0.84 and 0.72, respectively. In conclusion, low levels of EPA and DHA are risk factors for cardiogenic syncope in patients with BrS, which suggests that n-3 PUFAs play important roles in preventing ventricular fibrillation in BrS.
(Keyword)
Adult / Aged / Aged, 80 and over / Biomarkers / Brugada Syndrome / Chromatography, Gas / Docosahexaenoic Acids / Eicosapentaenoic Acid / Electrocardiography / Follow-Up Studies / Humans / Incidence / Japan / Male / Middle Aged / Prevalence / ROC Curve / Retrospective Studies / Risk Assessment / Risk Factors / Syncope / Young Adult
Yuriko Takagawa, Shusuke Yagi, Takayuki Ise, Ayumi Ishii, Koji Nishikawa, Daiju Fukuda, Kenya Kusunose, Tomomi Matsuura, Takeshi Tobiume, Koji Yamaguchi, Hirotsugu Yamada, Takeshi Soeki, Tetsuzo Wakatsuki, Michio Shimabukuro, Shinsuke Katoh, Ken-ichi Aihara, Masashi Akaike and Masataka Sata : Improved Exercise Capacity After Cardiac Rehabilitation Is Associated with Reduced Visceral Fat in Patients with Chronic Heart Failure., International Heart Journal, Vol.58, No.5, 746-751, 2017.
(Summary)
Participation in a comprehensive cardiac rehabilitation (CR) program has been shown to reduce mortality and improve exercise capacity and symptoms in patients with chronic heart failure (CHF). Reduced exercise capacity leads to a concomitant reduction of skeletal muscle mass and accumulation of body fat. However, it is currently unknown whether CR reduces visceral adipose tissue (VAT) and/or subcutaneous abdominal adipose tissue (SAT) in patients with CHF. In addition, the body composition associated with improved exercise capacity after CR in patients with CHF has not been previously studied. Nineteen CHF patients who were categorized as NYHA functional class II or III and had received optimal medical treatment including a CR program for 5 months were enrolled in this study. The CR program significantly increased peak VO and reduced B-type natriuretic peptide. In addition, fat and body composition analysis showed reductions in the visceral fat tissue (VAT) area, subcutaneous abdominal adipose tissue (SAT) area, body weight, and total fat weight after CR. There were no changes in total water weight and total muscle weight. Single regression analysis revealed that the amelioration of reduced exercise capacity seen after CR is associated with reduced VAT area but not with SAT area or body weight. In conclusion, CR reduces VAT and improves exercise capacity in patients with CHF. This suggests that reducing VAT is important for CR to be most effective in the treatment of CHF.
Shusuke Yagi, Yukina Hirata, Takayuki Ise, Kenya Kusunose, Hirotsugu Yamada, Daiju Fukuda, Salim Masdan Hotimah, G Maimaituxun, Susumu Nishio, Yuriko Takagawa, Saori Hama, Tomomi Matsuura, Koji Yamaguchi, Takeshi Tobiume, Takeshi Soeki, Tetsuzo Wakatsuki, Ken-ichi Aihara, Masashi Akaike, Michio Shimabukuro and Masataka Sata : Canagliflozin reduces epicardial fat in patients with type 2 diabetes mellitus., Diabetology & Metabolic Syndrome, Vol.9, 78, 2017.
(Summary)
It is unknown whether canagliflozin, a selective sodium glucose co-transporter 2 inhibitor, reduces epicardial adipose tissue (EAT) thickness, which is associated with insulin resistance and is a risk factor for coronary artery disease. We administered 100 mg of canagliflozin for 6 months to 13 patients with type 2 diabetes mellitus. We evaluated glycemic control, visceral adipose tissue (VAT) area and subcutaneous adipose tissue (SAT) area, and skeletal muscle mass by using impedance methods, and EAT thickness by using echocardiography. Canagliflozin treatment for 6 months decreased hemoglobin A1c level from 7.1 ± 0.5% to 6.7 ± 0.6% (P < 0.05) and decreased EAT thickness from 9.3 ± 2.5 to 7.3 ± 2.0 mm (P < 0.001), along with a trend of decreasing VAT and SAT area. No association was found between any of these changes. Canagliflozin reduced EAT thickness in patients with type 2 diabetes mellitus independent of its effect on lowering blood glucose, suggesting that canagliflozin may have an effect in preventing cardiovascular events in these patients (UMIN000021327).
Kenya Kusunose, Hirotsugu Yamada, Susumu Nishio, Yuta Torii, Yukina Hirata, Hiromitsu Seno, Yoshihito Saijo, Takayuki Ise, Koji Yamaguchi, Shusuke Yagi, Takeshi Soeki, Tetsuzo Wakatsuki and Masataka Sata : Preload Stress Echocardiography Predicts Outcomes in Patients With Preserved Ejection FractionandLow-GradientAorticStenosis, Circulation. Cardiovascular Imaging, Vol.10, No.10, 2017.
(Summary)
The projected aortic valve area (AVA) at a normal transvalvular flow rate using dobutamine is helpful to determine the actual severity of aortic stenosis (AS) and to predict risk of adverse events in low-gradient AS cases with unclear surgical indication. Our study aimed to identify the independent and incremental value of preload stress echocardiography-derived AVA to predict outcomes in patients with preserved ejection fraction and low-gradient AS. We prospectively performed echocardiographic studies in 79 patients with low-gradient AS (age, 77±7 years; 30% men) with preload stress echocardiography using leg positive pressure. AVA was calculated using AVA and transvalvular flow rate at baseline and during leg positive pressure. The primary end point was the decision for aortic valve surgery or cardiac death. During a median period of 19 months, 23 patients had the decision for aortic valve surgery, and none died during follow-up. In a stepwise multivariable analysis, indexed AVA (AVAi; hazard ratio, 2.00 per 0.1 cm/m decrease; 95% confidence interval, 1.36-2.96; <0.001) was associated with the primary end point. Using a receiver operating characteristic curve analysis, the best cutoff value of AVAi for predicting cardiac events was <0.72 cm/m. By incorporating AVAi into AVAi at baseline, continuous net reclassification index for cardiac events was 0.48 (=0.04). In patients with low-gradient AS, indexed AVA derived from preload stress echocardiography can be useful to predict risk of adverse events. The present article should be considered as a proof of concept study, and we think that larger multicenter studies are warranted.
(Keyword)
Aged / Aged, 80 and over / Aortic Valve / Aortic Valve Stenosis / Area Under Curve / Disease Progression / Disease-Free Survival / Echocardiography, Stress / Female / Humans / Kaplan-Meier Estimate / Male / Models, Cardiovascular / Predictive Value of Tests / Prospective Studies / ROC Curve / Severity of Illness Index / Stroke Volume / Time Factors / Ventricular Function, Left
Susumu Nishio, Kenya Kusunose, Hirotsugu Yamada, Yukina Hirata, Takayuki Ise, Koji Yamaguchi, Shusuke Yagi, Takeshi Soeki, Tetsuzo Wakatsuki, Michio Shimabukuro and Masataka Sata : Echocardiographic Epicardial Adipose Tissue Thickness Is Associated with Symptomatic Coronary Vasospasm during Provocative Testing., Journal of the American Society of Echocardiography, Vol.30, No.10, 1021-1027, 2017.
(Summary)
Epicardial adipose tissue (EAT) is the ectopic visceral fat surrounding the heart, which plays an important role in atherosclerosis of the coronary arteries via endothelial damage. Several studies have also suggested that vasospasm with angina (VSA) causes endothelial dysfunction in the coronary arteries. The aim of this study was to evaluate the thickness of EAT in the anterior interventricular groove (EAT-AIG) using echocardiography in patients who had no obstructive coronary artery disease and were suspected of having VSA. Sixty-five patients who underwent intracoronary acetylcholine provocation testing for clinical indications were prospectively enrolled. VSA was diagnosed by coronary artery stenosis increase of >90% and the presentation of chest pain with ischemic changes on electrocardiography. Subjects were divided into two groups, with and without significant coronary spasm (VSA group, 30 patients; non-VSA group, 35 patients), consistent with acetylcholine provocation testing. EAT-AIG thickness was significantly greater in the VSA group than in the non-VSA group (8.2 2.7 vs 6.1 2.5 mm, P = .002). By receiver operating characteristic analysis, EAT-AIG thickness had a high C statistic (area under the curve = 0.81, P < .001) after adjustment for conventional risk factors (smoking, diabetes mellitus, and dyslipidemia). EAT-AIG thickness had incremental diagnostic value over other conventional risk factors (area under the curve = 0.81 vs 0.64, P for comparison = .020). EAT-AIG thickness, which is noninvasively and easily measured using transthoracic echocardiography, can be one of multiple clinical variables associated with VSA.
Yukina Hirata, Kenya Kusunose, Hirotsugu Yamada, Rikuto Shimizu, Yuta Torii, Susumu Nishio, Yoshihito Saijo, Shoichiro Takao, Takeshi Soeki and Masataka Sata : Age-related changes in morphology of left atrial appendage in patients with atrial fibrillation., The International Journal of Cardiovascular Imaging, Vol.34, No.2, 321-328, 2017.
(Summary)
The purpose of this study was to evaluate the relationship between age and frequency of left atrial appendage (LAA) morphology in patients with atrial fibrillation (AF) compared with sinus rhythm (SR). We enrolled 145 AF patients, and 199 SR patients for the control group without any cardiovascular disease. LAA volume index (LAAVi) and morphology were assessed by electrocardiogram-gated computed tomography angiography. LAA morphology was classified into "chicken wing" or "non-chicken wing" according to the previously described classification. There was no significant trend in frequency of non-chicken wing morphology among ages in the SR group (p = 0.36 for trend), whereas the frequency was negatively related to age in the AF group (p = 0.002 for trend). In multivariable logistic regression, age > 65 (odds ratio [OR] 0.42, p = 0.002) and duration of AF (OR 0.53, p = 0.010) and LAAVi (OR 0.62, p = 0.017) were independent factors of non-chicken wing LAA morphology in the AF group. LAA morphology is affected by age, especially in patients with AF. When we utilize non-chicken wing LAA morphology as a stroke risk factor in patients with AF, we should pay attention to their age.
Kenya Kusunose, Hirotsugu Yamada, Susumu Nishio, Yukina Hirata, Hiromitsu Seno, Y Saijo, Takayuki Ise, Takeshi Tobiume, Koji Yamaguchi, Shusuke Yagi, Takeshi Soeki, Tetsuzo Wakatsuki and Masataka Sata : Echocardiographic Predictors for Worsening of Six-Minute Walk Distances in Patients With Systemic Sclerosis (Scleroderma), The American Journal of Cardiology, Vol.120, No.2, 315-321, 2017.
(Summary)
Change in 6-minute walk distance (6MWD) has been used as a clinical marker in pulmonary hypertension. Determinants and worsening of 6MWD remain a matter of debate because nonpulmonary factors have an impact on the 6MWD. We hypothesized that future reduction of 6MWD in patients with systemic sclerosis (SSc) was more closely associated with cardiac dysfunction. We prospectively performed standard clinical and echocardiographic evaluations in SSc patients with the 6-minute walk test at enrollment. Features associated with the 6MWD were sought in a multiple linear regression analysis and compared using standardized . Worsening of the 6MWD was defined as a 15% reduction and served as the primary outcome. Eighty-one patients were included. In the multivariate analysis, baseline 6MWD was related to SSc severity score ( = -0.250, p = 0.024), left atrial volume index ( = -0.222, p = 0.046), right ventricular fractional area change ( = 0.252, p = 0.025), and the ratio of mean pulmonary artery pressure and cardiac output ( = -0.31, p = 0.002). During follow-up, 20 patients reached the primary outcome. In sequential Cox models, a model based on right ventricular fractional area change at baseline (chi-square 4.8) was improved by left atrial volume index (chi-square 10.3, p = 0.007). In conclusion, determinants and worsening of 6MWD are explained by cardiac factors. When using the 6MWD as a clinical marker in pulmonary hypertension patients, their left ventricular diastolic function and right ventricular systolic function should be taken into consideration.
(Keyword)
Diastole / Disease Progression / Echocardiography, Doppler / Female / Follow-Up Studies / Humans / Hypertension, Pulmonary / Male / Middle Aged / Predictive Value of Tests / Prospective Studies / Scleroderma, Systemic / Stroke Volume / Systole / Time Factors / Ventricular Function, Left / Ventricular Function, Right / Walking
Kenya Kusunose, Hirotsugu Yamada, Susumu Nishio, Ayumi Ishii, Yukina Hirata, Hiromitsu Seno, Yoshihito Saijo, Takayuki Ise, Koji Yamaguchi, Shusuke Yagi, Takeshi Soeki, Tetsuzo Wakatsuki and Masataka Sata : RV Myocardial Strain During Pre-Load Augmentation Is Associated With Exercise Capacity in Patients With Chronic HF, JACC. Cardiovascular Imaging, Vol.10, No.10, 1240-1249, 2017.
(Summary)
The aim of this study was to assess the relationship between right ventricular (RV) function during pre-load augmentation and exercise tolerance. Peak oxygen uptake (VO2) is a strong predictor of mortality in chronic heart failure. Cardiac function during pre-load augmentation is an important part of the phenomenon in the evaluation of exercise capacity. We prospectively performed echocardiographic studies in 68 chronic heart failure patients with cardiopulmonary exercise testing (mean age 60 ± 12 years; 69% male). After resting evaluations, echocardiographic parameters were repeated during leg positive pressure (LPP). Exercise capacity was assessed by peak VO2 in all patients (left ventricular ejection fraction: 43 ± 15%). Patients with severely reduced exercise capacity (peak VO2 <14 ml/kg/min) had significantly lower stroke volume index, left ventricular global longitudinal strain and RV strain and higher filling pressure (E/e' and pulmonary arterial systolic pressure) than the remainder. Stroke volume index ( = 0.49), global longitudinal strain ( = -0.61), E/e' ( = -0.32), pulmonary arterial systolic pressure ( = -0.57), and RV strain ( = -0.66) during LPP were independently correlated to peak VO2 (all p < 0.01). RV strain during LPP was the most powerful predictor in identifying patients with severely reduced exercise capacity (cut off value: -17%; sensitivity: 81%; specificity: 88%; areas under the curve: 0.88; p < 0.001) compared with other variables including resting parameters. RV strain during pre-load augmentation correlated independently to peak VO2 and was a powerful predictor in identifying patients with severely reduced exercise capacity.
S Bando, Takeshi Soeki, Tomomi Matsuura, Takeshi Tobiume, Takayuki Ise, Kenya Kusunose, Koji Yamaguchi, Shusuke Yagi, Daiju Fukuda, Takashi Iwase, Hirotsugu Yamada, Tetsuzo Wakatsuki, Michio Shimabukuro, Naoki Muguruma, Tetsuji Takayama, I Kishimoto, Kenji Kangawa and Masataka Sata : Plasma brain natriuretic peptide levels are elevated in patients with cancer, PLoS ONE, Vol.12, No.6, e0178607, 2017.
(Summary)
Natriuretic peptides have been proposed as biomarkers of cardiovascular disease, especially heart failure. Brain natriuretic peptide (BNP) has also been shown to be upregulated at the transcriptional and translational levels by pro-inflammatory cytokines in cardiac myocytes. Although we often measure plasma BNP levels in cancer patients, it remains unknown whether cancer-related inflammation affects the plasma BNP levels. We investigated the relationship between the BNP and human cancers. We retrospectively studied 2,923 patients in whom the plasma BNP levels and serum C-reactive protein (CRP) were measured and echocardiography was performed. Patients with clinically evident heart failure (NYHA II or higher), heart disease requiring medical treatment or surgery, renal dysfunction, and inflammatory disease were excluded. There were 234 patients in the final analysis. Blood sampling was performed before surgery and chemotherapy. In addition, we evaluated the relationship between the inflammation and plasma BNP levels in mouse models of colon cancer. Of the 234 patients, 80 were diagnosed with cancer. Both the plasma BNP and serum CRP levels were significantly higher in cancer patients than those without. There were no significant differences in the echocardiographic parameters. There was a significant positive correlation between the plasma BNP and serum CRP levels in cancer patients (r = 0.360, P<0.01) but not in those without. In cancer patients, only the CRP correlated with the BNP independent of the age, creatinine level, hypertension, and body mass index. In addition, in nude mice with subcutaneous colon cancer, the plasma BNP level was elevated compared with that in non-cancer mice, and there was a significant relationship between the plasma BNP and serum levels of the inflammatory markers. In cancer patients, as well as colon cancer model mice, the plasma BNP levels were elevated, possibly due to cancer-related inflammation. The effect of cancer on the BNP levels should be considered when using BNP as an indicator of heart failure in cancer patients.
Hirotsugu Yamada, Atsushi Tanaka, Kenya Kusunose, Rie Amano, Munehide Matsuhisa, Hiroyuki Daida, Masaaki Ito, Hiroyuki Tsutsui, Mamoru Nanasato, Haruo Kamiya, K Yasuko Bando, Masato Odawara, Hisako Yoshida, Toyoaki Murohara, Masataka Sata and Koichi Node : Effect of sitagliptin on the echocardiographic parameters of left ventricular diastolic function in patients with type 2 diabetes: a subgroup analysis of the PROLOGUE study., Cardiovascular Diabetology, Vol.16, No.1, 63, 2017.
(Summary)
Diabetes is associated closely with an increased risk of cardiovascular events, including diastolic dysfunction and heart failure that leads to a shortening of life expectancy. It is therefore extremely valuable to evaluate the impact of antidiabetic agents on cardiac function. However, the influence of dipeptidyl peptidase 4 inhibitors on cardiac function is controversial and a major matter of clinical concern. We therefore evaluated the effect of sitagliptin on echocardiographic parameters of diastolic function in patients with type 2 diabetes as a sub-analysis of the PROLOGUE study.
Kenya Kusunose, Yuta Torii, Hirotsugu Yamada, Susumu Nishio, Yukina Hirata, Hiromitsu Seno, Yoshihito Saijo, Takayuki Ise, Koji Yamaguchi, Takeshi Tobiume, Shusuke Yagi, Takeshi Soeki, Tetsuzo Wakatsuki and Masataka Sata : Clinical Utility of Longitudinal Strain to Predict Functional Recovery in Patients With Tachyarrhythmia and Reduced LVEF., JACC. Cardiovascular Imaging, Vol.10, No.2, 118-126, 2017.
(Summary)
Objectives: The aim of this study was to assess the time course of presumptive TIC and the predictors of LV functional recovery in such patients.Background: Tachycardia-induced cardiomyopathy (TIC) is a potentially reversible cardiomyopathy with effective treatment of the tachyarrhythmia. However, cases without improvement of left ventricular (LV) systolic function were found occasionally. The diagnosis of TIC can be challenging, and the role of echocardiographic imaging in the prediction of LV functional recovery is limited.Methods: LV segmental longitudinal strains (LS) were evaluated by 2-dimensional speckle tracking in 71 consecutive patients (65±16 years; 61% men) with tachyarrhythmia and reduced LV ejection fraction (EF) without any other known cardiovascular disease, and 30 age and gender matched control subjects. Relative apical LS ratio (RALSR) was defined using the equation: average apical LS / (average basal LS + average mid LS) as a marker of strain distribution.Results: Compared to control subjects, patients with tachyarrhythmia had significantly lower global LS. Improvement in LVEF within 6 months after treatment of index arrhythmia was observed in 41 patients, and LVEF did not improve in 30 patients. In univariate analysis, lower LVEF at baseline (hazard ratio: HR: 0.59 per 1SD, p=0.04) and higher RALSR (HR: 11.2 per 1SD, p <0.001) were associated with no recovery in LVEF during follow-up. In a multivariate logistic regression model, the significant predictor of LV systolic functional recovery was RALSR (HR: 22.9 per 1SD, p=0.001). A RALSR of 0.61 was sensitive (71%) and specific (90%) in differentiating LV systolic functional recovery (area under the curve: 0.88).Conclusions: The RALSR was associated with LV systolic functional recovery. This information might be useful for clinical evaluation and follow-up in patients with reduced LVEF.
鳥居 裕太, 西尾 進, 松本 力三, 平田 有紀奈, 天野 里江, 山尾 雅美, Kenya Kusunose, Hirotsugu Yamada and Masataka Sata : 超音波検査が診断に有用であった右5指動静脈奇形の1例, Japanese Journal of Medical Ultrasound Technology, Vol.42, No.6, 726, 2017.
143.
A Takashima, Shusuke Yagi, Koji Yamaguchi, S Watanabe, N Yamamoto, H Ito, M Kadota, T Hara, H Yamazaki, Takayuki Ise, Kenya Kusunose, Takeshi Tobiume, Hirotsugu Yamada, Takeshi Soeki, Tetsuzo Wakatsuki and Masataka Sata : Purulent pericarditis accompanying pericardial abscess induced by nocardia in an immunocompromised patient., Circulation Journal, Vol.80, No.11, 2409-2411, 2016.
鳥居 裕太, 西尾 進, 玉井 佑里恵, 山崎 宙, Shoichiro Takao, Kenya Kusunose, Koji Yamaguchi, Tetsuzo Wakatsuki, Hirotsugu Yamada and Masataka Sata : 解剖学的異常を認めない膝窩動脈捕捉症候群の1例, Japanese Journal of Medical Ultrasound Technology, Vol.41, No.5, 513-520, 2016.
Marwa A. Sabe, Sharif A. Sabe, Kenya Kusunose, Scott D. Flamm, Brian P. Griffin and Deborah H. Kwon : Predictors and Prognostic Significance of Right Ventricular Ejection Fraction in Patients With Ischemic Cardiomyopathy., Circulation, Vol.134, No.9, 656-665, 2016.
(Summary)
Decreased right ventricular (RV) ejection fraction (RVEF) portends poor prognosis in patients with ischemic cardiomyopathy, and previous studies have suggested an association between mitral regurgitation (MR) and RVEF. We sought to evaluate this association and whether mitral valve repair or replacement affects the relationship between RV function and mortality. We included 588 patients (mean age, 63±11 years; 75% male) with ischemic cardiomyopathy who underwent cardiac magnetic resonance imaging between 2002 and 2008. Baseline characteristics, left ventricular ejection fraction, MR severity, treatment modality, scar burden, and RVEF were assessed. Multivariable linear regression and Cox proportional hazards models were used to assess the association between MR and RVEF and between RVEF and mortality, respectively. After adjustment for age, sex, left ventricular ejection fraction, right bundle-branch block, and RV scar, MR severity was found to be associated independently with RVEF. There were a total of 240 deaths during a median follow-up time of 5.7 years. After multivariable adjustment, every 10% decrease in RVEF was associated with a 17% increased risk of death (P=0.008). Although decreasing RVEF was associated with a poor prognosis in the nonrepair group (hazard ratio, 1.28; 95% confidence interval, 1.12-1.47; P<0.001), it was not associated with death in the mitral valve repair or replacement group (P for interaction=0.046). MR severity was found to be an independent predictor of RVEF, as were right bundle-branch block, left ventricular ejection fraction, and the presence of RV scar. Decreasing RVEF is associated with increased mortality in patients with ischemic cardiomyopathy; however, this association may be mitigated in patients who undergo mitral valve repair or replacement.
(Keyword)
Aged / Cardiomyopathies / Cohort Studies / Female / Follow-Up Studies / Humans / Male / Middle Aged / myocardial ischemia / Predictive Value of Tests / Prognosis / Risk Factors / Stroke Volume / Ventricular Dysfunction, Right / Ventricular Function, Right
Kenya Kusunose, Dermot Phelan, Sinziana Seicean, Andreea Seicean, Patrick Collier, Kaeleen A. Boden, Reena Mehra and Brian P. Griffin : Relation of Echocardiographic Characteristics of the Right-Sided Heart With Incident Heart Failure and Mortality in Patients With Sleep-Disordered Breathing and Preserved Left Ventricular Ejection Fraction., The American Journal of Cardiology, Vol.118, No.8, 1268-1273, 2016.
(Summary)
Sleep-disordered breathing (SDB) has been associated with right-sided heart dysfunction and adverse cardiovascular outcomes. Longitudinal data are sparse in terms of understanding the prognostic implications of right ventricular remodeling in SDB on cardiovascular risk. We therefore investigated the predictive value of right-sided cardiac functional alterations on incident heart failure (HF) or death in SDB. Patients with SDB who underwent echocardiography within 1 month of index polysomnogram from January 2002 to July 2011 with normal left ventricular ejection fraction were included. Cox proportional prognostic hazard models predicting HF or death were used. Of a potential 375 subjects, 202 fulfilled the inclusion criteria (58 ± 14 years; 50% men). Subjects were followed for 3.1 ± 2.4 years with a total of 34 (16.8%) developing HF or death. Right ventricular end-systolic area (hazard ratio [HR] 1.3, 95% CI 1.01 to 1.6, p = 0.038), pulmonary vascular resistance (PVR; HR 1.4, 95% CI 1.1 to 1.7, p = 0.005) and also left atrial volume index (HR 1.7, 95%, CI 1.3 to 2.3, p <0.001) and E/A ratio (HR 1.4, 95% CI 1.1 to 1.7, p <0.001), were predictive of HF or death. Patients with increased PVR had significantly shorter event-free survival than without increased PVR (p = 0.04). In sequential Cox models, a model based on clinical data and left ventricular ejection fraction (χ(2), 5.4) was improved by left atrial volume index (χ(2), 12.7; p = 0.011) and further increased by PVR (χ(2), 19.7; p = 0.015). In conclusion, right-sided heart dysfunction provides important prognostic information in SDB and may aid in identifying those at highest risk to target for closer follow-up.
(Keyword)
Adult / Aged / Atrial Function, Right / Cause of Death / Echocardiography / Female / Follow-Up Studies / Heart Atria / heart failure / Humans / Incidence / Longitudinal Studies / Male / Middle Aged / Mortality / Organ Size / Polysomnography / Prognosis / Proportional Hazards Models / Retrospective Studies / Sleep Apnea Syndromes / Stroke Volume / Vascular Resistance / Ventricular Dysfunction, Right / Ventricular Function, Right
Rami Kafa, Kenya Kusunose, Andrew L. Goodman, Lars G. Svensson, Joseph F. Sabik, Brian P. Griffin and Milind Y. Desai : Association of Abnormal Postoperative Left Ventricular Global Longitudinal Strain With Outcomes in Severe Aortic Stenosis Following Aortic Valve Replacement., JAMA Cardiology, Vol.1, No.4, 494-496, 2016.
Deborah H. Kwon, Kenya Kusunose, Nancy A. Obuchowski, João L. Cavalcante, Zoran B. Popovic, James D. Thomas, Milind Y. Desai, Scott D. Flamm and Brian P. Griffin : Predictors and Prognostic Impact of Progressive Ischemic Mitral Regurgitation in Patients With Advanced Ischemic Cardiomyopathy: A Multimodality Study., Circulation. Cardiovascular Imaging, Vol.9, No.7, 2016.
(Summary)
Ischemic mitral regurgitation (IMR) is associated with poor outcomes. It is unknown what factors contribute to progression of IMR and how progressive IMR affects outcomes. We sought to determine imaging predictors of IMR progression and to determine if progressive IMR is an independent predictor of survival in patients with advanced ischemic cardiomyopathy. Consecutive advanced ischemic cardiomyopathy patients who underwent cardiac magnetic resonance and echocardiograms at baseline with echocardiographic follow-up were studied. Cardiac magnetic resonance was used to assess left ventricular volumes, infarct size, and mitral valve geometry. The effective regurgitant orifice area (EROA) was calculated from the proximal isovelocity surface area by echocardiography. Repeated measures mixed effects and Cox proportional hazards regression models were built to identify predictors of IMR progression and survival. We evaluated 336 patients (age, 62±11 years) over a median follow-up time of 54 months: 154 patients were subsequently revascularized, and 182 patients were medically treated. Ninety-eight patients (29%) demonstrated an increase in EROA values of ≥0.1 cm(2). There were 87 adverse events (death or transplant). On multivariable analysis, infarct size (P<0.001), progression in IMR (P=0.008), age (P=0.003), and baseline EROA (P=0.010) were independently associated with adverse events. Independent predictors of IMR progression were as follows: baseline EROA (P<0.001), left ventricular end-systolic volume index (P=0.014), and total scar (P=0.036). IMR frequently increases in severity, and progression is independently associated with adverse left ventricular remodeling and infarct size, as assessed by cardiac magnetic resonance. Furthermore, IMR progression is a powerful independent predictor of adverse events, even after controlling for the severity of IMR at baseline.
(Keyword)
Aged / Cardiomyopathies / Chi-Square Distribution / Coronary Stenosis / Disease Progression / Echocardiography / Female / Humans / Image Interpretation, Computer-Assisted / Magnetic Resonance Imaging, Cine / Male / Middle Aged / Mitral Valve Insufficiency / multimodal imaging / Multivariate Analysis / Myocardial Infarction / myocardium / Observer Variation / Predictive Value of Tests / Prognosis / Proportional Hazards Models / Reproducibility of Results / Retrospective Studies / Risk Factors / Severity of Illness Index / Stroke Volume / Time Factors / Ventricular Function, Left / Ventricular Remodeling
Kenya Kusunose and Hirotsugu Yamada : Noninvasive Vascular Function Tests - Long Journey for Predicting Cardiovascular Events., Circulation Journal, Vol.80, No.6, 1321-1322, 2016.
T Hayashi, S Yamada, H Iwano, M Nakabachi, M Sakakibara, K Okada, D Murai, H Nishino, Kenya Kusunose, K Watanabe, T Ishizu, K Wakami, Hirotsugu Yamada, K Dohi, Y Seo, N Ohte, T Mikami and H Tsutsui : Left Ventricular Global Strain for Estimating Relaxation and Filling Pressure- A Multicenter Study., Circulation Journal, Vol.80, No.5, 1163-1170, 2016.
(Summary)
BACKGROUND: Speckle-tracking echocardiography (STE)-derived parameters may have better correlation with left ventricular (LV) relaxation and filling pressure than tissue Doppler-derived parameters. However, it has not been elucidated which parameter - strain or strain rate - and which direction of myocardial deformation - longitudinal or circumferential - is the most useful marker of LV relaxation and filling pressure.METHODSANDRESULTS: We conducted a prospective multicenter study and compared the correlation of tissue Doppler- and STE-derived parameters with the time constant of LV pressure decay () and LV mean diastolic pressure (MDP) in 77 patients. The correlation of early-diastolic mitral annular velocity (e´) with was weak (r=-0.32, P<0.01), and that of peak longitudinal strain (LS) was the strongest (r=-0.45, P<0.001) among the STE-derived parameters. There was a modest correlation between LVMDP and the ratio of early-diastolic inflow velocity (E) to e´ (E/e´) (r=0.50, P<0.001). In contrast, the ratio of E to LS (E/LS) correlated strongly with LVMDP (r=0.70, P<0.001). The correlation of E/LS with LVMDP was significantly better than that for E/e´ (P<0.01). Receiver-operating characteristic analysis showed that E/LS had the largest area under the curve for distinguishing elevated LVMDP (E/LS 0.86, E/e´ 0.74, E/A 0.67).CONCLUSIONS: STE-derived longitudinal parameters correlated well with LV relaxation and filling pressure. In particular, E/LS could be more accurate than E/e´ for estimating LV filling pressure. (Circ J 2016; 80: 1163-1170).
Kenya Kusunose, M Sato, Hirotsugu Yamada, Y Saijo, Mika Bando, Y Hirata, S Nishio, S Hayashi and Masataka Sata : Prognostic implications of non-invasive vascular function tests in high-risk atherosclerosis patients., Circulation Journal, Vol.80, No.4, 1034-1040, 2016.
(Summary)
BACKGROUND: The aim of this study was to assess the role of clinically available vascular function tests as predictors of cardiovascular events and decline in kidney function.MethodsandResults:One hundred and fourteen patients who had at least 2 cardiovascular risk factors were recruited for vascular function assessment including ankle-brachial blood pressure index (ABI), brachial-ankle pulse wave velocity (baPWV), cardio-ankle vascular index (CAVI) and flow-mediated vasodilatation (%FMD). During a median period of 51 months, 35 patients reached the primary endpoint (29 cardiovascular events and 6 cardiac deaths), and 30 patients reached the secondary endpoint (decline in kidney function: defined as a 5% per year decline of estimated glomerular filtration rate). In sequential Cox models, a model on the basis of the Framingham risk score, hemoglobin, and high-sensitivity C-reactive protein (chi-squared, 16.6) was improved by the ABI (chi-squared: 21.5; P=0.047). The baPWV (hazard ratio: 1.42 per 1 SD increase; P=0.025) and the CAVI (hazard ratio: 1.52 per 1 SD increase; P=0.040) were associated with the secondary endpoint. The %FMD was only slightly associated with the primary and secondary endpoints.CONCLUSIONS: Both ABI and baPWV are significantly associated with future cardiovascular events in high-risk patients with cardiovascular disease. The predictive capabilities of these parameters are greater than that of other parameters in this cohort.
(Keyword)
Cardiovascular event / Endothelial function / Kidney function / Vascular function
Takeshi Soeki, Tomomi Matsuura, Sachiko Bando, Takeshi Tobiume, Etsuko Uematsu, Takayuki Ise, Kenya Kusunose, Koji Yamaguchi, Shusuke Yagi, Daiju Fukuda, Hirotsugu Yamada, Tetsuzo Wakatsuki, Michio Shimabukuro and Masataka Sata : Relationship between local production of microRNA-328 and atrial substrate remodeling in atrial fibrillation., Journal of Cardiology, Vol.68, No.6, 472-477, 2016.
(Summary)
BACKGROUND: The underlying mechanism of atrial substrate remodeling in atrial fibrillation (AF) remains unknown. In this study, we investigated whether local and systemic levels of microRNA (miR) might be associated with the presence of AF and with left atrial (LA) substrate properties.METHODS: Blood from the periphery, pulmonary vein (PV), and left atrial appendage (LAA) was sampled from 30 patients with AF undergoing PV isolation, and from 10 control subjects with Wolff-Parkinson-White syndrome and without AF. We measured peripheral, PV, and LAA plasma levels of miR-1, -26, -133a, -328, and -590 by reverse transcription-polymerase chain reaction. LA global contact mapping during sinus rhythm was performed before PV isolation.RESULTS: Plasma levels of miR-328 were higher in patients with AF than in control subjects. Plasma miR-328 levels were significantly higher in the LAA than in the periphery and PV in patients with AF, but not in control subjects. Plasma miR-1 levels were also higher in the LAA than in the PV in AF patients. Interestingly, LAA plasma levels of miR-328 showed a positive correlation with the LA voltage zone index (area with voltage <0.5mV divided by total LA surface area) and a weak correlation with LA volume.CONCLUSION: Local production of miR-328 in the left atrium may be involved in the process of atrial remodeling in patients with AF.
Yuta Torii, Hirotsugu Yamada, Susumu Matsukuma, Susumu Nishio, Kenya Kusunose, Miho Abe and Masataka Sata : Left Ventricular lipomatous hamartoma mimicking a calcified amorphous tumor., Circulation, Vol.133, No.8, e408-e410, 2016.
Alpana Senapati, Brett W. Sperry, Justin L. Grodin, Kenya Kusunose, Paaladinesh Thavendiranathan, Wael Jaber, Patrick Collier, Mazen Hanna, Zoran B. Popovic and Dermot Phelan : Prognostic implication of relative regional strain ratio in cardiac amyloidosis., Heart, 2016.
(Summary)
Cardiac amyloidosis (CA) is a rapidly progressive disease that portends poor prognosis. Our objective was to evaluate the prognostic impact of relative regional strain ratio (RRSR, a measure of the relative apical sparing of longitudinal strain (LS)) in CA. This is a retrospective study evaluating 97 patients with CA from 2004 to 2013. Patients were included if they met criteria for CA based on endomyocardial biopsy or advanced imaging criteria coupled with either extracardiac biopsy or genetic analysis. Baseline clinical and imaging data were collected and compared between light-chain amyloidosis (AL) (n=59) and transthyretin amyloidosis (ATTR) (n=38) subtypes. RRSR was defined as the average apical LS divided by the sum of the average mid and basal LS values. A Cox proportional hazards model was used to assess the effects of clinical and echocardiographic characteristics, including RRSR, on the outcome of time to death or heart transplantation. Despite younger age, the AL subtype had a statistically significant association with the composite outcome as compared with ATTR (p=0.022). Log-transformed RRSR was independently associated with the composite outcome at 5 years (HR 2.45 (1.36 to 4.40), p=0.003). Patients with low ejection fraction and high RRSR had the worst prognosis. In multivariable analysis, RRSR remained predictive of the primary outcome (p=0.018). Addition of covariates related to systolic function (global LS and ejection fraction) to the model attenuated this effect. High RRSR is adversely prognostic in patients with cardiac amyloid. This novel tool is both diagnostic and prognostic and may have implications in management and suitability for treatment.
Toshiyuki Niki, Tetsuzo Wakatsuki, Koji Yamaguchi, Yoshio Taketani, Hiroyasu Oeduka, Kenya Kusunose, Takayuki Ise, Takashi Iwase, Hirotsugu Yamada, Takeshi Soeki and Masataka Sata : Effects of the addition of eicosapentaenoic acid to strong statin therapy on inflammatory cytokines and coronary plaque components assessed by integrated backscatter intravascular ultrasound., Circulation Journal, Vol.80, No.2, 450-460, 2016.
(Summary)
BACKGROUND: The effects of eicosapentaenoic acid (EPA) on coronary artery disease have been previously reported; however, those of the addition of EPA to strong statins on coronary plaque components and local inflammatory cytokines are not known.METHODSANDRESULTS: A total of 95 patients who had been treated with strong statin for at least 6 months were randomized into 2 groups: an EPA group (additional treatment with EPA at 1,800 mg/day, n=48) or a control group (no additional treatment, n=47), for 6 months. The tissue characteristics of target coronary plaque in each patient were analyzed using IB-IVUS before and after treatment. We also measured plasma levels of inflammatory cytokines sampled in the coronary sinus (CS) and peripheral vein.A significant reduction in lipid volume (18.5±1.3 to 15.0±1.5 mm(3), P=0.007) and a significant increase in fibrous volume (22.9±0.8 to 25.6±1.1 mm(3), P=0.01) were observed in IB-IVUS image analyses in the EPA group, but no significant changes in the plaque components in the control group. CS levels of pentraxin 3 and monocyte chemoattractant protein-1 were lower after than before treatment with EPA (3.3±2.1 to 2.6±1.2 ng/ml, 120.4±26.2 to 110.2±26.8 pg/ml, P=0.015 and P=0.008, respectively); however, there were no significant changes in those inflammatory cytokines between pre- and post-treatment in the control group.CONCLUSIONS: The addition of EPA was associated with reduced lipid volume in coronary plaques and decreased inflammatory cytokines. (Circ J 2016; 80: 450-460).
Yuta Torii, Kenya Kusunose, Hirotsugu Yamada, Susumu Nishio, Yukina Hirata, Rie Amano, Masami Yamao, Mika Bando, Shuji Hayashi and Masataka Sata : Comparison of tricuspid annular plane systolic excursion in patients with atrial fibrillation vs sinus rhythm., The American Journal of Cardiology, Vol.117, No.2, 226-232, 2016.
(Summary)
Echocardiography now plays a central guiding role in the management of patients with atrial fibrillation (AF). However, the current guidelines mention little about the presence AF during the assessment of echocardiographic variables in the clinical setting. AF itself may impact on tricuspid annular plane systolic excursion (TAPSE) as a right ventricular systolic function compared with sinus rhythm (SR). The aim of this study was to compare and assess the echocardiographic parameters including TAPSE in patients with AF and SR. From January 1, 2013, to September 30, 2014, patients with AF without any cardiovascular disease were retrospectively evaluated using echocardiography. Age-, gender-, and left ventricular ejection fraction-matched patients with SR were selected from our database on the basis of a comprehensive history, physical examination, and echocardiographic findings. During the study period, we identified 239 patients with AF (74 ± 9 years; 65% men) and without any cardiac disease who underwent echocardiography. We also included 281 patients in the SR group (74 ± 8 years; 67% men). In all study subjects, TAPSE in AF was smaller than in SR regardless of age (17 ± 3 vs 20 ± 3 mm, p <0.001). In the stepwise multiple regression model, TAPSE was strongly associated with the presence of AF (standardized β = -0.362, p <0.001) and stroke volume index (standardized β = 0.173, p <0.001) after adjustment for age, gender, heart rate, left ventricular ejection fraction, and tricuspid regurgitant grade. In conclusions, patients with AF had lower TAPSE than those with SR regardless of age. When we assess TAPSE in the clinical setting, we must pay attention to the presence of AF.
Adam Goldberg, Kenya Kusunose, Salima Qamruddin, L Leonardo Rodriguez, Todor N. Mazgalev, Brian P. Griffin, David Wagoner R. Van, Youhua Zhang and Zoran B. Popović : Left Atrial Size and Function in a Canine Model of Chronic Atrial Fibrillation and Heart Failure., PLoS ONE, Vol.11, No.1, e0147015, 2016.
(Summary)
Our aim was to assess how atrial fibrillation (AF) induction, chronicity, and RR interval irregularity affect left atrial (LA) function and size in the setting of underlying heart failure (HF), and to determine whether AF effects can be mitigated by vagal nerve stimulation (VNS). HF was induced by 4-weeks of rapid ventricular pacing in 24 dogs. Subsequently, AF was induced and maintained by atrial pacing at 600 bpm. Dogs were randomized into control (n = 9) and VNS (n = 15) groups. In the VNS group, atrioventricular node fat pad stimulation (310 μs, 20 Hz, 3-7 mA) was delivered continuously for 6 months. LA volume and LA strain data were calculated from bi-weekly echocardiograms. RR intervals decreased with HF in both groups (p = 0.001), and decreased further during AF in control group (p = 0.014), with a non-significant increase in the VNS group during AF. LA size increased with HF (p<0.0001), with no additional increase during AF. LA strain decreased with HF (p = 0.025) and further decreased after induction of AF (p = 0.0001). LA strain decreased less (p = 0.001) in the VNS than in the control group. Beat-by-beat analysis showed a curvilinear increase of LA strain with longer preceding RR interval, (r = 0.45, p <0.0001) with LA strain 1.1% higher (p = 0.02) in the VNS-treated animals, independent of preceding RR interval duration. The curvilinear relationship between ratio of preceding and pre-preceding RR intervals, and subsequent LA strain was weaker, (r = 0.28, p = 0.001). However, VNS-treated animals again had higher LA strain (by 2.2%, p = 0.002) independently of the ratio of preceding and pre-preceding RR intervals. In the underlying presence of pacing-induced HF, AF decreased LA strain, with little impact on LA size. LA strain depends on the preceding RR interval duration.
Akira Takashima, Shusuke Yagi, Koji Yamaguchi, Eri Takagi, Tamotsu Kanbara, Hirohisa Ogawa, Takayuki Ise, Kenya Kusunose, Takeshi Tobiume, Hirotsugu Yamada, Takeshi Soeki, Tetsuzo Wakatsuki, Tetsuya Kitagawa and Masataka Sata : Vegetation in the coronary sinus that concealed the presence of a coronary arteriovenous fistula in a patient with infectious endocarditis., International Journal of Cardiology, Vol.207, 266-268, 2016.
Andrew Goodman, Kenya Kusunose, Zoran B. Popovic, Roosha Parikh, Tyler Barr, Joseph F. Sabik, L Leonardo Rodriguez, Lars G. Svensson, Brian P. Griffin and Milind Y. Desai : Synergistic Utility of Brain Natriuretic Peptide and Left Ventricular Strain in Patients With Significant Aortic Stenosis., Journal of the American Heart Association, Vol.5, No.1, 2016.
(Summary)
In aortic stenosis (AS), symptoms and left ventricular (LV) dysfunction represent a later disease state, and objective parameters that identify incipient LV dysfunction are needed. We sought to determine prognostic utility of brain natriuretic peptide (BNP) and left ventricular global longitudinal strain (LV-GLS) in patients with aortic valve area <1.3 cm(2). Five-hundred and thirty-one patients between January 2007 and December 2008 with aortic valve area <1.3 cm(2) (86% with aortic valve area ≤1.1 cm(2)) and left ventricular ejection fraction ≥50% who had BNP drawn ≤90 days from initial echo were included. Society of Thoracic Surgeons (STS) score and mortality were recorded. Mean STS score, glomerular filtration rate, and median BNP were 11±5, 73±35 mL/min per 1.73 m , and 141 (60-313) pg/mL, respectively; 78% were in New York Heart Association class ≥II. Mean LV-stroke volume index (LV-SVI) and LV-GLS were 39±10 mL/m(2) and -13.9±3%. At 4.7±2 years, 405 patients (76%) underwent aortic valve replacement; 161 died (30%). On multivariable survival analysis, age (hazard ratio [HR] 1.46), New York Heart Association class (HR 1.27), coronary artery disease (HR 1.72), decreasing glomerular filtration rate (HR 1.15), increasing BNP (HR 1.16), worsening LV-GLS (HR 1.13) and aortic valve replacement (time dependent) (HR 0.34) predicted survival (all P<0.01). For mortality, the c-statistic incrementally increased as follows (all P<0.01): STS score (0.60 [0.58-0.64]), STS score+BNP (0.67 [0.62-0.70]), and STS score+BNP+LV-GLS (0.74 [0.68-0.78]). In normal LVEF patients with significant aortic stenosis, BNP and LV-GLS provide incremental (additive not duplicative) prognostic information over established predictors, suggesting that both play a synergistic role in defining outcomes.
Mika Bando, Hirotsugu Yamada, Kenya Kusunose, Shuji Hayashi, Yuriko Takagawa, Yoshihito Saijo, Susumu Nishio, Kozue Ogasawara and Masataka Sata : Pulmonary embolism due to right atrial free-floating thrombus during echocardiographic examination: a case of a pulmonary saddle thrombus., Journal of Echocardiography, Vol.13, No.4, 145-147, 2015.
(Summary)
A 69-year-old female with polymyositis was referred to our hospital with a chief complaint of dyspnea. Transthoracic echocardiography showed right ventricular overloading. In addition to two-dimensional echocardiography, observation of the abnormal free-floating string-like mass by three-dimensional echocardiography provided superior visualization of the features of the mass which protruded into the right ventricle across the tricuspid valve during diastole. These findings enabled us to confirm the diagnosis of venous thrombus. The thrombus disappeared during the echocardiographic examination. Multidetector-row computed tomography showed a string-like thrombus across the bifurcation of the main pulmonary artery. Anticoagulation therapy was initiated with heparin and warfarin, and fondaparinux was started on the fourth day. Three-dimensional echocardiography was useful in characterizing the motion and extent of the thrombus.
(Keyword)
Anticoagulation / Echocardiography / Pulmonary embolism / Right atrial thrombus
Naoko Sawada, Hirotsugu Yamada, Kenya Kusunose, Shuji Hayashi, Takashi Iwase and Masataka Sata : 3D transthoracic echocardiography provides accurate cross-sectional area of the RV outflow tract., JACC. Cardiovascular Imaging, Vol.8, No.11, 1343-1345, 2015.
Shusuke Yagi, Ken-ichi Aihara, Daiju Fukuda, Akira Takashima, Mika Bando, Tomoya Hara, Sachiko Nishimoto, Takayuki Ise, Kenya Kusunose, Koji Yamaguchi, Takeshi Tobiume, Takashi Iwase, Hirotsugu Yamada, Takeshi Soeki, Tetsuzo Wakatsuki, Michio Shimabukuro, Masashi Akaike and Masataka Sata : Reduced ratio of eicosapentaenoic acid and docosahexaenoic acid to arachidonic acid is associated with early onset of acute coronary syndrome., Nutrition Journal, Vol.14, No.1, 111, 2015.
(Summary)
BACKGROUND: The hospitalization rate for acute coronary syndrome (ACS) for people aged 50 has remained stable over the past decade. Increased serum levels of n-3 polyunsaturated fatty acids (PUFAs), such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), are associated with a decreased incidence of cardiovascular events and mortality in older patients; however, it is currently unknown whether reduced serum levels of n-3 PUFAs is also a risk factor for ACS in patients aged 50 years.METHODS AND RESULTS: We retrospectively reviewed 102 (male/ female 73/29) Japanese ACS patients whose serum levels of EPA/arachidonic acid (AA) and DHA/AA were evaluated on admission. The EPA/AA ratio was the lowest in patients aged 50 compared to patients aged 51-74 and 75. Pearson correlation analysis showed that early ACS onset was associated with low EPA/AA and DHA/AA ratios, and multiple regression analysis determined that decreased ratios of EPA/AA and DHA/AA, and male sex, current smoker status, increased body mass index and triglyceride levels, independently correlated with early ACS onset. Conversely, low-density and high-density lipoproteins, glycated hemoglobin, and hypertension did not correlate with early ACS onset. Subgroup analyses of male patients revealed that decreased ratios of EPA/AA and DHA/AA independently correlated with early ACS onset.CONCLUSION: Decreased EPA/AA and DHA/AA ratios may be risk factors for early onset of ACS, suggesting that reduced EPA/AA and DHA/AA may represent targets for preventing ACS in Japanese young people.
Susumu Nishio, Kenya Kusunose, Hirotsugu Yamada, Masami Yamao, Yukina Hirata, Kazuhiro Mori, Suguru Matsuoka and Masataka Sata : Echocardiographic screening for congenital heart disease in 8819 children: A report from local community events for children's healthcare., Journal of Cardiology, Vol.66, No.4, 315-319, 2015.
(Summary)
BACKGROUND: We had the opportunity to perform echocardiographic screening of children at local community events for children's healthcare sponsored by the prefectural government. The aim of this study was to assess the utility of echocardiographic screening by measuring the prevalence of congenital heart disease (CHD) and abnormal findings in children without history of diagnosed CHD.METHODS: Subjects consisted of 8819 infants and preschool children (1 month to 6 years) who underwent echocardiographic examination at public events from 2001 to 2013. Children with known CHD were excluded.RESULTS: We performed echocardiographic screening on 752 (range: 464-993) children at each event. At a total of 12 events, subjects consisted of 3175 infants less than one year (36%), 2292 one-year-olds (26%), 1058 two-year-olds (12%), 794 three-year-olds (9%), and other children up to age six years. We identified echocardiographic abnormalities in 137 children (15.5/1000 subjects), and 89 children (10.1/1000 subjects) were diagnosed with CHD. The prevalence of an echocardiographic abnormality did not change over the 12-year period (Kendall's tau=-0.272, p=0.19).CONCLUSIONS: CHD which could not be identified by prenatal echocardiography and neonatal auscultation could be detected in a substantial number of young children by echocardiographic screening. Echocardiographic screening may be useful for early diagnosis of CHD. However, our study is based on cross-sectional data without follow-up. Larger prospective studies are needed to verify the utility of echocardiographic screening with follow-up data in this cohort.
Peyman Naji, Brian P. Griffin, Joseph F. Sabik, Kenya Kusunose, Fadi Asfahan, Zoran B. Popovic, L Leonardo Rodriguez, Bruce W. Lytle, Richard A. Grimm, Lars G. Svensson and Milind Y. Desai : Characteristics and Outcomes of Patients With Severe Bioprosthetic Aortic Valve Stenosis Undergoing Redo Surgical Aortic Valve Replacement., Circulation, Vol.132, No.21, 1953-1960, 2015.
(Summary)
With improved event-free survival of patients undergoing primary bioprosthetic aortic valve replacement (AVR), reoperation to relieve severe prosthetic aortic stenosis (PAS) is increasing. We sought to (1) identify of the characteristics of patients with severe bioprosthetic PAS undergoing redo AVR, and (2) assess the outcomes of these patients, along with factors associated with adverse outcomes. We studied 276 patients with severe bioprosthetic PAS (64±16 years, 58% men) who underwent redo-AVR between 2000 and 2012 (excluding mechanical PAS, severe other valve disease, and transcatheter AVR). Society of Thoracic Surgeons score was calculated. Severe PAS was defined as AV area <0.8 cm(2), mean AV gradient ≥40 mm Hg, or dimensionless index <0.25. A composite outcome of death and congestive heart failure admission was recorded. Mean Society of Thoracic Surgeons score and mean AV gradients were 8±8 and 53±17 mm Hg, whereas 28% had >II+ aortic regurgitation. Only 39% had an isolated redo AVR, the rest were combination surgeries (coronary bypass and/or aortic surgeries). At 4.2±3 years, 64 (23%) patients met the composite end point (48 deaths and 19 congestive heart failure admissions, 2.5% 30-day deaths). On multivariable Cox survival analysis, higher Society of Thoracic Surgeons score (hazard ratio, 1.35), higher grades of aortic regurgitation (hazard ratio, 1.29), and higher right ventricular systolic pressure (hazard ratio, 1.3) were associated with worse longer-term outcomes (all P<0.01). At an experienced center, in patients with severe bioprosthetic PAS undergoing redo AVR, the majority undergo combination surgeries but have excellent outcomes.
Yukina Hirata, Hirotsugu Yamada, Kenya Kusunose, Takashi Iwase, Susumu Nishio, Shuji Hayashi, Mika Bando, Rie Amano, Koji Yamaguchi, Takeshi Soeki, Tetsuzo Wakatsuki and Masataka Sata : Clinical Utility of Measuring Epicardial Adipose Tissue Thickness with Echocardiography Using a High-Frequency Linear Probe in Patients with Coronary Artery Disease., Journal of the American Society of Echocardiography, Vol.28, No.10, 1240-1246.e1, 2015.
(Summary)
The relationship between epicardial adipose tissue (EAT) and coronary artery disease (CAD) has recently attracted a great deal of attention in the medical community. The objective of this study was to determine whether measuring EAT thickness in the anterior interventricular groove (AIG) using echocardiography is feasible and whether this index can be a marker of CAD. A total of 311 patients (mean age, 67 ± 11 years; 208 men) who underwent coronary angiography between December 2011 and December 2013 were prospectively enrolled. EAT-AIG thickness and EAT thickness on the free wall of the right ventricle (RV) were measured in systole using a high-frequency linear probe. Seventy-one patients who underwent multidetector-row computed tomography were enrolled to validate the method for measuring EAT thickness using echocardiography. Subjects were divided into two groups, those with and without significant coronary stenosis, on the basis of findings on coronary angiography (≥ 75% luminal narrowing). EAT-AIG thickness measured using echocardiography was validated by computed tomography. EAT-AIG thickness was strongly correlated with EAT volume (r = 0.714, P < .001). The CAD group had thicker EAT-AIG than the non-CAD group (8.3 ± 3.0 vs 6.3 ± 2.5 mm, P < .001). EAT-RV thickness was greater in the CAD group than in the non-CAD group (5.0 ± 2.1 vs 4.4 ± 2.3 mm, P = .009) as well. The area under the curve on receiver operating characteristic curve analysis of EAT-AIG thickness for predicting CAD was 0.704, which was higher than the EAT-RV thickness. Measuring EAT thickness using echocardiography with a high-frequency linear probe was validated with computed tomography. EAT-AIG was thicker in the CAD group than in the non-CAD group, as was EAT-RV thickness. This noninvasive index may have potential as a diagnostic marker for predicting coronary atherosclerosis.
Kenya Kusunose, Hirotsugu Yamada, Junko Hotsuchi, Mika Bando, Susumu Nishio, Yukina Hirata, Takayuki Ise, Koji Yamaguchi, Shusuke Yagi, Takeshi Soeki, Tetsuzo Wakatsuki, Jun Kishi and Masataka Sata : Prediction of Future Overt Pulmonary Hypertension by 6-Min Walk Stress Echocardiography in Patients With Connective Tissue Disease., Journal of the American College of Cardiology, Vol.66, No.4, 376-384, 2015.
(Summary)
BACKGROUND: Early detection of pulmonary hypertension (PH) in connective tissue disease (CTD) is crucial to ensuring that patients receive timely treatment for this progressive disease. Exercise stress tests have been used to screen patients in an attempt to identify early-stage PH. Recent studies have described abnormal mean pulmonary artery pressure (mPAP)-cardiac output (Q) responses as having the potential to assess the disease state.OBJECTIVES: This study hypothesized that pulmonary circulation pressure-flow relationships obtained by 6-min walk (6MW) stress echocardiography would better delineate differential progression of PH and predict development of PH during follow-up.METHODS: We prospectively performed 6MW stress echocardiographic studies in 78 CTD patients (age 58 ± 12 years; 9% male) at baseline and follow-up. All patients underwent yearly echocardiographic follow-up studies for up to 5 years.RESULTS: During a median period of 32 months (range: 15 to 62 months), 16 patients reached the clinical endpoint of development of PH and none died during follow-up. PH was confirmed by right heart catheterization in all 16 patients (mPAP 25 mm Hg and pulmonary capillary wedge pressure 15 mm Hg). In a Cox proportional-hazards survival model, 6MW distance (hazard ratio [HR]: 0.99; p = 0.010), early diastolic tricuspid annulus motion velocity (HR: 0.79; p = 0.025), and mPAP/Q by 6MW stress (HR: 1.10; p = 0.005) were associated with development of PH. In sequential Cox models, a model on the basis of 6MW distance (chi-square, 6.6) was improved by mPAP/Q (chi-square: 14.4; p = 0.019). Using a receiver-operating characteristic curve, we found that the best cutoff value of mPAP/Q for predicting development of pulmonary hypertension was >3.3 mm Hg/l/min.CONCLUSIONS: The 6MW stress echocardiography noninvasively provides an incremental prognostic value of PH development in CTD. This is a single-center prospective cohort study. Larger multicenter studies are warranted to confirm this result.
Mika Bando, Hirotsugu Yamada, Kenya Kusunose, Daiju Fukuda, Rie Amano, Rina Tamai, Yuta Torii, Yukina Hirata, Susumu Nishio, Koji Yamaguchi, Takeshi Soeki, Tetsuzo Wakatsuki and Masataka Sata : Comparison of carotid plaque tissue characteristics in patients with acute coronary syndrome or stable angina pectoris: assessment by iPlaque, transcutaneous carotid ultrasonography with integrated backscatter analysis., Cardiovascular Ultrasound, Vol.13, No.1, 34, 2015.
(Summary)
BACKGROUND: The association of the tissue characteristics of carotid plaques with coronary artery disease has attracted interest. The present study compared the tissue characteristics of carotid plaques in patients with acute coronary syndrome (ACS) with those in patients with stable angina pectoris (SAP) using the iPlaque system, which is based on ultrasound integrated backscatter.METHODS AND RESULTS: Carotid ultrasound examinations were performed in 26 patients with ACS, and 38 age- and gender-matched patients with SAP. Neither plaque area nor maximal intima-media thickness differed significantly between the two groups. However, the average integrated backscatter value within the plaque was greater in the ACS patients than in the SAP patients. iPlaque analysis revealed that the percentage blue area (lipid pool) was greater in the ACS patients than in the SAP patients (43.4±11.2 vs 18.3±10.3 %, p<0.0001), and that the percentage green area (fibrosis) was lower in the ACS than in the SAP patients (7.5±7.5 % vs 20.7±11.7 %, p<0.0001).CONCLUSIONS: The lipid component of carotid plaques is greater in ACS patients than in SAP patients. Our iPlaque system provides a useful and feasible method for the tissue characterization of carotid plaques in the clinical setting.
Hiromu Yamazaki, Koji Yamaguchi, Takeshi Soeki, Tetsuzo Wakatsuki, Toshiyuki Niki, Yoshio Taketani, Atsunori Kitaoka, Kenya Kusunose, Takayuki Ise, Takeshi Tobiume, Shusuke Yagi, Takashi Iwase, Hirotsugu Yamada and Masataka Sata : Impact of indoxyl sulfate, a uremic toxin, on non-culprit coronary plaque composition assessed by integrated backscatter intravascular ultrasound., Circulation Journal, Vol.79, No.8, 1773-1779, 2015.
(Summary)
BACKGROUND: Uremic toxin has emerged as an important determinant of cardiovascular risk. The aim of this study was to examine the relationship between serum uremic toxin and coronary plaque composition on integrated backscatter intravascular ultrasound (IB-IVUS).MethodsandResults:IB-IVUS was performed in 47 patients with planned treatment for angina pectoris. Non-culprit intermediate plaque analyzed in this study had to be >5 mm apart from the intervention site. 3-D IB-IVUS analysis was performed to determine percent lipid volume (LV) and fibrous volume (FV). We also measured serum uremic toxins (indoxyl sulfate [IS], asymmetric dimethylarginine [ADMA], and p-cresol [PC]). Glomerular filtration rate correlated with IS (r=-0.329, P=0.04), but did not correlate with ADMA or PC. Percent LV correlated with IS (r=0.365, P=0.02), but did not correlate with ADMA or PC. Percent FV also correlated with IS (r=-0.356, P=0.03), but did not correlate with ADMA or PC. On multivariate regression, only IS was associated with percent LV (r=0.359, P=0.04) and percent FV (r=-0.305, P=0.04) independently of potentially confounding coronary risk factors.CONCLUSIONS: Among the uremic toxins, serum IS might be a novel useful biomarker to detect and monitor lipid-rich coronary plaque on IB imaging. (Circ J 2015; 79: 1773-1779).
Jae-Hyeong Park, Kenya Kusunose, Hirohiko Motoki, Deborah H. Kwon, Richard A. Grimm, Brian P. Griffin, Thomas H. Marwick and Zoran B. Popović : Assessment of Right Ventricular Longitudinal Strain in Patients with Ischemic Cardiomyopathy: Head-to-Head Comparison between Two-Dimensional Speckle-Based Strain and Velocity Vector Imaging Using Volumetric Assessment by Cardiac Magnetic Resonance as a "Gold Standard"., Echocardiography, Vol.32, No.6, 956-965, 2015.
(Summary)
Longitudinal strain of right ventricle (RV) can be used to determine RV systolic function. This study compared RV longitudinal strain values of two different speckle tracking software technologies, velocity vector imaging (VVI) and two-dimensional speckle tracking echocardiography (2DSTE), and longitudinal strain by cardiac magnetic resonance (CMR). We studied 36 patients (28 men, 63 ± 11 years) with ischemic cardiomyopathy (ICM) who underwent echocardiography with GE machines and CMR. Longitudinal strain of RV analyzed with 2DSTE and VVI in same DICOM files. Longitudinal RV strain analyzed with 2DSTE and VVI in same raw data. These values were compared with RVEF and longitudinal strain by CMR. VVI strain showed significant correlations with RVEF by CMR (global RV: r = -0.56, P < 0.01, free wall: r = -0.52, P < 0.01, and septum: r = -0.49, P < 0.01). 2DSTE strain also revealed significant correlations (global RV: r = -0.40, P = 0.02, and septum: r = -0.35, P = 0.04). 2DSTE strain had significant bias with wide limits of agreement in global RV and septum compared with CMR strain. 2DSTE strain had significantly lower intra-observer variability than VVI (P = 0.03) or CMR strain (P = 0.04) in RV-free wall. RV longitudinal strains by VVI and 2SDTE demonstrated relatively good correlations with RVEF and longitudinal strain by CMR. However, when compared to CMR-derived strain, 2DSTE-derived strain underestimates longitudinal strain of RV septum and of global right ventricle. 2DSTE strain had significantly lower intra-observer variability compared with VVI or CMR strain analysis.
Kenya Kusunose, Junko Hotsuchi, Y Takagawa, S Nishio, Takayuki Ise, Takeshi Tobiume, Koji Yamaguchi, Shusuke Yagi, Takashi Iwase, Hirotsugu Yamada, Takeshi Soeki, Tetsuzo Wakatsuki and Masataka Sata : Serial imaging changes during treatment of immunoglobulin G4-related disease with multiple pseudotumors., Circulation, Vol.131, No.21, 1882-1883, 2015.
Jae-Hyeong Park, Kenya Kusunose, Deborah H. Kwon, Margaret M. Park, Serpil C. Erzurum, James D. Thomas, Richard A. Grimm, Brian P. Griffin, Thomas H. Marwick and Zoran B. Popović : Relationship between Right Ventricular Longitudinal Strain, Invasive Hemodynamics, and Functional Assessment in Pulmonary Arterial Hypertension., Korean Circulation Journal, Vol.45, No.5, 398-407, 2015.
(Summary)
Right ventricular longitudinal strain (RVLS) is a new parameter of RV function. We evaluated the relationship of RVLS by speckle-tracking echocardiography with functional and invasive parameters in pulmonary arterial hypertension (PAH) patients. Thirty four patients with World Health Organization group 1 PAH (29 females, mean age 45±13 years old). RVLS were analyzed with velocity vector imaging. Patients with advanced symptoms {New York Heart Association (NYHA) functional class III/IV} had impaired RVLS in global RV (RVLSglobal, -17±5 vs. -12±3%, p<0.01) and RV free wall (RVLSFW, -19±5 vs. -14±4%, p<0.01 to NYHA class I/II). Baseline RVLSglobal and RVLSFW showed significant correlation with 6-minute walking distance (r=-0.54 and r=-0.57, p<0.01 respectively) and logarithmic transformation of brain natriuretic peptide concentration (r=0.65 and r=0.65, p<0.01, respectively). These revealed significant correlations with cardiac index (r=-0.50 and r=-0.47, p<0.01, respectively) and pulmonary vascular resistance (PVR, r=0.45 and r=0.45, p=0.01, respectively). During a median follow-up of 33 months, 25 patients (74%) had follow-up examinations. Mean pulmonary arterial pressure (mPAP, 54±13 to 46±16 mmHg, p=0.03) and PVR (11±5 to 6±2 wood units, p<0.01) were significantly decreased with pulmonary vasodilator treatment. RVLSglobal (-12±5 to -16±5%, p<0.01) and RVLSFW (-14±5 to -18±5%, p<0.01) were significantly improved. The decrease of mPAP was significantly correlated with improvement of RVLSglobal (r=0.45, p<0.01) and RVLSFW (r=0.43, p<0.01). The PVR change demonstrated significant correlation with improvement of RVLSglobal (r=0.40, p<0.01). RVLS correlates with functional and invasive hemodynamic parameters in PAH patients. Decrease of mPAP and PVR as a result of treatment was associated with improvement of RVLS.
Michael A. Bolen, Prabhakar Rajiah, Kenya Kusunose, Patrick Collier, Allan Klein, Zoran B. Popović and Scott D. Flamm : Cardiac MR imaging in constrictive pericarditis: multiparametric assessment in patients with surgically proven constriction., The International Journal of Cardiovascular Imaging, Vol.31, No.4, 859-866, 2015.
(Summary)
To assess the utility of cardiac magnetic resonance (MR) imaging in the diagnosis of constrictive pericarditis (CP). This study was approved by the institutional review board, with a waiver of informed consent. A total of 42 consecutive patients (mean age, 55 ± 16 years; 3 women, 39 men) with CP treated with pericardiectomy who had undergone cardiac MR before surgery were evaluated retrospectively. An additional 21 patients were evaluated as a control group; of these, 10 consecutive patients received cardiac MR for reasons other than suspected pericardial disease, and 11 consecutive patients had a history of pericarditis but no clinical suspicion of pericardial constriction. MR imaging parameters were analyzed independently and with a decision tree algorithm for usefulness in the prediction of CP. Catheterization data were also reviewed when available. A model combining pericardial thickness and relative interventricular septal (IVS) excursion provided the best overall performance in prediction of CP (C statistic, 0.98, 100% sensitivity, 90% specificity). Several individual parameters also showed strong predictive value in the assessment of constriction, including relative IVS excursion (sensitivity, 93%; specificity, 95%), pericardial thickness (sensitivity, 83%; specificity, 100%), qualitative assessment of pathologic coupling (sensitivity, 88%; specificity, 100%), diastolic IVS bounce (sensitivity, 90%; specificity, 85%), left ventricle area change (sensitivity, 86%; specificity, 100%), and eccentricity index (sensitivity, 86%; specificity, 90%; all P < 0.001). Strong agreement was observed between catheterization and surgical findings of constriction (97%). Cardiac MR provides robust quantitative and qualitative analysis for the diagnosis of CP.
(Keyword)
Adult / Aged / Algorithms / Cardiac Catheterization / Cardiac Output / Central Venous Pressure / Decision Trees / Female / Humans / Magnetic Resonance Imaging, Cine / Male / Middle Aged / Pericardiectomy / Pericarditis, Constrictive / Pericardium / Predictive Value of Tests / Pulmonary Wedge Pressure / Retrospective Studies / Treatment Outcome / Ventricular Function, Left / Ventricular Function, Right / Ventricular Pressure
Takeshi Soeki, Koji Yamaguchi, Toshiyuki Niki, E Uematsu, S Bando, T Matsuura, Takayuki Ise, Kenya Kusunose, Junko Hotsuchi, Takeshi Tobiume, Shusuke Yagi, Daiju Fukuda, Yoshio Taketani, Takashi Iwase, Hirotsugu Yamada, Tetsuzo Wakatsuki, Michio Shimabukuro and Masataka Sata : Plasma microRNA-100 is associated with coronary plaque vulnerability., Circulation Journal, Vol.79, No.2, 413-418, 2015.
(Summary)
BACKGROUND: Although numerous studies have reported altered plasma levels of various microRNAs (miRNAs) in patients with cardiovascular disease, there are no data on the relationship between plasma miRNAs and vulnerable coronary plaque. In this study, we investigated whether plasma miRNAs might be a sensitive marker of coronary plaque vulnerability.MethodsandResults:Integrated backscatter intravascular ultrasound (IB-IVUS) was performed in 32 consecutive patients with angina pectoris who underwent percutaneous coronary intervention. Three-dimensional analysis of IB-IVUS was performed to determine the percentage of lipid volume (%LV) and fibrous volume (%FV). Circulating miRNAs were measured in EDTA-plasma simultaneously obtained from the aorta and the coronary sinus (CS). Muscle-enriched (miR-133a, miR-208a, miR-499), vascular-enriched (miR-92a, miR-100, miR-126, miR-127, miR-145), and myeloid cell-enriched miRNAs (miR-155, miR-223) were measured. Plasma miR-100 was higher in the CS than in the aorta, but there were no significant differences in the levels of other miRNAs between the aorta and CS. Plasma miR-100 in the aorta was positively correlated with %LV (r=0.48, P<0.01) and negatively correlated with %FV (r=-0.41, P<0.05). Importantly, transcoronary concentration gradient of circulating miR-100 was more strongly correlated with %LV (r=0.53, P<0.01) and %FV (r=-0.56, P<0.01).CONCLUSIONS: miR-100 might be released into the coronary circulation from vulnerable coronary plaques. This study provides insights into the role of miRNAs in coronary atherosclerotic disease. (Circ J 2015; 79: 413-418).
Danai Khemasuwan, Teerapat Yingchoncharoen, Pichapong Tunsupon, Kenya Kusunose, Ajit Moghekar, Allan Klein and Adriano R. Tonelli : Right ventricular echocardiographic parameters are associated with mortality after acute pulmonary embolism., Journal of the American Society of Echocardiography, Vol.28, No.3, 355-362, 2015.
(Summary)
There is limited information on the utility of certain echocardiographic measurements, such as right ventricular (RV) strain analysis, in predicting mortality in patients with acute pulmonary embolism (PE). A total of 211 patients with acute PE admitted to a medical intensive care unit (ICU) were retrospectively identified. Echocardiographic variables were prospectively measured in this cohort. The focus was on ICU, hospital, and long-term mortality. The mean age was 61 ± 15 years. Median Acute Physiology and Chronic Health Evaluation IV and simplified Pulmonary Embolism Severity Index scores were 60 (interquartile range, 40-71) and 2 (interquartile range, 1-2), respectively. Thirty-eight patients (18%) died during the sentinel hospitalization (13% died in the ICU). A total of 61 patients (28.9%) died during a median follow-up period of 15 months (interquartile range, 5-26 months). The echocardiographic variables associated with long-term mortality (from PE diagnosis) were ratio of RV to left ventricular end-diastolic diameter (hazard ratio [HR], 2.4; 95% confidence interval [CI], 1.2-4.8), tricuspid annular plane systolic excursion (HR, 0.53; 95% CI, 0.31-0.92), and RV-right atrial gradient (HR, 1.02; 95% CI, 1.01-1.4). ICU mortality was associated with ratio of RV to LV end-diastolic diameter (HR, 4.4; 95% CI, 1.3-15), RV systolic pressure (HR, 1.03; 95% CI, 1.01-1.05), tricuspid annular plane systolic excursion (HR, 0.4; 95% CI, 0.18-0.9), and inferior vena cava collapsibility < 50% (HR, 4.3; 95% CI, 1.7-11). These variables remain significantly associated with mortality after adjusting by Acute Physiology and Chronic Health Evaluation IV score, Pulmonary Embolism Severity Index score, or the use of thrombolytic agents. RV strain parameters were not correlated with hospital or long-term mortality. Four simple parameters that measure different aspects of the right ventricle (ratio of RV to left ventricular end-diastolic diameter, RV systolic pressure, tricuspid annular plane systolic excursion, and inferior vena cava collapsibility) were independently associated with mortality in patients presenting with acute PE who were admitted to the ICU.
Kenya Kusunose, Paul C. Cremer, Rayji S. Tsutsui, Richard A. Grimm, James D. Thomas, Brian P. Griffin and Zoran B. Popović : Regurgitant volume informs rate of progressive cardiac dysfunction in asymptomatic patients with chronic aortic or mitral regurgitation., JACC. Cardiovascular Imaging, Vol.8, No.1, 14-23, 2015.
(Summary)
This study hypothesized that regurgitation severity, as determined by using the regurgitant volume index, would better delineate differential cardiac dysfunction in asymptomatic patients with moderate to severe aortic regurgitation (AR) and mitral regurgitation (MR). Frequent surveillance echocardiography is considered appropriate in asymptomatic patients with moderate to severe AR and MR. However, the evidence to support this practice and to define the appropriate frequency is limited. This was an observational cohort study of consecutive patients with moderate to severe asymptomatic AR or MR who underwent exercise echocardiography. Our cohort included 130 patients with moderate to severe asymptomatic MR and 130 patients with moderate to severe asymptomatic AR who were matched according to age and regurgitant volume index. All patients underwent yearly echocardiographic follow-up studies. Regurgitation severity was determined according to regurgitant volume index, with a level ≥30 ml/m(2) considered a marker of severe regurgitation. During follow-up, regardless of etiology, patients with severe regurgitation demonstrated increasing left ventricular volume indexes (4.2 ± 1.5 ml/m(2) per year; p = 0.01) and decreasing left ventricular ejection fractions (1.3 ± 0.4% per year; p = 0.002). In patients with moderate regurgitation, left ventricular volumes and ejection fractions did not significantly change. In addition, patients with severe regurgitation experienced a similar drop in contractility (end-systolic pressure/end-systolic volume ratio and single-beat pre-load recruitable stroke work) during follow-up independent of regurgitation etiology. Contractility parameters did not change in patients with moderate regurgitation. These asymptomatic patients with moderate AR or MR had stable cardiac function during 3 years of follow-up; thus, frequent echocardiography without a change in clinical status may not be necessary. In the setting of severe regurgitation, further cardiac deterioration occurred at a similar rate and manner irrespective of whether the dysfunction was related to AR or MR.
Takeshi Soeki, Kunihiko Koshiba, Toshiyuki Niki, Kenya Kusunose, Koji Yamaguchi, Hirotsugu Yamada, Tetsuzo Wakatsuki, Michio Shimabukuro, Kazuo Minakuchi, I Kishimoto, Kenji Kangawa and Masataka Sata : Effect of ghrelin on autonomic activity in healthy volunteers., Peptides, Vol.62, 1-5, 2014.
(Summary)
Ghrelin is a novel growth hormone (GH)-releasing peptide originally isolated from the stomach. Recently, we have shown that ghrelin suppresses cardiac sympathetic activity and prevents early left ventricular remodeling in rats with myocardial infarction. In the present study, we evaluated the effect of ghrelin on autonomic nerve activity in healthy human subjects. An intravenous bolus of human synthetic ghrelin (10g/kg) was administered to 10 healthy men (mean age, 33 years). Holter monitoring assessment was performed before and during 2h after the ghrelin therapy. The standard deviation of normal RR intervals (SDNN), square root of the mean of the sum of the squares of differences between adjacent RR intervals (rMSSD), high-frequency power (HF), and low-frequency power (LF) were analyzed. Blood samples were also obtained before and after the therapy. A single administration of ghrelin decreased both heart rate and blood pressure. Interestingly, ghrelin significantly decreased the LF and LF/HF ratio of heart rate variability and increased the SDNN, rMSSD, and HF. Ghrelin also elicited a marked increase in circulating GH, but not insulin-like growth factor-1. These data suggest that ghrelin might suppress cardiac sympathetic nerve activity and stimulate cardiac parasympathetic nerve activity.
Koji Yamaguchi, Tetsuzo Wakatsuki, Takeshi Soeki, Toshiyuki Niki, Yoshio Taketani, Hiroyasu Oeduka, Kenya Kusunose, Takayuki Ise, Takashi Iwase, Hirotsugu Yamada and Masataka Sata : Effects of telmisartan on inflammatory cytokines and coronary plaque component as assessed on integrated backscatter intravascular ultrasound in hypertensive patients., Circulation Journal, Vol.78, No.1, 240-247, 2014.
(Summary)
Telmisartan has unique pleiotropic effects in addition to renin-angiotensin system (RAS)-inhibition effects. The aim of this study was to evaluate the effects of telmisartan on the coronary plaque component and local inflammatory cytokines. A total of 50 patients with hypertension were randomized to 2 groups: the telmisartan group (additional treatment with telmisartan 80mg/day, n=25) or the control group (additional treatment with other anti-hypertensive drugs except RAS blockers, n=25) for 6 months. Tissue characteristics of target coronary plaque were analyzed using integrated backscatter intravascular ultrasound (IB-IVUS) before and after treatment. Plasma levels of inflammatory cytokines sampled in the coronary sinus (CS) and peripheral vein were also measured. Significant increases in fibrous volume (51.2±10.4 to 58.3±7.7%, P=0.03) and reductions in lipid volume (38.4±12.4 to 32.8±9.7%, P=0.03) were observed on IB in the telmisartan group, while there were no significant changes in the plaque component in the control group. CS levels of inflammatory cytokines (matrix metalloproteinase [MMP]3, tumor necrosis factor-, high-sensitivity C-reactive protein and MMP9) were lower after than before treatment in the only telmisartan group (7.7±6.1 to 5.5±4.9ng/ml, 3.1±1.9 to 2.3±2.0pg/ml, 5.6±6.0 to 2.2±2.4mg/L, 36.1±39.3 to 19.9±27.5ng/ml, P=0.02, P=0.03, P=0.04, P=0.07, respectively). Decreased local inflammatory response and plaque stabilization on IB imaging were observed after 6 months of telmisartan treatment. These findings might be associated with local anti-inflammatory and anti-arteriosclerotic effects of telmisartan.
Kenya Kusunose, Andrew Goodman, Roosha Parikh, Tyler Barr, Shikhar Agarwal, Zoran B. Popovic, Richard A. Grimm, Brian P. Griffin and Milind Y. Desai : Incremental prognostic value of left ventricular global longitudinal strain in patients with aortic stenosis and preserved ejection fraction., Circulation. Cardiovascular Imaging, Vol.7, No.6, 938-945, 2014.
(Summary)
We sought to assess the utility of left ventricular global longitudinal strain (LV-GLS) in predicting mortality in moderate to severe and paradoxical severe aortic stenosis (AS) patients with preserved ejection fraction. We studied 395 AS patients (70 ± 14 years, 57% men) with aortic valve area <1.3 cm(2) evaluated between January to June 2008 (excluding severe other valve disease and LV ejection fraction <50%). Clinical and echocardiographic data were recorded. LV-GLS was analyzed using Velocity Vector Imaging. AS patients were classified as (a) moderate-severe (n=93; aortic valve area, 1.1-1.3 cm(2)), (b) standard severe (n=161; aortic valve area, ≤1 cm(2); mean gradient ≥40 mm Hg), and (c) paradoxical severe (n=141; aortic valve area, ≤1 cm2 and mean gradient <40 mm Hg). Additive Euroscore was 7 ± 3. The association of LV-GLS with all-cause mortality was assessed after risk-adjustment using Cox proportional hazards models. Median LV-GLS was -14.8% (interquartile range, -17.2%, -12.1%). At 4.4±1.4 years, there were 92 (23%) deaths. On multivariable Cox analysis, additive Euroscore (hazard ratio, 1.19; 1.13-1.27; P<0.001), New York Heart Association class (hazard ratio, 1.44; 1.11-1.87; P<0.001), AV surgery with time-dependent covariate analysis (hazard ratio, 0.29; 0.19-0.45; P<0.001), and LV-GLS (hazard ratio, 1.05; 1.03-1.07; P<0.001) were independent predictors of mortality. LV-GLS <-12.1% (4th quartile) was associated with significantly reduced survival. Addition of LV-GLS to clinical parameters (additive Euroscore+New York Heart Association class) led to significant improvement in prediction of mortality (χ(2) increased from 48 to 58; P<0.01). LV-GLS independently predicts mortality in moderate-severe and severe AS patients with preserved LV ejection fraction, providing incremental prognostic utility, in addition to standard clinical and echocardiographic parameters.
(Keyword)
Aged / Aged, 80 and over / Aortic Valve Stenosis / Chi-Square Distribution / Echocardiography, Doppler, Pulsed / Female / Humans / Linear Models / Male / Middle Aged / Multivariate Analysis / Nonlinear Dynamics / Predictive Value of Tests / Prognosis / Proportional Hazards Models / Retrospective Studies / Risk Assessment / Risk Factors / Severity of Illness Index / Stroke Volume / Time Factors / Ventricular Function, Left
Kenya Kusunose, N Tomita, S Nishio, Mika Bando, S Hayashi, Junko Hotsuchi, Takashi Iwase, Hirotsugu Yamada and Masataka Sata : Left main coronary artery compression syndrome with an incomplete atrioventricular septal defect presenting as angina induced by hyperthyroidism., Internal Medicine, Vol.53, No.18, 2083-2085, 2014.
(Summary)
We herein report the case of a 29-year-old woman who was diagnosed with incomplete atrioventricular septal defect and extrinsic compression of the left main coronary artery (LMCA) with chest pain due to postpartum thyroiditis. She exhibited chest pain with ST elevation, and coronary computed tomography showed that the LMCA was compressed between the dilated pulmonary artery and aorta. After her hyperthyroidism was treated, her chest pain resolved. Surgical repair of endocardiosis and coronary bypass grafting were performed. On the one-year follow-up visit, the dilation of the pulmonary artery and right heart was decreased. It is important to consider the possibility of compression of the LMCA in patients presenting with pulmonary hypertension and chest pain.
(Keyword)
left main compression syndrome / congenital heart disease / postpartum thyroiditis
Takeshi Soeki, S Bando, E Uematsu, T Matsuura, Toshiyuki Niki, Takayuki Ise, Kenya Kusunose, Junko Hotsuchi, Yuka Ueda, N Tomita, Koji Yamaguchi, Shusuke Yagi, Daiju Fukuda, Yoshio Taketani, Takashi Iwase, Hirotsugu Yamada, Tetsuzo Wakatsuki, Michio Shimabukuro and Masataka Sata : Pentraxin 3 is a local inflammatory marker in atrial fibrillation., Heart and Vessels, Vol.29, No.5, 653-658, 2014.
(Summary)
Increasing evidence indicates that inflammation contributes to the pathogenesis of atrial fibrillation (AF). Pentraxin 3 (PTX3) is produced abundantly in local inflammatory lesions while C-reactive protein (CRP) is produced mainly in the liver. In this study, we investigated whether a local level of PTX3 might be a sensitive marker for the local inflammation of AF. Blood from the periphery and left atrial appendage (LAA) was sampled from 23 patients with AF undergoing pulmonary vein isolation, and from 10 control subjects with Wolff-Parkinson-White syndrome. We measured peripheral and LAA plasma concentrations of CRP, interleukin-6 (IL-6), tumor necrosis factor- (TNF-), and PTX3. Plasma PTX3 concentrations in both locations were higher in patients with AF than in control subjects. PTX3 concentrations were significantly higher in the LAA than the periphery in patients with AF (3.7 ± 1.4 vs 3.3 ± 1.2 ng/ml, P < 0.01), but not in control subjects (2.4 ± 0.5 vs 2.4 ± 0.5 ng/ml, not significant). Patients and controls showed no significant differences in CRP, IL-6, or TNF- concentrations between the periphery and LAA. Interestingly, there was a significant positive correlation between LAA plasma concentrations of PTX3 and left atrial volume (r = 0.55, P < 0.01). These data demonstrate that Local PTX3 production in the left atrium might reflect the local inflammation of AF.
S Nishio, Kenya Kusunose, Hirotsugu Yamada, Junko Hotsuchi, S Hayashi, Mika Bando, Y Saijo, Y Hirata, M Abe and Masataka Sata : Multimodality imaging of biatrial myxomas in an asymptomatic patient., Journal of Cardiology Cases, Vol.10, No.3, 85-87, 2014.
(Summary)
Myxomas are located in the left atrium in 7580% of cases and almost always present with signs and symptoms of a thromboembolic event. Biatrial myxomas are rare, and their incidence is generally less than 2.5% of all myxomas. We herein present a case of biatrial myxomas as an incidental finding by echocardiography where the patient underwent surgery. Echocardiography continues to be the initial imaging modality for intracardiac masses. Cardiac magnetic resonance provides superior tissue characterization, particularly important in differentiating a myxoma from a thrombus. Appropriate use of these non-invasive imaging modalities may lead to a correct diagnosis and good outcome.
Hirotsugu Yamada, Kenya Kusunose, S Nishio, Mika Bando, Junko Hotsuchi, S Hayashi, Takayuki Ise, Shusuke Yagi, Koji Yamaguchi, Takashi Iwase, Takeshi Soeki, Tetsuzo Wakatsuki and Masataka Sata : Pre-load stress echocardiography for predicting the prognosis in mild heart failure., JACC. Cardiovascular Imaging, Vol.7, No.7, 641-649, 2014.
Kenya Kusunose, T Chono, Tomotsugu Tabata, Hirotsugu Yamada and Masataka Sata : Echocardiographic image tracker with a speckle adaptive noise reduction filter for the automatic measurement of the left atrial volume curve., European Heart Journal Cardiovascular Imaging, Vol.15, No.5, 509-514, 2014.
(Summary)
Aims: Since tracking accuracy in left atrial (LA) images decreases due to low image quality around the LA in the apical view, a practical tracking method for LA images has not yet been proposed. The aim of this study was to assess an accurate and high-speed LA volume tracking (LAVT) method for the automatic measurement of LA volume (LAV) curves. Methods and results: We used three approved protocols in this study: (i) LAV curves were measured by LAVT on computer-simulated images; (ii) in 20 healthy volunteers, we assessed the feasibility and accuracy of this method compared with expert's measurements; and (iii) echocardiography and multi-detector row computed tomography (MDCT) imaging were performed on the same day in 20 patients with suspected coronary artery disease. On computer-simulated images, mean absolute percentage LAVT error in one cardiac cycle was 3% in filtered images and 16% in original images. In 20 healthy volunteers, there are strong correlations between LAVT and the expert's LA measurements (LA maximum volume; R = 0.93, P < 0.001). In 400 LA images with 20 patients, an excellent correlation was obtained between LAVs using echocardiography and MDCT (R = 0.98, P < 0.001), with a small bias (14% of the mean) and narrow limits of agreement (+15% of the mean). The mean time required for the LAVT analysis was 1.8 min, for the MDCT analysis was 35.8 min, and for the manual echocardiographic analysis was 14.0 min. Conclusion: This LAVT method is fast, valid, accurate, and reproducible for determining LAV in both simulated images and the clinical setting.
Kenya Kusunose, Youhua Zhang, Todor N. Mazgalev, James D. Thomas and Zoran B. Popović : Left ventricular strain distribution in healthy dogs and in dogs with tachycardia-induced dilated cardiomyopathy., Cardiovascular Ultrasound, Vol.11, 43, 2013.
(Summary)
Recently, left ventricular (LV) strain distribution pattern has been assessed in several cardiac disease states. Tachycardia-induced cardiomyopathy (TIC) is an animal model of non-ischemic cardiomyopathy well characterized in terms of global LV dysfunction but with poor understanding of regional variability in LV function. We hypothesized that TIC induces specific changes in LV strain distribution pattern. Twenty five adult mongrel conscious dogs were trained to lie down calmly for echocardiography. In seven selected dogs, we implanted pacing system for TIC induction under general anesthesia. We measured LV geometry and function, strains, and torsion before and after the development of TIC in awake non-sedated state. In 25 healthy dogs, all three types of normal strain significantly increased from base to apex (p <0.05), while a definite and recognizable twist could be measured due to presence of shear strain. In 7 dogs with TIC, marked changes in LV mechanics occurred throughout the cardiac cycle, resulting in decrease of strain (p <0.001), twist (p <0.05), and negative peak twist rate (p <0.05). Interestingly, the relative decrease of strain due to TIC was more pronounced in the apex (p < 0.001), with the radial strain decreasing the most (p < 0.05). TIC is accompanied by decreased systolic LV strain and twist deformation, as well as loss of early diastolic recoil. In addition, the decrease of strain was more profound in the apex. This "reverse" distribution of LV strain may help us understand LV dysfunction in the presence of nonischemic etiology.
Takeshi Soeki, Toshiyuki Niki, E. Uematsu, S. Bando, T. Matsuura, Kenya Kusunose, Takayuki Ise, Yuka Ueda, N. Tomita, Koji Yamaguchi, Kunihiko Koshiba, Shusuke Yagi, Daiju Fukuda, Yoshio Taketani, Takashi Iwase, Hirotsugu Yamada, Tetsuzo Wakatsuki, Masashi Akaike, Michio Shimabukuro, I. Kishimoto, Kenji Kangawa and Masataka Sata : Ghrelin protects the heart against ischemia-induced arrhythmias by preserving connexin-43 protein., Heart and Vessels, Vol.28, No.6, 795-801, 2013.
(Summary)
Vagal nerve stimulation has been postulated to confer an antifibrillatory effect. We studied whether ghrelin administration would exert an antiarrhythmic effect via modulation of autonomic nerve activity in rats after acute myocardial ischemia (MI). Male Sprague-Dawley rats were exposed to 30 min of ischemia following ligation of the left coronary artery. Animals were then randomized to receive either ghrelin (n = 26) or saline (n = 26) during the period of coronary ligation. Power spectral analysis of heart-rate variability revealed that the administration of ghrelin increased the high-frequency (HF) power and decreased the low-frequency (LF)/HF ratio. Ventricular tachyarrhythmias were less frequent in rats after MI who received ghrelin in comparison with rats that received saline. Immunoblotting and immunohistochemistry revealed that rats given saline alone during MI exhibited a marked reduction in phosphorylated connexin-43 within the left ventricle, whereas those that received ghrelin displayed only minor reductions in comparison with sham-operated rats. These effects of ghrelin were diminished by the coadministration of atropine or the blockade of vagal afferents. These data demonstrate that the beneficial effect of ghrelin might be mediated by modulation of cardiac autonomic nerve activity.
Kenya Kusunose, Deborah H. Kwon, Hirohiko Motoki, Scott D. Flamm and Thomas H. Marwick : Comparison of three-dimensional echocardiographic findings to those of magnetic resonance imaging for determination of left ventricular mass in patients with ischemic and non-ischemic cardiomyopathy., The American Journal of Cardiology, Vol.112, No.4, 604-611, 2013.
(Summary)
The standard echocardiographic evaluation of left ventricular (LV) mass, particularly in ischemic cardiomyopathy (IC) is challenging because it is based on geometric assumptions. The aim of this study was to assess the accuracy of LV mass calculation using echocardiographic modalities compared with cardiac magnetic resonance (CMR) in IC and in nonischemic cardiomyopathy (non-IC). Echocardiography was performed in 104 patients (mean age 55 ± 15 years) referred for CMR: 63 with IC and 41 with non-IC. CMR, M-mode echocardiography, 2-dimensional echocardiography, and 3-dimensional echocardiography (3DE) were analyzed using standard commercial tools to obtain LV mass. LV mass on 3DE showed a higher correlation with CMR than 2-dimensional echocardiography (r = 0.87 vs r = 0.70, p <0.001). M-mode echocardiography overestimated LV mass (bias +30%) and 2-dimensional echocardiography underestimated LV mass (bias -11%), whereas measurements on 3DE showed only minimal bias (-2%). LV mass on 3DE in non-IC showed a significantly higher correlation with CMR than in IC (r = 0.92 vs r = 0.84, z = 2.3, p <0.05). In non-IC, the mean difference was -2 g (-1% of the mean), with 95% limits of agreement of ±33 g (±19% of the mean). In IC, the mean difference was -7 g (-4% of the mean), with limits of agreement of ±56 g (±31% of the mean). There was a correlation between the absolute LV mass differences (3DE derived and CMR derived) and scar percentage (infarcted mass/total LV mass) using delayed-hyperenhancement images (r = 0.40, p <0.05). The net reclassification index with 3DE was +16% for concentric LV hypertrophy. In conclusion, the most accurate and reliable echocardiographic measurement of LV mass is 3DE, but underestimation and variability remain challenges in IC.
(Keyword)
Cardiomyopathies / Echocardiography, Three-Dimensional / Female / Humans / Hypertrophy, Left Ventricular / Magnetic Resonance Imaging / Male / Middle Aged / Myocardial Ischemia / ROC Curve / Risk Assessment
Kenya Kusunose, Hirotsugu Yamada, S. Nishio, N. Tomita, Toshiyuki Niki, Koji Yamaguchi, Yoshio Taketani, Takashi Iwase, Takeshi Soeki, Tetsuzo Wakatsuki and Masataka Sata : Interval from the Onset of Transmitral Flow to Annular Velocity Is a Marker of LV Filling Pressure., JACC. Cardiovascular Imaging, Vol.6, No.4, 528-530, 2013.
(Keyword)
Angina, Stable / Atrial Function, Left / Atrial Pressure / Cardiac Catheterization / Case-Control Studies / Echocardiography, Doppler, Color / Humans / Mitral Valve / Multivariate Analysis / Predictive Value of Tests / Prospective Studies / Time Factors / Ventricular Function, Left / Ventricular Pressure
N Tomita, Hirotsugu Yamada, S Nishio, R Tamai, Kenya Kusunose, S Hayashi, Junko Hotsuchi and Masataka Sata : Patent foramen ovale diagnosed by real-time three-dimensional contrast transesophageal echocardiography: A case report., Journal of Cardiology Cases, Vol.7, No.4, e91-e92, 2013.
(Summary)
A 67-year-old man was admitted due to insensitiveness of right upper limb and dysarthria, and treated for suspected lacunar infarction or branch atherosclerotic disease. Carotid ultrasonography showed no abnormalities, and agitated contrast transesophageal echocardiography was performed to detect patent foramen ovale (PFO). Intravenously administered microbubbles did not appear in left atrium by 2-dimensional echocardiography, while contrasts were observed in left atrium using 3-dimensional echocardiography. Real-time 3-dimensional contrast transesophageal echocardiography may be the most useful method for the diagnosis of small PFO.
Kenya Kusunose, Arun Dahiya, Zoran B. Popović, Hirohiko Motoki, M Chadi Alraies, Andrew O. Zurick, Michael A. Bolen, Deborah H. Kwon, Scott D. Flamm and Allan L. Klein : Biventricular mechanics in constrictive pericarditis comparison with restrictive cardiomyopathy and impact of pericardiectomy., Circulation. Cardiovascular Imaging, Vol.6, No.3, 399-406, 2013.
(Summary)
The aim of our study was to compare myocardial mechanics of constrictive pericarditis (CP) with restrictive cardiomyopathy (RCM), or healthy controls; to assess the impact of pericardial thickening detected by cardiac magnetic resonance on regional myocardial mechanics in CP; and to quantitate the effect of pericardiectomy on myocardial mechanics in CP. Myocardial mechanics were evaluated by 2-dimensional speckle tracking in 52 consecutive patients with CP who underwent cardiac magnetic resonance examination before pericardiectomy, 35 patients with RCM, and 26 control subjects. CP patients had selectively depressed left ventricular (LV) anterolateral wall strain (LWS) and right ventricular (RV) free wall longitudinal systolic strain (FWS) but preserved LV septal wall systolic strain (SWS). In a comparison of RCM and normals, CP patients had significantly lower regional longitudinal systolic strain ratios (CP versus RCM and normal; LVLWS/LVSWS: 0.8±0.2 versus 1.1±0.2 and 1.0±0.2; P<0.001, RVFWS/LVSWS: 0.8±0.4 vs. 1.4±0.5 and 1.2±0.2; P<0.001). LVLWS/LVSWS was more robust than the LV lateral wall to LV septal wall ratio of early diastolic velocities at the LV base (LE'/SE') in differentiating CP from RCM (area under the curve=0.91 versus 0.76; P=0.011). There was a significant inverse correlation between pericardial thickness and respective ventricular strains (P=0.001). Pericardiectomy resulted in the improvement of the depressed LVLWS/LVSWS (0.83±0.18-0.95±0.12; P<0.001). Regional longitudinal systolic strain ratios are robust novel diagnostic tools for CP. Regional myocardial mechanics inversely correlates with adjacent pericardial segment thickness detected by cardiac magnetic resonance, and pericardiectomy leads to systolic strain improvement, which is more pronounced in right ventricular and LV free walls.
(Keyword)
Aged / Analysis of Variance / Biomechanical Phenomena / Cardiomyopathy, Restrictive / Echocardiography, Doppler, Pulsed / Female / Humans / Linear Models / Magnetic Resonance Imaging / Male / Middle Aged / Myocardium / Pericardiectomy / Pericarditis, Constrictive / Predictive Value of Tests / Recovery of Function / Retrospective Studies / Stress, Mechanical / Systole / Treatment Outcome / Ventricular Function, Left / Ventricular Function, Right
Kenya Kusunose, Zoran B. Popović, Motoki Hirohiko and Thomas H. Marwick : Prognostic significance of exercise-induced right ventricular dysfunction in asymptomatic degenerative mitral regurgitation., Circulation. Cardiovascular Imaging, Vol.6, No.2, 167-176, 2013.
(Summary)
The role of exercise-induced pulmonary hypertension in decision making regarding surgical timing for asymptomatic chronic mitral regurgitation is controversial. We reasoned that the exercise-induced pulmonary hypertension response could not be interpreted without knowledge of right ventricular (RV) function. The aim of this study was to assess the role of RV measures at rest and during exercise as predictors of prognosis in asymptomatic mitral regurgitation. Comprehensive resting and exercise echocardiography was performed in 196 consecutive patients (56±13 years; 64% male) with isolated moderate to severe mitral regurgitation (effective regurgitant orifice area, 38±18 mm(2)) and preserved left ventricular function in whom initial management was expectant. Left ventricular and RV longitudinal strain were analyzed at rest using velocity vector imaging. Tricuspid annular plane systolic excursion and systolic pulmonary arterial pressure were measured at rest and during exercise. Valve surgery was performed in 88 patients (45%) over 27±15 months. After adjustment for age and sex in a Cox proportional-hazards model, exercise tricuspid annular plane systolic excursion (hazard ratio, 0.26; P<0.001), was associated with valve surgery-free survival, independent of resting left ventricular strain (hazard ratio, 1.09; P=0.027), exercise systolic pulmonary arterial pressure (hazard ratio, 1.03; P<0.001), and resting RV strain (hazard ratio, 1.10; P=0.004). In sequential Cox models, a model based on clinical data and left ventricular strain (χ(2), 15.9) was improved by RV strain and RV chamber size (χ(2), 28.8; P=0.003) and exercise systolic pulmonary arterial pressure (χ(2), 40.1; P=0.002) and further increased by exercise tricuspid annular plane systolic excursion (χ(2), 52.2; P=0.002). Exercise-induced RV dysfunction provides important incremental prognostic value in the management of asymptomatic mitral regurgitation.
(Keyword)
Adult / Aged / Arterial Pressure / Asymptomatic Diseases / Cardiac Surgical Procedures / Chi-Square Distribution / Disease-Free Survival / Echocardiography, Stress / Exercise / Exercise Test / Female / Humans / Kaplan-Meier Estimate / Linear Models / Male / Middle Aged / Mitral Valve Insufficiency / Multivariate Analysis / Prognosis / Proportional Hazards Models / Pulmonary Artery / Risk Factors / Severity of Illness Index / Tricuspid Valve / Ventricular Dysfunction, Right / Ventricular Function, Left / Ventricular Function, Right
Munkhbaatar Dagvasumberel, Michio Shimabukuro, Nishiuchi Takeshi, Junji Ueno, Shoichiro Takao, Daiju Fukuda, Hirata Yoichiro, Hirotsugu Kurobe, Takeshi Soeki, Takashi Iwase, Kenya Kusunose, Toshiyuki Niki, Koji Yamaguchi, Yoshio Taketani, Shusuke Yagi, Tomita Noriko, Hirotsugu Yamada, Tetsuzo Wakatsuki, Masafumi Harada, Tetsuya Kitagawa and Masataka Sata : Gender disparities in the association between epicardial adipose tissue volume and coronary atherosclerosis: A 3-dimensional cardiac computed tomography imaging study in Japanese subjects., Cardiovascular Diabetology, Vol.11, No.1, 106, 2012.
(Summary)
Growing evidence suggests that epicardial adipose tissue (EAT) may contribute to the development of coronary artery disease (CAD). In this study, we explored gender disparities in EAT volume (EATV) and its impact on coronary atherosclerosis. The study population consisted of 90 consecutive subjects (age: 63 ± 12 years; men: 47, women: 43) who underwent 256-slice multi-detector computed tomography (MDCT) coronary angiography. EATV was measured as the sum of cross-sectional epicardial fat area on CT images, from the lower surface of the left pulmonary artery origin to the apex. Subjects were segregated into the CAD group (coronary luminal narrowing > 50%) and non-CAD group. EATV/body surface area (BSA) was higher among men in the CAD group than in the non-CAD group (62 ± 13 vs. 33 ± 10 cm3/m2, p < 0.0001), but did not differ significantly among women in the 2 groups (49 ± 18 vs. 42 ± 9 cm3/m2, not significant). Multivariate logistic analysis showed that EATV/BSA was the single predictor for >50% coronary luminal narrowing in men (p < 0.0001). Predictors excluded were age, body mass index, hypertension, diabetes mellitus, and hyperlipidemia. Increased EATV is strongly associated with coronary atherosclerosis in men.
(Keyword)
Adipose Tissue / Age Factors / Aged / Asian Continental Ancestry Group / Body Surface Area / Chi-Square Distribution / Coronary Angiography / Coronary Artery Disease / Coronary Stenosis / Female / Health Status Disparities / Humans / Japan / Logistic Models / Male / Middle Aged / Multidetector Computed Tomography / Multivariate Analysis / Pericardium / Predictive Value of Tests / Risk Assessment / Risk Factors / Severity of Illness Index / Sex Factors
Kenya Kusunose, Hirotsugu Yamada, Susumu Nishio, Noriko Tomita, Junko Hotchi, Mika Bando, Toshiyuki Niki, Koji Yamaguchi, Yoshio Taketani, Takashi Iwase, Takeshi Soeki, Tetsuzo Wakatsuki and Masataka Sata : Index-beat Assessment of Left Ventricular Systolic and Diastolic Function during Atrial Fibrillation using Myocardial Strain and Strain Rate., Journal of the American Society of Echocardiography, Vol.25, No.9, 953-959, 2012.
(Summary)
Accurate assessment of left ventricular (LV) function in patients with atrial fibrillation (AF) remains difficult, mainly because of the beat-to-beat variability of many echocardiographic parameters. The aim of this study was to assess the hypothesis that LV function can be estimated from an index-beat echocardiographic assessment in patients with AF using myocardial strain and strain rate. A prospective study was conducted to assess 25 patients with AF (mean age, 66 ± 10 years). Peak systolic longitudinal strain (LS) and peak diastolic longitudinal strain rate (dSR) were measured using two different methods: (1) mean LS and dSR, the averages of instantaneous LS and dSR over 10 sec, and (2) index-beat LS and dSR, calculated when the ratio of the preceding (RR1) to the pre-preceding (RR2) interval was 1 (range, 0.96-1.04). These variables were compared with simultaneously measured LV pressure parameters using Millar catheters. There was a positive linear relationship between mean LS and index-beat LS at RR1/RR2 = 1 (r = 0.94, P < .001) and a positive linear relationship between mean dSR and index-beat dSR (r = 0.69, P < .001). Index-beat LS was correlated with the maximal positive derivative of LV pressure (peak +dP/dt) (r = -0.73, P < .001). Index-beat dSR was correlated with the time constant of isovolumic LV pressure decay (τ) (r = -0.63, P < .001). To investigate the independent predictors of τ, a stepwise multilinear regression analysis showed that index-beat dSR was the best predictor of τ. Index-beat parameters accurately reflect the mean values of parameters in patients with AF. These noninvasively obtained index-beat parameters are useful to assess surrogate LV function even in patients with AF.
T. Hara, Takeshi Soeki, Toshiyuki Niki, Kenya Kusunose, Koji Yamaguchi, Yoshio Taketani, Takashi Iwase, Hirotsugu Yamada, Tetsuzo Wakatsuki, Tetsuzo Wakatsuki and Masataka Sata : Bicuspid aortic valve endocarditis complicated by perivalvular abscess., The Journal of Medical Investigation : JMI, Vol.59, No.3,4, 261-265, 2012.
(Summary)
A 37-year-old man presenting with fever and chest pain was admitted to our hospital. Electrocardiogram showed sinus tachycardia and complete left bundle branch block. Transthoracic echocardiogram showed infective endocarditis in the bicuspid aortic valve, complicated by multiple hyperechoic vegetations and severe aortic regurgitation. Blood cultures were negative and intravenous empiric antibiotic therapy was begun. However, fever lasted for 7 days and follow-up echocardiography revealed a newly emerged perivalvular abscess. The patient eventually underwent an urgent aortic root replacement that confirmed the echocardiographic findings. Our case report emphasizes that all patients with suspected aortic valve endocarditis should undergo early and follow-up echocardiographic studies.
山田 聡, 岩野 弘幸, 大手 信之, 瀬尾 由広, Hirotsugu Yamada, 石津 智子, Kenya Kusunose, 若見 和明, 三神 大世 and 筒井 裕之 : Limitation of echocardiographic indexes for the accurate estimation of left ventricular relaxation and filling pressure : interim results of SMAP, a multicenter study in Japan, Japanese Journal of Medical Ultrasonics, Vol.39, No.4, 449-456, 2012.
(Keyword)
diastolic function / e' / echocardiography / left ventricular filling pressure / relaxation
Takeshi Soeki, Mitsuhiro Kitani, Kenya Kusunose, Shusuke Yagi, Yoshio Taketani, Kunihiko Koshiba, Tetsuzo Wakatsuki, Shunsuke Orino, Kazuhiro Kawano and Masataka Sata : Renoprotective and antioxidant effects of cilnidipine in hypertensive patients., Hypertension Research, Vol.35, No.11, 1058-1062, 2012.
(Summary)
Cilnidipine, an L/N-type calcium channel blocker (CCB), has been reported to have more beneficial effects on proteinuria progression in hypertensive patients than amlodipine, an L-type CCB. The N-type calcium channel blockade that inhibits renal sympathetic nerve activity might reduce glomerular hypertension by facilitating vasodilation of the efferent arterioles. However, the precise mechanism of the renoprotective effect of cilnidipine remains unknown. Because cilnidipine exerted significantly higher antioxidant activity than amlodipine in cultured human mesangial cells, we hypothesized that cilnidipine might exert a renoprotective effect by suppressing oxidative stress. A total of 35 hypertensive patients receiving a renin-angiotensin system inhibitor were randomly assigned to a cilnidipine (n=18; 10 mg per day cilnidipine titrated to 20 mg per day) or amlodipine (n=17; 5 mg per day amlodipine titrated to 10 mg per day) group; the target blood pressure (BP) was set at 130/85 mmHg. After 6 months of treatment, systolic and diastolic BPs were significantly reduced in both of the groups, without any significant difference between the groups. The urinary albumin, 8-hydroxy-2'-deoxyguanosine (OHdG) and liver-type fatty-acid-binding protein (L-FABP) to creatinine ratios significantly decreased in the cilnidipine group (P<0.05) compared with those in the amlodipine group. The reductions in urinary albumin, 8-OHdG and L-FABP were not correlated with the change in systolic BP. In conclusion, cilnidipine, but not amlodipine, ameliorated urinary albumin excretion and decreased urinary 8-OHdG and L-FABP in the hypertensive patients. Cilnidipine probably exerts a greater renoprotective effect through its antioxidative properties.Hypertension Research advance online publication, 5 July 2012; doi:10.1038/hr.2012.96.
Koji Yamaguchi, Tetsuzo Wakatsuki, Toshiyuki Niki, Kenya Kusunose, Kunihiko Koshiba, Shusuke Yagi, Yoshio Taketani, Takashi Iwase, Noriko Tomita, Hirotsugu Yamada, Takeshi Soeki, Masashi Akaike and Masataka Sata : Local persistent hypercoagulability after sirolimus-eluting stent implantation in patients with stable angina., International Journal of Cardiology, Vol.153, No.3, 272-276, 2011.
(Summary)
Late stent thrombosis (LST) after sirolimus-eluting stent (SES) implantation has been demonstrated previously. Although incomplete neointimal coverage after SES implantation has been reported, local long-term hypercoagulability remains unknown. We evaluated the local persistent coagulative response in eighty-three consecutive patients with stable angina, treated with either SES (n=51) or BMS (n=32) implantation for isolated de novo left anterior descending (LAD) stenosis. We measured prothrombin fragment F1+2 (frF1+2) and D-dimer levels sampled in the coronary sinus (CS) and sinus of Valsalva (V). The transcardiac gradient (Δ) was defined as the CS level minus V level. The ΔfrF1 + 2 and ΔD-dimer were significantly greater in the SES group than in the BMS group (0.50 ± 0.35 vs -0.14 ± 0.15 nmol/l, p=0.009 and 0.24 ± 0.21 vs -0.05 ± 0.16 μg/ml, p=0.041, respectively). We selected the hypocoagulative [ΔfrF1 + 2<0.15 (mean value-SD) nmol/l, n=21] and hypercoagulative [ΔfrF1 + 2>0.85 (mean value+SD) nmol/l, n=14] groups out of the SES patients. Multivariate analysis was performed to identify independent predictors of local hypercoagulability. Total SES length was the only independent predictor of local hypercoagulability. There was a significant positive correlation between the ΔfrF1 + 2 and total stent length in the SES group (r=0.57, p<0.05). An increased local coagulative response was observed in the convalescent phase after SES implantation as compared to BMS. Careful long-term follow-up of patients after longer SES implantation is recommended in order to avoid LST.
Hiromu Yamazaki, Koji Yamaguchi, Takashi Iwase, Toshiyuki Niki, Kenya Kusunose, Noriko Tomita, Yoshio Taketani, Hirotsugu Yamada, Takeshi Soeki, Tetsuzo Wakatsuki, Yutaka Fukunaga, Hideki Nakanishi, Haruhiko Maruyama, Hiroyuki Matsuoka and Masataka Sata : A patient who developed toe necrosis due to poor blood circulation after an interdigital tick bite., Journal of Cardiology Cases, Vol.4, No.2, e106-e109, 2011.
Takeshi Soeki, Toshiyuki Niki, Kenya Kusunose, Sachiko Bando, Yoichiro Hirata, Noriko Tomita, Koji Yamaguchi, Kunihiko Koshiba, Shusuke Yagi, Yoshio Taketani, Takashi Iwase, Hirotsugu Yamada, Tetsuzo Wakatsuki, Masashi Akaike and Masataka Sata : Elevated concentrations of pentraxin 3 are associated with coronary plaque vulnerability., Journal of Cardiology, Vol.58, No.2, 151-157, 2011.
(Summary)
Inflammation is a critical contributing factor to the development and progression of atherosclerosis. Pentraxin 3 (PTX3) is produced abundantly in atherosclerotic lesions while C-reactive protein (CRP) is mainly produced in the liver. In this study, we investigated whether plasma levels of PTX3 might be a sensitive marker both for the severity of coronary artery disease and vulnerable plaques. Next, we determined whether assays for inflammatory molecules can be used to monitor the therapeutic effects of telmisartan on stabilization of vulnerable atherosclerotic plaques. We measured PTX3 concentrations in the peripheral and coronary sinus plasma of 40 patients with angina pectoris (AP) and 20 control subjects. Next, in 28 patients with AP, we determined the correlation between levels of inflammatory molecules and the computed tomography (CT) density of plaques as a quantitative index of plaque vulnerability. There was no significant difference in peripheral plasma PTX3 concentrations between patients with AP and control subjects, while coronary sinus plasma PTX3 concentrations were significantly higher in AP patients than control subjects. The concentrations of PTX3 in coronary sinus and peripheral plasma correlated with Gensini scores as an index of severity of coronary atherosclerosis. Interestingly, there was a significantly negative correlation between plasma PTX3 concentrations and CT density (r=-0.67, p<0.01). On the other hand, CT density did not correlate with the peripheral plasma concentrations of monocyte chemoattractant protein-1 (MCP-1) or high-sensitivity CRP (hsCRP). Furthermore, telmisartan treatment for 6 months decreased plasma concentrations of PTX3 but not those of MCP-1 or hsCRP in 12 patients with essential hypertension. Multivariate regression analysis revealed that changes in PTX3 levels were independent of blood pressure changes. PTX3 is likely more specific than hsCRP as an indicator of coronary plaque vulnerability that could lead to plaque rupture.
(Keyword)
Aged / Angina Pectoris / Angiotensin II Type 1 Receptor Blockers / Benzimidazoles / Benzoates / Biological Markers / C-Reactive Protein / Coronary Artery Disease / Coronary Sinus / Disease Progression / Drug Monitoring / Female / Humans / Inflammation Mediators / Male / Middle Aged / Plaque, Atherosclerotic / Serum Amyloid P-Component / Severity of Illness Index / Tomography, Spiral Computed
Toshiyuki Niki, Tetsuzo Wakatsuki, Koji Yamaguchi, Kenya Kusunose, Kunihiko Koshiba, Shusuke Yagi, Yoshio Taketani, Takashi Iwase, Noriko Tomita, Hirotsugu Yamada, Takeshi Soeki, Masashi Akaike and Masataka Sata : Comparison of chronic-stage histopathological findings among 3 coronary stents implanted in the same patient., International Journal of Cardiology, Vol.150, No.1, e25-e27, 2011.
(Summary)
A 73-year-old woman suffering from anterior thoracic pain on exertion presented to our hospital. We performed coronary angiography and noted three stenotic legions in each coronary artery. For each angiographic finding, we implanted a bare metal stent (BMS), sirolimus-eluting stent (SES) and paclitaxel-eluting stent (PES) into the right coronary artery, left anterior descending and left circumflex coronary arteries, respectively. Nine months later, she died of lung disease, and we could compare the histopathological findings among the three coronary stents. In the drug-eluting stents, very thin intima, infiltration of inflammatory cells, and fibrin deposition were observed, while thick intima and no inflammatory findings were observed in the BMS. Fibrin deposition was more marked in the PES than in the SES. This report shows marked differences in the subsequent pathological course among three stents in the same patient.
M Bando, Takeshi Soeki, Toshiyuki Niki, Kenya Kusunose, N Tomita, Koji Yamaguchi, Kunihiko Koshiba, Yoshio Taketani, Takashi Iwase, Hirotsugu Yamada, Tetsuzo Wakatsuki, Masashi Akaike and Masataka Sata : Ventricular tachycardia in cardiac sarcoidosis controlled by radiofrequency catheter ablation., Internal Medicine, Vol.50, No.11, 1201-1206, 2011.
(Summary)
We report a case of a 78-year-old woman with cardiac sarcoidosis with a history of syncope and palpitation. Further assessment with echocardiography, gadolinium-enhanced cardiovascular magnetic resonance (CMR) and histology led to a diagnosis of cardiac sarcoidosis. As the patient suffered from ventricular tachycardia (VT) despite active corticosteroid therapy, an implantable cardioverter-defibrillator (ICD) was positioned. She was also administered a beta blocker, but an electrical storm appeared every several days requiring ICD therapy. The drug-refractory VT was finally controlled with a catheter ablation session, during which we could detect the VT focus in the right ventricular outflow tract next to the aneurysm by using an electroanatomic mapping system (CARTO). Referring to echocardiographic and CMR images proved very useful in detecting the aneurysm using the CARTO system.
Kenya Kusunose, Hirotsugu Yamada, Noriko Tomita, Susumu Nishio, Toshiyuki Niki, Koji Yamaguchi, Kunihiko Koshiba, Shusuke Yagi, Yoshio Taketani, Takashi Iwase, Takeshi Soeki, Tetsuzo Wakatsuki, Masashi Akaike and Masataka Sata : Serial imaging changes during treatment of Takayasu arteritis with pulmonary artery stenosis., International Journal of Cardiology, Vol.148, No.3, 47-50, 2011.
(Summary)
Most cases of chronic stenosis or occlusive lesions of the pulmonary arteries are attributed to thromboembolism, and pulmonary arteritis is extremely rare as the primary cause of these entities. We report a case of pulmonary stenosis and occlusion caused by Takayasu arteritis. The patient was a 54-year-old woman who presented with dyspnea. Total occlusion of the left pulmonary artery and significant stenosis of the right pulmonary artery caused by Takayasu arteritis were confirmed by various imaging modalities including pulmonary angiography, (18)fluorodeoxyglucose-positron emission tomography, magnetic resonance imaging and real-time three-dimensional transesophageal echocardiography. After 6 weeks of steroid therapy, follow-up imaging studies showed that the stenotic lesion had resolved.
Shusuke Yagi, Masashi Akaike, Ken-ichi Aihara, Takashi Iwase, Kazue Ishikawa, Sumiko Yoshida, Yuka Sumitomo-Ueda, Kenya Kusunose, Toshiyuki Niki, Koji Yamaguchi, Kunihiko Koshiba, Yoshio Taketani, Noriko Tomita, Hirotsugu Yamada, Takeshi Soeki, Tetsuzo Wakatsuki, Toshio Matsumoto and Masataka Sata : Effect of low-dose (1 mg/day) pitavastatin on left ventricular diastolic function and albuminuria in patients with hyperlipidemia., The American Journal of Cardiology, Vol.107, No.11, 1644-1649, 2011.
(Summary)
The aim of the present study was to evaluate the factors that modulate the protective action of statins on cardiorenal function, regardless of the lipid-lowering effect. To treat abnormal serum lipid profiles, low-dose pitavastatin (1.0 mg/day) was administered to 65 hyperlipidemic patients. The exclusion criteria included left ventricular ejection fraction <40% and apparent renal disease. Age- and gender-matched patients with hyperlipidemia (n = 40) served as the controls. After 12 to 16 weeks of pitavastatin treatment, pitavastatin had decreased low-density lipoprotein cholesterol (from 143.5 ± 31.4 to 98.2 ± 19.4 mg/dl, p <0.01), triglycerides (from 157.7 ± 57.2 to 140.5 ± 60.7 mg/dl, p <0.01), E/e' (from 10.8 ± 6.2 to 9.0 ± 4.5, p <0.05), a parameter of left ventricular diastolic function, and albuminuria (from 47.6 ± 55.9 to 28.5 ± 40.0 mg/g creatinine, p <0.01). Furthermore, pitavastatin decreased serum transforming growth factor-1 (from 709 ± 242 to 550 ± 299 pg/ml, p <0.01), urinary 8-hydroxy-2'-deoxyguanosine (from 6.6 ± 4.1 to 5.0 ± 3.1 g/g creatinine, p <0.01), an oxidative stress marker, and increased urinary nitrate and nitrite (from 22.5 ± 14.6 to 29.4 ± 27.6 nmol/g creatinine, p <0.05). No such changes were observed in the controls. Multiple regression analysis in the pitavastatin group revealed the effect of pitavastatin on cardiorenal function was associated with suppression of oxidative stress, but not on low-density lipoprotein cholesterol reduction. In conclusion, pitavastatin decreases E/e' and albuminuria, which is associated with suppression of oxidative stress.
Kojiro Nagai, Kenya Kusunose, 西尾 進, Yoshio Taketani, Hirotsugu Yamada, Masataka Sata, 近藤 直樹, 岸 史, Seiji Kishi, 荒岡 利和, Motokazu Matsuura, Akira Mima, Hideharu Abe, Taichi Murakami, Masayuki Nakamura and Toshio Doi : Case of renal artery stenosis in an elderly patient after nephrectomy diagnosed by ultrasound sonography, showing improvement of blood pressure and renal dysfunction after renal artery stenting, Japanese Journal of Nephrology, Vol.53, No.1, 68-74, 2011.
(Summary)
Arteriosclerotic renal artery stenosis is one of the increasingly common diseases that affects many aged patients. There are various non-invasive methods to diagnose renal artery stenosis, such as contrast enhanced CT or MRI. However, these methods are not appropriate for patients with renal dysfunction. Ultrasound sonography is becoming one of the promising methods to diagnose artery stenosis because of photographic improvements. In this case, a 72-year-old woman was hospitalized 7 months after nephrectomy because of severe hypertension, heart failure and kidney dysfunction. The heart failure was quite uncontrollable in spite of massive administration of diuretics, and finally, hemodialysis was started to control her volume status. In consideration of her past history and abdominal bruit, we evaluated the renal artery stenosis by ultrasound sonography and confirmed the diagnosis by renal angiography. To improve hypertension control, we performed renal artery stenting, which resulted in an impressive improvement of her blood pressure and renal function. We recognized the importance of careful causal evaluation of renal dysfunction, even though it is difficult to apply invasive therapy to patients after nephrectomy.
Koji Yamaguchi, Tetsuzo Wakatsuki, Toshiyuki Niki, Yoshio Taketani, H. Oezuka, Kenya Kusunose, Takashi Iwase, Hirotsugu Yamada, Takeshi Soeki and Masataka Sata : Observation of short-term atorvastatin-induced changes in coronary arterial plaque properties using integrated backscatter intravascular ultrasound in a patient., Journal of Cardiology Cases, Vol.3, No.3, e111-e114, 2011.
Kenya Kusunose, Hirotsugu Yamada, Susumu Nishio, Yukio Mizuguchi, Masahito Choraku, Yasuhiro Maeda, Shinobu Hosokawa, Nobuo Yamazaki, Noriko Tomita, Toshiyuki Niki, Koji Yamaguchi, Kunihiko Koshiba, Takeshi Soeki, Tetsuzo Wakatsuki, Masashi Akaike and Masataka Sata : Validation of longitudinal peak systolic strain by speckle tracking echocardiography with visual assessment and myocardial perfusion SPECT in patients with regional asynergy., Circulation Journal, Vol.75, No.1, 141-147, 2011.
(Summary)
Automated function imaging (AFI) is a recently developed method of calculating the longitudinal peak systolic strains (LS) of the regional left ventricular (LV) wall using speckle tracking echocardiography and displaying them on a single bull's-eye map. The feasibility of AFI in patients with regional LV wall motion abnormalities caused by myocardial infarction (MI) was evaluated by comparison with visual assessment and myocardial perfusion single-photon emission computed tomography (SPECT). Segmental LS was measured by AFI in 60 patients with MI (67 ± 11 years) and 58 controls (71 ± 9 years). Wall thickening (WT) was measured by SPECT in 20 patients with MI. There was a strong positive linear relationship between the wall motion score index by expert visual assessment and global LS. The receiver-operating characteristic analysis revealed the best cutoff value of 11% < LS to identify hypokinetic segments. The overall accuracy of wall motion scoring by LS in the 2,006 segments was 96.8% (κ = 0.90) compared with visual assessment. The correlation coefficient between LS and WT was R² = 0.65 in the 340 segments. Assessment of LV regional asynergy by AFI showed good agreement with visual and SPECT assessments. AFI is clinically useful for quantitative assessment of LV regional wall motion abnormalities.
(Keyword)
Aged / Aged, 80 and over / Algorithms / Case-Control Studies / Echocardiography, Doppler / Feasibility Studies / Humans / Image Interpretation, Computer-Assisted / Japan / Middle Aged / Myocardial Contraction / Myocardial Infarction / Myocardial Perfusion Imaging / Observer Variation / Predictive Value of Tests / Reproducibility of Results / Tomography, Emission-Computed, Single-Photon / Ventricular Dysfunction, Left / Ventricular Function, Left
Pulmonary arterial hypertension (PAH) is a frequent complication in patients with systemic sclerosis. Bosentan is used in patients with symptomatic PAH; however, it has not been established whether or not bosentan ameliorates the progression of PAH in patients with no PAH-related symptoms. We present a case of systemic sclerosis with no PAH-related symptoms in which bosentan ameliorated exercise-induced PAH evaluated by 6-minute walk stress echocardiography, brachial flow-mediated dilation, and skin temperature of hands and feet. The results suggest that administration of bosentan in patients with early-stage PAH ameliorates pulmonary arterial vasodilatation through improvement of endothelial function.
Shusuke Yagi, Masashi Akaike, Mitsunori Fujimura, Takehiko Kimura, Takeshi Nishiuchi, Takashi Iwase, Ken-ichi Aihara, Sumiko Yoshida, Yuka Sumitomo-Ueda, Kenya Kusunose, Toshiyuki Niki, Koji Yamaguchi, Kunihiko Koshiba, Yoichiro Hirata, Munkhbaatar Dagvasumberel, Yoshio Taketani, Noriko Tomita, Hirotsugu Yamada, Takeshi Soeki, Tetsuzo Wakatsuki, Toshio Matsumoto and Masataka Sata : Congenital ventricular aneurysm as an unexpected complication of monomorphic premature ventricular contractions., Internal Medicine, Vol.49, No.10, 907-912, 2010.
(Summary)
Congenital ventricular diverticulum (CVD) in adults is a rare cardiac malformation, which includes fibrous type congenital ventricular aneurysm (CVA). CVA is often clinically asymptomatic and shows no abnormality in the electrocardiogram or chest X-ray. However, some cases of sudden death resulting from ventricular tachycardia, cardiac embolism or ventricular rupture have been reported. Therefore, physicians should perform further cardiac imaging studies to detect a CVA if ventricular arrhythmia originating from the left ventricle is observed. Here, we report two successfully followed cases of CVA which were diagnosed from premature ventricular contractions.
Hirotsugu Yamada, Yuichiro Mishiro, Kenya Kusunose and Masataka Sata : Effects of additional administration of low-dose indapamide on patients with hypertension treated with angiotensin II receptor blocker., Journal of Cardiovascular Pharmacology and Therapeutics, Vol.15, No.2, 145-150, 2010.
(Summary)
BACKGROUND: Low-dose thiazide or thiazide-like diuretics have proven useful for the management of blood pressure in patients older than 65 years (elderly group). However, there are few reports about the antihypertensive effects of antihypertensive diuretic agents in patients younger than 65 years (middle-aged group). So, we evaluated the efficacy of low-dose indapamide on blood pressure. METHODS: Indapamide(1 mg) was given daily for 3 months and was then given every other day for 3 months to patients whose hypertension was poorly controlled with angiotensin II receptor blocker (ARB)-based treatment. RESULTS: After daily administration of indapamide, blood pressure was significantly decreased in both the middle-aged and elderly groups. Blood pressure was not significantly changed by every-other-day administration compared with that observed after daily administration in either group. The rate of attainment of the target blood pressure was 90.3% and 85.7% in the middle-aged and elderly groups, respectively. The serum uric acid levels were reduced after every-other-day administration compared to daily administration but tended to be higher than the levels at the baseline in both groups. CONCLUSIONS: The addition of low-dose indapamide is a useful strategy for the management of hypertension, as it reduced blood pressure without marked side effects.
Shusuke Yagi, Masashi Akaike, Ken-ichi Aihara, Takashi Iwase, Kazue Ishikawa, Sumiko Yoshida, Yuka Sumitomo-Ueda, Kenya Kusunose, Toshiyuki Niki, Koji Yamaguchi, Kunihiko Koshiba, Yoichiro Hirata, Munkhbaatar Dagvasumberel, Yoshio Taketani, Noriko Tomita, Hirotsugu Yamada, Takeshi Soeki, Tetsuzo Wakatsuki, Toshio Matsumoto and Masataka Sata : Ezetimibe ameliorates metabolic disorders and microalbuminuria in patients with hypercholesterolemia., Journal of Atherosclerosis and Thrombosis, Vol.17, No.2, 173-180, 2010.
(Summary)
AIM: Ezetimibe, an inhibitor of Niemann-Pick C1-like 1 protein, has been shown to reduce the intestinal absorption of cholesterol. We investigated whether it also has beneficial effects on metabolic disorder and/or renal insufficiency in patients with hypercholesterolemia. METHODS: Ezetimibe was administered to 38 Japanese patients with hypercholesterolemia to obtain appropriate low-density lipoprotein cholesterol (LDL-chol) levels. Age- and sex-matched patients with hypercholesterolemia (n=38) were the controls. We evaluated the effects of ezetimibe before and 4 to 8 weeks after ezetimibe treatment. RESULTS: Ezetimibe significantly decreased LDL-chol levels and metabolic syndrome-related factors, including body weight, waist circumference, blood pressure; homeostasis model assessment insulin resistance (HOMA-IR), and urinary albumin excretion, were significantly reduced. In addition, it decreased the level of high-sensitivity C-reactive protein (hs-CRP), tumor necrosis factor (TNF)-alpha, the urinary excretion of 8-hydroxy-2'-deoxyguanosine, a parameter of oxidative stress, and increased the urinary excretion of nitrate and nitrite (NOx). In the controls we observed no such changes. Excepting the decrease in the serum TNF-alpha level, the effects of ezetimibe were not correlated with decreased LDL-chol levels. CONCLUSION: Ezetimibe ameliorated the status of metabolic syndrome and microalbuminuria, reduced inflammation and oxidative stress, and increased nitric oxide bioavailability in a LDL-chol reduction-dependent and -independent manner.
Takashi Iwase, Shoichiro Takao, Masashi Akaike, K Adachi, Y Sumitomo-Ueda, Shusuke Yagi, T Niki, Kenya Kusunose, N Tomita, Y Hirata, Koji Yamaguchi, Kunihiko Koshiba, Yoshio Taketani, Hirotsugu Yamada, Takeshi Soeki, Tetsuzo Wakatsuki, KI Aihara, Masafumi Harada, H Nishitani and Masataka Sata : Diagnostic utility of cardiac magnetic resonance for detection of cardiac involvement in female carriers of Duchenne muscular dystrophy., Heart Asia, Vol.2, 52-55, 2010.
Kenya Kusunose, Hirotsugu Yamada, S Nishio, N Tomita, T Niki, K Yamaguchi, Kunihiko Koshiba, Shusuke Yagi, Y Taketani, Takashi Iwase, Takeshi Soeki, Tetsuzo Wakatsuki, Masashi Akaike and Masataka Sata : Clinical Utility of Single Beat E/e' Obtained by Simultaneous Recording of Flow and Tissue Doppler Velocities in Atrial Fibrillation with Preserved Systolic Function., JACC. Cardiovascular Imaging, Vol.2, No.10, 1147-1156, 2009.
(Summary)
We evaluated the usefulness of the ratio of the early diastolic transmitral flow velocity (E) to the mitral annular velocity (e') calculated from simultaneously recorded E and e' in atrial fibrillation (AF). The ratio of the E to the e' (E/e') has been reported as a useful index even in AF patients. However, E and e' were measured during different beats in the previous studies. Fifty-six AF patients with preserved systolic function (mean age 66 +/- 11 years) underwent routine echocardiographic study. The E/e' was calculated from the E and e' simultaneously recorded by the dual Doppler echocardiography. A single-beat E/e' was calculated from simultaneously recorded E and e' when the preceding RR interval/pre-preceding RR interval = 1. Brain natriuretic peptide (BNP) levels were also examined. Twenty-one patients underwent simultaneous pulmonary artery catheterization. The single-beat lateral E/e' correlated with pulmonary capillary wedge pressure (PCWP) (r = 0.74, p < 0.001). The single-beat lateral E/e' of >or=11 could predict elevated PCWP (>or=15 mm Hg) with a sensitivity of 90% and a specificity of 90%. The single-beat lateral E/e' also correlated well with the log BNP concentration. The single-beat lateral E/e' of >or=9.2 predicted a plasma BNP level of >or=200 pg/ml with 88% sensitivity and 84% specificity. The single-beat lateral E/e' correlated with plasma BNP level and PCWP in AF patients with preserved systolic function. In addition, the single-beat lateral E/e' (>or=11) was a good predictor of elevated PCWP (>or=15 mm Hg). Dual Doppler echocardiography offers an advantage of providing the single-beat lateral E/e' correctly even in AF patients, for the evaluation of left ventricular diastolic function.
(Keyword)
Adult / Aged / Aged, 80 and over / Atrial Fibrillation / Biological Markers / Catheterization, Swan-Ganz / Coronary Circulation / Diastole / Echocardiography, Doppler, Color / Echocardiography, Doppler, Pulsed / Female / Heart Rate / Humans / Linear Models / Male / Middle Aged / Mitral Valve / Natriuretic Peptide, Brain / Predictive Value of Tests / Pulmonary Wedge Pressure / Sensitivity and Specificity / Systole / Ventricular Function, Left
Kenya Kusunose, Hirotsugu Yamada, Takashi Todoroki, Susumu Nishio, Toshiyuki Niki, Koji Yamaguchi, Kunihiko Koshiba, Shusuke Yagi, Takashi Iwase, Takeshi Soeki, Tetsuzo Wakatsuki, Masashi Akaike, Tetsuya Kitagawa and Masataka Sata : Platypnea-orthodeoxia syndrome associated with patent foramen ovale and aortic ectasia., Echocardiography, Vol.26, No.1, 114-117, 2008.
(Summary)
A 59-year-old man was admitted for dyspnea on exertion and edema. The patient did not have any pulmonary diseases that could cause dyspnea. Transesophageal echocardiography on the tilting bed with contrast infusion revealed a right-to-left shunt through the patent foramen ovale. Therefore, he was diagosed as platypnea-orthodeoxia syndrome due to the patent foramen ovale. Surgical closure was done and all of his symptoms had improved.
K Yamaguchi, Tetsuzo Wakatsuki, Kenya Kusunose, T Niki, K Koshiba, Hirotsugu Yamada, Takeshi Soeki and Masashi Akaike : A case of neurogenic myocardial stunning presenting transient left ventricular mid-portion ballooning simulating atypical takotsubo cardiomyopathy., Journal of Cardiology, Vol.52, No.1, 53-58, 2008.
(Summary)
A 57-year-old female patient, who was initially suspected to have subarachnoid hemorrhage, was admitted to our hospital. She experienced severe dyspnea and chest pain owing to pneumonia on the fourth admission day. Electrocardiography showed ST-segment elevation in leads V(2) through V(5), and echocardiography revealed hypokinetic left ventricular wall motion. No stenosis was found in the coronary arteries by urgent coronary angiography. However, left ventriculography revealed that the basal and apical areas were hyperkinetic and the mid portion was akinetic. After a month, left ventricular wall motion was improved and coronary artery spasm provocation tests were negative. Although the clinical course of this patient was similar to that of neurogenic myocardial stunning, the shape of her left ventricle was not typical.
Daisuke Ogawa, Makoto Yoshizawa, Akira Tanaka, Ken-ichi Abe, Paul Olegario, Tadashi Motomura, Hisashi Okubo, Takeshi Oda, Toshiya Okahisa, SR Igo and Kenya Kusunose : Indirect flow rate estimation of the NEDO PI Gyro pump for chronic BVAD experiments., ASAIO Journal, Vol.52, No.3, 266-271, 2006.
(Summary)
In totally implantable ventricular assist device systems, measuring flow rate of the pump is necessary to ensure proper operation of the pump in response to the recipient's condition or pump malfunction. To avoid problems associated with the use of flow probes, several methods for estimating flow rate of a rotary blood pump used as a ventricular assist device have been studied. In the present study, we have performed a chronic animal experiment with two NEDO PI gyro pumps as the biventricular assist device for 63 days to evaluate our estimation method by comparing the estimated flow rate with the measured one every 2 days. Up to 15 days after identification of the parameters, our estimations were accurate. Errors increased during postoperation days 20 to 30. Meanwhile, their correlation coefficient r was higher than 0.9 in all the acquired data, and estimated flow rate could simulate the profile of the measured one.
細川 忍, 戸根 沙織, Naoko Matsui, Kenya Kusunose, Kumiko Kagawa, 山上 圭, 廣島 裕也 and 田村 洋人 : 症例検討:妊婦に発症した脳梗塞の1例, The Journal of the Japanese Society of Internal Medicine, Vol.106, No.10, 2265-2272, 2017.
T Niki, Takeshi Soeki, Kenya Kusunose, K Yamaguchi, K Koshiba, Tomohito Kawano, Hirotsugu Yamada, Tetsuzo Wakatsuki and Kenji Kangawa : Elevated Concentration of Interferon-Inducible Protein of 10kd (IP-10) is Associated with Coronary Atherosclerosis., Circulation Journal, Vol.72, No.0, 715_OJ233, 2008.
K Yamaguchi, Tetsuzo Wakatsuki, Kenya Kusunose, T Niki, K Koshiba, Tomohito Kawano, Hirotsugu Yamada and Takeshi Soeki : Predictors of Local Hypercoagulability after Sirolimus-Eluting Stent Implantation: Implication for Correlates of Late Stent Thrombosis., Circulation Journal, Vol.72, No.0, 249_FRS022, 2008.
Takeshi Soeki, T Niki, K Koshiba, Kenya Kusunose, K Yamaguchi, Tomohito Kawano, Hirotsugu Yamada and Tetsuzo Wakatsuki : Elevated Concentration of Pentraxin 3 is Associated with Coronary Plaque Vulnerability., Circulation Journal, Vol.72, No.0, 632_PE499, 2008.
Takeshi Soeki, K Koshiba, T Niki, Kenya Kusunose, K Yamaguchi, Tomohito Kawano, Hirotsugu Yamada, Tetsuzo Wakatsuki and Kenji Kangawa : Ghrelin Attenuates Myocardial Ischemia/Reperfusion Injury via the Extracellular Signal-Regulated Kinase 1/2 and Phosphatidylinositol., Circulation Journal, Vol.72, No.0, 145_OE022, 2008.
Tetsuzo Wakatsuki, K Yamaguchi, T Niki, Kenya Kusunose, K Koshiba, Takeshi Soeki and Hirotsugu Yamada : Long-Term Local Inflammatory Response after Coronary Artery Stenting with Drug-Eluting Stent., Circulation Journal, Vol.72, 421_PJ456, 2008.
Kenya Kusunose, Hirotsugu Yamada, A Iga, T Niki, K Yamaguchi, K Koshiba, Takeshi Soeki and Tetsuzo Wakatsuki : Left Atrial Volume does not reflect Brain Natriuretic Peptide Levels in Patients with Atrial Fibrillation., Circulation Journal, Vol.72, 508_PE367, 2008.
Kenya Kusunose, Hirotsugu Yamada, A Iga, T Niki, K Yamaguchi, K Koshiba, Takeshi Soeki and Tetsuzo Wakatsuki : Importance of Left Atrial Function for the Pseudonormalization of Transmitral Flow Velocity Pattern in Patients with Hypertrophic Cardiomyopathy., Circulation Journal, Vol.72, 426_PJ492, 2008.
Hirotsugu Yamada, Kenya Kusunose, A Iga, T Niki, K Yamaguchi, K Koshiba, Takeshi Soeki and Tetsuzo Wakatsuki : E/e' as a Predictor of the Cardiac Response to Increment of Preload in Patients with Atrial Fibrillation., Circulation Journal, Vol.72, No.0, S_749, 2008.
Tetsuzo Wakatsuki, K Yamaguchi, T Niki, Kenya Kusunose, K Koshiba, Hirotsugu Yamada, Takeshi Soeki, Shusuke Yagi, Takashi Iwase, Masashi Akaike and Masataka Sata : Long-term endothelial dysfunction after coronary artery stenting with drug-eluting stent associated with local inflammatory response., Circulation, Vol.118, S_749, 2008.
11.
K Yamaguchi, Tetsuzo Wakatsuki, T Niki, Kenya Kusunose, K Koshiba, Shusuke Yagi, Takashi Iwase, Hirotsugu Yamada, Takeshi Soeki, Masashi Akaike and Masataka Sata : Local hypercoagulability and endothelial dysfunction after sirolimus-eluting stent implantation: implication for late stent thrombosis., Circulation, Vol.118, S_651, 2008.
12.
Takeshi Soeki, T Niki, K Koshiba, Kenya Kusunose, K Yamaguchi, Hirotsugu Yamada and Tetsuzo Wakatsuki : Elevated concentration of Pentraxin 3 is associated with coronary plaque vulnerability., Eur Heart J, Vol.29, 505-732, 2008.
13.
Tetsuzo Wakatsuki, K Yamaguchi, Kenya Kusunose, T Niki, K Koshiba, Hirotsugu Yamada, Takeshi Soeki, Masashi Akaike and Masataka Sata : Long-term local inflammatory response after coronary artery stenting with drug-eluting stent., Eur Heart J, Vol.29, 505-732, 2008.
14.
K Koshiba, Takeshi Soeki, T Niki, Kenya Kusunose, H Yamaguchi, Hirotsugu Yamada and Tetsuzo Wakatsuki : C-type natriuretic peptide ameliorates the progression of experimental autommune myocarditis., Eur Heart J, Vol.29, 505-732, 2008.
15.
S Nishio, Hirotsugu Yamada, H Motonari, H Okada, Kenya Kusunose, Y Tadatsu, M Sato, H Hiraoka, H Kawano, Takeshi Soeki, Tetsuzo Wakatsuki and Masashi Akaike : Assessment of Left Atrial Ejection Force in Patients with Hypertensive Heart Disease., Journal of the American Society of Echocardiography, Vol.21, 552, 2008.
16.
Kenya Kusunose, Hirotsugu Yamada, S Nishio, M Sato, H Hiraoka, H Kawano, Y Tadatsu, Takeshi Soeki, Tetsuzo Wakatsuki and Masashi Akaike : Importance of Left Atrial Function in Cardiac Response to Increment of Preload in Patients with Old Myocardial Infarction: Assessment by Automated Left Atrial Volume Tracking Method., Journal of the American Society of Echocardiography, Vol.21, 552, 2008.
17.
S Nishio, Hirotsugu Yamada, H Motonari, Kenya Kusunose, Y Tadatsu, M Sato, H Hiraoka, H Kawano, Takeshi Soeki, Tetsuzo Wakatsuki and Masashi Akaike : Beat-To-Beat Variation of Mitral Annular Velocities in Atrial Fibrillation., Journal of the American Society of Echocardiography, Vol.21, 550, 2008.
18.
Hirotsugu Yamada, Kenya Kusunose, S Nishio, Y Tadatsu, M Sato, H Hiraoka, H Kawano, T Niki, K Yamaguchi, K Koshiba, Takeshi Soeki, Tetsuzo Wakatsuki and Masashi Akaike : The Mitral L-Wave Predicts the Cardiac Response to Preload Increment in Atrial Fibrillation., Journal of the American Society of Echocardiography, Vol.21, 545, 2008.
19.
S Nishio, Hirotsugu Yamada, H Motonari, Kenya Kusunose, Y Tadatsu, M Sato, H Hiraoka, H Kawano, T Niki, K Yamaguchi, K Koshiba, Takeshi Soeki, Tetsuzo Wakatsuki and Masashi Akaike : Usefulness of Tei Index in Atrial Fibrillation: Assessment by Dual Doppler Echocardiography., Journal of the American Society of Echocardiography, Vol.21, 543, 2008.
20.
Kenya Kusunose, K Takechi, Hirotsugu Yamada, S Nishio, Y Tadatsu, T Niki, K Yamaguchi, K Koshiba, Takeshi Soeki, Tetsuzo Wakatsuki, Masashi Akaike, M Choraku and Y Maeda : Multicenter Trial for the Validation of Automated Function Imaging in Patients with Local Left Ventricular Asynergy (VANILLA Study)., Journal of the American Society of Echocardiography, Vol.21, 538, 2008.
21.
Kenya Kusunose, Hirotsugu Yamada, S Nishio, T Niki, K Yamaguchi, K Koshiba, Takeshi Soeki, Tetsuzo Wakatsuki and Masashi Akaike : Role of Left Atrial Function for Pseudonormalization of Transmitral Flow Velocity Pattern in Patients with Hypertrophic Cardiomyopathy., Journal of the American Society of Echocardiography, Vol.21, 524, 2008.
22.
Hirotsugu Yamada, Kenya Kusunose, Y Uzuuchi, H Niki, T Nakajima, K Yamaguchi, K Koshiba, Tomohito Kawano, Takeshi Soeki and Tetsuzo Wakatsuki : Assessment of the cardiac response to increment of preload in patients with atrial fibrillation using dual pulsed Doppler echocardiography., Journal of the American Society of Echocardiography, Vol.20, 594, 2007.
23.
Kenya Kusunose, Hirotsugu Yamada, T Chono, H Niki, T Nakajima, K Yamaguchi, K Koshiba, Tomohito Kawano, Takeshi Soeki, Tetsuzo Wakatsuki, K Aihara and Hiromu Nishitani : Measurement of left atrial volume curve by advanced 2D tissue tracking technique: validation by contrast multidetector computed tomography., Journal of the American Society of Echocardiography, Vol.20, 603, 2007.
24.
Kenya Kusunose, Hirotsugu Yamada, T Niki, T Nakajima, K Yamaguchi, K Koshiba, Tomohito Kawano, Takeshi Soeki, Tetsuzo Wakatsuki and Susumu Ito : Relationship Between the Ratio of Peak Early Diastolic Transmitral Flow and Mitral Annular Velocities and the Plasma B-Type Natriuretic Peptide (BNP) Concentration in Patients with Atrial Fibrillation: Assessment by Simultaneous Recording of Transmitral Flow and Mitral Annular Velocity., Journal of the American College of Cardiology, Vol.49, No.9, 137A, 2007.
Academic Letter:
1.
Kenya Kusunose, Hirotsugu Yamada, Yoshihito Saijo, Susumu Nishio, Yukina Hirata, Takayuki Ise, Koji Yamaguchi, Daiju Fukuda, Shusuke Yagi, Takeshi Soeki, Tetsuzo Wakatsuki and Masataka Sata : Preload Stress Echocardiography for the Assessment of Heart Failure With Preserved Ejection Fraction, JACC. Cardiovascular Imaging, Vol.15, No.2, 375-378, 2022.
Kenya Kusunose, K Matsunaga, Hirotsugu Yamada and Masataka Sata : Identifying the extent of oral fluid droplets on echocardiographic machine consoles in COVID-19 era, Journal of Echocardiography, Vol.18, No.4, 268-270, 2020.
Kenya Kusunose, Hirotsugu Yamada, Rino Suzukawa, Yukina Hirata, Masami Yamao, Takayuki Ise, Shusuke Yagi, Masashi Akaike and Masataka Sata : Effects of Transthoracic Echocardiographic Simulator Training on Performance and Satisfaction in Medical Students., Journal of the American Society of Echocardiography, Vol.29, No.4, 375-377, 2016.
Hirotsugu Yamada, Kenya Kusunose and 杉本 匡史 : EuroEcho - Imaging 2018, 心エコー, Vol.20, No.4, 436-439, Apr. 2019.
3.
Kenya Kusunose and Hirotsugu Yamada : 【右心不全を考える】 診る 心エコーによる右室機能評価法はどこまで進んでいるか, Heart View, Vol.22, No.1, 10-17, Jan. 2018.
(Keyword)
*右心室機能
4.
Yuta Torii, Kenya Kusunose, Hirotsugu Yamada, Y Saijo, Hiromitsu Seno, Susumu Nishio, Yukina Hirata and Masataka Sata : Pre-Discharge LV Filling Pressure and Pulmonary Artery Pressure Were Associated With Hospital Readmission in Heart Failure With Reduced and Preserved Ejection Fraction, AHA Scientific Sessions2017, Nov. 2017.
5.
Kenya Kusunose and Hirotsugu Yamada : Rest and exercise echocardiography for early detection of pulmonary hypertension, Journal of Echocardiography, Vol.14, No.1, 2-12, Nov. 2015.
Takayuki Ise, 高木 恵理, Takashi Iwase, Kenya Kusunose, Koji Yamaguchi, Shusuke Yagi, Hirotsugu Yamada, Takeshi Soeki, Tetsuzo Wakatsuki and Masataka Sata : 心臓サルコイドーシス再燃に対してメトトレキサートの併用が有効であった1例, The Journal of the Japanese Society of Internal Medicine, Vol.104, No.6, 1175-1179, 2015.
Kenya Kusunose and Hirotsugu Yamada : 感染性心内膜炎のエコーレポート-診断と今後の方針を意識する, 心エコー, Vol.14, No.6, 594-601, 2013.
14.
Kenya Kusunose and Hirotsugu Yamada : 心臓弁膜症に3次元心エコー法をどう活用すべきか?, 心エコー, Vol.13, No.7, 680-687, 2012.
15.
Kenya Kusunose, 西尾 進 and Hirotsugu Yamada : 診断につながる血管検査の基本テクニック 検査レポートとカルテ徹底比較 心臓, Vascular Lab, No.8, 229-250, Aug. 2011.
16.
Kenya Kusunose and Hirotsugu Yamada : 心房細動で拡張機能は評価可能か?, 心エコー, No.12, 1156-1163, 2011.
17.
Kenya Kusunose, 玉井 利奈 and Hirotsugu Yamada : 最短ルートで塞栓源をさがす!経胸壁心エコー, Vascular Lab, No.8, 26-30, 2011.
18.
Hirotsugu Yamada, Kenya Kusunose, 西尾 進, Takeshi Soeki and Masataka Sata : Atrial fibrillation and thromboembolic stroke: when and how can it be treated, Shikoku Acta Medica, Vol.66, No.3, 63-70, Aug. 2010.
(Summary)
Atrial fibrillation(AF)is a common arrhythmia and the prevalence of this arrhythmia is increasing as aging. Secondary AF is defined as AF with organic heart disease and lone AF as AF without it. The AF is divided into paroxysmal, persistent and chronic by its onset and persistence. It is clinically important that any type AF causes thromboembolic stroke. The preventive Qumadin therapy should be applied to patients with AF. Transesophageal echocardiography has been utilized for the diagnosis of left atrial thrombus and for the prediction of stroke. CHADS2 score is a clinical prediction rule for estimating the risk of stroke in patients with non-rheumatic AF. Patients with CHADS2 score_1should be treated with Qumadin. Rhythm control and rate control are two different strategies for the treatment of AF. There is no evidence that indicate better choice between rhythm control and rate control. Recently, inhibitors of the renin-angiotensin system have a potential to prevent new onset of AF in patients who has risk factors.
Hirotsugu Yamada, Kenya Kusunose and 西尾 進 : 僧帽弁口血流と僧帽弁輪運動速波形の撮り方・読み方, 心エコー, Vol.11, 24-34, 2010.
20.
Kenya Kusunose, Hirotsugu Yamada and 西尾 進 : 弁膜症の評価を見直す-昔と何が変わったか- 大動脈弁疾患の手術適応, 心エコー, Vol.11, 422-429, 2010.
21.
Kenya Kusunose and Hirotsugu Yamada : Dual-Doppler Systemによる心房細動の左室拡張能評価, Medix 日立インターメディックス, Vol.52, 23-26, 2010.
22.
Kenya Kusunose, Hirotsugu Yamada and 西尾 進 : 弁疾患を評価する場合, Vascular Lab, Vol.6, No.5, 488-495, 2009.
23.
Kenya Kusunose, Hirotsugu Yamada and 西尾 進 : 心房細動例での心不全評価法, 心エコー, Vol.10, No.3, 232-238, 2009.
24.
Kenya Kusunose, Hirotsugu Yamada and 西尾 進 : 右房を知る 下大静脈の見方, 心エコー, Vol.10, No.10, 966-974, 2009.
25.
Kenya Kusunose and Hirotsugu Yamada : 心房細動における血栓形成の一機序, BRAIN RESCUE, Vol.19, 14-17, 2009.
26.
Kenya Kusunose, Hirotsugu Yamada and 西尾 進 : 心エコー法を心不全の診断・治療に活かす心房細動例での心不全評価法, 心エコー, Vol.10, No.3, 232-238, 2009.
27.
西尾 進, Hirotsugu Yamada and Kenya Kusunose : 左心耳, 心エコー, Vol.10, 34-38, 2009.
28.
Hirotsugu Yamada and Kenya Kusunose : 心房細動と経食道心エコー-心筋スタニングについて, 脳と循環, Vol.13, 244-246, 2008.
29.
Hirotsugu Yamada and Kenya Kusunose : 僧帽弁口血流速波形, 心エコー, Vol.9, 382-395, 2008.
30.
Hirotsugu Yamada and Kenya Kusunose : Dual Doppler法を使った左室拡張能の評価, Rad Fan, Vol.6, 98-101, 2008.
31.
Kenya Kusunose and Hirotsugu Yamada : Costrictionとtrestrictionの鑑別, Heart View, Vol.11, 98-102, 2007.
32.
Hirotsugu Yamada and Kenya Kusunose : 心房機能, Heart View, Vol.11, 78-79, 2007.
Proceeding of International Conference:
1.
TOMONORI Takahashi, K Yamaji, S Kohsaka, H Ishii, Y Mori, Tetsuzo Wakatsuki, Koji Yamaguchi, D Nisioka, Kenya Kusunose, T Amano and Masataka Sata : Drug-Coated Balloon versus Drug-Eluting Stent for DeNovo Culprit Lesion in Acute Coronary Syndromes: A Report from Nationwide Registry in Japan, ESC 2024, London, Aug. 2024.
2.
N Yamaguchi, Kenya Kusunose, Yukina Hirata, Susumu Nishio, TOMONORI Takahashi, Yoshihito Saijo, Muneyuki Kadota, Takayuki Ise, Koji Yamaguchi, Shusuke Yagi, Hirotsugu Yamada, Takeshi Soeki, Tetsuzo Wakatsuki and Masataka Sata : Improved Pressure-Flow Relationship With Sacubitril/Valsartan: A 6-min Walk Stress Echocardiographic Study, AHA2023, Philadelphia, Nov. 2023.
3.
TOMONORI Takahashi, Tetsuzo Wakatsuki, Kenya Kusunose, Takayuki Ise and Masataka Sata : The aneurysm that vanished into thin air:Spontaneous thrombosis of a giant aneurysm complicated with the coronary to pulmonary artery fistula, ESC2023, Amsterdam, Aug. 2023.
4.
Ryou Bando, Tetsuzo Wakatsuki, Koji Yamaguchi, Yutaka Kawabata, TOMONORI Takahashi, Yoshihito Saijyo, Muneyuki Kadota, Tomomi Matsuura, Takayuki Ise, Kenya Kusunose, S Yagi, Hirotsugu Yamada, T Soeki, M Akaike and Masataka Sata : Two-year outcomes of drug-coated balloon only strategy for de novo lesions in large coronary vessels, ESC2023, Amsterdam, Aug. 2023.
5.
Kenya Kusunose, Yukina Hirata, T Tsuji, J Kotoku and Masataka Sata : Deep Learning Approach for Analyzing Chest X-rays to Predict Cardiac Events in Heart Failure, AHA 2022, Chicago, Nov. 2022.
6.
Y Okushi, Kenya Kusunose, Hiromitsu Seno, TOMONORI Takahashi, Yoshihito Saijyo, Takayuki Ise, Koji Yamaguchi, Shusuke Yagi, Hirotsugu Yamada, Takeshi Soeki, Tetsuzo Wakatsuki and Masataka Sata : The Impact of Surveillance of Cancer Therapeutics-Related Cardiac Dysfunction by Periodic Echocardiography, ASE2022, Seattle, Jun. 2022.
7.
Koji Yamaguchi, Tetsuzo Wakatsuki, Y Okushi, Kumiko Suto, Kazuhisa Matsumoto, Tomonori Takahashi, Muneyuki Kadota, Yutaka Kawabata, Tomomi Matsuura, Takayuki Ise, Kenya Kusunose, Shusuke Yagi, Hirotsugu Yamada, Takeshi Soeki and Masataka Sata : Early and chronic phased local coagulative responses following bioresorbable-polymer drug-eluting stent implantation, European Heart Journal, Vol.42, No.S1, ehab724.1245, Aug. 2021.
Yukina Hirata, Kenya Kusunose, Hirotsugu Yamada, T Tsuji, K Fujimori, J Kotoku and Masataka Sata : Deep Learning For Detection Of Elevated Pulmonary Artery Wedge Pressure Using Standard Chest X-ray, The Canadian Journal of Cardiology, Dallas, Nov. 2020.
Miharu Arase, Kenya Kusunose, Sae Morita, N Yamaguchi, Yukina Hirata, Susumu Nishio, Takayuki Ise, Koji Yamaguchi, Daiju Fukuda, Shusuke Yagi, Hirotsugu Yamada, Takeshi Soeki, Tetsuzo Wakatsuki and Masataka Sata : Clinical Utility of Noninvasive Assessment of Flow-pressure Relationship in Scleroderma, American Heart Associeition, Dallas, Nov. 2020.
10.
Y Okushi, Kenya Kusunose, Takayuki Ise, Takeshi Tobiume, Koji Yamaguchi, Shusuke Yagi, Daiju Fukuda, Hirotsugu Yamada, Takeshi Soeki, Tetsuzo Wakatsuki and Masataka Sata : Differences ofCancer Types in Hospital Mortality in Patients With Venous Thromboembolism, American Heart Association, Dallas, Nov. 2020.
Koji Yamaguchi, Tetsuzo Wakatsuki, Tomonori Takahashi, Muneyuki Kadota, Yutaka Kawabata, Tomomi Matsuura, Takayuki Ise, Kenya Kusunose, Takeshi Tobiume, Shusuke Yagi, Hirotsugu Yamada, Takeshi Soeki and Masataka Sata : Suppressed Local Coagulative Response After Newer-generation Ultrathin Strut SES Implantation Compared to Older-generation SES Implantation, American Heart Association, Dallas, Nov. 2020.
Kenya Kusunose : Usefulness of stress echocardiography in pulmonary hypertension, XIX NATIONAL CONGRESS OF CARDIOLOGY Joint session JAPANESE SOCIETY OF ECHOCARDIOGRAPHY / ANCAM, ANCAM, Oct. 2020.
13.
Takeshi Soeki, Kazuhisa Matsumoto, Daiju Fukuda, E Uematsu, Tomomi Matsuura, Takeshi Tobiume, Kenya Kusunose, Takayuki Ise, Koji Yamaguchi, Shusuke Yagi, Hirotsugu Yamada, Tetsuzo Wakatsuki and Masataka Sata : Toll-like receptor 9 is a novel therapeutic target to prevent atrial fibrillation, European Heart Journal, Vol.41, No.S2, ehaa946.0463, Aug. 2020.
Yukina Hirata, Kenya Kusunose, Natumi Yamaguchi, Sae Morita, Susumu Nishio, Yuichiro Okushi, Tomonori Takahashi, Hirotsugu Yamada, T Tsuji, K Fujimori, J Kotoku and Masataka Sata : Deep learning for screening of pulmonary hypertension using standard chest X-Ray, European Heart Journal, Amsterdam, Aug. 2020.
Natsumi Yamaguchi, Kenya Kusunose, S Haga, Sae Morita, Yukina Hirata, Yuta Torii, Susumu Nishio, Yuichiroh Ohkushi, Tomonori Takahashi, Hirotsugu Yamada, nao Yamada and Masataka Sata : Assessment of left ventricular ejection fraction from echocardiographic images using machine learning algorithm, Euro Echo 2019, Wien, Dec. 2019.
16.
Tomonori Takahashi, Kenya Kusunose, Shuji Hayashi, Sae Morita, Yuta Torii, Yukina Hirata, M Yamao, Susumu Nishio, Yuichiroh Ohkushi, M Abe, Hirotsugu Yamada, Tetsuzo Wakatsuki and Masataka Sata : Updated prevalence of lambls excrescences using the latest three-dimensional tansesophageal echocardiography, Euro Echo 2019, Wien, Dec. 2019.
17.
Kenya Kusunose, Nishio Susumu, Hirata Yukina, Takayuki Ise, Koji Yamaguchi, Daiju Fukuda, Shusuke Yagi, Hirotsugu Yamada, Takeshi Soeki, Tetsuzo Wakatsuki and Masataka Sata : Pulmonary Artery Hypertension Specific Therapy Improves Exercise Tolerance and Outcomes in Exercise-Induced Pulmonary Hypertension, JACC. Cardiovascular Imaging, Vol.12, No.12, 2576-2579, Dec. 2019.
(Keyword)
Adult / Aged / Antihypertensive Agents / Arterial Pressure / Disease Progression / Echocardiography, Stress / Exercise / Exercise Tolerance / Female / Humans / Male / Middle Aged / Progression-Free Survival / Prospective Studies / Pulmonary Arterial Hypertension / Pulmonary Artery / Recovery of Function / Time Factors / Vasodilator Agents / Walk Test
Yutaka Kawabata, Kenya Kusunose, Shusuke Yagi, Hirotsugu Yamada, Daiju Fukuda, Takeshi Soeki and Masataka Sata : The relationship among local epicardial adipose tissue, coronary intraplaque microluminal structure, and coronary plaque formation -a fresh cadaveric study, AHA2019, Philadelphia, Nov. 2019.
19.
Yukina Hirata, Masataka Sata, Kenya Kusunose, Hirotsugu Yamada, Yuta Torii, Susumu Nishio, nao Yamada, Koji Yamaguchi, Takeshi Soeki and Tetsuzo Wakatsuki : Usefulness of echocardiographic epicardial adipose tissue thickness for predicting coronary artery disease regardless of body mass index, AHA2019, Philadelphia, Nov. 2019.
20.
B Ganbaatar, Daiju Fukuda, Shusuke Yagi, Kenya Kusunose, Hirotsugu Yamada, Takeshi Soeki and Masataka Sata : S1p2 Receptor Antagonist Attenuates Endothelial Dysfunction And Inhibits Atherogenesis In Apolipoprotein-e-deficient Mice, AHA2019, Philadelphia, Nov. 2019.
21.
Yuta Torii, Kenya Kusunose, Yukina Hirata, Hirotsugu Yamada and Masataka Sata : Clinical utility of left atrial strain to predict functional recovery in patients with optimal treatments of heart failure, AHA2019, Philadelphia, Nov. 2019.
22.
Kenya Kusunose, A Haga, T Abe, Daiju Fukuda, Hirotsugu Yamada and Masataka Sata : Assessment of left ventricular ejection fraction from echocardiographic images using deep learning algorithm, AHA2019, Philadelphia, Nov. 2019.
23.
Sutou Kumiko, Daiju Fukuda, B Ganbaatar, Shusuke Yagi, Kenya Kusunose, Hirotsugu Yamada, Takeshi Soeki and Masataka Sata : Pemafibrate, a novel selective peroxisome proliferator-activated receptor-a modulator, ameliorated diabetes-induced endothelial dysfunction, AHA2019, Philadelphia, Nov. 2019.
24.
A Kunduziayi, Daiju Fukuda, Shusuke Yagi, Kenya Kusunose, Hirotsugu Yamada, Takeshi Soeki and Masataka Sata : Vildagliptin, a DPP-4 inhibitor, attenuates endothelial dysfunction and atherogenesis independent of its glucose lowering effect in apolipoprotein e-deficient mice, AHA2019, Philadelphia, Nov. 2019.
25.
Byambasuren Ganbaatar, Daiju Fukuda, Shusuke Yagi, Kenya Kusunose, Hirotsugu Yamada, Takeshi Soeki and Masataka Sata : Empagliflozin, a SGLT2 inhibitor, attenuates endothelial dysfuntion and atherogenesis by inhibiting inflammatory responses in the vasculature and adipose tissue in disbetic apolipoprotein E-deficient, ESC Congress 2019, Paris, Sep. 2019.
26.
Takeshi Soeki, Kazuhisa Matsumoto, Daiju Fukuda, 植松 悦子, Tomomi Matsuura, Takeshi Tobiume, Kenya Kusunose, Takayuki Ise, Koji Yamaguchi, Hirotsugu Yamada, Tetsuzo Wakatsuki and Masataka Sata : Vildagliptin reduces inducitiligy of arterial fibrillation in hypertensive rats complicated with diabetes mellitus, ESC Congress 2019, Paris, Sep. 2019.
27.
Koji Yamaguchi, Tetsuzo Wakatsuki, Rie Ueno, Yutaka Kawabata, Tomomi Matsuura, Takayuki Ise, Kenya Kusunose, Takeshi Tobiume, Shusuke Yagi, Hirotsugu Yamada, Takeshi Soeki and Masataka Sata : The improvement of chronic local coagulative response according to the progress of drug eluting stent, ESC Congress 2019, Paris, Sep. 2019.
28.
Maimaituxun Gulinu, Kenya Kusunose, Daiju Fukuda, Shusuke Yagi, Yuta Torii, Yukina Hirata, Susumu Nishio, nao Yamada, Hirotsugu Yamada, Takeshi Soeki, Tetsuzo Wakatsuki, Masataka Sata and Michio Shimabukuro : Impact of epicardial adipose tissue on global longitudinal strain: a study in patients with normal left ventricular ejection fraction, ESC Congress 2019, Paris, Sep. 2019.
29.
Rahadian Arief, Daiju Fukuda, Hotimah Masdan Salim, Shusuke Yagi, Kenya Kusunose, Hirotsugu Yamada, Takeshi Soeki and Masataka Sata : Glycemic control with canagliflozin, a SGLT-2 inhibitor, attenuates atherosclerosis and endothelial dysfuntion in diabetic apolipoprotein e-deficient mice, ESC Congress 2019, Paris, Aug. 2019.
30.
Kenya Kusunose : Artificial Intelligence for Assessment of Regional Wall Motion Abnormality from Echocardiographic Images, The American Society of Echocardiography - Scientific Sessions, Portland, Jun. 2019.
31.
Kenya Kusunose : Stress echo in valvular heart disease, Advanced Echo Symposium 2019, Brisbane, May 2019.
32.
Kenya Kusunose : Role of stress echo to pulmonary hypertension, Advanced Echo Symposium 2019, Brisbane, May 2019.
33.
Phuong Tran Pham, D Fukuda, Shusuke Yagi, Kenya Kusunose, Hirotsugu Yamada, Takeshi Soeki, Michio Shimabukuro and Masataka Sata : Rivaroxaban, a Direct Inhibitor of Factor Xa, Attenuates Endothelial Dysfunction in Streptozotocin-Induced Diabetic Mice Through the Inhibition of Protease-Activated Receptor 2 Signaling, AHA, Chicago, Nov. 2018.
34.
Daiju Fukuda, Shusuke Yagi, Kenya Kusunose, Hirotsugu Yamada, Takeshi Soeki and Masataka Sata : Inhibition of Thrombin-PARs Signaling by Dabigatran, a Direct Thrombin Inhibitor, Attenuates Endothelial Dysfunction in Diabetic Mice, AHA, Chicago, Nov. 2018.
35.
Y Saijo, Kenya Kusunose, Hirotsugu Yamada, Susumu Nishio, Yuta Torii, Y Hirata, Takayuki Ise, Koji Yamaguchi, Shusuke Yagi, Takeshi Soeki, Tetsuzo Wakatsuki and Masataka Sata : Right Ventricular Contractile Function Predicts Cardiac Events in Passive and Reactive Pulmonary Hypertension, AHA, Chicago, Nov. 2018.
36.
Kenya Kusunose, T Abe, A Haga, Hirotsugu Yamada, Daiju Fukuda, M Harada and Masataka Sata : A Deep Learning Approach for Automated Diagnosis of Regional Wall Motion Abnormality on Echocardiography, AHA, Chicago, Nov. 2018.
37.
Yukina Hirata, Kenya Kusunose, Hirotsugu Yamada, Susumu Nishio, O Harada, N Miyazato, A Haraguni, A Ito, Koji Yamaguchi, Takeshi Soeki, Tetsuzo Wakatsuki and Masataka Sata : Epicardial Adipose Tissue Thickness Measured by Echocardiography is Useful Marker for Predicting Coronary Artery Disease, AHA, Chicago, Nov. 2018.
38.
Takeshi Soeki, E Uematsu, Tomomi Matsuura, Takeshi Tobiume, Kenya Kusunose, Takayuki Ise, Koji Yamaguchi, Shusuke Yagi, Daiju Fukuda, Hirotsugu Yamada, Tetsuzo Wakatsuki and Masataka Sata : C-type natriuretic peptide improves left ventricular diastolic dysfunction and ischemia/reperfusion injury-associated ventricular arrhythmias., ESC2018, Munich, Aug. 2018.
39.
Hiroyuki Ito, Tetsuzo Wakatsuki, Koji Yamaguchi, Daiju Fukuda, Yutaka Kawabata, Takafumi Todoroki, Tomomi Matsuura, Takayuki Ise, Kenya Kusunose, Takeshi Tobiume, Shusuke Yagi, Hirotsugu Yamada, Takeshi Soeki and Masataka Sata : Growth of vasa vasorum is associated with local inflammation around coronary plaque in fresh cadavers, ESC2018, Munich, Aug. 2018.
40.
Y Saijo, Kenya Kusunose, Mika Bando, H Seno, Robert Zheng, Susumu Nishio, Yukina Hirata, Y Tori, R Amano, Hirotsugu Yamada and Masataka Sata : Localization of myocardial injury in anthracycline-induced cardiotoxicity: evaluation using two-dimensional speckle tracking echocardiography, ESC2018, Munich, Aug. 2018.
41.
Maimaituxun Gulinu, Michio Shimabukuro, Daiju Fukuda, Shusuke Yagi, Hirata Yukina, Takashi Iwase, Tomomi Matsuura, Takayuki Ise, Kenya Kusunose, Takeshi Tobiume, Koji Yamaguchi, Hirotsugu Yamada, Takeshi Soeki, Tetsuzo Wakatsuki and Masataka Sata : Gender disparities of distribution of epicardial adipose tissue and its impact on coronary artery disease, ESC2018, Munich, Aug. 2018.
42.
Kenya Kusunose : Right Ventricular Funcon and Beneficial Effects of Cardiac Rehabilitaon in Paents with Chronic Heart Failure, ASE2018, Tennessee , America, Jun. 2018.
43.
Kenya Kusunose : Coffee and Cases: From Around the World, Echo Hawaii 2018, Kona, USA, Jan. 2018.
44.
Kenya Kusunose : Diastology and Advanced Strain, Echo Hawaii 2018, Kona, USA, Jan. 2018.
45.
Kenya Kusunose : Pulmonary Hypertension and Pulmonary Embolism: Role of Echo, Echo Hawaii 2018, Kona, USA, Jan. 2018.
46.
Kenya Kusunose : Role of Stress Echo in Valvular Heart Disease, Echo Hawaii 2018, Kona, USA, Jan. 2018.
47.
Kenya Kusunose : How to Interpret 3D Echoes, Echo Hawaii 2018, Kona, USA, Jan. 2018.
48.
Junya Kuwahata, Y Saijo, Hirotsugu Yamada, Kenya Kusunose, Hiromitsu Seno, Y Okushi, Susumu Nishio, Yukina Hirata, Torii Yuta and Masataka Sata : Detection of Subtle Changes in Stroke Volume during Pre-load Stress Echocardiography by Three-dimensional Echocardiography using Automated Adaptive Analytics Algorithm, EACVI meeting 2018, Dec. 2017.
49.
Yukina Hirata, Kenya Kusunose, Hirotsugu Yamada, R Shimizu, Yuta Torii, Susumu Nishio, Y Okushi, Hiromitsu Seno, Y Saijo, Takeshi Soeki, Tetsuzo Wakatsuki and Masataka Sata : Quantitative Classification of Left Atrial Appendage is Superior to Visual Classification for Risk Stratification of Stroke in Atrial Fibrillation, EACVI meeting 2018, Dec. 2017.
50.
J. Kuwahata, Y. Saijo, Hirotsugu Yamada, Kenya Kusunose, H. Seno, Y. Okushi, S. Nishio, Y. Hirata, Y. Torii, S. Morita and Masataka Sata : Detection of subtle changes in stroke volume during pre-load stress echocardiography by three-dimensional echocardiography using automated adaptive analytics algorithm, Euro Echo 2017, Portugal, Dec. 2017.
51.
Y. Hirata, Kenya Kusunose, Hirotsugu Yamada, J. Kuwahata, R. Shimizu, Y. Torii, R. Amano, M. Yamao, S. Nishio, H. Seno, Y. Saijo, Takeshi Soeki and Masataka Sata : Association between left atrial appendage morphology and stroke in atrial fibrillation: comparison between quantitative and visual classification, Euro Echo 2017, Portugal, Dec. 2017.
52.
Kenya Kusunose : Clinical Utility of Preload Stress Echocardiography to Predict Outcomes in Low Gradient Aortic Stenosis, Euro Echo 2017, Portugal, Dec. 2017.
53.
Takeshi Soeki, Tomomi Matsuura, E Uematsu, Takeshi Tobiume, Kenya Kusunose, Takayuki Ise, Koji Yamaguchi, Shusuke Yagi, Daiju Fukuda, Hirotsugu Yamada, Tetsuzo Wakatsuki and Masataka Sata : Epicardial Adipose Tissue Produces Proinflammatory Cytokines and Influences the Pathogenesis of Atrial Fibrillation, AHA Scientific Sessions2017, California, America, Nov. 2017.
54.
Yukina Hirata, Kenya Kusunose, Hirotsugu Yamada, J Kuwahata, Y Torii, S Nishio, H Seno, Y Saijo, Koji Yamaguchi, Tetsuzo Wakatsuki and Masataka Sata : Detection of Coronary Artery Stenosis by Epicardial Adipose Tissue Thickness in Type 2 Diabetes, AHA Scientific Sessions2017, California, America, Nov. 2017.
55.
Maimaituxun. Gulinu, Michio Shimabukuro, Y Hirata, Takashi Iwase, S Takao, Tomomi Matsuura, Takayuki Ise, Kenya Kusunose, Takeshi Tobiume, Koji Yamaguchi, Shusuke Yagi, Daiju Fukuda, Hirotsugu Yamada, Takeshi Soeki, Tetsuzo Wakatsuki, M Harada and Masataka Sata : Local Epicardial Adipose Tissue Thickness in Left Anterior Descending Artery Provides a New Prediction Model for Coronary Artery Disease, AHA Scientific Sessions2017, California, America, Nov. 2017.
56.
Kenya Kusunose, Hirotsugu Yamada, S Nishio, Y Torii, Yukina Hirata, H Seno, Y Saijo, Takayuki Ise, Koji Yamaguchi, Shusuke Yagi, Takeshi Soeki, Tetsuzo Wakatsuki and Masataka Sata : Echocardiography Predicts Outcomes in Patients With Preserved Ejection Fraction and Low Gradient Aortic Stenosis, AHA Scientific Sessions2017, California, America, Nov. 2017.
57.
Takeshi Soeki, Tomomi Matsuura, Daiju Fukuda, Etsuko Uematsu, Takeshi Tobiume, T Hara, Kenya Kusunose, Takayuki Ise, Koji Yamaguchi, Shusuke Yagi, Hirotsugu Yamada, Tetsuzo Wakatsuki and Masataka Sata : Activated Factor X Signaling Pathway via Protease-Activated Receptor-2 is a Novel Therapeutic Target to Prevent Atrial Fibrillation, AHA Scientific Sessions2017, California, America, Nov. 2017.
58.
Koji Yamaguchi, Tetsuzo Wakatsuki, Yutaka Kawabata, H Ito, Tomomi Matsuura, Takayuki Ise, Kenya Kusunose, Takeshi Tobiume, Shusuke Yagi, Hirotsugu Yamada, Takeshi Soeki and Masataka Sata : Preserved Endothelial Function and Suppressed Local Coagulative and Inflammatory Response After Biodegradable Polymer SES Implantation Compared to Durable Polymer SES, AHA Scientific Sessions2017, California, America, Nov. 2017.
59.
Tomomi Matsuura, Takeshi Tobiume, Takeshi Soeki, R Kato, M Hara, Kenya Kusunose, Koji Yamaguchi, Shusuke Yagi, Hirotsugu Yamada, Tetsuzo Wakatsuki and Masataka Sata : Direct Slow Pathway Capture: A New Electrophysiological Method of Catheter Ablation for Atrioventricular Nodal Reentrant Tachycardia, AHA Scientific Sessions2017, California, America, Nov. 2017.
60.
Susumu Nishio, Kenya Kusunose, Hirotsugu Yamada, Yukina Hirata, H Seno, Y Saijo, Takayuki Ise, Koji Yamaguchi, Shusuke Yagi, Takeshi Soeki, Tetsuzo Wakatsuki and Masataka Sata : Echocardiographic Epicardial Adipose Tissue Thickness is a Marker for the Detection of Vasospastic Angina, ASE2017, Baltimore, Jun. 2017.
61.
Y Saijo, Hirotsugu Yamada, Kenya Kusunose, H Seno, Y Okushi, Susumu Nishio, Yukina Hirata, Y Torii and Masataka Sata : Left Atrial Dysfunction in Patients with Infarction of Proximal Left Circumflex Artery, ASE2017, Baltimore, Jun. 2017.