Most paroxysmal atrial fibrillation (PAF) ultimately becomes chronic atrial fibrillation (CAF), even in the presence of antiarrhythmic drugs. Upstream therapies such as calcium channel blockers (CCB), angiotensin-converting enzyme inhibitors (ACEI), or statins have attracted attention for treating AF patients. We have previously reported that ACEI inhibited the progression of PAF to CAF. CCB and statins were also reported to inhibit the development of AF, but the follow-up periods in several of the papers appeared to be too short to allow a clear verdict on the antiarrhythmic effects. We therefore conducted a retrospective analysis of the relationship between long-term treatment (over 5 years) with an ACEI, CCB, or statin and outcome in patients with PAF (n = 125).
The follow-up period was 7.7 ± 3.1 years. Class I antiarrhythmic drugs were prescribed for 76.6% of the patients, ACEI for 36.0%, CCB for 47.2%, and statins for 20.0%. We assessed the cardiac rhythm from the medical records or electrocardiograms and determined the time from the first visit to the development of CAF. Kaplan-Meier analysis showed that the use of an ACEI significantly decreased the cumulative probability of CAF, while class I antiarrhythmics, CCB, and statins did not inhibit progression to CAF. Multivariate analysis showed that only ACEI was related to a reduced progression to CAF (odds ratio, 0.112; 95% confidence interval, 0.034 to 0.374, P = 0.001). Class I antiarrhythmic drugs, CCBs, and statins showed no such association.
ACEI thus appear to be superior to CCB or statins with respect to upstream therapy.

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Recent data have shown that statins can help prevent atrial fibrillation (AF). We hypothesized that statins vary in their ability to prevent AF after successful electrical cardioversion (EC).
Sixty-five patients (29 receiving atorvastatin and 36 receiving simvastatin) who had undergone successful EC for persistent AF were included in the study. They received statins at least one month before EC, and continued the treatment through 2 years of follow-up. The statins they received were selected independently by their attending physicians.
In the follow-up period, AF reoccurred in 11 (38.0%) patients of the atorvastatin group and in 24 (66.7%) patients of the simvastatin group. Using a logistic regression model, the unadjusted odds ratio (OR) of having an AF recurrence for patients on atorvastatin versus those on simvastatin was 0.31 (95% CI 0.11-0.85, P = 0.02). After adjustment for other potentially confounding variables (age, sex, hypertension, diabetes, ischemic heart disease, echocardiographic characteristics, and therapy), treatment with atorvastatin retained its significance for maintaining sinus rhythm in a multivariate model (OR 0.20, CI 0.04 to 0.98, P < 0.05).
Our study suggests that atorvastatin and simvastatin exert different effects on the AF recurrence rate after successful EC. Larger prospective randomized trials are needed to definitively evaluate the role of different statins in patients with AF, especially on AF recurrence after EC.

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Although ultrasonic diagnostic imaging and fetal heart monitors have undergone great technological improvements, the development and use of fetal electrocardiograms to evaluate fetal arrhythmias and autonomic nervous activity have not been fully established. We verified the clinical significance of the novel signal-averaged vector-projected high amplification ECG (SAVP-ECG) method in fetuses from 48 gravidas at 32-41 weeks of gestation and in 34 neonates. SAVP-ECGs from fetuses and newborns were recorded using a modified XYZ-leads system. Once noise and maternal QRS waves were removed, the P, QRS, and T wave intervals were measured from the signal-averaged fetal ECGs. We also compared fetal and neonatal heart rates (HRs), coefficients of variation of heart rate variability (CV) as a parasympathetic nervous activity, and the ratio of low to high frequency (LF/HF ratio) as a sympathetic nervous activity. The rate of detection of a fetal ECG by SAVP-ECG was 72.9%, and the fetal and neonatal QRS and QTc intervals were not significantly different. The neonatal CVs and LF/HF ratios were significantly increased compared with those in the fetus. In conclusion, we have developed a fetal ECG recording method using the SAVP-ECG system, which we used to evaluate autonomic nervous system development.

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Plasma brain natriuretic peptide (BNP) level is known to reflect left ventricular wall stress (LVWS). Recent studies have shown that obese individuals have lower BNP levels. However, the usefulness of BNP level as a marker of LVWS in obese individuals remains unclear. This study examined whether BNP reflects LVWS even in obese individuals.
This study enrolled 136 hospital inpatients who had suffered chronic heart failure (NYHA class I or II), or who had undergone a thorough examination for angina pectoris. On the basis of body mass index (BMI), we divided the inpatients into nonobese (< 25) and obese (≥ 25) groups. All BNP measurements, cardiac catheterizations, and echocardiographic examinations were carried out within 24 hours.
Although no significant differences were found between the two groups in the hemodynamic parameters examined, including end-diastolic LVWS (LV-EDWS) and end-systolic LVWS (LV-ESWS), BNP levels were significantly lower in the obese group compared to the nonobese group. In the nonobese group, a definite correlation between LV-EDWS or LV-ESWS and BNP (r = 0.43, r = 0.46, respectively) was observed, whereas no correlation was found between LV-EDWS or LV-ESWS and BNP in the obese group (r = -0.09, r = 0.06, respectively). To explore the mechanism for suppressed BNP levels in obese individuals, the correlation of BNP with biochemical markers was analyzed. Statistical significance was found only between adiponectin and BNP (r = 0.44), implying that BNP or adiponectin might influence the plasma levels of the other.
In conclusion, BNP levels cannot be used as a marker of LVWS in obese individuals.

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Because both atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) competitively bind to natriuretic peptide receptors but not N-terminal proBNP (NT-proBNP), the diagnostic value of BNP as a marker of the severity of heart failure in comparison with NT-proBNP during exogenous ANP (carperitide) infusion remains unclear.
Forty-two patients with CHF (NYHA class III or IV) treated with the infusion of carperitide were included in the present study. We measured plasma levels of BNP and NT-proBNP at baseline and after the improvement of symptoms. We also measured these parameters before and 1 hour after stopping the infusion of carperitide.
After stopping the infusion of carperitide, the plasma BNP level was significantly decreased by about 20% (394 ± 53.8 versus 312.8 ± 46 pg/mL, P < 0.0001) but plasma NT-proBNP did not change (1674.5 ± 282.1 versus 1777.5 ± 300.3 pg/mL, P = 0.259). The molar ratio of plasma BNP/NT-proBNP was significantly higher during carperitide infusion (0.74 ± 0.08) than those at baseline (0.63 ± 0.06) and after stopping carperitide (0.59 ± 0.07).
During carperitide infusion, plasma NT-proBNP may be a more reliable marker of endogenous cardiac natriuretic peptides than plasmaBNP, which may be increased by carperitide infusion.

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This experimental study investigated the impact of hyperglycemic control on left ventricular (LV) function using a model of diabetes mellitus (DM) (induced by streptozocin 60 mg/kg). Sixteen adult-Sprague Dawley rats were divided into group 1 (poor hyperglycemic control, n = 8) and group 2 (good hyperglycemic control, n = 8). Diabetic rats and 8 healthy rats serving as controls (group 3) were sacrificed on day 28 after DM induction. The results demonstrated that HbA_1C on day 28 was higher in group 1 than in groups 2 and 3 (P < 0.0001). The mRNA expressions of MMP-9 and endothelin-1 were elevated in group 1 compared with that in groups 2 and 3 (P < 0.05), whereas PGC-1α and eNOS were lower in group 1 than in groups 2 and 3 (P < 0.05). The number of apoptotic nuclei was higher in group 1 than in groups 2 and 3 (P < 0.01). The integrated area (μm²) of connexin43 (Cx43), Cx43 protein expression, and LV function were lower in group 1 than in groups 2 and 3 (P < 0.05). Moreover, PKC-ε expression in the mitochondrial compartment was decreased in group 1 compared to that in groups 2 and 3 (P < 0.005).

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Antrodia camphorata (AC) is a well-known traditional Chinese medicine that has been shown to inhibit proliferation and migration of cancer cells. We examined whether AC could inhibit rat aortic smooth muscle cell (RASMC) proliferation and migration and evaluated its effect on neointima formation in mouse carotid artery after injury.
In Transwell migration assay and wound scratch assay, RASMCs were treated with AC or saline, and the number of migrated cells was counted or the distance was determined. Both assays showed that AC significantly inhibited platelet-derived growth factor (PDGF)-induced SMC migration. In 3-(4,5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) and 5-bromo-2’ deoxyuridine (BrdU) proliferation assays, RASMCs were pretreated with AC or saline and stimulated with PDGF. Both assays showed that AC inhibited PDGF-induced SMC proliferation. The left common carotid arteries of C57BL/6 mice were ligated near the carotid bifurcation. The mice were given water or AC for 4 weeks. The severity of neointima formation was expressed as the neointima/media (N/M) ratio. The AC-treated mice had less neointima formation at 4 weeks after carotid ligation (N/M ratio, water versus 250 versus 1250 mg/kg AC; 1.33 ± 0.87 versus 0.83 ± 0.45 versus 0.63 ± 0.32, P < 0.05).
Our data indicate that AC is an effective inhibitor of PDGF-induced RASMC proliferation and migration. AC treatment reduced neointima formation in this mouse carotid ligation model.

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This study investigated six-month angiographic results of autologous bone marrow mononuclear cell (BMMNC) transplantation immediately following acute myocardial in-farction (AMI) in a mini-pig model.
AMI was induced by left anterior descending artery ligation. Twenty-four mini-pigs were equally divided into group 1 [AMI plus saline injection in infarcted area (IA)], group 2 (AMI plus BMMNC transplantation into non-IA), group 3 (AMI plus BMMNC implantation into IA), and group 4 (sham control). One-week cultured BMMNCs (3.0 × 10⁷) were immediately transplanted following AMI induction. Angiographic studies over 6 months demonstrated that mitral regurgitation (MR) was lower in groups 3 and 4 than in groups 1 and 2 (all P < 0.01). Wall motion scores and left ventricular ejection fraction (LVEF) were higher in groups 3 and 4 than in groups 1 and 2 (all P < 0.05). Collateral circulation was higher in group 3 than in groups 1 and 2 ( P < 0.01). The wall thickness of the IA was higher, whereas the heart weight was lower in group 3 than in groups 1 and 2 (all P < 0.01).
Immediate autologous BMMNC transplantation into IA is superior to saline-treated only or BMMNC transplantation into non-IA following AMI for reducing MR and improving LVEF.

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We evaluated the effectiveness of a suppressant of the production of proinflammatory cytokines such as interleukin (IL)-1 and tumor necrosis factor (TNF)-α on a canine heart transplantation model with non-heart-beating donors (NHBDs).
Adult mongrel dogs were divided into 3 groups of 5: a control group; FR-1 in which donors were given FR167653, a potent suppressant of IL-1β and TNF-α production; and FR-2 in which both donors and recipients were given FR167653. After measuring the baseline hemodynamic parameters, including cardiac output (CO), left ventricular pressure (LVP), and maximum and minimum rates of increase in LVP (± LVdp/dt), FR167653 was administered continuously for 30 minutes before ischemia in the FR-1 and FR-2 groups. Cardiac arrest was obtained by rapid exsanguination from the abdominal aorta and inferior vena cava. The organ was left in the cadaver for 30 minutes. The coronary vascular beds were washed out with 4°C Celsior solution, and then the donor heart was preserved in 4°C Celsior solution for 4 hours. The donor heart was transplanted orthotopically with cardiopulmonary bypass (CPB). FR167653 was administered intravenously from 15 minutes before aortic-cross clamping until the end of the experiment in the FR-2 group. The recipient was weaned from CPB 1 hour after reperfusion. We compared the hemodynamic parameters at 3 hours after reperfusion with the preoperative values in donor animals with the right atrial pressure at 10 mmHg and a 5 μg/kg/min dopamine infusion. Histopathological analysis was also performed.
There were no significant differences in the recovery rates of the hemodynamic parameters between the control and FR-1 groups and between the FR-1 and FR-2 groups. However, the recovery rates of CO and -LVdp/dt in the FR-2 group were significantly (P < 0.05) higher than those in the control group. Histopathological analysis showed that myofilaments were better preserved in the FR-2 group compared with the control group.
The administration of a suppressant of proinflammatory cytokines before both ischemia and reperfusion effectively preserves donor heart function after transplantation with NHBDs.

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The aim of this study was to assess whether mast cells are involved in the recovery of diminished cutaneous blood flow (CBF) by bone marrow cell transplantation (BMCT) in limb arterial occlusion. In a hindlimb ischemia model, CBF was measured by laser Doppler perfusion imaging in White spot (Ws) rats which genetically lack mast cells, and their wild-type with or without BMCT. After 14 days, tissue mast cell density was assessed by toluidine blue staining. To evaluate angiogenesis, we also determined CD 31-positive capillary density in the ischemic limbs.
CBF in ischemic limbs decreased to 36 ± 2% of nonischemic limbs, but 7 to 14 days later it naturally recovered to 65 ± 2% and reached a plateau in both types of rats. BMCT further (P < 0.05) increased CBF with increases in tissue mast cell and capillary densities in wild-type rats, but not in Ws rats. Treatment with sodium cromoglycate, an inhibitor of mast cell degranulation, diminished the increases in mast cell and capillary densities, and CBF by BMCT in ischemic limbs of wild-type rats.
Mast cells may not be involved in ischemia-induced natural angiogenesis and a partial recovery of CBF, however, they appear to be involved in the therapeutic angiogenesis by BMCT.

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A 23-year-old woman with pre-excitation who was resuscitated from ventricular fibrillation underwent electrophysiologic testing. Successful catheter ablation of a left posteroseptal accessory pathway was achieved. Though the JT and JTc intervals as well as QT and QTc intervals were prolonged before and one day after the ablation, they normalized within about 5 hours after the ablation. This case demonstrated that in a patient with pre-excitation and long QT syndrome (LQTs), the JTc interval was useful for diagnosing LQTs and a longer follow-up of the JTc interval after the ablation was necessary in order not to miss the diagnosis of LQTs.

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A 40-year-old man, who had been diagnosed with stage 2 pulmonary sarcoidosis, was referred to our hospital for further evaluation of dyspnea and cardiac function. The echocardiogram displayed thinning of the basal interventricular septum (IVS) and a reduced ejection fraction of 21%. Contrast-enhanced cardiac high resolution MRI (3 tesla) showed patchy subepicardial late gadolinium enhancement in the IVS, and anterior and lateral walls. There was no abnormality in the coronary angiography and the cardiac biopsy showed several small and well-defined noncaseating epithelioid granulomas. The granulomas contained multinucleated giant cells and asteroid bodies (a typical finding of sarcoidosis). Late gadolinium enhancement in high resolution MRI provided information on the pathophysiological condition of cardiac sarcoidosis very clearly, because 3 of 5 samples of endomyocardial biopsy from the septal wall of the right ventricle where late gadolinium enhancement was detected had positive findings for cardiac sarcoidosis (very high rate). These findings indicate that high resolution late gadolinium enhanced MRI might be very useful as a guide for endomyocardial biopsy in patients with cardiac sarcoidosis.

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