Impact of indoxyl sulfate, a uremic toxin, on non-culprit coronary plaque composition assessed by integrated backscatter intravascular ultrasound.

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).


Serial imaging changes during treatment of immunoglobulin G4-related disease with multiple pseudotumors.


Effects of docosahexaenoic acid on the endothelial function in patients with coronary artery disease.

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.

Journal of Atherosclerosis and Thrombosis


Elevated concentration of interferon-inducible protein of 10 kD (IP-10) is associated with coronary atherosclerosis.

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.


Plasma microRNA-100 is associated with coronary plaque vulnerability.

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).


Impact of supervised cardiac rehabilitation on urinary albumin excretion in patients with cardiovascular disease.

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.


Effect of combination tablets containing amlodipine 10 mg and irbesartan 100 mg on blood pressure and cardiovascular risk factors in patients with hypertension.

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.

Therapeutics and Clinical Risk Management


Serum concentration of eicosapentaenoic acid is associated with cognitive function in patients with coronary artery disease.

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.


Effect of ghrelin on autonomic activity in healthy volunteers.

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.


Effects of telmisartan on inflammatory cytokines and coronary plaque component as assessed on integrated backscatter intravascular ultrasound in hypertensive patients.

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.


Cardiac rehabilitation reduces serum levels of oxidized low-density lipoprotein.

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).


Pentraxin 3 is a local inflammatory marker in atrial fibrillation.

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.


Increase in serum triglyceride was associated with coronary plaque vulnerability in a patient with rheumatoid arthritis.

Rates of morbidity and mortality from cardiovascular disease are high in patients with rheumatoid arthritis (RA); however, the mechanisms and biomarkers that reflect coronary plaque vulnerability have not yet been established. We present a case of acute coronary syndrome (ACS) presumably caused by exacerbation of chronic inflammation of RA, in which an abrupt increase in serum triglyceride was seen on the day of onset of ACS but not during effort angina. This case suggests that RA patients with an abrupt increase in triglyceride need intensive care including anti-platelet and statin therapy for the prevention of coronary plaque rupture.<Learning objective: Triglyceride might be a sensitive biomarker of activated macrophages and plaque vulnerability in patients with RA. RA patients with an abrupt increase in triglyceride might need intensive care including anti-platelet and statin therapy for the prevention of coronary plaque rupture.>


Pre-load stress echocardiography for predicting the prognosis in mild heart failure.


Congenital long QT syndrome with compound mutations in the KCNH2 gene.

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.


Augmentation Index does not Reflect the Risk of Coronary Artery Disease in Elderly Patients.

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


Acute pulmonary thromboembolism from deep vein thrombosis induced by trauma to the popliteal vein with a tennis racket.

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.


Ghrelin protects the heart against ischemia-induced arrhythmias by preserving connexin-43 protein.

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.


Pharmacology of Aldosterone and the Effects of Mineralocorticoid Receptor Blockade on Cardiovascular Systems.


Interval from the Onset of Transmitral Flow to Annular Velocity Is a Marker of LV Filling Pressure.


Constrictive pericarditis with intrapericardial abscess.


Two cases of acute myocardial infarction during combined chemotherapy in young patients with testicular cancer.


Cardiac rehabilitation reduces level of oxidized LDL

心臓リハビリテーションは酸化LDLを低下させる


Eosinophilic Myocarditis due to Churg-Strauss syndrome with markedly elevated Eosinophil Cationic Protein.

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.


A case of successful use of microsnare to hold and pull the retrograde guidewire for the intervention to peripheral chronic total occlusion.

A basket-shaped microsnare has various uses such as the pull through technique during coronary intervention to chronic total occlusion (CTO). A 79-year-old man underwent angioplasty for the femoral artery occlusion. We performed a controlled antegrade and retrograde tracking (CART) with dilatation of a balloon on the antegrade guidewire. The retrograde guidewire partly ran in the true lumen but could not pass through the CTO lesion because of inadequate CART. Eventually, we successfully gripped the top of the retrograde guidewire in the CTO lesion using the basket-shaped microsnare (Soutenir(®)). The microsnare may be useful for bidirectional approach in peripheral CTO lesions.

Cardiovascular Intervention and Therapeutics


Gender disparities in the association between epicardial adipose tissue volume and coronary atherosclerosis: A 3-dimensional cardiac computed tomography imaging study in Japanese subjects.

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.


高血圧症に対するRAAS抑制薬の有用性

高血圧症に対するRAAS抑制薬の有用性

Nihon Rinsho. Japanese Journal of Clinical Medicine


Index-beat Assessment of Left Ventricular Systolic and Diastolic Function during Atrial Fibrillation using Myocardial Strain and Strain Rate.

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.

Journal of the American Society of Echocardiography


Bicuspid aortic valve endocarditis complicated by perivalvular abscess.

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.

The Journal of Medical Investigation : JMI


Effect of statin therapy on carotid artery plaque assessed by integrated backscatter color mapping : Development of imaging analytical software and its application on 3 cases

脂質低下療法による頸動脈プラーク安定化の評価:超音波integrated backscatterを用いたカラーマッピングシステムの開発と臨床応用 症例報告 (第28回 徳島医学会賞受賞論文)

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.


Massive splenic infarction due to left ventricular apical thrombus in a patient with giant splenomegaly.


(若手優秀演題セッション)尿中アルブミン排泄量に及ぼす心臓リハビリテーションの効果


Local persistent hypercoagulability after sirolimus-eluting stent implantation in patients with stable angina.

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.


A patient who developed toe necrosis due to poor blood circulation after an interdigital tick bite.


Elevated concentrations of pentraxin 3 are associated with coronary plaque vulnerability.

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.


Comparison of chronic-stage histopathological findings among 3 coronary stents implanted in the same patient.

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.


Ventricular tachycardia in cardiac sarcoidosis controlled by radiofrequency catheter ablation.

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.


Serial imaging changes during treatment of Takayasu arteritis with pulmonary artery stenosis.

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.


Acute hemodynamic effects of adaptive servo ventilation in patients with pulmonary hypertension.


Effect of low-dose (1 mg/day) pitavastatin on left ventricular diastolic function and albuminuria in patients with hyperlipidemia.

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.


Observation of short-term atorvastatin-induced changes in coronary arterial plaque properties using integrated backscatter intravascular ultrasound in a patient.


Validation of longitudinal peak systolic strain by speckle tracking echocardiography with visual assessment and myocardial perfusion SPECT in patients with regional asynergy.

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.


繰り返す心不全と維持透析導入から離脱しえた腎動脈狭窄症の一例

繰り返す心不全と維持透析導入から離脱しえた腎動脈狭窄症の一例


Bosentan ameliorated exercise-induced pulmonary arterial hypertension complicated with systemic sclerosis.

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.


Images in cardiovascular medicine. Cardiac magnetic resonance imaging and 2-dimensional speckle tracking echocardiography in secondary cardiac amyloidosis.


Congenital ventricular aneurysm as an unexpected complication of monomorphic premature ventricular contractions.

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.


Ezetimibe ameliorates metabolic disorders and microalbuminuria in patients with hypercholesterolemia.

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.

Journal of Atherosclerosis and Thrombosis


Diagnostic utility of cardiac magnetic resonance for detection of cardiac involvement in female carriers of Duchenne muscular dystrophy.


Platypnea-orthodeoxia syndrome associated with patent foramen ovale and aortic ectasia.

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.


血管保護をふまえた脂質異常症の薬物治療

血管保護をふまえた脂質異常症の薬物治療


狭心症の薬物療法 スタチンに関する最近の話題―strong statinとvascular statinをどのように選択するのか?


Preload Stress Echocardiography for the Assessment of Heart Failure With Preserved Ejection Fraction