There is evidence supporting the notion that excess abdominal fat is predictive of insulin resistance and the presence of related metabolic abnormalities currently referred to as the metabolic syndrome (MetS). Despite the fact that abdominal obesity is a highly prevalent feature of MetS, the mechanisms by which abdominal obesity is causally related to MetS are not fully elucidated. Besides visceral fat accumulation, ectopic lipid deposition, especially in the liver and skeletal muscle, has been implicated in the pathophysiology of diabetes, insulin resistance and obesity-related disorders. In addition, ectopic fat deposition play a critical role in the heart components such as (1) circulatory and locally recruited fat, (2) intra-and extra-myocellular fat, (3) perivascular fat, and (4) pericardial fat. In this review, the contribution of ectopic lipid deposition to global cardiometabolic risk is discussed via possible mechanisms including adipocytokine, insulin resistance and lipotoxicity.
Nobuo Fukuda, Takashi Oki, Arata Iuchi, Tomotsugu Tabata, Hirotsugu Yamada, N Takeichi, H Shinohara and T Soeki : Right heart flow dynamics after tricuspid valve annuloplasty. Characteristics and time course., Japanese Heart Journal Association, Tokyo, 1998.
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.
(要約)
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.
(要約)
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.
(要約)
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.
(要約)
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.
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.
(要約)
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.
(要約)
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.
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.
(要約)
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.
(要約)
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.
(要約)
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.
(要約)
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.
(要約)
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.
(要約)
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.
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.
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.
(要約)
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.
(要約)
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.
(キーワード)
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.
(要約)
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.
(要約)
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.
(要約)
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.
(要約)
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.
(要約)
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.
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.
(要約)
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.
(要約)
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.
(キーワード)
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.
(要約)
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.
(キーワード)
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.
(要約)
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.
(要約)
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.
(要約)
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.
(要約)
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.
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.
(要約)
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.
(要約)
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.
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.
(要約)
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.
(要約)
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.
(要約)
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.
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.
(要約)
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.
T Ogata, H Shimada, T Inoue, S Takeshita, Y Tsuboi, N Uesugi, M Fujiwara, Masataka Sata and Hirotsugu Yamada : Quantification of Carotid Plaque Histology Using iPlaque Software, Ultrasound in Medicine & Biology, Vol.47, No.4, 928-931, 2021.
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.
(要約)
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.
(要約)
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.
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.
(要約)
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, 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.
(要約)
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.
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.
(要約)
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.
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.
(要約)
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, 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.
(要約)
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, 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.
(要約)
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.
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.
(要約)
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.
(要約)
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.
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.
(要約)
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.
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.
(要約)
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.
(要約)
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.
(要約)
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.
(キーワード)
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.
(要約)
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.
(要約)
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.
M Kajikawa, T Maruhashi, T Hidaka, S Matsui, H Hashimoto, Y Takaeko, Y Nakano, S Kurisu, Y Kihara, FM Yusoff, S Kishimoto, K Chayama, C Goto, K Noma, A Nakashima, T Hiro, A Hirayama, K Shiina, H Tomiyama, Shusuke Yagi, Amano Rie, Hirotsugu Yamada, Masataka Sata and Y Higashi : Effect of Saxagliptin on Endothelial Function in Patients with Type 2 Diabetes: A Prospective Multicenter Study, Scientific Reports, Vol.9, No.1, 10206, 2019.
(要約)
The dipeptidyl peptidase-4 inhibitor saxagliptin is a widely used antihyperglycemic agent in patients with type 2 diabetes. The purpose of this study was to evaluate the effects of saxagliptin on endothelial function in patients with type 2 diabetes. This was a prospective, multicenter, interventional study. A total of 34 patients with type 2 diabetes were enrolled at four university hospitals in Japan. Treatment of patients was initially started with saxagliptin at a dose of 5 mg daily. Assessment of endothelial function assessed by flow-mediated vasodilation (FMD) and measurement of stromal cell-derived factor-1α (SDF-1α) were conducted at baseline and at 3 months after treatment with saxagliptin. A total of 31 patients with type 2 diabetes were included in the analysis. Saxagliptin significantly increased FMD from 3.1 ± 3.1% to 4.2 ± 2.4% (P = 0.032) and significantly decreased total cholesterol from 190 ± 24 mg/dL to 181 ± 25 mg/dL (P = 0.002), glucose from 160 ± 53 mg/dL to 133 ± 25 mg/dL (P < 0.001), HbA1c from 7.5 ± 0.6% to 7.0 ± 0.6% (P < 0.001), urine albumin-to-creatinine ratio from 63.8 ± 134.2 mg/g to 40.9 ± 83.0 mg/g (P = 0.043), and total SDF-1α from 2108 ± 243 pg/mL to 1284 ± 345 pg/mL (P < 0.001). These findings suggest that saxagliptin is effective for improving endothelial function.
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.
(要約)
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.
(要約)
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.
(要約)
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.
(要約)
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.
Atsuko Yoshida, Takashi Kaji, Hirotsugu Yamada, Naoto Yonetani, Eishi Sogawa, Masami Yamao, Kazuhisa Maeda, Masataka Sata and Minoru Irahara : Measurement of hemodynamics immediately after vaginal delivery in healthy pregnant women by electrical cardiometry., The Journal of Medical Investigation : JMI, Vol.66, No.1.2, 75-80, 2019.
(要約)
Few reports have focused on hemodynamics around delivery in pregnant women because of the difficulty of continuous and noninvasive measurement. Electrical cardiometry allows noninvasive continuous monitoring of hemodynamics and has recently been used in non-pregnant subjects. We compared the use of electrical cardiometry versus transthoracic echocardiography in healthy pregnant women and evaluated hemodynamics immediately after vaginal delivery. In Study 1, electrical cardiometry and transthoracic echocardiography were used to measure cardiac output in 20 pregnant women with threatened premature delivery. A significant correlation was found between the two methods, with electrical cardiometry showing the higher cardiac output. In Study 2, heart rate, stroke volume, and cardiac output were continuously measured in 15 women during vaginal delivery up to 2 h postpartum. Cardiac output increased markedly because of an increased heart rate and stroke volume at the time of newborn delivery. The heart rate then immediately returned to baseline, while cardiac output remained elevated for at least 2 h after delivery because of a sustained high stroke volume. Electrical cardiometry was as readily available as transthoracic echocardiography for evaluating hemodynamics and allowed for continuous measurement during labor. High intrapartum cardiac output was sustained for at least 2 h after vaginal delivery. J. Med. Invest. 66 : 75-80, February, 2019.
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.
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.
(要約)
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.
(要約)
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.
(キーワード)
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.
(要約)
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.
Yuishin Izumi, Ryosuke Miyamoto, Koji Fujita, Yuki Yamamoto, Hirotsugu Yamada, Tomoyasu Matsubara, Yuki Unai, Ai Tsukamoto, Naoko Takamatsu, Hiroyuki Nodera, Shinya Hayashi, Masaya Oda, Atsuko Mori, Yoshihiko Nishida, Shunsuke Watanabe, Hirohisa Ogawa, Hisanori Uehara, Shigeo Murayama, Masataka Sata and Ryuji Kaji : Distinct Incidence of Takotsubo Syndrome Between Amyotrophic Lateral Sclerosis and Synucleinopathies: A Cohort Study., Frontiers in Neurology, Vol.9, 1099, 2018.
(要約)
Takotsubo syndrome (TTS) is an acute cardiac syndrome characterized by regional left ventricular dysfunction with a peculiar circumferential pattern, which typically results in apical ballooning. Evidence indicates a pivotal role of catecholamines in TTS, and researchers have discussed multiple hypotheses on the etiology, including multivessel coronary spasm, myocardial stunning, excessive transient ventricular afterload, and cardiac sympathetic overactivity with local noradrenaline spillover. Although central nervous system disorders, such as stroke and epilepsy, are known to trigger TTS, the incidence and clinical features of TTS in neurodegenerative disorders are poorly understood. Here, we retrospectively examined TTS cases in a single-center cohort composed of 250 patients with amyotrophic lateral sclerosis (ALS) and 870 patients with synucleinopathies [582 patients with Parkinson's disease (PD), 125 patients with dementia with Lewy bodies (DLB), and 163 patients with multiple system atrophy (MSA)] and identified 4 (1.6%, including 2 women) cases with ALS and no cases with synucleinopathies. Two ALS patients underwent autopsy and the pathological findings were compatible with the chronological changes identified in catecholamine-induced cardiomyopathy. A literature review identified 16 TTS cases with ALS, 1 case each with PD and DLB, and no cases with MSA. When current and previous TTS cases with ALS were concatenated: 55% (11/20) were female; 35% (7/20) had a bulbar-onset and 45% (9/20) had a limb-onset; the mean age of TTS onset was 63.3 ± 9.0 years and the mean interval time from ALS onset to TTS development was 4.9 ± 3.0 years; no (0/16) patients developed TTS within 12 months after ALS onset; 50% (10/20) underwent artificial ventilations; the mortality was 17% (3/18); and most cases had precipitating factors, and TTS development was associated with gastrostomy, tracheostomy, or infections in 45% (9/20) of the patients. This study demonstrated that ALS is a considerable predisposing factor of TTS and that synucleinopathies rarely cause TTS. The distinct TTS incidence between ALS and synucleinopathies may be due to cardiac sympathetic overactivity in ALS and may also be affected by cardiac sympathetic denervation in synucleinopathies. Moreover, the etiology of TTS in ALS may be reasonably explained by the two-hit theory.
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.
(要約)
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.
Yukina Hirata, Hirotsugu Yamada and Masataka Sata : Epicardial Fat and Pericardial Fat Surrounding the Heart Have Different Characteristics., Circulation Journal, Vol.82, No.10, 2475-2476, 2018.
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.
(要約)
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.
(要約)
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.
(要約)
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.
(要約)
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.
(要約)
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.
(要約)
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.
(要約)
-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.
(要約)
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.
K Adachi, S Hashiguchi, M Saito, S Kashiwagi, T Miyazaki, H Kawai, Hirotsugu Yamada, T Iwase, Masashi Akaike, Shoichiro Takao, M Kobayashi, M Ishizaki, T Matsumura, M Mori-Yoshimura and E Kimura : Detection and management of cardiomyopathy in female dystrophinopathy carriers, Journal of the Neurological Sciences, Vol.386, 74-80, 2018.
(要約)
Regular health checkups for mothers of patients with Duchenne muscular dystrophy have been performed at National Hospital Organization Tokushima Hospital since 1994. Among 43 mothers participated in this study, 28 dystrophinopathy carriers were identified. Skeletal and cardiac muscle functions of these subjects were examined. High serum creatine kinase was found in 23 subjects (82.1%). Obvious muscle weakness was present in 5 (17.8%) and had progressed from 1994 to 2015. Cardiomyopathy was observed in 15 subjects (60.0%), including dilated cardiomyopathy-like damage that was more common in the left ventricular (LV) posterior wall. Late gadolinium enhancement on cardiac MRI was found in 5 of 6 subjects, suggesting fibrotic cardiac muscle. In speckle tracking echocardiography performed seven years later, global longitudinal strain was decreased in these subjects, indicating LV myocardial contractile abnormality. These results suggest that female dystrophinopathy carriers should receive regular checkups for detection and treatment of cardiomyopathy, even if they have no cardiac symptoms.
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.
(要約)
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.
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.
(要約)
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.
(要約)
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.
(要約)
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.
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.
(要約)
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.
(要約)
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.
(要約)
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.
(キーワード)
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.
(要約)
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.
(要約)
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.
Dean S. Picone, Martin G. Schultz, Petr Otahal, Svend Aakhus, Ahmed M. Al-Jumaily, J Andrew Black, Willem J. Bos, John B. Chambers, Chen-Huan Chen, Hao-Min Cheng, Antoine Cremer, Justin E. Davies, Nathan Dwyer, Brian A. Gould, Alun D. Hughes, Peter S. Lacy, Esben Laugesen, Fuyou Liang, Roman Melamed, Sandy Muecke, Nobuyuki Ohte, Sho Okada, Stefano Omboni, Christian Ott, Xiaoqing Peng, Telmo Pereira, Giacomo Pucci, Ronak Rajani, Philip Roberts-Thomson, Niklas B. Rossen, Daisuke Sueta, Manish D. Sinha, Roland E. Schmieder, Harold Smulyan, Velandai K. Srikanth, Ralph Stewart, George A. Stouffer, Kenji Takazawa, Jiguang Wang, Berend E. Westerhof, Franz Weber, Thomas Weber, Bryan Williams, Hirotsugu Yamada, Eiichiro Yamamoto and James E. Sharman : Accuracy of Cuff-Measured Blood Pressure: Systematic Reviews and Meta-Analyses., Journal of the American College of Cardiology, Vol.70, No.5, 572-586, 2017.
(要約)
Hypertension (HTN) is the single greatest cardiovascular risk factor worldwide. HTN management is usually guided by brachial cuff blood pressure (BP), but questions have been raised regarding accuracy. This comprehensive analysis determined the accuracy of cuff BP and the consequent effect on BP classification compared with intra-arterial BP reference standards. Three individual participant data meta-analyses were conducted among studies (from the 1950s to 2016) that measured intra-arterial aortic BP, intra-arterial brachial BP, and cuff BP. A total of 74 studies with 3,073 participants were included. Intra-arterial brachial systolic blood pressure (SBP) was higher than aortic values (8.0 mm Hg; 95% confidence interval [CI]: 5.9 to 10.1 mm Hg; p < 0.0001) and intra-arterial brachial diastolic BP was lower than aortic values (-1.0 mm Hg; 95% CI: -2.0 to -0.1 mm Hg; p = 0.038). Cuff BP underestimated intra-arterial brachial SBP (-5.7 mm Hg; 95% CI: -8.0 to -3.5 mm Hg; p < 0.0001) but overestimated intra-arterial diastolic BP (5.5 mm Hg; 95% CI: 3.5 to 7.5 mm Hg; p < 0.0001). Cuff and intra-arterial aortic SBP showed a small mean difference (0.3 mm Hg; 95% CI: -1.5 to 2.1 mm Hg; p = 0.77) but poor agreement (mean absolute difference 8.0 mm Hg; 95% CI: 7.1 to 8.9 mm Hg). Concordance between BP classification using the Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure cuff BP (normal, pre-HTN, and HTN stages 1 and 2) compared with intra-arterial brachial BP was 60%, 50%, 53%, and 80%, and using intra-arterial aortic BP was 79%, 57%, 52%, and 76%, respectively. Using revised intra-arterial thresholds based on cuff BP percentile rank, concordance between BP classification using cuff BP compared with intra-arterial brachial BP was 71%, 66%, 52%, and 76%, and using intra-arterial aortic BP was 74%, 61%, 56%, and 65%, respectively. Cuff BP has variable accuracy for measuring either brachial or aortic intra-arterial BP, and this adversely influences correct BP classification. These findings indicate that stronger accuracy standards for BP devices may improve cardiovascular risk management.
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.
(要約)
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.
(キーワード)
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.
(要約)
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.
Hiroki Matsuzoe, Kensuke Matsumoto, Hidekazu Tanaka, Yutaka Hatani, Keiko Hatazawa, Hiroyuki Shimoura, Junichi Ooka, Hiroyuki Sano, Keiko Ryo-Koriyama, Toshiro Shinke, Hirotsugu Yamada, Yutaka Okita and Ken-Ichi Hirata : Significant Prognostic Value of Acute Preload Stress Echocardiography Using Leg-Positive Pressure Maneuver for Patients With Symptomatic Severe Aortic Stenosis Awaiting Aortic Valve Intervention., Circulation Journal, Vol.81, No.12, 1927-1935, 2017.
(要約)
Although aortic valve intervention is recommended for virtually all symptomatic patients with aortic stenosis (AS), how urgently the intervention should be performed remains controversial. The aim of this study was thus to determine whether the preload reserve in response to leg-positive pressure (LPP) maneuver could serve for decision-making for AS patients awaiting aortic valve intervention.Methods and esults:Sixty-eight patients with symptomatic AS, who were referred for aortic valve intervention, were recruited. Stroke volume (SV) was assessed by means of pulsed-wave Doppler, and the ratio between transmitral E wave and mitral annular velocity (e') was calculated to estimate ventricular filling pressure. While waiting for intervention, 11 patients experienced preoperative cardiac events. During acute preload stress, forward SV for patients without cardiac events increased significantly (from 43 9 to 49 10 mL/m, P<0.01) along with a minimal change in filling pressure (E/e': from 20 8 to 21 9, NS). For patients with cardiac events, the Frank-Starling mechanism was significantly impaired (SVi: from 40 9 to 38 7 mL/m, NS), while filling pressure increased to the critical level (E/e': from 24 8 to 31 8, P<0.001). Both the patients without flow reserve ( SVi <4.5 mL/m) and those without diastolic reserve ( E/e' ·2.9) exhibited significantly worse event-free survival than the others (P<0.05, respectively). Assessment of preload reserve during LPP stress could facilitate risk stratification of patients with severe AS waiting for aortic valve intervention.
(キーワード)
Aged / Aged, 80 and over / Aortic Valve / Aortic Valve Stenosis / Echocardiography, Stress / Female / Humans / Male / Prognosis / Risk Assessment / Ventricular Pressure
Maimaituxun Gulinu, Michio Shimabukuro, Hotimah Masdan Salim, Minoru Tabata, Daisuke Yuji, Yoshihisa Morimoto, Takeshi Akasaka, Tomomi Matsuura, Shusuke Yagi, Daiju Fukuda, Hirotsugu Yamada, Takeshi Soeki, Takaki Sugimoto, Masashi Tanaka, Shuichiro Takanashi and Masataka Sata : Gender-linked impact of epicardial adipose tissue volume in patients who underwent coronary artery bypass graft surgery or non-coronary valve surgery, PLoS ONE, Vol.12, No.6, e0177170, 2017.
(要約)
Traditional and non-traditional risk factors for atherosclerotic cardiovascular disease (ASCVD) are different between men and women. Gender-linked impact of epicardial adipose tissue volume (EATV) in patients undergoing coronary artery bypass grafting (CABG) remains unknown. Gender-linked impact of EATV, abdominal fat distribution and other traditional ASCVD risk factors were compared in 172 patients (men: 115; women: 57) who underwent CABG or non-coronary valvular surgery (non-CABG). In men, EATV, EATV index (EATV/body surface area) and the markers of adiposity such as body mass index, waist circumference and visceral fat area were higher in the CABG group than in the non-CABG group. Traditional ASCVD risk factors were also prevalent in the CABG group. In women, EATV and EATV index were higher in the CABG group, but other adiposity markers were comparable between CABG and non-CABG groups. Multivariate logistic regression analysis showed that in men, CABG was determined by EATV Index and other ASCVD risk factors including hypertension, dyslipidemia, adiponectin, high sensitive C-reactive protein (hsCRP) and type 2 diabetes mellitus (Corrected R2 = 0.262, p < 0.0001), while in women, type 2 diabetes mellitus is a single strong predictor for CABG, excluding EATV Index (Corrected R2 = 0.266, p = 0.005). Our study found that multiple risk factors, including epicardial adipose tissue volume and traditional ASCVD factors are determinants for CABG in men, but type 2 diabetes mellitus was the sole determinant in women. Gender-specific disparities in risk factors of CABG prompt us to evaluate new diagnostic and treatment strategies and to seek underlying mechanisms.
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.
(要約)
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.
(要約)
Adding sitagliptin to conventional antidiabetic regimens in patients with T2DM for 24 months attenuated the annual exacerbation in the echocardiographic parameter of diastolic dysfunction (E/e') independent of other clinical variables such as blood pressure and glycemic control. Trial registration UMIN000004490 (University Hospital Medical Information Network Clinical Trials). https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000005356 ; registered November 1, 2010.
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.
(要約)
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.
Hirofumi Tomiyama, Takashi Miwa, Kenshi Kan, Munehide Matsuhisa, Haruo Kamiya, Mamoru Nanasato, Tomoki Kitano, Hiroaki Sano, Jun Ohno, Masato Iida, Masataka Sata, Hirotsugu Yamada, Koji Maemura, Atsushi Tanaka, Toyoaki Murohara and Koichi Node : Impact of glycemic control with sitagliptin on the 2-year progression of arterial stiffness: a sub-analysis of the PROLOGUE study., Cardiovascular Diabetology, Vol.15, No.1, 150, 2016.
(要約)
No conclusive evidence has been obtained yet on the significance of the effects of dipeptidyl peptidase-4 (DPP-4 inhibitor) treatment on the arterial stiffness in clinical settings. In addition, the effects of good glycemic control on the arterial stiffness have also not been clarified yet. As a sub-analysis of the PROLOGUE study, we examined the effect of a DPP-4 inhibitor (sitagliptin) on the 2-year progression of the arterial stiffness and also to determine the effect of good glycemic control on the rate of progression of the arterial stiffness. In the PROLOGUE study, the study participants were either allocated to add-on sitagliptin treatment or to continued treatment with conventional anti-diabetic agents. Among the 463 participants of the PROLOGUE study, we succeeded in measuring the brachial-ankle pulse wave velocity (baPWV) at least two times during the 2-year study period in 96 subjects. The changes in the baPWV during the study period were similar between the both groups (i.e., with/without staglipitin), overall. On the other hand, when the study subjects were divided into two groups according to the glycemic control status during the study period {good glycemic control group (GC) = hemoglobin (Hb)A1c <7.0 at both 12 and 24 months after the treatment randomization; poor glycemic control group (PC) = HbA1c ≥7.0 at either 12 months, 24 months, or both}, the 2-year increase of the baPWV was marginally significantly larger in the PC group (144 ± 235 cm/s) as compared to that the GC group (-10 ± 282 cm/s) (p = 0.036). While the present study could not confirm the beneficial effect of sitagliptin per se on the arterial stiffness, the results suggested that good glycemic control appears to be beneficial for delaying the annual progression of the arterial stiffness. Trial registration University Hospital Medical Information Network Clinical Trials Registry UMIN000004490.
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.
A Takashima, Daiju Fukuda, K Tanaka, Y Higashikuni, Y Hirata, S Nishimoto, Shusuke Yagi, Hirotsugu Yamada, Takeshi Soeki, Tetsuzo Wakatsuki, Yutaka Taketani, Michio Shimabukuro and Masataka Sata : Combination of n-3 polyunsaturated fatty acids reduces atherogenesis in apolipoprotein E-deficient mice by inhibiting macrophage activation., Atherosclerosis, Vol.254, 142-150, 2016.
(要約)
BACKGROUND AND AIMS: Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are major components of n-3 polyunsaturated fatty acids (n-3 PUFAs) which inhibit atherogenesis, although few studies have examined the effects of the combination of EPA and DHA on atherogenesis. The aim of this study was to investigate whether DHA has additional anti-atherosclerotic effects when combined with EPA.METHODS: Male 8-week-old apolipoprotein E-deficient (Apoe-/-) mice were fed a western-type diet supplemented with different amounts of EPA and DHA; EPA (2.5%, w/w), low-dose EPA + DHA (2.5%, w/w), or high-dose EPA + DHA (5%, w/w) for 20 weeks. The control group was fed a western-type diet containing no n-3 PUFA. Histological and gene expression analysis were performed in atherosclerotic lesions in the aorta. To address the mechanisms, RAW264.7 cells were used.RESULTS: All n-3 PUFA treatments significantly attenuated the development and destabilization of atherosclerotic plaques compared with the control. The anti-atherosclerotic effects were enhanced in the high-dose EPA + DHA group (p < 0.001), whereas the pure EPA group and low-dose EPA + DHA group showed similar results. EPA and DHA additively attenuated the expression of inflammatory molecules in RAW264.7 cells stimulated with LPS. DHA or EPA + DHA suppressed LPS-induced toll-like receptor 4 (TLR4) expression in lipid rafts on RAW264.7 cells (p < 0.05). Lipid raft disruption by methyl--cyclodextrin suppressed mRNA expression of inflammatory molecules in LPS-stimulated macrophages.CONCLUSION: n-3 PUFAs suppressed atherogenesis. DHA combined with EPA had additional anti-inflammatory effects and inhibited atherogenesis in Apoe-/- mice. The reduction of TLR4 expression in lipid rafts in macrophages by DHA might be involved in this mechanism, at least partially.
Tatsuya Maruhashi, Yukihito Higashi, Yasuki Kihara, Hirotsugu Yamada, Masataka Sata, Shinichiro Ueda, Masato Odawara, Yasuo Terauchi, Kazuoki Dai, Jun Ohno, Masato Iida, Hiroaki Sano, Hirofumi Tomiyama, Teruo Inoue, Atsushi Tanaka, Toyoaki Murohara and Koichi Node : Long-term effect of sitagliptin on endothelial function in type 2 diabetes: a sub-analysis of the PROLOGUE study., Cardiovascular Diabetology, Vol.15, No.1, 134, 2016.
(要約)
As a sub-analysis of the PROLOGUE study, we evaluated the long-term effect of sitagliptin, a dipeptidyl peptidase 4 inhibitor, on endothelial function in the conduit brachial artery in patients with type 2 diabetes. In the PROLOGUE study, patients were randomly assigned to either add-on sitagliptin treatment (sitagliptin group) or continued conventional antihyperglycemic treatment (conventional group). Among the 463 participants in the PROLOGUE study, FMD was measured in 17 patients in the sitagliptin group and 18 patients in the conventional group at the beginning and after 12 and 24 months of treatment. HbA1c levels were significantly decreased after 12 and 24 months of treatment compared to baseline values in both groups (7.0 0.4 vs. 6.6 0.3 and 6.6 0.4 % in the sitagliptin group; 7.0 0.6 vs. 6.6 0.7 and 6.6 0.7 % in the conventional group; P < 0.05, respectively). There was no significant difference between FMD values at baseline and after 12 and 24 months in the sitagliptin group (4.3 2.6 vs. 4.4 2.1 and 4.4 2.3 %, P = 1.0, respectively). Although FMD had a tendency to increase from 4.3 2.4 % at baseline to 5.2 1.9 % after 12 months and 5.1 2.2 % after 24 months in the conventional group, there was no significant difference between FMD values at baseline and after 12 and 24 months (P = 0.36 and 0.33, respectively). Add-on sitagliptin to conventional antihyperglycemic drugs in patients with type 2 diabetes did not alter endothelial function in the conduit brachial artery measured by FMD during a 2-year study period. Sitagliptin may be used without concern for an adverse effect on endothelial function in patients with type 2 diabetes. University hospital Medical Information Network (UMIN) Center: ID UMIN000004490.
(キーワード)
Aged / Biomarkers / Blood Glucose / Brachial Artery / Diabetes Mellitus, Type 2 / Dipeptidyl-Peptidase IV Inhibitors / Drug Therapy, Combination / Endothelium, Vascular / Female / Glycated Hemoglobin A / Humans / 日本 (Japan) / Male / Middle Aged / Prospective Studies / Sitagliptin Phosphate / Time Factors / Treatment Outcome / Vasodilation
A Tanaka, T Murohara, I Taguchi, K Eguchi, M Suzuki, M Kitakaze, Y Sato, T Ishizu, Y Higashi, Hirotsugu Yamada, M Nanasato, Michio Shimabukuro, H Teragawa, S Ueda, S Kodera, Munehide Matsuhisa, T Kadokami, K Kario, Y Nishio, T Inoue, K Maemura, J Oyama, M Ohishi, Masataka Sata, H Tomiyama, K Node and Investigators Study PROTECT : Rationale and design of a multicenter randomized controlled study to evaluate the preventive effect of ipragliflozin on carotid atherosclerosis: the PROTECT study., Cardiovascular Diabetology, Vol.15, No.1, 133, 2016.
(要約)
BACKGROUND: Type 2 diabetes mellitus is associated strongly with an increased risk of micro- and macro-vascular complications, leading to impaired quality of life and shortened life expectancy. In addition to appropriate glycemic control, multi-factorial intervention for a wide range of risk factors, such as hypertension and dyslipidemia, is crucial for management of diabetes. A recent cardiovascular outcome trial in diabetes patients with higher cardiovascular risk demonstrated that a SGLT2 inhibitor markedly reduced mortality, but not macro-vascular events. However, to date there is no clinical evidence regarding the therapeutic effects of SGLT2 inhibitors on arteriosclerosis. The ongoing PROTECT trial was designed to assess whether the SGLT2 inhibitors, ipragliflozin, prevented progression of carotid intima-media thickness in Japanese patients with type 2 diabetes mellitus.METHODS: A total of 480 participants with type 2 diabetes mellitus with a HbA1c between 6 and 10 % despite receiving diet/exercise therapy and/or standard anti-diabetic agents for at least 3 months, will be randomized systematically (1:1) into either ipragliflozin or control (continuation of conventional therapy) groups. After randomization, ipragliflozin (50-100 mg once daily) will be added on to the background therapy in participants assigned to the ipragliflozin group. The primary endpoint of the study is the change in mean intima-media thickness of the common carotid artery from baseline to 24 months. Images of carotid intima-media thickness will be analyzed at a central core laboratory in a blinded manner. The key secondary endpoints include the change from baseline in other parameters of carotid intima-media thickness, various metabolic parameters, and renal function. Other cardiovascular functional tests are also planned for several sub-studies.DISCUSSION: The PROTECT study is the first to assess the preventive effect of ipragliflozin on progression of carotid atherosclerosis using carotid intima-media thickness as a surrogate marker. The study has potential to clarify the protective effects of ipragliflozin on atherosclerosis. Trial registration Unique Trial Number, UMIN000018440 ( https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000021348 ).
(キーワード)
Adult / Aged / Biomarkers / Carotid Artery Diseases / Carotid Artery, Common / Carotid Intima-Media Thickness / Clinical Protocols / Diabetes Mellitus, Type 2 / Diabetic Angiopathies / Drug Therapy, Combination / Female / Glucosides / Hemoglobin A, Glycosylated / Humans / Hypoglycemic Agents / Japan / Male / Middle Aged / Prospective Studies / Research Design / Sodium-Glucose Transporter 2 / Thiophenes / Time Factors / Treatment Outcome / Young Adult
M Kadota, Takayuki Ise, Shusuke Yagi, Takashi Iwase, Masashi Akaike, R Ueno, Y Kawabata, T Hara, K Ogasawara, Mika Bando, S Bando, Tomomi Matsuura, Koji Yamaguchi, Hirotsugu Yamada, Takeshi Soeki, Tetsuzo Wakatsuki and Masataka Sata : Response prediction and influence of tolvaptan in chronic heart failure patients considering the interaction of the renin-angiotensin-aldosterone system and arginine vasopressin., International Heart Journal, Vol.57, No.4, 461-465, 2016.
(要約)
The renin-angiotensin-aldosterone system (RAAS) and arginine vasopressin (AVP) regulate body fluids. Although conventional diuretics have been used for treating heart failure, they activate RAAS and exacerbate renal function. Tolvaptan, a newly developed vasopressin-2 receptor antagonist, elicits aquaresis and improves volume overload in heart failure patients, however, the predictors of tolvaptan effectiveness and the influence on the RAAS and renal function according to tolvaptan therapy are not established. We evaluated 26 chronic heart failure patients receiving therapy with 15 mg/day tolvaptan and examined their laboratory and urinary data before and after tolvaptan therapy. A response to tolvaptan was defined as a body weight decrease by more than 2 kg in a week and a urine volume increase by 500 mL/ day compared with that before tolvaptan administration. Body weight, urine volume, and brain natriuretic peptide levels significantly improved (P < 0.05), without any worsening of renal function represented by serum creatinine, sodium, and potassium. Moreover, no significant changes were observed in the plasma renin activity and plasma aldosterone concentration (PAC). In the responder group, urine osmolality before tolvaptan administration was significantly higher (P < 0.05) but declined significantly after tolvaptan administration (P < 0.05). The AVP/PAC ratio before administration was positively correlated with the efficacy of tolvaptan. Tolvaptan treatment could prevent RAAS activation in chronic heart failure patients. Moreover, monitoring the AVP/PAC ratio may be useful in predicting the tolvaptan response.
(キーワード)
Adult / Aged / Aged, 80 and over / Antidiuretic Hormone Receptor Antagonists / Arginine Vasopressin / Benzazepines / Body Mass Index / Female / Heart Failure / Humans / Male / Middle Aged / Prospective Studies / Renin-Angiotensin System / Treatment Outcome
J Oyama, T Murohara, M Kitakaze, T Ishizu, Y Sato, K Kitagawa, H Kamiya, M Ajioka, M Ishiara, K Dai, M Nanasato, Masataka Sata, K Maemura, H Tomiyama, Y Higashi, K Kaku, Hirotsugu Yamada, Munehide Matsuhisa, K Yamashita, YK Bando, N Kashihara, S Ueda, T Inoue, K Node and Investigators Study PROLOGUE : The Effect of Sitagliptin on Carotid Artery Atherosclerosis in Type 2 Diabetes: The PROLOGUE Randomized Controlled Trial., PLoS Medicine, Vol.13, No.6, e1002051, 2016.
(要約)
BACKGROUND: Experimental studies have suggested that dipeptidyl peptidase-4 (DPP-4) inhibitors provide cardiovascular protective effects. We performed a randomized study to evaluate the effects of sitagliptin added on to the conventional therapy compared with conventional therapy alone (diet, exercise, and/or drugs, except for incretin-related agents) on the intima-media thickness (IMT) of the carotid artery, a surrogate marker for the evaluation of atherosclerotic cardiovascular disease, in people with type 2 diabetes mellitus (T2DM).METHODS AND FINDINGS: We used a multicenter PROBE (prospective, randomized, open label, blinded endpoint) design. Individuals aged 30 y with T2DM (6.2% HbA1c < 9.4%) were randomly allocated to receive either sitagliptin (25 to 100 mg/d) or conventional therapy. Carotid ultrasound was performed at participating medical centers, and all parameters were measured in a core laboratory. Of the 463 enrolled participants with T2DM, 442 were included in the primary analysis (sitagliptin group, 222; conventional therapy group, 220). Estimated mean (± standard error) common carotid artery IMT at 24 mo of follow-up in the sitagliptin and conventional therapy groups was 0.827 ± 0.007 mm and 0.837 ± 0.007 mm, respectively, with a mean difference of -0.009 mm (97.2% CI -0.028 to 0.011, p = 0.309). HbA1c level at 24 mo was significantly lower with sitagliptin than with conventional therapy (6.56% ± 0.05% versus 6.72% ± 0.05%, p = 0.008; group mean difference -0.159, 95% CI -0.278 to -0.041). Episodes of serious hypoglycemia were recorded only in the conventional therapy group, and the rate of other adverse events was not different between the two groups. As it was not a placebo-controlled trial and carotid IMT was measured as a surrogate marker of atherosclerosis, there were some limitations of interpretation.CONCLUSIONS: In the PROLOGUE study, there was no evidence that treatment with sitagliptin had an additional effect on the progression of carotid IMT in participants with T2DM beyond that achieved with conventional treatment.TRIAL REGISTRATION: University Hospital Medical Information Network Clinical Trials Registry UMIN000004490.
Jun-Ichi Oyama, Atsushi Tanaka, Yasunori Sato, Hirofumi Tomiyama, Masataka Sata, Tomoko Ishizu, Isao Taguchi, Takanori Kuroyanagi, Hiroki Teragawa, Nobukazu Ishizaka, Yumiko Kanzaki, Mitsuru Ohishi, Kazuo Eguchi, Yukihito Higashi, Hirotsugu Yamada, Koji Maemura, Junya Ako, Yasuko K. Bando, Shinichiro Ueda, Teruo Inoue, Toyoaki Murohara and Koichi Node : Rationale and design of a multicenter randomized study for evaluating vascular function under uric acid control using the xanthine oxidase inhibitor, febuxostat: the PRIZE study., Cardiovascular Diabetology, Vol.15, No.1, 87, 2016.
(要約)
BACKGROUND: Xanthine oxidase inhibitors are anti-hyperuricemic drugs that decrease serum uric acid levels by inhibiting its synthesis. Xanthine oxidase is also recognized as a pivotal enzyme in the production of oxidative stress. Excess oxidative stress induces endothelial dysfunction and inflammatory reactions in vascular systems, leading to atherosclerosis. Many experimental studies have suggested that xanthine oxidase inhibitors have anti-atherosclerotic effects by decreasing in vitro and in vivo oxidative stress. However, there is only limited evidence on the clinical implications of xanthine oxidase inhibitors on atherosclerotic cardiovascular disease in patients with hyperuricemia. We designed the PRIZE study to evaluate the effects of febuxostat on a surrogate marker of cardiovascular disease risk, ultrasonography-based intima-media thickness of the carotid artery in patients with hyperuricemia.METHODS: The study is a multicenter, prospective, randomized, open-label and blinded-endpoint evaluation (PROBE) design. A total of 500 patients with asymptomatic hyperuricemia (uric acid >7.0 mg/dL) and carotid intima-media thickness 1.1 mm will be randomized centrally to receive either febuxostat (10-60 mg/day) or non-pharmacological treatment. Randomization is carried out using the dynamic allocation method stratified according to age (<65, 65 year), gender, presence or absence of diabetes mellitus, serum uric acid (<8.0, 8.0 mg/dL), and carotid intima-media thickness (<1.3, 1.3 mm). In addition to administering the study drug, we will also direct lifestyle modification in all participants, including advice on control of body weight, sleep, exercise and healthy diet. Carotid intima-media thickness will be evaluated using ultrasonography performed by skilled technicians at a central laboratory. Follow-up will be continued for 24 months. The primary endpoint is percentage change in mean intima-media thickness of the common carotid artery 24 months after baseline, measured by carotid ultrasound imaging.CONCLUSIONS: PRIZE will be the first study to provide important data on the effects of febuxostat on atherosclerosis in patients with asymptomatic hyperuricemia. Trial Registration Unique trial Number, UMIN000012911 ( https://upload.umin.ac.jp/cgi-open-bin/ctr/ctr.cgi?function=brows&action=brows&type=summary&recptno=R000015081&language=E ).
M Akaishi, T Asanuma, C Izumi, S Iwanaga, H Kawai, M Daimon, H Toide, S Hashimoto, A Hayashida, Hirotsugu Yamada and S Nakatani : Guidelines for conducting transesophageal echocardiography (TEE) : Task force for guidelines for conducting TEE., Journal of Echocardiography, Vol.14, No.2, 47-48, 2016.
Michio Shimabukuro, C Okawa, Hirotsugu Yamada, S Yanagi, E Uematsu, N Sugasawa, Hirotsugu Kurobe, Y Hirata, JR Kim-Kaneyama, XF Lei, S Takao, Y Tanaka, Daiju Fukuda, Shusuke Yagi, Takeshi Soeki, Tetsuya Kitagawa, H Masuzaki, M Sato and Masataka Sata : The pathophysiological role of oxidized cholesterols in epicardial fat accumulation and cardiac dysfunction: A study in swine fed a high caloric diet with an inhibitor of intestinal cholesterol absorption, ezetimibe., The Journal of Nutritional Biochemistry, Vol.35, 66-73, 2016.
(要約)
Oxidized cholesterols (oxycholesterols) in food have been recognized as strong atherogenic components, but their tissue distributions and roles in cardiovascular diseases remain unclear. To investigate whether accumulation of oxycholesterols is linked to cardiac morphology and function, and whether reduction of oxycholesterols can improve cardiac performance, domestic male swine were randomized to a control diet (C), high caloric diet (HCD) or HCD+Ezetimibe, an inhibitor of intestinal cholesterol absorption, group (HCD+E) and evaluated for: (1) distribution of oxycholesterol components in serum and tissues, (2) levels of oxycholesterol-related enzymes, (3) paracardial and epicardial coronary fat thickness, and (4) cardiac performance. Ezetimibe treatment for 8weeks attenuated increases in oxycholesterols in the HCD group almost completely in liver, but reduced only levels of 4β-hydroxycholesterol in left ventricular (LV) myocardium. Ezetimibe treatment altered the expression of genes for cholesterol and fatty acid metabolism and decreased the expression of CYP3A46, which catabolizes cholesterol to 4β-hydroxycholesterol, strongly in liver. An increase in epicardial fat thickness and impaired cardiac performance in the HCD group were improved by ezetimibe treatment, and the improvement was closely related to the reduction in levels of 4β-hydroxycholesterol in LV myocardium. In conclusion, an increase in oxycholesterols in the HCD group was closely related to cardiac hypertrophy and dysfunction, as well as an increase in epicardial fat thickness. Ezetimibe may directly reduce oxycholesterol in liver and LV myocardium, and improve cardiac morphology and function.
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.
(要約)
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.
(要約)
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.
(キーワード)
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.
(要約)
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.
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.
(要約)
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.
(要約)
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.
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.
S Hayashi, Hirotsugu Yamada, Makoto Fukui, Hiro-O Ito and Masataka Sata : Correlation between arteriosclerosis and periodontal condition assessed by lactoferrin and [alpha]1-antitrypsin levels in gingival crevicular fluid., International Heart Journal, Vol.56, No.6, 639-643, 2015.
(要約)
Patients with periodontal disease exhibit exacerbated atherosclerosis, aortic stiffness, or vascular endothelial dysfunction. However, in a recent scientific statement, the American Heart Association noted that neither has periodontal disease been proven to cause atherosclerotic vascular disease nor has the treatment of periodontal disease been proven to prevent atherosclerotic vascular disease. Therefore, the aim of the present study was to examine the correlation between periodontal condition and arteriosclerosis in patients with coronary artery disease (CAD), which is usually accompanied by systemic arteriosclerosis.We measured levels of gingival crevicular fluid lactoferrin (GCF-Lf) and 1-antitrypsin (GCF-AT) in 72 patients (67 ± 8 years, 56 men) with CAD. Furthermore, we evaluated the maximum intima-media thickness (max IMT) and plaque score of the carotid arteries as well as brachial-ankle pulse wave velocity (baPWV) and flow-mediated dilation (FMD) of the brachial artery, each of which is a parameter for determining arteriosclerosis status. The average level of GCF-Lf was 0.29 ± 0.36 µg/mL and that of GCF-AT was 0.31 ± 0.66 µg/mL, with significant correlation between the two (r = 0.701, P < 0.001). No significant difference in GCF-Lf and GCF-AT levels was observed between patients with single-, double-, and triple-vessel CAD. There were no significant correlations between the arteriosclerosis parameters (ie, max IMT, plaque score, baPWV, and FMD) and GCF-Lf or GCF-AT.No correlation between the GCF biomarkers and the severity of arteriosclerosis was detected. This result may suggest that worsening of the periodontal condition assessed by GCF biomarkers is not a major potential risk factor for arteriosclerosis.
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.
(要約)
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.
(キーワード)
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.
(要約)
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.
S Bando, Daiju Fukuda, Takeshi Soeki, S Nishimoto, E Uematsu, Tomomi Matsuura, Takayuki Ise, Takeshi Tobiume, Koji Yamaguchi, Shusuke Yagi, Takashi Iwase, Hirotsugu Yamada, Tetsuzo Wakatsuki, Michio Shimabukuro and Masataka Sata : Expression of NLRP3 in subcutaneous adipose tissue is associated with coronary atherosclerosis., Atherosclerosis, Vol.242, No.2, 407-414, 2015.
(要約)
ObjectivesThe promotion of adipose tissue inflammation by lifestyle-related diseases such as obesity and diabetes accelerates atherogenesis; however, the underlying mechanisms remain incompletely understood. Nucleotide-binding domain, leucine-rich-containing family, pyrin domain-containing-3 (NLRP3) inflammasome contributes to chronic inflammation in adipose tissue. Here, we investigated the link between NLRP3 expression in subcutaneous adipose tissue (SAT) and the severity of coronary atherosclerosis.Methods and resultsSAT was obtained from 72 patients who underwent heart device implantation and coronary angiography. Expression of NLRP3 inflammasome-related molecules (NLRP3, IL-1 and IL-18) in SAT were evaluated by quantitative RT-PCR. Laboratory markers related to lifestyle-related diseases were measured. Patients with obesity, dyslipidemia (P < 0.05, respectively), diabetes or hyperuricemia (P < 0.01, respectively) had significantly higher expression of NLRP3. Multivariate analysis demonstrated that body mass index and serum level of uric acid were predictors of NLRP3 expression in SAT. The expression of NLRP3 in SAT correlated negatively with serum adiponectin level (r = 0.23, P < 0.05). Patients with coronary artery disease showed higher NLRP3 expression than patients without significant stenosis (P < 0.01). Furthermore, the expression of NLRP3 in SAT correlated positively with the severity of coronary atherosclerosis as determined by Gensini score (r = 0.47, P < 0.0001) or SYNTAX score (r = 0.55, P < 0.0001). Multiple regression analysis revealed that the expression of NLRP3 in SAT remains as an independent predictors for the severity of coronary atherosclerosis.ConclusionsThe expression of NLRP3 in SAT, which is affected by lifestyle-related diseases, is associated with the severity of coronary atherosclerosis. Our results suggest that NLRP3 inflammasome in SAT may have a role in atherogenesis.
Hara Tomoya, Daiju Fukuda, Tanaka Kimie, Higashikuni Yasutomi, Hirata Yoichiro, Shusuke Yagi, Hirotsugu Yamada, Takeshi Soeki, Tetsuzo Wakatsuki, Michio Shimabukuro and Masataka Sata : Rivaroxaban, a novel oral anticoagulant, attenuates atherosclerotic plaque progression and destabilization in ApoE-deficient mice., Atherosclerosis, Vol.242, No.2, 639-646, 2015.
(要約)
OBJECTIVE: Activated factor X (FXa) plays a key role in the coagulation cascade, whereas accumulating evidence suggests that it also contributes to the pathophysiology of chronic inflammation on the vasculature. In this study, we assessed the hypothesis that rivaroxaban (Riv), a direct FXa inhibitor, inhibits atherogenesis by reducing macrophage activation.METHODS AND RESULTS: Expression levels of PAR-1 and PAR-2, receptors for FXa, increased in the aorta of apolipoprotein E-deficient (ApoE(-/-)) mice compared with wild-type mice (P < 0.01, P < 0.05, respectively). Administration of Riv (5 mg/kg/day) for 20 weeks to 8-week-old ApoE(-/-) mice reduced atherosclerotic lesion progression in the aortic arch as determined by en-face Sudan IV staining compared with the non-treated group (P < 0.05) without alteration of plasma lipid levels and blood pressure. Histological analyses demonstrated that Riv significantly decreased lipid deposition, collagen loss, macrophage accumulation and matrix metallopeptidase-9 (MMP-9) expression in atherosclerotic plaques in the aortic root. Quantitative RT-PCR analyses using abdominal aorta revealed that Riv significantly reduced mRNA expression of inflammatory molecules, such as MMP-9, tumor necrosis factor- (TNF-). In vitro experiments using mouse peritoneal macrophages or murine macrophage cell line RAW264.7 demonstrated that FXa increased mRNA expression of inflammatory molecules (e.g., interleukin (IL)-1 and TNF-), which was blocked in the presence of Riv.CONCLUSIONS: Riv attenuates atherosclerotic plaque progression and destabilization in ApoE(-/-) mice, at least in part by inhibiting pro-inflammatory activation of macrophages. These results indicate that Riv may be particularly beneficial for the management of atherosclerotic diseases, in addition to its antithrombotic activity.
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.
(要約)
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.
Michio Shimabukuro, Yoshimasa Hasegawa, Moritake Higa, Rie Amano, Hirotsugu Yamada, Shunsaku Mizushima, Hiroaki Masuzaki and Masataka Sata : Subclinical carotid atherosclerosis burden in Japanese: comparison between Okinawa and Nagano residents., Journal of Atherosclerosis and Thrombosis, Vol.22, No.8, 854-868, 2015.
(要約)
AIM: The prevalence of overweight and a change in atherosclerotic lipid profiles may be linked to region-specific differences in atherosclerotic diseases. We evaluated whether the lipid phenotype could be linked to region- and sex-specific differences in the degree of atherosclerosis.METHODS: Non-diabetic subjects included Okinawa (n=1674) and Nagano (n=1392) residents aged 30-75 years who underwent carotid ultrasonography for the measurement of maximum intima-media thickness (max IMT).RESULTS: Average max IMT was higher in Okinawa men and women, and the increase in max IMT with age was enhanced in men. Multiple regression analysis showed that in addition to age and systolic blood pressure, low-density lipoprotein cholesterol and non-high-density lipoprotein cholesterol were IMT determinants only in men for both Okinawa and Nagano. Meanwhile, HDL-cholesterol was a determinant for Okinawa men and women, but not for Nagano men and women.CONCLUSIONS: This is the first report to show region- and sex-specific differences in the determinants for max IMT in a Japanese population. The evaluation of the relationship between lipid profile patterns and region- and sex-specific differences in carotid atherosclerosis burden may be required.
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.
(要約)
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.
Shusuke Yagi, Ken-ichi Aihara, Masashi Akaike, Daiju Fukuda, HM Salim, Masayoshi Ishida, Tomomi Matsuura, Takayuki Ise, Koji Yamaguchi, Takashi Iwase, Hirotsugu Yamada, Takeshi Soeki, Tetsuzo Wakatsuki, Michio Shimabukuro, Toshio Matsumoto and Masataka Sata : Predictive factors for efficacy of dipeptidyl peptidase-4 inhibitors in patients with type 2 diabetes mellitus., Diabetes & Metabolism Journal, Vol.39, No.4, 342-347, 2015.
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BACKGROUND: Predictive factors for the efficacy of dipeptidyl peptidase-4 (DPP-4) inhibitors for lowering glycosylated hemoglobin (HbA1c) remain unclear in patients with type 2 diabetes mellitus. The aim of this study is therefore to clarify predictive factors of the efficacy of DPP-4 inhibitors for lowering HbA1c after 12 months of treatment.METHODS: A total of 191 consecutive type 2 diabetic patients (male sex 55%, mean age, 68.3±35.8 years), who had been treated with DPP-4 inhibitors for 12 months, were enrolled in this study and evaluated retrospectively.RESULTS: After 12 months of DPP-4 inhibitor treatment, random blood glucose level, and HbA1c level, decreased from 167±63 to 151±49 mg/dL (P<0.01), and from 7.5%±1.3% to 6.9%±0.9% (P<0.01) respectively, without severe side effects. Multiple regression analysis showed that predictors of DPP-4 inhibitor treatment efficacy in lowering HbA1c level after 12 months were a decrease in HbA1c level after 3 months of treatment, a high baseline HbA1c level, a low baseline body mass index, and the absence of coronary artery disease.CONCLUSION: Most suitable candidates for treatment with DPP-4 inhibitors are diabetics who are not obese and do not have coronary artery disease. In addition, long-term efficacy of DPP-4 inhibitors can be predicted by decrement of HbA1c after 3 months of treatment.
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.
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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.
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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.
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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).
S Hayashi, Hirotsugu Yamada, Mika Bando, Y Saijo, S Nishio, Y Hirata, AL Klein and Masataka Sata : Optimal analysis of left atrial strain by speckle tracking echocardiography: P-wave versus R-wave trigger., Echocardiography, Vol.32, No.8, 1241-1249, 2015.
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BACKGROUND: Left atrial (LA) strain analysis using speckle tracking echocardiography is useful for assessing LA function. However, there is no established procedure for this method. Most investigators have determined the electrocardiographic R-wave peak as the starting point for LA strain analysis. To test our hypothesis that P-wave onset should be used as the starting point, we measured LA strain using 2 different starting points and compared the strain values with the corresponding LA volume indices obtained by three-dimensional (3D) echocardiography.METHODS: We enrolled 78 subjects (61 ± 17 years, 25 males) with and without various cardiac diseases in this study and assessed global longitudinal LA strain by two-dimensional speckle tracking strain echocardiography using EchoPac software. We used either R-wave peak or P-wave onset as the starting point for determining LA strains during the reservoir (Rres, Pres), conduit (Rcon, Pcon), and booster pump (Rpump, Ppump) phases. We determined the maximum, minimum, and preatrial contraction LA volumes, and calculated the LA total, passive, and active emptying fractions using 3D echocardiography.RESULTS: The correlation between Pres and LA total emptying fraction was better than the correlation between Rres and LA total emptying fraction (r = 0.458 vs. 0.308, P = 0.026). Pcon and Ppump exhibited better correlation with the corresponding 3D echocardiographic parameters than Rcon (r = 0.560 vs. 0.479, P = 0.133) and Rpump (r = 0.577 vs. 0.345, P = 0.003), respectively.CONCLUSIONS: LA strain in any phase should be analyzed using P-wave onset as the starting point rather than R-wave peak.
Hirotsugu Yamada and Masataka Sata : Does echocardiographic epicardial adipose tissue thickness become a useful biomarker?, Journal of Atherosclerosis and Thrombosis, Vol.22, No.6, 555-556, 2015.
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.
Shusuke Yagi, Ken-ichi Aihara, Daiju Fukuda, Akira Takashima, Tomoya Hara, Junko Hotsuchi, Takayuki Ise, Koji Yamaguchi, Takeshi Tobiume, Takashi Iwase, Hirotsugu Yamada, Takeshi Soeki, Tetsuzo Wakatsuki, Michio Shimabukuro, Masashi Akaike and Masataka Sata : Effects of docosahexaenoic acid on the endothelial function in patients with coronary artery disease., Journal of Atherosclerosis and Thrombosis, Vol.22, No.5, 447-454, 2015.
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AIM: The consumption of n-3 polyunsaturated fatty acids (PUFA), including docosahexaenoic acid DHA), reduces the incidence of cardiovascular events, and reduced serum levels of n-3 PUFA may be associated with an increased risk of cardiovascular events. However, controversy remains regarding which components of PUFA are associated with the endothelial function in patients with coronary artery disease (CAD). We therefore examined the associations between the n-3 and n-6 PUFA levels and CAD.METHODS: We retrospectively reviewed 160 consecutive Japanese patients with CAD whose endothelial function was measured according to the percent change in flow-mediated dilation (FMD) and the serum levels of n-3 PUFA, including eicosapentaenoic acid (EPA) and DHA, and n-6 PUFA, including arachidonic acid (AA) and dihomo-gamma-linolenic acid (DHLA).RESULTS: A single regression analysis showed no relationships between the FMD and the serum levels of PUFA, including EPA, DHA, AA and DHLA. In contrast, a multiple regression analysis showed that the DHA level was a positive (P0.01) and age was a negative (P0.001) contributor to an increased FMD; however, sex, body mass index, systolic and diastolic blood pressure, current/past smoking and the levels of HbA1c, triglycerides, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, EPA, AA and DHLA did not significantly affect the outcome.CONCLUSIONS: The serum level of DHA is associated with the endothelial function evaluated according to the FMD in patients with CAD, thus suggesting that a low serum level of DHA may be a predictive biomarker for endothelial dysfunction.
Toshiyuki Niki, Takeshi Soeki, Koji Yamaguchi, Yoshio Taketani, Shusuke Yagi, Takashi Iwase, Hirotsugu Yamada, Tetsuzo Wakatsuki, Michio Shimabukuro and Masataka Sata : Elevated concentration of interferon-inducible protein of 10 kD (IP-10) is associated with coronary atherosclerosis., International Heart Journal, Vol.56, No.3, 269-272, 2015.
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Several studies have shown that various chemokines are more highly expressed in atherosclerotic plaques than in normal vessel walls. In the present study, we investigated the relationship between coronary atherosclerosis and noteworthy chemokines, including interferon-inducible protein of 10 kD (IP-10); monocyte chemoattractant protein 1 (MCP-1); regulated on activation, normal T-cell expressed and secreted (RANTES); and high-sensitivity C-reactive protein (hsCRP), an established marker of atherosclerotic disease. We studied 28 patients who underwent coronary angiography because of suspected coronary artery disease (CAD). CAD was defined as stenosis of more than 50% of the vessel diameter on coronary angiograms. Blood samples were obtained both from the aorta and the coronary sinus (CS) just before coronary angiography. Relative to CAD (-) patients, those who were CAD (+) tended to have higher plasma concentrations of IP-10 in the aorta, as well as significantly higher transcoronary concentration gradients of circulating IP-10. There were no significant differences between the two groups in aortic plasma concentrations or transcoronary concentration gradients of MCP-1, RANTES, and hsCRP. Furthermore, both the aortic plasma concentrations and transcoronary concentration gradients of IP-10 correlated with the Gensini score (r = 0.58 and r = 0.63, respectively, P < 0.01), while the plasma MCP-1, RANTES, and serum hsCRP concentrations did not. This study suggests that IP-10 is a good surrogate marker of coronary atherosclerosis.
S Hayashi, Hirotsugu Yamada, S Nishio, Junko Hotsuchi, Mika Bando, Y Takagawa, Y Saijo, Y Hirata and Masataka Sata : Age-and gender-specific changes of tricuspid annular motion velocities in normal hearts., Journal of Cardiology, Vol.65, No.5, 397-402, 2015.
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Mitral annular motion (MAM) and tricuspid annular motion (TAM) velocities obtained by pulsed tissue Doppler echocardiography have been used to evaluate left ventricular (LV) and right ventricular (RV) functions. Although TAM velocity has been clinically applied for evaluating various cardiac diseases, the effects of age and gender remain unclear. Therefore, we aimed to determine the effects of age and gender on TAM velocity in normal hearts. We randomly selected 265 subjects (mean age, 59 years; range, 20-89 years) without abnormal clinical, electrocardiographic, and echocardiographic findings from a pool of subjects who had undergone transthoracic echocardiography. They were classified into four age groups: 20-39, 40-59, 60-79, and >80 years. Pulsed wave Doppler was applied to obtain MAM velocity of the lateral side and TAM velocity of the RV free wall side. The peak systolic (s'), early diastolic (e'), and atrial systolic (a') velocities of MAM and TAM were measured in all subjects. While MAM-s' (r=-0.267, p<0.001) correlated with age, TAM-s' did not (p=0.755). TAM-s' in any age groups had no significant gender differences. TAM-e' (r=-0.447, p<0.001) and MAM-e' (r=-0.724, p<0.001) correlated with age, respectively. In those aged 40-59 years, both TAM-e' (p=0.002) and MAM-e' (p=0.048) in females were significantly higher than those in males. The gender differences diminished in the ≥60 years age groups. There was no age-associated decline in TAM-s', while TAM-e' varied with age and gender as did MAM-e'. Although the same criteria for the TAM-s' can be used for identifying abnormal RV systolic function regardless of age and gender, age and gender differences must be considered when one utilizes the TAM-e' for the diagnosis or management of cardiovascular disease.
S Nakatani, M Akaishi, T Asanuma, S Hashimoto, C Izumi, S Iwanaga, H Kawai, M Daimon, H Toide, A Hayashida and Hirotsugu Yamada : Guidelines from the Japanese Society of Echocardiography: Guidance for the management and maintenance of echocardiography equipment., Journal of Echocardiography, No.13, 1-5, 2015.
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Echocardiography plays a pivotal role as an imaging modality in modern cardiology practice. Information derived from echocardiography is definitely helpful for patient care. The Japanese Society of Echocardiography has promoted echocardiography in routine clinical and research use. One of the missions of the Society is to provide information that is useful for high-quality examinations. To ensure this, we believe that equipment in good condition and a comfortable environment are important for both patient and examiner. Here, the Guideline Preparation Committee of the Japanese Society of Echocardiography has established brief guidance for the routine use of echocardiography equipment.
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.
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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).
S Kimura, Yuka Ueda, Takayuki Ise, Shusuke Yagi, Takashi Iwase, K Nishikawa, Koji Yamaguchi, Hirotsugu Yamada, Takeshi Soeki, Tetsuzo Wakatsuki, Shinsuke Katoh, Masashi Akaike, Natsuo Yasui and Masataka Sata : Impact of supervised cardiac rehabilitation on urinary albumin excretion in patients with cardiovascular disease., International Heart Journal, Vol.56, No.1, 105-109, 2015.
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Urinary albumin excretion is a predictor of cardiovascular death. Cardiac rehabilitation (CR) with exercise training (ET) has been shown to improve exercise capacity and prognosis in patients with cardiovascular disease (CVD). However, it remains unclear whether CR reduces urinary albumin excretion in CVD patients. We performed a retrospective, observational study using data obtained from 98 male CVD patients without macroalbuminuria and estimated glomerular filtration rate (eGFR) < 30 mL/minute/1.73 m(2) who participated in CR with ET during hospitalization. Twenty-three patients continued supervised ET for 6 months (supervised group) and 75 patients quit supervised ET (non-supervised group). The supervised ET program consisted of 60 minutes of supervised sessions 1-3 times a week and 30-60 minutes of home exercise at least twice a week. Urinary albumin/creatinine ratio (ACR) was significantly decreased in the supervised group at 6 months after enrollment (43 ± 71 mg/g to 17 ± 20 mg/g creatinine, P < 0.05) but not in the non-supervised group. eGFR was unchanged in the supervised group but was significantly decreased in the non-supervised group (72 ± 18 mL/minute/1.73 m(2) to 67 ± 17 mL/minute/1.73 m(2), P < 0.001). The results of multiple regression analysis showed that only supervised ET was an independent contributor to ACR. CR with supervised ET decreased urinary albumin excretion without deterioration of renal function. These findings suggest that continuation of a supervised ET program is associated with reduction in the development of CVD and reduction in cardiovascular morbidity and mortality in CVD patients.
(キーワード)
Cardiac rehabilitation / Renal function / Cardiovascular disease
Shusuke Yagi, A Takashima, M Mitsugi, T Wada, Junko Hotsuchi, Ken-ichi Aihara, T Hara, Masayoshi Ishida, Daiju Fukuda, Takayuki Ise, Koji Yamaguchi, Takeshi Tobiume, Takashi Iwase, Hirotsugu Yamada, Takeshi Soeki, Tetsuzo Wakatsuki, Michio Shimabukuro, Masashi Akaike and Masataka Sata : Effect of combination tablets containing amlodipine 10 mg and irbesartan 100 mg on blood pressure and cardiovascular risk factors in patients with hypertension., Therapeutics and Clinical Risk Management, Vol.11, 83-88, 2015.
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Background: Hypertension is one of the major risk factors for cardiovascular and cerebrovascular disease and mortality. Patients who receive insufficient doses of antihypertensive agents or who are poorly adherent to multidrug treatment regimens often fail to achieve adequate blood pressure (BP) control. The aim of this study was to determine the efficacy of an angiotensin II receptor blocker (ARB) and calcium channel blocker (CCB) combination tablet containing a regular dose of irbesartan (100 mg) and a high dose of amlodipine (10 mg) with regard to lowering BP and other risk factors for cardiovascular disease.Methods: We retrospectively evaluated data from 68 patients with essential hypertension whose treatment regimen was changed either from combination treatment with an independent ARB and a low-dose or regular-dose CCB or from a combination tablet of ARB and a low-dose or regular-dose CCB to a combination tablet containing amlodipine 10 mg and irbesartan 100 mg, because of incomplete BP control. Previous treatments did not include irbesartan as the ARB.Results: The combination tablet decreased systolic and diastolic BP. In addition, it significantly decreased serum uric acid, low-density lipoprotein cholesterol, and increased high-density lipoprotein cholesterol levels, independent of the BP-lowering effect. Treatment with the combination tablet did not affect serum triglycerides, plasma glucose, glycated hemoglobin, serum potassium or creatinine levels, or the urinary albumin excretion rate.Conclusion: The combination tablet containing amlodipine 10 mg and irbesartan 100 mg had a greater BP-lowering effect than an ARB and a low-dose or regular-dose CCB. In addition, the combination tablet had more favorable effects on serum uric acid, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol levels in patients with hypertension.
Shusuke Yagi, T Hara, R Ueno, Ken-ichi Aihara, Daiju Fukuda, A Takashima, Junko Hotsuchi, Takayuki Ise, Koji Yamaguchi, Takeshi Tobiume, Takashi Iwase, Hirotsugu Yamada, Takeshi Soeki, Tetsuzo Wakatsuki, Michio Shimabukuro, Masashi Akaike and Masataka Sata : Serum concentration of eicosapentaenoic acid is associated with cognitive function in patients with coronary artery disease., Nutrition Journal, Vol.13, No.1, 112, 2014.
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BACKGROUND: Recent studies have shown that intake of n-3 polyunsaturated fatty acids (PUFAs) is associated with reduced risk of cognitive impairment and coronary artery disease (CAD); however, it is currently unknown whether reduced serum n-3 PUFA is associated with cognitive impairment in patients with CAD.METHODS: We retrospectively evaluated cognitive function with the mini-mental state examination (MMSE), serum levels of PUFAs (including eicosapentaenoic acid [EPA], docosahexaenoic acid [DHA], dihomogammalinolenic acid [DGLA], and arachidonic acid [AA]), cardiovascular risk factors (hypertension, dyslipidemia, diabetes mellitus, cerebrovascular disease, and history of current/previous smoking), and parameters of cardiac function (left ventricular ejection fraction and brain natriuretic peptide levels) in 146 Japanese CAD patients. The associations between the MMSE scores and the other parameters were evaluated.RESULTS: Pearson correlation analysis showed that EPA (R =0.25, P <0.01), EPA/AA ratio (R =0.22, P =0.01), and left ventricular ejection fraction (R =0.15, P =0.04) were positively associated with MMSE score, and that age (R = -0.20, P <0.01) and brain natriuretic peptide levels (R = -0.28, P <0.01) were inversely associated with MMSE score. Multiple regression analysis showed that age (P <0.05) was negatively associated with MMSE score, while EPA (P <0.01) and EPA/AA ratio (P <0.05) were positively associated with MMSE score; however, sex; body mass index; left ventricular ejection fraction; levels of DHA, AA, and DGLA; DHA/AA ratio; brain natriuretic peptide; and presence of hypertension, dyslipidemia, diabetes mellitus, cerebrovascular disease, and history of current/previous smoking were statistically excluded.CONCLUSIONS: Serum EPA concentration is associated with cognitive function in patients with CAD, suggesting that a low serum EPA level is a risk factor for cognitive impairment independent of cardiac function, including left ventricular ejection fraction. This correlation potentially lends further support to a role of dietary n-3 PUFAs in preventing the cognitive decline in CAD patients.
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.
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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.
(要約)
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.
A Takashima, Takayuki Ise, Shusuke Yagi, Takashi Iwase, S Kimura, Yuka Ueda, K Nishikawa, A Ishii, Toshiyuki Niki, Koji Yamaguchi, Yoshio Taketani, Hirotsugu Yamada, Takeshi Soeki, Tetsuzo Wakatsuki, Shinsuke Katoh, Masashi Akaike and Masataka Sata : Cardiac rehabilitation reduces serum levels of oxidized low-density lipoprotein., Circulation Journal, Vol.78, No.11, 2682-2687, 2014.
(要約)
BACKGROUND: Oxidized low-density lipoprotein (oxLDL) levels have been found to play an important role in the progression of atherosclerosis. However, methods for effectively reducing oxLDL levels have not been established. Comprehensive cardiac rehabilitation (CR) with exercise training prevents the progression of atherosclerosis, and might reduce oxLDL levels.MethodsandResults:We measured the serum levels of malondialdehyde-modified LDL (MDA-LDL), a marker of oxLDL, in 136 patients who were enrolled in a 6-month CR program. Peak oxygen consumption (VO2) and MDA-LDL levels were analyzed, before and 6 months after enrolment. In total, 67 patients completed the CR program (CR group) and 69 patients failed to complete the program (non-CR group). Peak VO2increased significantly in the CR group (P<0.01). The levels of MDA-LDL decreased significantly in the CR group (P<0.01) but not in the non-CR group. VO2(peak VO2after CR-peak VO2before CR) was negatively associated with MDA-LDL (MDA-LDL after CR-MDA-LDL before CR) (R(2)=0.11, P=0.01). Multiple regression analysis showed that continuing CR was an independent determining factor for lowering MDA-LDL levels.CONCLUSIONS: CR decreases oxLDL levels in patients with cardiovascular diseases. Moreover, CR may prevent cardiovascular events through an antioxidative effect. (Circ J 2014; 78: 2682-2687).
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.
(要約)
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.
(キーワード)
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.
(要約)
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.
(要約)
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.
T Hara, K Kishi-Tanaka, Takashi Iwase, Hirotsugu Yamada, Masashi Akaike and Masataka Sata : Utility of lower limb positive pressure test for diagnosis of diastolic heart failure: a case report., The Journal of Medical Investigation : JMI, Vol.61, No.3-4, 404-408, 2014.
(要約)
A 70-year-old woman with dyspnea on exertion was admitted to our hospital. She had a history of apical hypertrophic cardiomyopathy (HCM) and repeated hospitalization for heart failure. Results of physical examination were normal except for leg edema. Echocardiography showed apical HCM with preserved LV systolic function (LVEF = 70%). Although dyspnea on exertion and leg edema improved rapidly with the use of diuretics, her symptoms soon worsened when daily activity was started again. In order to examine the effect of preload on hemodynamics, we performed a lower limb positive pressure test by compressing both legs using a household air leg massager. Echocardiography showed increases in mitral E velocity, E/A ratio and pulmonary venous D flow as well as decrease in stroke volume during the lower limb positive pressure test. Simultaneously-recorded pressure study also showed elevated LVEDP and increased v wave of pulmonary capillary wedge pressure. These results suggested that even a small increase in preload led to elevation of LVEDP and symptomatic worsening due to severe diastolic heart failure in the present case. The lower limb positive pressure test may be useful for assessing the effect of preload on hemodynamics in patients with diastolic heart failure.
Michio Shimabukuro, C. Okawa, X. F. Lei, J. R. Kim-Kaneyama, Hirotsugu Yamada, Hirotsugu Kurobe, Daiju Fukuda, M. Sato, Tetsuya Kitagawa and Masataka Sata : Effects of ezetimibe on oxidized cholesterol components in epicardial fat and myocardium: a gas chromatography-mass spectrometry analysis, Atherosclerosis, Vol.235, No.2, 113, 2014.
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.
S Bando, Takeshi Soeki, T Matsuura, Toshiyuki Niki, Takayuki Ise, Koji Yamaguchi, Yoshio Taketani, Takashi Iwase, Hirotsugu Yamada, Tetsuzo Wakatsuki, Masashi Akaike, T Aiba, W Shimizu and Masataka Sata : Congenital long QT syndrome with compound mutations in the KCNH2 gene., Heart and Vessels, Vol.29, No.4, 554-559, 2014.
(要約)
Congenital long QT syndrome is a genetic disorder encompassing a family of mutations that can lead to aberrant ventricular electrical activity. We report on two brothers with long QT syndrome caused by compound mutations in the KCNH2 gene inherited from parents who had no prolonged QT interval on electrocardiography. The proband had syncope, and his elder brother suffered from ventricular fibrillation. Genetic testing revealed that both brothers had multiple mutations in the KCNH2 gene, including a missense mutation of C1474T (exon 6) as well as a frameshift/nonsense mutation, resulting from the insertion of 25 nucleotides, which caused an altered amino acid sequence beginning at codon 302 and a premature termination codon (i.e., TAG) at codon 339 (exon 4). Family genetic screening found that their father had the same frameshift mutation, and their mother and sister had the same missense mutation, in the KCNH2 gene. However, these other family members were asymptomatic, with normal QT intervals on electrocardiography. These results suggest that compound mutations in the KCNH2 gene inherited independently from the parents made the phenotypes of their sons more severe.
S Hayashi, Hirotsugu Yamada, Mika Bando, Junko Hotsuchi, Takayuki Ise, Koji Yamaguchi, Takashi Iwase, Takeshi Soeki, Tetsuzo Wakatsuki, Toshiaki Tamaki and Masataka Sata : Augmentation Index does not Reflect the Risk of Coronary Artery Disease in Elderly Patients., Circulation Journal, Vol.78, No.5, 1176-1182, 2014.
(要約)
BACKGROUND: Augmentation index (AI) has been used as a clinical index of arterial stiffness and has been reported to be an independent predictor of cardiovascular events, but some investigators have reported that AI is not a useful marker to identify coronary artery disease (CAD) in elderly patients. The majority of CAD patients are elderly people, therefore the aim of this study was to examine whether AI is a useful marker to identify the risk of CAD.METHODS AND RESULTS: A total of 120 patients (69±10 years of age; 83 male) who underwent cardiac catheterization for suspected CAD were enrolled. Invasive central blood pressure (BP) was measured using a fluid-filled catheter. Non-invasive AI was calculated by the SphygmoCor (AtCor Medical) system at the end of catheterization. Subjects consisted of 99 patients with CAD and 21 patients without CAD. There was no significant difference in AI between the CAD and the non-CAD groups (24±10 vs. 24±14%). Non-invasive systolic central BP was lower than the invasive systolic central BP (115±18 vs. 130±23 mmHg, P<0.001) in all patients. Non-invasive diastolic central BP was greater than the invasive diastolic central BP (67±10 vs. 63±10 mmHg, P<0.001).CONCLUSIONS: In elderly patients, AI may not be a useful marker to identify CAD
(キーワード)
Arterial stiffness / Augmentation index / Central blood pressure / Coronary artery disease
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.
(要約)
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.
Takayuki Ise, Takashi Iwase, S Masuda, Shusuke Yagi, Masashi Akaike, S Nishio, Toshiyuki Niki, Koji Yamaguchi, Yoshio Taketani, Hirotsugu Yamada, Takeshi Soeki, Tetsuzo Wakatsuki and Masataka Sata : Acute pulmonary thromboembolism from deep vein thrombosis induced by trauma to the popliteal vein with a tennis racket., Journal of Cardiology Cases, Vol.9, No.4, 162-164, 2014.
(要約)
Acute pulmonary thromboembolism (PTE) is mainly caused by deep vein thrombosis (DVT) and sometimes leads to a fatal outcome. Few cases of sport-related lower extremity DVT, involving direct external trauma, have been reported. A 58-year-old man, without any risk factors for thromboembolism suffered acute PTE from DVT after playing tennis. A detailed history revealed that he had hit his popliteal vein with each swing of his tennis racket and the site of the trauma, at popliteal fossa, was exactly the same as the site of the DVT formation. Therefore, the cause of DVT was suspected to be the repeated trauma to the popliteal vein. The repeated external trauma to the popliteal vein may have caused vascular endothelial damage, leading to DVT.
(キーワード)
Acute pulmonary thromboembolism / Deep vein thrombosis / Trauma
Kazumi Takaishi, Shinji Kawahito, Hirotsugu Yamada, Takeshi Soeki, Masataka Sata and Hiroshi Kitahata : Increase in prominence of electrocardiographic J waves after a single dose of propofol in a patient with early ventricular repolarisation., Anaesthesia, Vol.69, No.2, 170-175, 2014.
(要約)
J waves appear on an electrocardiogram as an elevation of the J point in the terminal portion of the QRS complex. J waves are often benign, but may be associated with malignant ventricular arrhythmias. In some cases, such problems appear to have been precipitated by propofol infusions. We observed a sudden increase in J waves and profound hypotension following a single intravenous dose of propofol in an 84-year-old woman with early repolarisation in the inferior ventricular wall. When early repolarisation (as shown by electrocardiographic J waves) is observed in the inferior ventricular wall pre-operatively, patients should be carefully monitored. Myocardial ischaemia and the use of drugs that might worsen J waves should be avoided.
R Tamai, T Hara, Hirotsugu Yamada, S Nishio, M Bando, J Hotchi, S Hayashi, Toshiyuki Niki, Tetsuya Kitagawa and Masataka Sata : Massive tricuspid regurgitation due to pacemaker-lead puncture of the tricuspid valve: successful diagnosis by 3-dimensional echocardiography., Journal of Medical Ultrasonics, Vol.41, No.1, 69-71, 2014.
(要約)
An 83-year-old woman presented to our echocardiographic center with symptoms of right heart failure. A dual-chamber DDDR pacemaker had been implanted 9 years earlier. Two-dimensional echocardiography revealed right atrial and ventricular enlargement and massive tricuspid regurgitation with immobilization of the anterior leaflet of the tricuspid valve. Three-dimensional transesophageal echocardiography showed that the pacemaker lead had punctured the leaflet. These echocardiographic findings were confirmed during surgery. The pacemaker lead was transected and removed, and pericardial patch closure of the leaflet hole and tricuspid annuloplasty were performed. The mechanism of regurgitation was elucidated by real-time three-dimensional echocardiography, and surgical repair was straightforward.
Hayato Nose, Hideki Otsuka, Youichi Otomi, K Terazawa, Shoichiro Takao, Seiji Iwamoto, Takashi Iwase, Hirotsugu Yamada, Masataka Sata and Masafumi Harada : The physiological uptake pattern of (18)F-FDG in the left ventricular myocardium of patients without heart disease., The Journal of Medical Investigation : JMI, Vol.61, No.1, 2, 53-58, 2014.
(要約)
Purpose: The purpose of this study was to evaluate the physiological uptake pattern of 18F-FDG in the left ventricular myocardium of patients under preparation for tumor FDG-PET. Patients and Methods: We enrolled 188 patients without cardiac disease. The accumulation patterns were classified as either none, diffuse, focal or focal on diffuse. When a focal uptake was only observed on the basal wall, then the patterns were classified as having either a ring, over half or spot uptake. Results: The frequencies of the myocardial FDG uptake patterns were as follows: none, n=52 (27.7%); diffuse, n=63 (33.5%); focal on diffuse, n=40 (21.3%) and focal, n=33 (17.6%). The age, blood glucose level, weight and dose of FDG did not differ significantly for each pattern. The focal and focal on diffuse patterns were seen in 73 patients, and 65 patients had a focal uptake only on the basal wall; ring uptake in 29 patients, over half in 20 and spot uptake in 16 patients. Conclusions: The physiological myocardial uptake showed several patterns. Focal uptake was often seen in patients with cardiac disease, but it did not always indicate an abnormal finding when the accumulation was only on the basal wall.
(キーワード)
F-FDG PET / heart / physiological myocardial uptake / fasting state
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.
(要約)
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.
Hirotsugu Yamada : Report of the American College of Cardiology (ACC) Scientific Sessions 2013,San Francisco - Highlighting Late-Breaking Trials -, Circulation Journal, Vol.77, No.5, 1139-1145, 2013.
(要約)
The American College of Cardiology's (ACC) 62nd Annual Scientific Session was held at the Moscone Center, San Francisco, from March 9-11, 2013. The meeting focused on the "transformation of cardiovascular care, from discovery to delivery", featured over 20 late-breaking clinical trials and 2,000 abstracts. These sessions gave notable exposure and recognition of studies likely to significantly affect clinical practice. There were 21 trials scheduled for presentation in 5 featured Late-Breaking Clinical Trial sessions, but one, the PREVAIL trial, was not presented because of a failure to observe an embargo. I summarize and overview both the late-breaking trials presented at ACC 2013 and the PREVAIL trial. (Circ J 2013; 77: 1139-1145)
(キーワード)
American College of Cardiology / Congress / Late-breaking clinical trials
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.
(キーワード)
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.
(要約)
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.
N. Kawano, Koji Yamaguchi, Toshiyuki Niki, Yamamoto Takashi, Takashi Iwase, Yoshio Taketani, Takayuki Ise, Hirotsugu Yamada, Takeshi Soeki, Tetsuzo Wakatsuki, K Kawano, A. Kakutani and Masataka Sata : Two cases of acute myocardial infarction during combined chemotherapy in young patients with testicular cancer., Journal of Cardiology Cases, Vol.7, No.6, e176-e180, 2013.
T Hara, Koji Yamaguchi, Takashi Iwase, M Kadota, Mika Bando, K Ogasawara, S Bando, Takayuki Ise, Toshiyuki Niki, Yuka Ueda, N Tomita, Yoshio Taketani, Hirotsugu Yamada, Takeshi Soeki, Tetsuzo Wakatsuki and Masataka Sata : Eosinophilic Myocarditis due to Churg-Strauss syndrome with markedly elevated Eosinophil Cationic Protein., International Heart Journal, Vol.54, No.1, 51-53, 2013.
(要約)
A 67-year-old woman with asthma visited our hospital with increasing dyspnea and new-onset paresthesia and purpura in her legs. Physical examination showed a wheeze, pretibial edema, and surrounding purpura. Chest X-rays showed cardiac decompensation and an electrocardiogram revealed a new ST-T change. Laboratory data showed leukocytosis, hypereosinophilia (10,450/μL), troponin T(+), elevated BNP, and markedly elevated eosinophil cationic protein (ECP) (> 150 ng/mL). Echocardiography revealed diffuse left ventricular hypokinesis (ejection fraction 30%) with increased wall thickness. Coronary angiography was normal. Cardiac magnetic resonance imaging implied diffuse myocardial edema and subendocardial late gadolinium enhancement. Skin biopsy of purpura showed superfi cial perivascular dermatitis with remarkable eosinophilic infiltrations. No evidence of drug allergies, parasitic infection, or myeloproliferative disorder was detected. Based on these findings, a diagnosis of eosinophilic myocarditis due to Churg-Strauss syndrome was considered. She was administered prednisolone at a dose of 1 mg/kg, cyclophosphamide, and diuretics. Several markers of eosinophilic myocarditis and heart failure gradually improved, including ECP. She was discharged 30 days later with no cardiac event. Eosinophilic myocarditis is characterized by predominantly eosinophilic infi ltration. Eosinophilic granule proteins, such as ECP and major basic protein, play important roles in the pathogenesis of eosinophilic myocarditis. We experienced a rare case of eosinophilic myocarditis due to Churg-Strauss syndrome. Markedly elevated ECP played an important role in the early diagnosis and subsequent reduction in ECP served as a marker of monitoring. In an asthmatic patient with dyspnea, hypereosinophilia, and vasculitis, Churg-Strauss syndrome with eosinophilic myocarditis should be considered.
Hirata Yoichiro, Hirotsugu Kurobe, Uematsu Etsuko, Shusuke Yagi, Takeshi Soeki, Hirotsugu Yamada, Daiju Fukuda, Michio Shimabukuro, Nakayama Mizuho, Matsumoto Kunio, Sakai Yoshiki, Tetsuya Kitagawa and Masataka Sata : Beneficial effect of a synthetic prostacyclin agonist, ONO-1301, in rat autoimmune myocarditis model., European Journal of Pharmacology, Vol.699, No.1-3, 81-87, 2013.
(要約)
Injury to the heart can result in cardiomyocyte hypertrophy, fibrosis, and cell death. Myocarditis sometimes progresses to dilated cardiomyopathy. We previously reported that ONO-1301, a synthetic prostacyclin agonist with thromboxane-synthase inhibitory activity, promotes production of hepatocyte growth factor (HGF) from various cell types and ameliorates ischemia-induced left ventricle dysfunction in the mouse, rat and pig. Here, we investigated the therapeutic efficacy of ONO-1301 in a rat model of myosin-induced experimental autoimmune myocarditis, in which the heart transits from an acute inflammatory phase to a chronic dilated cardiomyopathy phase. Four weeks after myosin injection to Lewis rats, ONO-1301 (6 mg/kg/day) was orally administered for 4 weeks (ONO-1301 group). Hemodynamic parameters and plasma brain natriuretic peptide (BNP) level were significantly improved by ONO-1301. Histological analysis revealed that capillary density in the myocardium was significantly increased by ONO-1301. ONO-1301 increased circulating endothelial progenitor cells (EPC) as determined by FACS analysis. These beneficial effects of ONO-1301 were partially abrogated by a neutralizing anti-HGF antibody (8 mg/kg/dose). These findings indicate beneficial effects of ONO-1301 in a rat experimental autoimmune myocarditis model.
Shuji Hayashi, Hirotsugu Yamada, Susumu Nishio, Noriko Tomita, Junko Hotchi, Mika Bando, Maya Nakagawa, Rina Tamai, Daichi Hirota, Yukina Hirata and Masataka Sata : Double-chambered right ventricle presenting significant outflow tract obstruction only in the right decubitus position., Journal of Echocardiography, Vol.10, No.4, 146-147, 2012.
(キーワード)
double-chambered right ventricle / right mid-ventricular obstruction / postural change / doppler echocardiography / ventricular septal defect
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.
(要約)
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.
(キーワード)
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.
(要約)
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.
(要約)
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.
Background : The carotid plaque vulnerability is related to myocardial and cerebral infarction.We intended to develop an imaging system which enables to visualize tissue characteristics in thecarotid plaques based on ultrasound integrated backscatter(IB). And to test its clinical efficacy,effect of the statin therapy on the plaques was evaluated with our software. Methods and Results :Carotid ultrasound examination was performed and ultrasonographic RAW data of the plaqueswere obtained from8patients undergoing carotid artery endarterectomy. Tissue characteristicsin the plaques of resected examples were compared with preoperative ultrasonic images and thetissue IB values corresponding to the specimens were determined for developing our imaging system.Using this system, Color-coded maps of plaques in the three patients were constructed beforeand after lipid lowing therapy. We could demonstrate that lipid fraction in each plaque decreasedand fibrous or calcification fraction increased in the follow-up study. Conclusions : Changes inhistology of carotid plaques by statin could visualized with our imaging system. This techniquemay become a useful tool for the management of atherosclerosis.
(キーワード)
IBS (integrated backscatter) / carotid plaque / CEA (carotid endarterectomy)
Yoichiro Hirata, Michio Shimabukuro, Etsuko Uematsu, Takeshi Soeki, Hirotsugu Yamada, Yoshiki Sakai, Mizuho Nakayama, Kunio Matsumoto, Takashi Igarashi and Masataka Sata : A synthetic prostacyclin agonist thrombozane synthase inhibitory activity, ONO-1301, protects myocardium from ischemia/reperfusion injury., European Journal of Pharmacology, Vol.674, No.2-3, 352-358, 2012.
(要約)
ONO-1301, a synthetic prostacyclin agonist with thromboxane synthase inhibitory activity, promotes the production of hepatocyte growth factor (HGF) and vascular endothelial growth factor (VEGF) by various cell types. Here, we evaluated the therapeutic efficacy of ONO-1301 in rats with ischemia/reperfusion injury. Ligation of the left anterior descending arteries was performed in 10-week-old Wistar rats, and released 30 min later. A slow-release form of ONO-1301 was administered subcutaneously at 3h and 3 weeks after reperfusion injury. Hemodynamic parameters were significantly improved in the ONO-1301 group. Histological analysis revealed that ONO-1301 suppressed ischemic and fibrotic changes in the myocardium (ischemic area, control group: 58.6 ± 8.7% vs. ONO-1301 group: 44.4 ± 5.8%, fibrotic area, 33.5 ± 5.9% vs. 22.3 ± 6.2%, P<0.05, respectively), and enhanced neovascularization in the border zone. HGF expression was up-regulated by ONO-1301. Double-immunostaining revealed that myofibroblasts in the border zone of ischemic myocardium mainly expressed HGF. Our findings suggest that ONO-1301 might have therapeutic potential in treating ischemic heart disease.
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.
(要約)
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.
(要約)
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.
(キーワード)
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.
(要約)
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.
(要約)
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.
(要約)
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.
(要約)
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.
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.
(要約)
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.
(キーワード)
Aged / Aged, 80 and over / Algorithms / Case-Control Studies / Echocardiography, Doppler / Feasibility Studies / Humans / Image Interpretation, Computer-Assisted / 日本 (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
Takayuki Ise, Ken-ichi Aihara, Yuka Ueda, Sumiko Yoshida, Yasumasa Ikeda, Shusuke Yagi, Takashi Iwase, Hirotsugu Yamada, Masashi Akaike, Masataka Sata and Toshio Matsumoto : Plasma heparin cofactor II activity is inversely associated with left atrial volume and diastolic dysfunction in humans with cardiovascular risk factors., Hypertension Research, Vol.34, No.2, 225-231, 2010.
(要約)
Thrombin has a crucial role in cardiac remodeling through protease-activated receptor-1 activation in cardiac fibroblasts and cardiomyocytes. As heparin cofactor II (HCII) inhibits the action of tissue thrombin in the cardiovascular system, it is possible that HCII counteracts the development of cardiac remodeling. We investigated the relationships between plasma HCII activity and surrogate markers of cardiac geometry, including left atrial volume index (LAVI), relative wall thickness (RWT) and left ventricular mass index, and deceleration time (DcT) and the ratio of peak E velocity to early diastolic mitral annulus velocity (E/e' ratio) as surrogate markers of left ventricular diastolic dysfunction measured using echocardiography in 304 Japanese elderly individuals without systolic heart failure (169 men and 135 women; mean age: 65.4 ± 11.8 years). Mean plasma HCII activity in all participants was 95.8 ± 17.0% and there was no difference between the mean plasma HCII activities in males and females. Multiple regression analysis revealed that there were significant inverse relationships between plasma HCII activity and LAVI (coefficient: -0.2302, P<0.001), between HCII activity and RWT (coefficient: -0.0007, P<0.05), between HCII activity and DcT (coefficient: -0.5189, P<0.05) and between HCII activity and E/e' ratio (coefficient: -0.0558, P<0.01). Plasma HCII activity was independently and inversely associated with the development of cardiac remodeling, including cardiac concentric change, left atrial enlargement and left ventricular diastolic dysfunction. These findings suggest that cardiac tissue thrombin inactivation by HCII is a novel therapeutic target for cardiac remodeling and atherosclerosis.
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.
Hai-Yan Pan, Hirotsugu Yamada, Junji Chida, Siye Wang, Mihiro Yano, Min Yao, Jianhua Zhu and Hiroshi Kido : Up-regulation of ectopic trypsins in the myocardium by influenza A virus infection triggers acute myocarditis, Cardiovascular Research, Vol.89, No.3, 595-603, 2010.
(要約)
Influenza A virus (IAV) infection markedly up-regulates ectopic trypsins in various organs, viral envelope glycoprotein processing proteases, which are pre-requisites for virus entry and multiplication. We investigated the pathological roles of trypsin up-regulation in the progression of IAV-induced myocarditis, cytokine induction, and viral replication in the hearts, and also investigated the protective effects of trypsin inhibitor on cardiac dysfunction in vivo and selective knockdown of trypsin on IAV-induced cellular damage in cardiomyoblasts. The relationship of the expression among IAV RNA, trypsins, matrix metalloproteinase (MMP)-9, MMP-2, pro-inflammatory cytokines interleukin (IL)-6, IL-1β, and tumour necrosis factor-α was analysed in mice hearts and cardiomyoblasts after IAV infection. The severity of myocarditis was most noticeable during Day 6-9 post-infection, along with peak expression of viral RNA, trypsins, particularly trypsin , MMPs, and cytokines. Cardiac ATP levels were the lowest at Day 9. Up-regulated trypsins, viral protein, and tissue-injured loci in the myocardium were closely localized. Trypsin inhibitor aprotinin treatment in vivo and selective trypsin - and trypsin -knockdown, particularly the latter, in H9c2 cardiomyoblasts significantly suppressed viral replication, up-regulation of MMPs, and production of active MMP-9 and cytokines, resulting in marked protection against cellular damage, ATP depletion, and apoptosis. IAV infection-induced cardiac dysfunction monitored by echocardiography was improved significantly by aprotinin treatment. IAV-induced trypsins, particularly trypsin , in the myocardium trigger acute viral myocarditis through stimulation of IAV replication, proMMP-9 activation, and cytokine induction. These results suggest that up-regulation of trypsins is one of the key host pathological findings in IAV-induced myocarditis.
Hirotsugu Yamada and Klein. L. Allan : Diastology 2010: clinical approach to diastolic heart failure, Journal of Echocardiography, Vol.8, No.3, 65-79, 2010.
Sumiko Yoshida, Ken-ichi Aihara, Hiroyuki Azuma, Ryoko Uemoto, Yuka Sumitomo-Ueda, Shusuke Yagi, Yasumasa Ikeda, Takashi Iwase, Susumu Nishio, Hiromi Kawano, Junko Miki, Hirotsugu Yamada, Yoichiro Hirata, Masashi Akaike, Masataka Sata and Toshio Matsumoto : Dehydroepiandrosterone sulfate is inversely associated with sex-dependent diverse carotid atherosclerosis regardless of endothelial function., Atherosclerosis, Vol.212, No.1, 310-315, 2010.
(要約)
BACKGROUND: Dehydroepiandrosterone sulfate (DHEAS) is thought to be associated with life expectancy and anti-aging. However, its biological significance in atherosclerosis remains controversial. Therefore, the aim of this study was to determine whether DHEAS is associated with development of carotid atherosclerosis in subjects with cardiovascular risk factors. SUBJECTS AND METHODS: A total of 419 Japanese individuals (208 males and 211 females) were recruited from Tokushima University Hospital, Japan. In all subjects, maximum intima-media thickness (max-IMT) in all carotid arteries, and mean-IMT and mean blood flow volume (BFV) in the common carotid arteries (CCA) were measured by ultrasonography; endothelial function was assessed by flow-mediated vasodilation of the brachial artery (%FMD). Serum DHEAS and classical cardiovascular risk factors were also evaluated. Statistical significance was determined by multiple regression analysis to elucidate independent determinants of max-IMT, mean-IMT, mean CCA-BFV, and %FMD. RESULTS: Serum DHEAS levels were higher in males than in females. Multiple regression analysis revealed that DHEAS was an independent negative factor for both max-IMT and mean-IMT in males but not in females. In contrast, DHEAS was the sole positive factor for mean CCA-BFV in females but not in males. In addition, there was no significant relationship between %FMD and DHEAS regardless of sex and other confounding factors. CONCLUSION: Although DHEAS is not involved in endothelial function, DHEAS is inversely associated with sex-dependent diverse carotid atherosclerosis such as increased max-IMT and mean-IMT in males and decreased CCA-BFV in females.
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.
(要約)
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.
(要約)
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.
(要約)
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.
(要約)
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.
(キーワード)
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.
(要約)
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.
(要約)
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.
Y Notomi, ZB Popovic, Hirotsugu Yamada, DW Wallick, MG Martin, SJ Oryszak, T Shiota, NL Greenberg and JD Thomas : Ventricular untwisting: a temporal link between left ventricular relaxation and suction., American Journal of Physiology, Heart and Circulatory Physiology, Vol.294, No.1, H505-513, 2008.
(要約)
Left ventricular (LV) untwisting starts early during the isovolumic relaxation phase and proceeds throughout the early filling phase, releasing elastic energy stored by the preceding systolic deformation. Data relating untwisting, relaxation, and intraventricular pressure gradients (IVPG), which represent another manifestation of elastic recoil, are sparse. To understand the interaction between LV mechanics and inflow during early diastole, Doppler tissue images (DTI), catheter-derived pressures (apical and basal LV, left atrial, and aortic), and LV volume data were obtained at baseline, during varying pacing modes, and during dobutamine and esmolol infusion in seven closed-chest anesthetized dogs. LV torsion and torsional rate profiles were analyzed from DTI data sets (apical and basal short-axis images) with high temporal resolution (6.5 +/- 0.7 ms). Repeated-measures regression models showed moderately strong correlation of peak LV twisting with peak LV untwisting rate (r = 0.74), as well as correlations of peak LV untwisting rate with the time constant of LV pressure decay (tau, r = -0.66) and IVPG (r = 0.76, P < 0.0001 for all). In a multivariate analysis, peak LV untwisting rate was an independent predictor of tau and IVPG (P < 0.0001, for both). The start of LV untwisting coincided with the beginning of relaxation and preceded suction-aided filling resulting from elastic recoil. Untwisting rate may be a useful marker of diastolic function or even serve as a therapeutic target for improving diastolic function.
H Tanaka, Y Oishi, Y Mizuguchi, H Miyoshi, T Ishimoto, N Nagase, Hirotsugu Yamada and T Oki : Contribution of the pericardium to left ventricular torsion and regional myocardial function in patients with total absence of the left pericardium., Journal of the American Society of Echocardiography, Vol.21, No.3, 268-274, 2008.
(要約)
The relationship between left ventricular (LV) torsional deformation and myocardial function has recently been recognized. However, little is known about whether the pericardium affects this relationship. Our aim was to identify the contribution of the pericardium to LV torsion and regional myocardial function in the clinical setting. We examined LV torsion in basal and apical LV short-axis views, and regional LV myocardial function, such as longitudinal strain in apical 4-chamber view, and circumferential and radial strains in parasternal LV short-axis views using 2-dimensional speckle-tracking imaging method in 5 patients with congenital total absence of the left pericardium and systolic paradoxical ventricular septal motion on M-mode echocardiogram and in 10 control subjects. Diagnosis of the pericardial defect was based on chest radiograph, computed tomography, jugular phlebogram, and M-mode and 2-dimensional echocardiogram. LV torsion was defined as the net difference in LV rotation in the basal and apical planes. There was no significant difference in LV ejection fraction determined by 2-dimensional echocardiography between the pericardial defect and control groups. LV torsion was markedly decreased in the pericardial defect group compared with the control group. There were no significant differences in longitudinal, radial, and circumferential systolic strains and systolic and early diastolic strain rates in the LV walls and in longitudinal systolic strains and systolic and early diastolic strain rates in the left atrial walls between the two groups. Pericardial defects cause a lack of LV torsion while maintaining LV regional myocardial function in patients with systolic paradoxical ventricular septal motion. Therefore, pericardium plays an important role in LV torsion.
(キーワード)
Echocardiography / Female / Humans / Male / Middle Aged / Pericardium / Torsion Abnormality / Ventricular Dysfunction, Left
Hideji Tanaka, Yoshifumi Oishi, Yukio Mizuguchi, Shigefumi Emi, Takeo Ishimoto, Norio Nagase, Tomotsugu Tabata, Hirotsugu Yamada and Takashi Oki : Three-dimensional evaluation of dobutamine-induced changes in regional myocardial deformation in ischemic myocardium using ultrasonic strain measurements: the role of circumferential myocardial shortening., Journal of the American Society of Echocardiography, Vol.20, No.11, 1294-1299, 2007.
(要約)
Early identification of myocardial ischemia during high-dose dobutamine stress (DOB) has important clinical implications. Myocardial strain imaging can evaluate regional myocardial contractility in the radial, longitudinal, and circumferential directions. The aim of this study was to assess precisely the differences in deterioration of myocardial deformation among the 3 directions in patients with newly developed myocardial ischemia during high-dose (40 microg/kg/min) DOB infusion. Color Doppler tissue 2-dimensional images were recorded during DOB infusion in 20 patients without myocardial ischemia and 25 patients with scintigraphically diagnosed myocardial ischemia caused by left anterior descending coronary artery stenosis. In the offline analysis, systolic radial strain (Sr), longitudinal strain (Sl), and circumferential strain (Sc) were determined in the anteroseptal and anterolateral left ventricular walls. In 20 patients without myocardial ischemia, the peak systolic strains significantly increased in all 3 directions during DOB infusion at rates between 5 and 10 microg/kg/min (Sr 50%-69%, Sl 27%-36%, Sc 29%-38%, all P < .01) with a greater rate of change in the Sr (1.8 and 1.9 times, respectively, P < .001) than in the Sl and Sc. However, the peak systolic strains decreased significantly during DOB infusion at rates between 5 and 10 microg/kg/min in all 3 directions (Sr 56%-35%, Sl 27%-13%, both P < .01; Sc 29%-7%, P < .001) with the greatest rate of change in the Sc in 25 patients with newly developed myocardial ischemia. In conclusion, circumferential myocardial shortening deteriorated to a greater extent during DOB infusion in patients with coronary artery stenosis, and its measurement is a promising tool for detecting newly developed myocardial ischemia.
(キーワード)
Dobutamine / Dose-Response Relationship, Drug / Echocardiography, Three-Dimensional / Exercise Test / Female / Humans / Image Interpretation, Computer-Assisted / Male / Middle Aged / 心筋虚血 (myocardial ischemia) / Reproducibility of Results / Sensitivity and Specificity / Vasodilator Agents / Ventricular Dysfunction, Left
E Akagawa, K Murata, N Tanaka, Hirotsugu Yamada, T Miura, H Kunichika, Y Wada, Y Hadano, T Tanaka, Y Nose, K Yasutomo, M Kono and M Matsuzaki : Augmentation of left ventricular apical endocardial rotation with inotropic stimulation contributes to increased left ventricular torsion and radial strain in normal subjects, --- Quantitative assessment utilizing a novel automated tissue tracking technique ---, Circulation Journal, Vol.71, No.5, 661-668, 2007.
(要約)
The difference in the left ventricular (LV) torsion of the endo- and epicardium (Endo, Epi) with inotropic stimulation and its relation to radial strain (RS) remain unclear. LV basal and apical short-axis images were recorded in 13 normal subjects at rest and during dobutamine infusion (5, 10 microg x kg (-1) x min(-1)). A total of 8 points (anterior, lateral, posterior and septum in both Endo and Epi) were manually placed by 2-dimensional tissue tracking technique and the movement of these points during a cardiac cycle was tracked, after which the rotation angles and RS were calculated. LV torsion was defined as the net difference between the basal and apical rotations. In the LV apex, Endo-rotation increased (7.8+/-2.7 to 14.1+/-4.6 degrees, p<0.01), whereas Epi-rotation was unchanged, with dobutamine. The apical Endo-rotation was significantly greater than the Epi-rotation, although no difference was seen between the Endo and Epi in the LV base throughout the study. During dobutamine infusion, the LV Endo-torsion increased (9.5+/-2.8 to 19.3+/-4.8 degrees, p<0.01) and these values were greater than those for Epi. The apical RS increased with the dobutamine dose (39.0+/-9.3 to 61.9+/-15.5%, p<0.01), whereas basal RS initially increased at 5 microg x kg(-1) x min(-1), but thereafter showed no further increase at 10 microg x kg(-1) x min(-1) of dobutamine. Augmentation of LV rotation with inotropism was clearly observed in the apical Endo, thus causing increased LV endo-torsion and apical RS.
Hirotsugu Yamada, Tomotsugu Tabata, SJ Jaffer, JK Drinko, SE Jasper, MS Lauer, JD Thomas and AL Klein : Clinical features of mixed physiology of constriction and restriction, --- Echocardiographic characteristics and clinical outcome ---, European Journal of Echocardiography, Vol.8, No.3, 185-194, 2007.
(要約)
An entity of patients with mixed physiology of constriction and restriction has been reported, however, the characteristics of these patients have not been well documented. We evaluated the clinical features and the outcome of these patients. Study subjects consisted of 38 patients (57+/-14 years, 8 females, 30 males) who were diagnosed as having mixed physiology based on transthoracic and/or transesophageal echocardiography, MRI (or CT), cardiac catheterization, endomyocardial biopsy and/or surgical findings. Prior radiation therapy was the most frequent (50%) cause of mixed physiology followed by coronary artery bypass graft without prior radiation (24%) and heart transplantation (8%). The respiratory variation of peak early diastolic transmitral flow velocity by pulsed Doppler transesophageal echocardiography was 10.7% in patients with sinus rhythm and 18.1% in patients with atrial arrhythmia. Pericardial thickening was noted adjacent to the right-sided chambers in 19 patients, left-sided chambers in 10 patients, or both in 9 patients. All-cause 5-year mortality was 40% and unrelated to age, etiology, left ventricular systolic function and therapeutic course. There was a statistically significant difference (p<0.01) between the survival rates in patients with mixed physiology and in patients with pure constriction (n=125). Due to the high mortality in this disease, discrimination of the entity from the patients with pure constriction is mandatory. Transthoracic and transesophageal echocardiography are helpful noninvasive techniques in the diagnosis and the understanding of the physiology of patients with mixed constriction and restriction.
R Ramchandran, T Takezako, Y Saad, L Stull, B Fink, Hirotsugu Yamada, S Dikalov, DG Harrison, C Moravec and SS Karnik : Angiotensinergic stimulation of vascular endothelium in mice causes hypotension, bradycardia, and attenuated angiotensin response, Proceedings of the National Academy of Sciences of the United States of America, Vol.103, No.50, 19087-19092, 2006.
(要約)
It is not clear whether endothelial cell (EC) activation by the hormone angiotensin II (Ang II) modulates contraction of vascular smooth muscle cells (VSMCs) in the vasculature and whether impairment of this regulation in vivo contributes to hypertension. Delineation of the actions of Ang II through the type 1 receptor (AT1R) on ECs in the blood vessels has been a challenging problem because of the predominance of the AT1R functions in VSMCs that lie underneath the endothelium. We have obviated this limitation by generating transgenic (TG) mice engineered to target expression of the constitutively active N111G mutant AT1R only in ECs. In these TG mice, the enhanced angiotensinergic signal in ECs without infusion of Ang II resulted in hypotension and bradycardia. The pressor response to acute infusion of Ang II was significantly reduced. Increased expression of endothelial nitric oxide synthase and production of hypotensive mediators, nitric oxide and cyclic guanosine monophosphate, cause these phenotypes. Hypotension and bradycardia observed in the TG mice could be rescued by treatment with an AT1R-selective antagonist. Our results imply that the Ang II action by means of EC-AT1R is antagonistic to vasoconstriction in general, and it may moderate the magnitude of functional response to Ang II in VSMCs. This control mechanism in vivo most likely is a determinant of altered hemodynamic regulation involved in endothelial dysfunction in hypertensive cardiovascular disease.
Yoshio Ootaki, Hirotsugu Yamada, Masao Daimon, Kenji Kamohara, B Zoran Popovic, R Wagoner David Van, Yuanna Cheng and Kiyotaka Fukamachi : An experimental rabbit model for off-pump left ventricular reconstruction following left ventricular aneurysm, The Heart Surgery Forum, Vol.9, No.5, E786-E791, 2006.
(要約)
Cardiac electromechanical remodeling following left ventricular reconstruction (LVR) surgery is not fully understood. Further development of an animal model will facilitate investigations in this area. In the present study, we aimed to establish a novel LVR procedure without the use of cardiopulmonary bypass in a rabbit left ventricular (LV) aneurysm model. LV aneurysm was created in 6 rabbits by ligation of the distal left coronary artery. More than a month later, LVR aneurysm surgery was performed off-pump using a purse-string suture around the aneurysm. Cardiac dimensions and function were evaluated using echocardiographic techniques perioperatively and 4 weeks after LVR surgery. Six structurally normal hearts were used as controls. LVR surgery was successfully performed in all 6 rabbits. Both LV end-diastolic volume (LVEDV, 4.6 +/- 0.9 to 3.3 +/- 0.6 mL; P < .01) and LV end-systolic volume (LVESV, 2.5 +/- 0.6 to 1.5 +/- 0.2 mL, P < .01) were decreased immediately postsurgery versus presurgery, and LV ejection fraction (LVEF) was increased (44.5 +/- 5.3 to 55.6 +/- 4.8%, P < .001). For comparison, in normal rabbits (n = 6), LVEDV, LVESV and LVEF were 3.1 +/- 0.7 mL, 1.2 +/- 0.5 mL, and 64.5 +/- 8.8%, respectively. During follow-up, one rabbit died 3 weeks after surgery from an unknown cause. In the remaining 5 animals, improvements of LVEDV (3.7+/- 0.4 mL, P < .05), LVESV (1.7 +/- 0. 3 mL, P < .01), and LVEF (53.1 +/- 2.8%, P < .01) were maintained versus presurgery values for more than 4 weeks after LVR. Off-pump LVR of rabbit LV aneurysm is an effective and less invasive surgery that resulted in sustained improvement in cardiac function with no gross intraoperative or postoperative mortality. This may be a useful model for investigations of electromechanical remodeling following LVR.
Hirotsugu Yamada, ZB Popovic, DO Martin, KC Civello and DW Wallick : The effects of altering time delays of coupled pacing during acute atrial fibrillation, Heart Rhythm, Vol.3, No.6, 722-727, 2006.
(要約)
Coupled pacing (CP), which consists of delivering a premature electrical stimulation to the heart after the effective refractory period of ventricular activation, is a novel method for controlling ventricular rate during atrial fibrillation (AF). It also has been established that CP improves pump function by enhancing external cardiac work and myocardial efficiency. The purpose of the present study was to determine if two time delays for CP (short and long) would result in similar improvements in ventricular function. In a canine model, we applied CP at two time delays (CP-S and CP-L) during two stages: sinus rhythm (SR) and acute AF. The cardiac responses to CP during SR served as the nontachycardic and nondepressed control. During both rhythms, we shortened the coupling interval until we obtained maximal contractility, designated CP-S. Next, we increased the delay until we started to see a measurable secondary contraction (left ventricular pressure development of approximately 20 mmHg). These longer delays were designated CP-L. Our results showed that the ventricular rate of intrinsic activation (VRIA) remained decreased despite prolongation of the time delay of CP during both AF and SR. Also, both delays of CP increased left ventricular systolic pressure (LVSP) and dLVP/dt, which are indices of myocardial contractility. In contrast, CP increased external cardiac work only during AF. Prolonging this time delay did not markedly decrease the improvement in external cardiac work. Myocardial O(2) consumption (MVO(2)) did not significantly change as the result of CP during either SR or AF. Finally, myocardial efficiency improved during AF as the result of CP at both time delays. In conclusion, shorter time delays for CP increased contractile strength during both SR and AF. However, extending the time delay of CP had minimal effects on diminishing the improved ventricular pump function and energetics that resulted from CP during AF. Thus, the maximal enhancement of myocardial contractility via CP-S was not needed to maintain the improved ventricular function during acute AF when CP is applied.
Youhua Zhang, Hirotsugu Yamada, Steve Bibevski, Shaowei Zhuang, Kent A Mowrey, Don W Wallick, Seil Oh and Todor N Mazgalev : Chronic atrioventricular nodal vagal stimulation, --- first evidence for long-term ventricular rate control in canine atrial fibrillation model ---, Circulation, Vol.112, No.19, 2904-2911, 2005.
(要約)
We have previously demonstrated that selective atrioventricular nodal (AVN) vagal stimulation (AVN-VS) can be used to control ventricular rate during atrial fibrillation (AF) in acute experiments. However, it is not known whether this approach could provide a long-term treatment in conscious animals. Thus, this study reports the first observations on the long-term efficacy and safety of this novel approach to control ventricular rate during AF in chronically instrumented dogs. In 18 dogs, custom-made bipolar patch electrodes were sutured to the epicardial AVN fat pad for delivery of selective AVN-VS by a subcutaneously implanted nerve stimulator (pulse width 100 micros or 1 ms, frequency 20 or 160 Hz, amplitude 6 to 10 V). Fast-rate right atrial pacing (600 bpm) was used to induce and maintain AF. ECG, blood pressure, and body temperature were monitored telemetrically. One week after the induction of AF, AVN-VS was delivered and maintained for at least 5 weeks. It was found that AVN-VS had a consistent effect on ventricular rate slowing (on average 45+/-13 bpm) over the entire period of observation. Echocardiography showed improvement of cardiac indices with ventricular rate slowing. AVN-VS was well tolerated by the animals, causing no signs of distress or discomfort. Beneficial long-term ventricular rate slowing during AF can be achieved by implantation of a nerve stimulator attached to the epicardial AVN fat pad. This novel concept is an attractive alternative to other methods of rate control and may be applicable in a selected group of patients.
Erwan Donal, Hirotsugu Yamada, Christophe Leclercq and Daniel Herpin : The Left Atrial Appendage, a Small, Blind-Ended Structure. A Review of Its Echocardiographic Evaluation and Its Clinical Role, Chest, Vol.128, No.3, 1853-1862, 2005.
(要約)
The increasing prevalence of stroke and atrial fibrillation is a stimulus for new therapeutic strategies and also warrants a review of imaging modalities of the most important source of cardiac systemic embolic events: the left atrial appendage (LAA). This blind-ended, complex structure is embryologically distinct from the body of the left atrium and is sometimes regarded as just a minor extension of the atrium. However, it should routinely be analyzed as part of a transesophageal echocardiographic (TEE) examination. A pulsed Doppler TEE analysis of LAA emptying flow should supplement a two-dimensional (2-D) analysis; these examinations have proven to be highly reproducible and to help assess thromboembolic risk. In 2-D imaging, potential thrombus and spontaneous echo contrast should be sought. In addition, LAA plays a hemodynamic role that participates in atrial function and is influenced by various hemodynamic conditions. In view of the embolic risks from a dysfunctional appendage, the LAA is often ligated during cardiac valve surgery. New devices are under evaluation for percutaneous closure of the LAA, and further studies should improve the definition, understanding, and treatment of LAA dysfunction.
(キーワード)
Age Factors / Atrial Appendage / Atrial Function, Left / Echocardiography, Doppler, Pulsed / Echocardiography, Transesophageal / Heart Diseases / Heart Rate / Humans / Sex Factors
ZB Popovic, JP Sun, Hirotsugu Yamada, J Drinko, K Mauer, NL Greenberg, Y Cheng, CS Moravec, MS Penn, TN Mazgalev and JD Thomas : Differences in left ventricular long-axis function from mice to humans follow allometric scaling to ventricular size., The Journal of Physiology, Vol.568, No.Pt 1, 255-265, 2005.
(要約)
While the heart size maintains a constant proportion to body size, heart function parameters, such as heart rate and cardiac output, show a more complex scaling pattern. How these phenomena affect the long-axis left ventricular (LV) function is unknown. We studied 10 mice, 15 rats, 6 rabbits, 8 mongrel dogs and 38 human volunteers. Doppler tissue echocardiography data were postprocessed to reconstruct mitral annulus (MA) peak systolic velocity and displacement. The relationship between MA peak velocity, MA displacement and LV ejection time, and LV end-diastolic volume (and mass) were fit to an allometric (power-law) equation Y=kMbeta. LV mass varied from 0.062 to 255 g, while end-diastolic volume varied from 0.014 to 205 ml. beta values of the relation between LV ejection time and LV end-diastolic volume and mass were 0.247+/-0.017 and 0.267+/-0.018, respectively. beta values of the relationship between MA displacement and LV end-diastolic volume and mass were 0.358+/-0.047 and 0.390+/-0.051 (P<0.023 versus beta of LV ejection time). beta values of the relationship between MA peak systolic velocity and LV end-diastolic volume and mass were 0.096+/-0.012 and 0.100+/-0.013, respectively (P<0.0001 versus 0). Finally, beta values of the relationship between the long-to-short axis displacement ratio and LV end-diastolic volume and mass were 0.077+/-0.017 and 0.086+/-0.019 (P<0.0001 versus 0). We conclude that MA velocity, displacement, and long-to-short axis displacement ratio scale allometrically to heart size. This reduces the relative long-axis contribution to heart function in small mammals.
(キーワード)
Animals / Body Weight / Cardiac Output / Diastole / Dogs / Echocardiography, Doppler, Color / Heart / Humans / Mice / Models, Cardiovascular / Organ Size / Rabbits / Rats / Systole / Time Factors / Ventricular Function, Left
Erwan Donal, Carlos A Grimm, Hirotsugu Yamada, Yong Jin Kim, Nassir Marrouche, Andrea Natale and James D. Thomas : Usefulness of Doppler assessment of pulmonary vein and left atrial appendage flow following pulmonary vein isolation of chronic atrial fibrillation in predicting recovery of left atrial function, The American Journal of Cardiology, Vol.95, No.8, 941-947, 2005.
(要約)
Atrial fibrillation (AF) is a widespread condition that causes significant morbidity and mortality. Recently, pulmonary venous (PV) isolation using radiofrequency ablation has been used successfully to exclude the pulmonary venous ostia, resulting in correction of AF. Further, miniaturized high-frequency ultrasound phased-array transducers currently provide Doppler and 2-dimensional imaging during the ablation procedure. We examined atrial function and its determinants using intracardiac echocardiography before and after PV isolation in 45 patients who had chronic AF (56 +/- 11 years old). PV, left atrial (LA) appendage, and mitral and tricuspid flows were recorded. Recovery of booster pump function (defined by the presence of mitral inflow A wave, LA appendage a-wave, and PV A-reversal wave velocities >10 cm/s) was observed in 39 of 45 patients (86.6%). PV flow systolic wave before and after ablation correlated with the degree of LA booster pump function after PV isolation. An early systolic PV flow peak velocity >57.47 cm/s predicted "good" LA booster pump function recovery with 96% specificity. Diastolic LA appendage emptying in AF correlated (p <0.001) and predicted good LA booster pump function with 92% specificity for velocities >46.4 cm/s. Thus, monitoring LA function during PV isolation for chronic AF is feasible. Most patients recovered LA booster pump function immediately after PV isolation, and the degree of recovery correlated with LA reservoir function. Preserved reservoir function during AF is predictive of satisfactory recovery of booster pump function after PV isolation.
Yoko Eto, Hirotsugu Yamada, Joon-Han Shin, Deborah A. Agler, Hiroyuki Tsujino, Jian-Xin Qin, Giuseppe Saracino, Neil L. Greenberg, James D. Thomas and Takahiro Shiota : Automated mitral annular tracking, --- a novel method for evaluating mitral annular motion using two-dimensional echocardiography ---, Journal of the American Society of Echocardiography, Vol.18, No.4, 306-312, 2005.
(要約)
We developed an automated mitral annular tracking method based on a digital processing of high frame rate cineloop images of 2-dimensional echocardiography. In this study, its feasibility and accuracy was validated in 11 healthy volunteers and 16 patients with left ventricular (LV) dysfunction. The mitral annular excursion measured by automated mitral annular tracking agreed well with that measured by 3-dimensional echocardiography and correlated with LV ejection fraction. The longitudinal mitral annular excursion was reduced whereas the radial one was preserved for patients with LV dysfunction compared with control subjects. The novel automated mitral annular tracking method is clinically feasible and has potential capability to quantify the comprehensive mitral annular motion for evaluating LV function in a clinical setting.
Yuichi Notomi, Randolph M Setser, Takahiro Shiota, Maureen G Martin-Miklovic, Joan A Weaver, Zoran B Popović, Hirotsugu Yamada, Neil L Greenberg, Richard D White and James D Thomas : Assessment of left ventricular torsional deformation by Doppler tissue imaging, --- validation study with tagged magnetic resonance imaging ---, Circulation, Vol.111, No.9, 1141-1147, 2005.
(要約)
Left ventricular (LV) torsional deformation is a sensitive index for LV performance but difficult to measure. The present study tested the accuracy of a novel method that uses Doppler tissue imaging (DTI) for quantifying LV torsion in humans with tagged magnetic resonance imaging (MRI) as a reference. Twenty patients underwent DTI and tagged MRI studies. Images of the LV were acquired at apical and basal short-axis levels to assess LV torsion. We calculated LV rotation by integrating the rotational velocity, determined from DTI velocities of the septal and lateral regions, and correcting for the LV radius over time. LV torsion was defined as the difference in LV rotation between the 2 levels. DTI rotational and torsional profiles throughout systole and diastole were compared with those by tagged MRI at isochronal points. Rotation and torsion by DTI were closely correlated with tagged MRI results during systole and early diastole (apical and basal rotation, r=0.87 and 0.90, respectively; for torsion, 0.84; P<0.0001, by repeated-measures regression models). Maximal torsion showed even better correlation (r=0.95, P<0.0001). The present study has shown that DTI can quantify LV torsional deformation over time. This novel method may facilitate noninvasive quantification of LV torsion in clinical and research settings.
Hirotsugu Yamada, Kent A. Mowrey, Zoran B. Popović, David O. Martin, James D. Thomas and Don W. Wallick : Coupled pacing improves cardiac efficiency during acute atrial fibrillation with or without cardiac depression, American Journal of Physiology, Heart and Circulatory Physiology, Vol.287, No.5, H2016-H2022, 2004.
(要約)
Coupled pacing (CP), a method for controlling ventricular rate during atrial fibrillation (AF), consists of a single electrical stimulation applied to the ventricles after each spontaneous activation. CP results in a mechanical contraction rate approximately one-half the rate during AF. Paired stimulation in which two electrical stimuli are delivered to the ventricles has also been proposed as a therapy for heart failure. Although paired stimulation enhances contractility, it greatly increases energy consumption. The primary hypothesis of the present study is that CP improves cardiac function during acute AF without a similar increase in energy consumption because of the reduced rate of ventricular contractions. In a canine model, CP was applied during four stages: sinus rhythm (SR), acute AF, cardiac dysfunction (CD), and AF in the presence of cardiac dysfunction. The rate of ventricular contraction decreased in all four stages as the result of CP. In addition, we determined the changes in external cardiac work, myocardial oxygen consumption, and myocardial efficiency in the each of four stages. CP partially reversed the effects of AF and CD on external cardiac work, whereas myocardial oxygen consumption increased only moderately. In all stages but SR, CP increased myocardial efficiency because of the marked increases in cardiac work compared with the moderate increases in total energy consumed. Thus this pacing therapy may be a viable therapy for patients with concurrent atrial fibrillation and heart failure.
Atul Verma, Nassir F. Marrouche, Hirotsugu Yamada, Richard A. Grimm, Jennifer Cummings, J. David Burkhardt, Fethi Kilicaslan, Mandeep Bhargava, Abdul-Ahmad Karim, James D. Thomas and Andrea Natale : Usefulness of intracardiac Doppler assessment of left atrial function immediately post-pulmonary vein antrum isolation to predict short-term recurrence of atrial fibrillation, The American Journal of Cardiology, Vol.94, No.7, 951-954, 2004.
(要約)
Doppler assessments of pulmonary venous (PV) and left atrial appendage flows are useful surrogates of left atrial (LA) function, but it is unknown if these can predict atrial fibrillation (AF) recurrence after pulmonary vein antrum isolation. We compared Doppler surrogates of LA function immediately after pulmonary vein antrum isolation in patients with AF recurrence versus matched patients without recurrence. Patients with a 6-month recurrence had significantly lower LA appendage peak emptying velocity (19 +/- 10 vs 29 +/- 11 cm/s) and lower peak PV systolic wave velocity (36 +/- 17 vs 46 +/- 22 cm/s) compared with those without, suggesting that intracardiac Doppler assessment of LA function after AF ablation predicts AF recurrence.
Zoran B Popović, Hirotsugu Yamada, Kent A Mowrey, Youhua Zhang, Don W Wallick, Richard A Grimm, James D Thomas and Todor N Mazgalev : Frank-Starling mechanism contributes modestly to ventricular performance during atrial fibrillation, Heart Rhythm, Vol.1, No.4, 482-489, 2004.
(要約)
The aim of this study was to assess whether Frank-Starling mechanism has an independent effect on left ventricular (LV) performance in atrial fibrillation (AF). Ventricular performance in AF depends on variable contractility through the interval-force mechanism based on the ratio of preceding and pre-preceding RR intervals (RR(p)/RR(pp)). The impact of end-diastolic volume (EDV) variability, through the Frank-Starling mechanism, is not well understood. We induced AF in 16 open chest dogs. RR intervals, LV pressure, LV volume, and aortic flow were collected for >400 beats during rapid AF (ventricular cycle length 292 +/- 66 ms). In six of the dogs, additional data were collected while average ventricular cycle length was prolonged from 258 +/- 34 ms to 445 +/- 80 ms by selective vagal nerve stimulation of the AV node. The relations of maximal LV power (LVPower) and peak LV pressure derivative (dP/dt) versus RR(p)/RR(pp) were fitted to the equation y = A * (1 - EXP (RR(p)/RR(pp)min - RR(p)/RR(pp))/C) and the residuals (RES) of these relations were analyzed. LVPower and dP/dt strongly correlated with RR(p)/RR(pp) (r(2) = 0.67 +/- 0.12 and 0.66 +/- 0.12, P < .0001 for all correlations). Importantly, RES-LVPower and RES-dP/dt showed linear correlation with EDV (r(2) = 0.20 +/- 0.14 and r(2) = 0.24 +/- 0.17, P < .01 for all correlations). In the six dogs with slowed average ventricular rate, the slope of both residual relationships (RES-LVPower vs EDV and RES- dP/dt vs EDV) decreased (P < .03 for both). The Frank-Starling mechanism contributes to ventricular performance in AF independently of the interval-force effects of the beat-to-beat variability in cardiac contractility. The Frank-Starling mechanism is sensitive to the average ventricular rate.
Hideji Tanaka, Takashi Oki, Tomotsugu Tabata, Hirotsugu Yamada, Kenji Harada, Eriko Kimura, Yoshifumi Oishi, Takeo Ishimoto and Susumu Ito : Losartan improves regional left ventricular systolic and diastolic function in patients with hypertension, --- Accurate evaluation using a newly developed color-coded tissue Doppler imaging technique ---, Journal of Cardiac Failure, Vol.10, No.5, 412-420, 2004.
(要約)
Angiotensin II receptor antagonists have recently been accepted as antihypertensive therapy. Tissue Doppler imaging (TDI) has been developed as a noninvasive tool to assess quantitatively regional myocardial motion abnormalities. This study was designed to determine whether our newly developed technique of color-coded TDI may be a useful means of quantifying the improvement in regional left ventricular (LV) myocardial contractility and relaxation after treatment with losartan in patients with hypertension. Losartan (50 to 100 mg) was administered for 6 months to 37 previously untreated patients with essential hypertension. Averaged myocardial velocity profiles (MVPs) for color-coded TDI were recorded in the ventricular septum and LV posterior wall before and after treatment. Peak myocardial velocities and peak myocardial velocity gradients (MVGs) in the LV walls were determined during systole and early diastole. The plasma concentration of transforming growth factor (TGF)-beta1 also was measured in all patients. Blood pressure and plasma TGF-beta1 level decreased after initiation of losartan therapy. The LV mass index and LV meridional end-systolic wall stress also decreased after treatment with losartan. LV geometry changed from a pattern consistent with concentric hypertrophy to normal geometry in 10 patients and to a pattern consistent with concentric remodeling in 5 patients, and from concentric remodeling to normal geometry in 5 patients after treatment with losartan. The ratio of early to late diastolic filling for the transmitral flow velocity increased after losartan treatment. The peak systolic and early diastolic myocardial velocities and MVGs in the ventricular septum and LV posterior wall increased after treatment with losartan, although the values 6 months after treatment with losartan were still lower than those in normal individuals. There were good correlations between changes in plasma TGF-beta1 level and changes in systolic and early diastolic MVGs 6 months after losartan. However, there were no significant correlations between changes in the systolic blood pressure and LV end-systolic wall stress and changes in the TDI parameters. Losartan improves regional LV function in patients with hypertension. Our newly developed averaged MVP and MVG measurements may be useful for accurately evaluating regional LV myocardial contractility and relaxation in these patients.
Hirotsugu Yamada, Erwan Donal, Yong-Jin Kim, Deborah A. Agler, Youhua Zhang, Neil L. Greenberg, Todor N. Mazgalev, James D. Thomas and Richard A. Grimm : The "Pseud-Restrictive" Pattern of Transmitral Doppler Flow Pattern Following Conversion of Atrial Fibrillation to Sinus Rhythm, --- Is Atrial or Ventricular Dysfunction to Blame? ---, Journal of the American Society of Echocardiography, Vol.17, No.8, 813-818, 2004.
(要約)
Patients with paroxysmal atrial fibrillation (AF) who have recently converted from AF to sinus rhythm often exhibit a restrictive Doppler pattern in the transmitral flow (TMF) velocity. However, the mechanism of this phenomenon has not been well defined. We evaluated the temporal change of TMF pattern and hemodynamics after conversion of AF to in sinus rhythm in an animal model. Eight open-chest dogs underwent 3 hours of pacing-induced AF. TMF velocities and pressure data were acquired at baseline (sinus rhythm), immediately after conversion of AF, and every 10 minutes thereafter. Early diastolic TMF velocity was increased immediately after conversion and recovered to the baseline value in 20 minutes. Atrial systolic TMF velocity was reduced after AF and recovered to baseline value in 20 to 30 minutes. Early diastolic/atrial systolic TMF velocity was increased after conversion, and recovered to baseline value in 20 to 30 minutes. The mean left atrial (LA) pressure increased immediately, 10 and 20 minutes after the conversion of AF to sinus rhythm. The left ventricular end-diastolic pressure was increased and positive left ventricular dP/dt and tau were decreased immediately after AF, whereas they recovered within 10 minutes. In conclusion, a pseudorestrictive pattern of TMF after AF occurred as a result of transient LA mechanical functional impairment and increased LA pressure caused by LA stunning. Transient left ventricular diastolic dysfunction also effected the TMF velocity immediately after the conversion from AF to sinus rhythm, although it recovered faster than LA mechanical dysfunction.
Takashi Oki, Hideji Tanaka, Hirotsugu Yamada, Tomotsugu Tabata, Yoshifumi Oishi, Takeo Ishimoto, Norio Nagase, Hisanori Shinohara, Koichi Sakabe and Nobuo Fukuda : Diagnosis of cardiac amyloidosis based on the myocardial velocity profile in the hypertrophied left ventricular wall., The American Journal of Cardiology, Vol.93, No.7, 864-869, 2004.
(要約)
The myocardial velocity profile (MVP), derived from color-coded tissue Doppler imaging (TDI), can identify transmural heterogeneity based on the physiology and pathology of the myocardium. This study sought to clarify whether the MVP can differentiate cardiac amyloidosis from other causes of left ventricular hypertrophy. We recorded the MVP and determined its myocardial velocity gradient (MVG) in the ventricular septum and left ventricular posterior wall using color-coded TDI in 10 patients with cardiac amyloidosis, in 25 patients with hypertensive hypertrophied left ventricular wall, in 25 patients with asymmetric septal hypertrophy of hypertrophic cardiomyopathy, and in 20 clinically normal controls. End-diastolic ventricular septal thickness was similar among the cardiac amyloidosis, hypertension, and hypertrophic cardiomyopathy groups. Percent systolic thickening of the ventricular septum and left ventricular posterior wall calculated from M-mode left ventricular echocardiograms was lower in the cardiac amyloidosis group than in the hypertension, hypertrophic cardiomyopathy, or control group. Peak MVGs during systole and early diastole were lowest in the cardiac amyloidosis group, followed, in order, by the control, hypertension, and hypertrophic cardiomyopathy groups. The systolic and early diastolic MVPs in the ventricular septum and left ventricular posterior wall showed a characteristic serrated pattern in all patients with cardiac amyloidosis, but not in any other patient groups. In conclusion, MVPs in the ventricular septum and left ventricular posterior wall show a distinctive serrated pattern that may be related to amyloid deposition in the myocardium. Myocardial tissue characterization using color-coded TDI provides diagnostic information in patients with cardiac amyloidosis.
Hirotsugu Yamada, Takashi Oki, Takashi Yamamoto, Hideji Tanaka, Tomotsugu Tabata, Tetsuzo Wakatsuki, Masahiro Nomura, Susumu Ito and James D. Thomas : Potential application of tissue Doppler imaging to assess regional left ventricular diastolic function in patients with hypertrophic cardiomyopathy: Comparison with 123I-β-methyl iodophenyl pentadecanoic acid myocardial scintigraphy., Clinical Cardiology, Vol.27, No.1, 33-39, 2004.
(要約)
Tissue Doppler imaging (TDI) has been utilized to evaluate left ventricular myocardial dysfunction in patients with hypertrophic cardiomyopathy (HCM); however, no clear explanation for the abnormality of TDI variables has been forthcoming. Peak negative myocardial velocity gradient (MVG) derived from TDI may correlate with a disorder of fatty acid metabolism in patients with HCM. Tissue Doppler imaging and 123I-beta-methyl iodophenyl pentadecanoic acid (123I-BMIPP) myocardial scintigraphy were performed in 15 patients with asymmetric septal hypertrophy (mean age 47 +/- 18 years) and in 12 healthy controls (mean age 43 +/- 10 years). In early 123I-BMIPP images, accumulation defects were observed in the ventricular septum in 12 patients and in the posterior wall in 8 patients with HCM. Peak negative MVG in the ventricular septum (1.1 +/- 0.5 vs. 2.8 +/- 0.5, p < 0.0001) and posterior wall (5.2 +/- 1.4 vs. 6.7 +/- 0.8, p < 0.01 ) was significantly lower in the HCM group than in the controls; also, these parameters were significantly lower in patients with than in those without a defect in the region in question. The peak negative MVG in the ventricular septum and posterior wall correlated inversely with the washout rate in all subjects. Peak negative MVG according to TDI is related to disorder of fatty acid metabolism in the regional left ventricular myocardium of patients with HCM.
Tomotsugu Tabata, Richard A. Grimm, Junko Asada, Zoran B. Popovic, Hirotsugu Yamada, Neil L. Greenberg, Don W. Wallick, Youhua Zhang, Shaowei Zhuang, Kent A. Mowrey, James D. Thomas and Todor N. Mazgalev : Determinants of left ventlicular diastolic function during atrial fibrillation: Beat-by-beat analysis in acute dog experiments., American Journal of Physiology, Heart and Circulatory Physiology, Vol.286, No.1, H145-H152, 2004.
(要約)
Left ventricular (LV) diastolic function during atrial fibrillation (AF) remains poorly understood due to the complex interaction of factors and beat-to-beat variability. The purpose of the present study was to elucidate the physiological determinants of beat-to-beat changes in LV diastolic function during AF. The RR intervals preceding a given cardiac beat were measured from the right ventricular electrogram in 12 healthy open-chest mongrel dogs during AF. Doppler echocardiography and LV pressure and volume beat-to-beat analyses were performed. The LV filling time (FT) and early diastolic mitral inflow velocity-time integral (E(vti)) were measured using the pulsed Doppler method. The LV end-diastolic volume (EDV), peak systolic LV pressure (LVP), minimum value of the first derivative of LV pressure curve (dP/dt(min)), and the time constant of LV pressure decay (tau) were evaluated with the use of a conductance catheter for 100 consecutive cardiac cycles. Beat-to-beat analysis revealed a cascade of important causal relations. LV-FT showed a significant positive linear relationship with E(vti) (r = 0.87). Importantly, there was a significant positive linear relationship between the RR interval and LV-EDV in the same cardiac beat (r = 0.53). Consequently, there was a positive linear relationship between LV-EDV and subsequent peak systolic LVP (r = 0.82). Furthermore, there were significant positive linear and negative curvilinear relationships between peak systolic LVP and dP/dt(min) (r = 0.95) and tau (r = -0.85), respectively, in the same cardiac beat. In addition, there was a significant negative curvilinear relationship between dP/dt(min) and tau (r = -0.86). We have concluded that the determinants of LV diastolic function in individual beats during AF depend strongly on the peak systolic LVP. This suggests that the major benefit of slower ventricular rate appears related to lengthening of LV filling interval, promoting subsequent higher peak systolic LVP and greater LV relaxation.
Hirotsugu Yamada, David O. Martin, Kent A. Mowrey, Neil L. Greenberg and Don W. Wallick : The Effects of Coupled Pacing on Cardiac Performance during Acute Atrial Tachycardia and Fibrillation, --- An Old Therapy Revisited for a New Reason ---, American Journal of Physiology, Heart and Circulatory Physiology, Vol.285, No.6, H2630-H2638, 2003.
(要約)
Atrial tachycardia (AT) and fibrillation (AF) result in rapid ventricular rates that are detrimental to optimal cardiac function. The purpose of this study was to determine whether the application of a coupled pacing (CP) regimen would improve ventricular function by decreasing the ventricular rate of mechanical contractions (VRMCs). We simulated AT by pacing either atrium at a rate that resulted in a rapid but regular ventricular rate in seven anesthetized dogs. AF was induced by increasing the atrial pacing rate until atrial activation did not follow the pacing. After the induction of either AT or AF, we applied CP after each intrinsic ventricular activation. We measured the VRMCs and left ventricular (LV) pressures and volumes via a pressure-conductance catheter. The marked reductions in VRMCs during CP resulted in increases in LV end-diastolic volume. The CP resulted in virtually no mechanical contractions, whereas the strength of contractions from the normal electrical activation increased. The increases in the positive LV rate of pressure development over time and LV ejection fraction during CP were the result of postextrasystolic potentiation. The average stroke work (area of the pressure-volume loops) increased as a result of CP during both AT and AF. Despite the large increases in stroke volume (approximately 2x) during CP, the changes in cardiac output were moderate because the VRMCs markedly decreased (approximately 1/2). We conclude that CP therapy may be a viable therapy for slowing the heart rate and improving cardiac performance in patients with AT and AF.
Nassir F Marrouche, David O Martin, Oussama Wazni, Marc A Gillinov, Allan Klein, Mandeep Bhargava, Eduardo Saad, Dianna Bash, Hirotsugu Yamada, Wael Jaber, Robert Schweikert, Patric Tchou, Ahmad Abdul-Karim, Walid Saliba and Andrea Natale : Phased-Array Intracardiac Echocardiography Monitoring During Pulmonary Vein Isolation in Patients With Atrial Fibrillation., --- Impact on Outcome and Complications. ---, Circulation, Vol.107, No.21, 2710-2716, 2003.
(要約)
The objective of this study was to assess the impact of intracardiac echocardiography (ICE) on the long-term success and complications in patients undergoing pulmonary vein isolation (PVI) for treatment of atrial fibrillation (AF). Three hundred fifteen patients underwent PVI for treatment of AF. Each patient underwent ostial isolation of all PVs using a cooled-tip ablation catheter. PVI was performed using circular mapping (CM) alone (group 1, 56 patients), CM and ICE (group 2, 107 patients), and CM and ICE with titration of radiofrequency energy based on visualization of microbubbles by ICE (group 3, 152 patients). After a mean follow-up time of 417+/-145 days, 19.6% (11 of 56), 16.8% (18 of 107), and 9.8% (15 of 152) of patients in groups 1, 2, and 3 experienced recurrence of AF, respectively. Moreover, whereas no group 3 patient experienced severe (>70%) PV stenosis, severe PV stenosis was documented in 3 (3.5%) of 56 patients in group 1 and in 2 (1.8%) of 107 patients in group 2 (P<0.05). No embolic events were detected in group 3 patients. Intracardiac echocardiography improves the outcome of cooled-tip PVI. Power adjustment guided by direct visualization of microbubble formation reduces the risk of PV stenosis and improves long-term cure.
Sayuri Fujimoto, Takashi Oki, Tomotsugu Tabata, Hideji Tanaka, Hirotsugu Yamada, Yoshifumi Oishi, Takeo Ishimoto, Susumu Ito, Yasuhiko Abe and Ryoichi Kanda : Novel approach to the quantitation of regional left ventricular systolic and diastolic function using tissue Doppler imaging to create a myocardial velocity profile and gradient, Circulation Journal, Vol.67, No.5, 416-422, 2003.
(要約)
The myocardial velocity profile (MVP) and gradient (MVG) between the endocardium and epicardium of the left ventricular (LV) wall measured by color-coded tissue Doppler imaging (TDI) are new indices for evaluating regional LV myocardial function. However, accurate recording and measurement of the MVP is difficult using conventional methodology because of the stochastic nature of the ultrasound signal; that is, the effect of speckled noise. The aim of this study was to validate the accuracy and establish the validity of a newly developed method for measuring the MVP and MVG using 10 clinically normal controls and 10 patients with a hypertensive hypertrophied LV posterior wall. A non-isotropic, averaging algorithm was developed that was capable of obtaining a stable MVP (averaged MVP). Averaged MVP was recorded using parasternal, LV short-axis, color-coded TDI, placing regions of interest along the LV posterior wall with the reference point for angle-correction being at the center of LV contraction. The velocity from epicardium to endocardium within the region of interest was automatically angle-corrected to calculate the velocity component radially relative to the LV cavity and was spatially averaged along the circumference within the region of interest. Inter- and intraobserber variabilities of measurements were lower in the averaged MVP and MVG than in the conventional MVP and MVG. The correlation coefficients of the linear regression lines of systolic and early diastolic MVPs in the LV posterior wall were higher in all controls and hypertensive patients with the averaged method than with the conventional TDI procedures. The mean peak systolic and early diastolic MVGs were lower in the hypertensive group than in the controls. In conclusion, the newly developed averaged MVP provides a stable and reproducible index for the quantitative assessment of regional LV myocardial function.
(キーワード)
Adult / Algorithms / Diastole / Echocardiography, Doppler, Color / Female / Heart Rate / Humans / Hypertrophy, Left Ventricular / Image Processing, Computer-Assisted / Male / Middle Aged / Prospective Studies / Regression Analysis / Reproducibility of Results / Systole / Ventricular Dysfunction, Left / Ventricular Function, Left