Vascular endothelial dysfunction reflected by reduced nitric oxide (NO) availability is certainly the causative factor or promoting mechanism of arteriosclerosis. It is necessary to detect endothelial dysfunction at an early stage using appropriate methods, and to choose a treatment for the recovery of endothelial function. There are nonpharmacological and pharmacological therapies to attain endothelial repair. The former includes body weight reduction, aerobic exercise, and restriction of salt intake, while the latter includes the use of renin-angiotensin system inhibitors, calcium antagonists, some types of β blockers, statins, erythropoietin, tetrahydrobiopterin, and antioxidants. These therapies are intended to increase NO synthase activity and NO release, inhibit NO degradation, and enhance the activity of endothelial progenitor cells.

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The difference in neointimal stent coverage (NSC) between ruptured segments and adjacent nonruptured segments in infarct-related lesions (IRL) of acute myocardial infarction after bare metal stent (BMS) implantation was evaluated using coronary angioscopy. Serial angioscopic observations were performed for 19 IRLs immediately after the implantation of a BMS and at 1-month and 6-month follow-up. Stented segments were divided into the ruptured segment and the nonruptured segment based on the presence of a thrombus. The grade of NSC was divided into 0 = complete exposure, 1 = partial coverage, or 2 = complete coverage. The grade of plaque color was classified semiquantitatively as 0 = white, 1 = light yellow, or 2 = intense yellow. The existence of a thrombus was also determined. The grade of NSC in the ruptured segment was lower than that of the nonruptured segment at each follow-up. The grade of plaque color at the 1-month follow-up was higher in the ruptured segment than in the nonruptured segment. At 6 months, the grade of plaque color was similar between the ruptured and nonruptured segments. In all cases, thrombi existed in the ruptured segments immediately after stenting. Although thrombi still remained frequently at 1-month, most had disappeared at the 6-month follow-up. Neointimal proliferation of the ruptured segment in IRL advanced slowly in comparison to the adjacent nonruptured segment. The presence of an atherosclerotic yellow plaque and a thrombus may affect the delayed neointimal coverage after BMS implantation.

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Clopidogrel is used with aspirin as a standard combined treatment in patients with acute coronary syndrome. A proton pump inhibitor (PPI) is often administered to patients receiving antiplatelet therapy. However, PPI use with clopidogrel was recently shown to result in increased risk of major cardiovascular events when compared to clopidogrel use alone. Therefore, the aim of the present study was to evaluate the effects of omeprazole, a PPI, on the antiplatelet effect of clopidogrel.
We divided 20 healthy volunteers into 2 groups (n = 10 each). Twenty-four hours after a 300 mg loading dose of clopidogrel, one group received a dosage of 75 mg/day of clopidogrel and a placebo for 14 days, followed 3 weeks later by the same protocol but with coadministration of 75 mg/day clopidogrel and 20 mg/day omeprazole instead. The other group received the same treatment but in reverse order. Antiplatelet activity was assessed in terms of the P2Y12 reaction unit (PRU) and percentage inhibition using a VerifyNow P2Y12 assay system.
The PRU of the omeprazole-treated subjects was significantly higher than that of the omeprazole-untreated subjects on day 14 (281.3 ± 54.0 versus 240.0 ± 72.2, P = 0.048). The percentage inhibition showed a decrease after the 14-day omeprazole treatment (22.7 ± 29.9% versus 35.1 ± 18.7%, P = 0.014).
Consequently, omeprazole reduces the antiplatelet effect of clopidogrel, suggesting that careful treatment planning is required when administering omeprazole to patients on clopidogrel therapy.

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The reported pathogenesis of Brugada syndrome is phase 2 reentry resulting from shortening of the epicardial action potential duration at the right ventricular outflow tract (RVOT). However, several studies have revealed a high incidence of ventricular late potentials and high rate of ventricular fibrillation (VF) induced by programmed ventricular stimulation (PVS). The aim of the present study was to evaluate the role of slow conduction at the RVOT for the initiation of VF by PVS and any underlying pathological conditions in Brugada syndrome. Endocardial mapping of the RVOT and endomyocardial biopsy of the right ventricle were performed in 25 patients with Brugada syndrome with inducible VF. Late potentials were positive in 11 of the 25 (44%) patients. Low-amplitude fragmented and delayed electrograms were recorded at the RVOT in 13 of 18 (72.2%) patients. Histologic examination of the biopsy samples revealed fatty tissue infiltration, interstitial fibrosis, lymphocyte infiltration, and/or myocyte disorganization in 13 patients. Slow conduction at the RVOT may contribute to the induction of VF by PVS in Brugada syndrome. Various pathomorphologic changes may contribute to slow conduction at the RVOT.

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The CHADS₂ score has been proposed for stratifying patients with nonvalvular atrial fibrillation (NVAF) according to the risk of thromboembolism in the AHA/ACC/ESC guidelines. However, there is little information about its usefulness for predicting the long-term risk of ischemic stroke in Japanese patients with paroxysmal AF. We retrospectively evaluated the incidence of ischemic stroke and the efficacy of anticoagulant therapy in paroxysmal AF patients on rhythm control therapy who were stratified by their CHADS₂ score. The subjects were 334 NVAF patients (229 men and 105 women, mean age, 68 ± 12 years, mean follow-up period, 60 ± 35 months) who were categorized into low risk (score 0), moderate risk (1 or 2), and high risk (3 or more) groups for thromboembolism.
The low, moderate, and high risk groups accounted for 34%, 50%, and 16% of the patients, respectively. Among 257 patients without warfarin therapy, the annual rate of symptomatic ischemic stroke was 0.6% in the score 0 group, 0.5% in the score 1 group, 3.1% in the score 2 group, and 9.6% in the score 3 or more group. Among 77 patients treated with warfarin (target PT-INR: 1.6-3.0), the stroke rate was 0% in the score 0 group, 0% in the score 1 group, 1.4% in the score 2 group, and 6.6% in the score 3 or more group. The annual rate of ischemic stroke was 0.88% in patients treated with warfarin versus 2.67% in those without warfarin, or a decrease in risk of 68% with warfarin (P < 0.01). In Japanese patients with paroxysmal AF, the CHADS₂ score is useful for predicting the risk of ischemic stroke. Anticoagulant therapy is needed to prevent ischemic stroke in patients with paroxysmal AF, especially those who have a CHADS₂ score of 2 or more.

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Recent data suggest that elevated plasma levels of homocysteine could be associated with atrial fibrillation (AF). The aim of our study was to investigate whether elevated plasma Hcy levels were predictive of the recurrence rate of AF after successful electrical cardioversion.
Eighty-three patients (63 ± 12 years, 61.4% men) with persistent AF lasting at least 7 days were included after successful electrical cardioversion. Echocardiography and plasma homocysteine assay were performed prior to cardioversion and patient baseline characteristics were obtained. Patients were monitored for a period of 18 months.
The patients were divided into two groups using a cut-off value for the last quartile of plasma homocysteine concentration (> 14.4 μmol/L). Kaplan Meier analysis showed a statistically significant difference in AF recurrence rates between both groups after 18 months (P = 0.02, log rank test). Cox proportional hazards multivariate analysis showed that predictors of AF recurrence were the duration of AF (OR 1.05, 95% CI 1.02-1.08, P = 0.00), treatment with amiodarone (OR 0.39, 95% CI 0.21-0.72, P = 0.00), and homocysteine level ≤ 14.4 μmol/L (OR 0.39, 95% CI 0.21-0.73, P = 0.00).
We found that the homocysteine levels determined prior to electrical cardioversion can predict recurrence of AF after successful restoration of sinus rhythm.

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This study investigated the clinical course of arrhythmogenic right ventricular cardiomyopathy (ARVC) patients and in particular evaluated the contribution of radiofrequency catheter ablation (RFCA) and an implantable cardioverter-defibrillator (ICD) to the treatment of ARVC.
ARVC is a myocardial disorder and a cause of sudden cardiac death due to ventricular tachycardia (VT). Little is known about its prognosis in Japanese ARVC patients.
Thirty-five ARVC patients were studied. Mean age of patients whose onset of ARVC was congestive heart failure (CHF) (66.0 ± 4.0 years) was significantly higher than those whose onset was VT (44.5 ± 14.8 years, P < 0.05). ARVC patients with CHF onset showed significantly higher death rates compared to those with VT onset. ICD treatment significantly reduced episodes of hospitalization due to VT (0.1 ± 0.4 episodes) in comparison to treatment by RFCA (1.7 ± 2.2 episodes, P < 0.03). RFCA treatment did not reduce recurrence of VT in the follow-up period. ICD therapy showed comparable mortality to RFCA treatment.
The prognosis of ARVC with CHF onset is poor. ICD therapy significantly reduced hospitalization due to VT compared with RFCA treatment. ICD implantation in combination with medication may be a better treatment for ARVC.

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Increased QT dispersion (QTd) is a marker of myocardial electrical instability and predicts ventricular arrhythmias and sudden cardiac death. Exercise training (ET) has been shown to reduce both QTd and cardiovascular mortality in various populations. Patients with metabolic syndrome (MS) have been shown to have increased QTd. The effect of ET on QTd in MS patients however is unknown. We sought to assess the effect of a long-term (≥ 6 months) ET program on QTd parameters in MS patients with and without coronary heart disease (CHD). Fifteen CHD and 31 non-CHD patients with MS (mean age, 64 ± 7 and 57 ± 9 years, respectively) were identified at entry into identical ET programs. MS was defined using modified National Cholesterol Education Program criteria. A control group consisted of 8 MS patients with CHD (mean age, 65 ± 6 years). Ventricular repolarization (QT dispersion = QTd, standard deviation of QT = SDQT, relative dispersion of QT = RDQT, QT corrected dispersion = QTcd), metabolic and exercise parameters were measured before and after ET. Program duration was over 9 months (312 ± 100 versus 284 ± 101 days in CHD and non-CHD cohorts, P = NS). QTd decreased in both ET groups (QTd pre versus post = 66 versus 56 ms in CHD group, P < 0.01; 58 versus 51 ms in non-CHD group, P ≤ 0.01). Other ventricular repolarization parameters also improved significantly in both MS groups following ET, but remained unchanged in the control group. A long-term ET program improves QTd in patients with MS with and without CHD.

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We initiated an original papillary muscle head approximation procedure, commonly known as Sandwich plasty, for the treatment of ischemic mitral regurgitation (MR). In this study, we evaluated the appropriateness of this procedure for functional MR associated with aortic valve disease. Fifteen patients who had undergone Sandwich plasty combined with aortic valve surgery were included in this study. The mean age of the patients was 69 years. Predominant aortic valve diseases were regurgitation in 8 patients and stenosis in 7 patients. Aortic valve replacement was performed in 14 patients and David surgery in one. The mitral valve was approached through the aortic annulus in 9 patients (the transaortic group). Six other patients with mitral valve annulus of 30 mm or larger underwent concomitant mitral ring-annuloplasty through a left atrial incision (the LA group). The tenting height of the mitral valve and left ventricle diastolic diameter significantly decreased after surgery in both groups. After surgery, residual moderate or mild MR was detected in two patients in the transaortic group. In the LA group, residual mitral regurgitation was not detected. In the follow-up study, prominent MR occurred in two patients in the transaortic group. The MR free rate two years after surgery was 83% in the total patient population. Sandwich plasty was simple and effective in the treatment of functional mitral regurgitation combined with aortic valve surgery. A transaortic approach is effective in obviating a separate left atriotomy and reducing operation time.

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Adiponectin, which is an adipose-derived protein with antiatherosclerogenic activities, has been reported to be elevated in patients with heart failure. However, there are no reports on the significance of adiponectin in patients with hypertrophic cardiomyopathy (HCM). The purpose of this study was to elucidate the clinical significance of plasma adiponectin levels in HCM patients.
Clinical characteristics, echocardiographic parameters, and levels of plasma B-type natriuretic peptide (BNP) and adiponectin were evaluated in 106 HCM patients. The plasma adiponectin levels were 10.8 ± 6.3 (range, 2.7-37.3) μg/mL. Plasma adiponectin levels were positively related to age and inversely related to body mass index (BMI). Among echocardiographic parameters, % fractional shortening (r = -0.20, P = 0.03) and maximum LV wall thickness (r = -0.23, P = 0.02) were inversely related to plasma adiponectin levels. A significant correlation between plasma adiponectin levels and BNP levels was also observed (r = 0.27, P = 0.005). In multivariate analysis, BMI, % fractional shortening, and plasma BNP levels were independent predictors of plasma adiponectin levels.
Plasma adiponectin levels are associated with impaired LV systolic function in HCM patients, but not with the LV outflow gradient. Together with BNP, adiponectin can be a useful biomarker for assessing disease severity in HCM patients.

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The stretched size of an atrial septal defect (ASD) is important for device selection during transcatheter closure. However, balloon sizing carries potential risks such as hypotension, bradycardia, or laceration of the atrial septum. The aim of the present study was to investigate the accuracy of the predicted stretched size of ASD by intracardiac echocardiography (ICE).
From December 2004 to November 2007, 136 consecutive patients with single secundum type ASD undergoing transcatheter closure of their defect using the Amplatzer septal occluder under ICE guidance were enrolled for analysis.
There were 43 males and 93 females. The age ranged from 2.2 to 79.1 years with a median age of 13.4 years. The body weight ranged from 12.1 to 93.2 kg with a median body weight of 45.8 kg. The stretched size of ASD measured by a sizing plate was considered as the standard. ASD sizes measured by ICE in bicaval and short-axis views predicted the stretched size by formulae derived from linear regressions. The predicted stretched sizes obtained using 2 formulae, 1.34 × √bicaval ×short axis (formula 1) and 1.22 × larger diameter (formula 2), exhibited good agreement with the standard stretched size with Kappa values of 0.91 and 0.90, respectively. The accuracy rate of predicted stretched sizes within 2 mm, 3 mm, and 4 mm range of the standard size were 32.8%, 45.4%, and 57.7% (formula 1) and 33.1%, 50%, and 63.2% (formula 2).
The stretched size of ASD predicted by ICE exhibited good agreement with the standard stretched size. This prediction provides helpful information, especially if balloon sizing cannot be adequately performed.

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The beneficial effects of raloxifene, a selective estrogen receptor modulator, on cardiovascular risks and events have been investigated. Brachial arterial flow-mediated vasodilatation (FMD), carotid intima-media thickness (IMT), and pulse wave velocity (PWV) have been widely used in clinical settings as surrogate markers of atherosclerosis. This study investigated the simultaneous effects of raloxifene on brachial arterial FMD, carotid IMT, and PWV in osteoporotic postmenopausal women. A total of 31 postmenopausal women with osteoporosis or osteopenia were divided into 2 groups: a raloxifene group (n = 15; mean age ± SD, 66.1 ± 8.2 years) was treated with raloxifene hydrochloride (60 mg/day) orally for 12 months, and an untreated control group (n = 16; 64.1 ± 7.8 years). Brachial arterial FMD, carotid IMT, and brachial-ankle PWV (baPWV) were measured at baseline and at 12 months after the start of the study. The brachial arterial FMD increased significantly, from 4.5 ± 1.8% to 9.2 ± 3.0%, in the raloxifene group (P < 0.01) but did not change in the control group. Nitroglycerin-induced vasodilatation did not change in either group. The carotid IMT decreased significantly, from 0.82 ± 0.15 mm to 0.72 ± 0.11 mm, in the raloxifene group (P < 0.01) but did not change in the control group. The baPWV did not change in either group. In conclusion, raloxifene may have beneficial effects on brachial arterial endothelial function and carotid wall thickness in osteoporotic postmenopausal women.

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Recent evidence suggests an association between vasospastic angina and Brugada syndrome. Here we present two cases of coronary artery disease who presented with ECG abnormalities which might have been provoked or enhanced by ischemia of the conus branch of the right coronary artery. The 12-lead ECGs demonstrated normal sinus rhythm in these two cases. Interestingly, a saddle back or coved type ST segment elevation in leads V1-V3 was documented either in the percutaneous transluminal angioplasty procedure of the proximal right coronary artery or with an intracoronary acetylcholine (Ach) administration into the right coronary artery. These Brugada type ECG changes were restored to the baseline ECG waveform after improvement in the ischemia. In the second case, vasospasms of the conus branch of the right coronary artery were associated with a coved type ST segment elevation in leads V1 to V2. We discuss the possible interaction between ischemia caused by conus branch lesions and Brugada type electrocardiographic changes.

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Atrial tachycardia (AT) and atrial fibrillation (AF) were observed in a 21-year old male who had a history of patch closure for an atrial septal defect (ASD) at the age of 5 and a persistent left superior vena cava (LSVC). During electrophysiologic study, atrial extrastimuli reproducibly induced AT which spontaneously terminated or changed into AF. Electroanatomical mapping revealed focal AT arising from the floor of the proximal LSVC. Radio- frequency applications within LSVC targeted to the earliest activation site of AT as well as the complex fractionated potential eliminated both AT and AF without trans-septal puncture.

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