The volume of percutaneous coronary interventions (PCI) performed in a hospital has been suggested to correlate with favorable outcomes in patients undergoing primary PCI for acute myocardial infarction (AMI). However, studies that use current data and compare treatment and outcomes for AMI among hospitals with different volumes are still limited in Japan.
Between January 2004 and March 2006, 401 AMI patients underwent primary PCI in the 11 hospitals participating in the Ibaraki Coronary Artery Disease Study (ICAS). Clinical characteristics, treatment, and in-hospital outcomes were retrospectively compared between 254 patients admitted to high-volume PCI hospitals and 147 patients admitted to low-volume hospitals. Low-volume hospitals had a higher prevalence of multivessel disease patients. High-volume hospitals had longer onset-to-door times, which were offset by faster door-to-balloon times. Rates of coronary stent use and successful PCI were comparable between the groups. Low-volume hospitals more frequently performed intra-aortic balloon pumping. Length of stay was longer in low-volume hospitals, whereas in-hospital mortality, bypass surgery, and repeat PCI rates did not differ between groups.
Although the present study assessed limited data based on small sample size, we observed that contemporary standard treatments including stent implantation were performed for AMI patients undergoing primary PCI in hospitals with both high and low case volumes. We did not find an obvious relationship between hospital PCI volume and in-hospital outcomes in our data. However, further prospective surveys should be attempted to confirm these results.

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It has been shown that cigarette smoking increases blood pressure (BP) and heart rate (HR), and decreases muscle sympathetic nerve activity (MSNA) in healthy young smokers. The decrease in MSNA might be secondary to baroreflex responses to the pressor effect. We tested the hypothesis that cigarette smoking increases MSNA in smokers with impaired baroreflex function.
The effects of cigarette smoking on BP, HR, forearm blood flow (FBF), forearm vascular resistance (FVR), and MSNA were examined in 14 patients with stable effort angina (59 ± 3 years, group CAD) and 10 healthy smokers (23 ± 1 years, group C). In group CAD, the arterial baroreflex sensitivity (BRS) was significantly lower than in group C (4.7 ± 0.8 versus 15.1 ± 2.2 msec/mmHg, P < 0.01). In both groups, cigarette smoking increased the plasma concentration of nicotine, systolic and diastolic BP, HR, and FVR significantly (P < 0.01), but decreased FBF significantly (P < 0.01). After smoking, MSNA was decreased significantly in group C (from 35.2 ± 3.5 to 23.5 ± 3.2 bursts/100 beats, P < 0.01), but increased significantly in group CAD (from 48.8 ± 5.4 to 57.3 ± 5.5 bursts/100 beats, P < 0.01). There was significant correlation between BRS and changes in MSNA (r = -0.62, P < 0.01).
Cigarette smoking increased MSNA in smokers with impaired baroreflex function. This demonstrates that cigarette smoking stimulates sympathetic nerve activity by both a direct peripheral effect and a centrally mediated effect.

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Atrial overdrive provides the best opportunity to suppress atrial arrhythmias. Atrial preference pacing (APP) algorithm has been designed to achieve a high percentage of atrial pacing. The aim of this study was to assess the efficacy of APP algorithm in patients with implanted pacemakers and tachycardia-bradycardia syndrome.
The subjects were 17 patients (mean age, 71.7 ± 9.0 years old, 4 males) implanted with a DDDR pacemaker Thera DR (Medtronic, Minneapolis, MN, USA). All patients had sick sinus syndrome and paroxysmal atrial fibrillation before pacemaker implantation. Informed consent was obtained from each participant before enrollment. DDDR and mode switch or APP were randomly programmed. After two weeks, the pacing mode was switched to another mode. The percentage of atrial pacing was significantly higher in APP than in DDDR (97.7 ± 1.4 versus 52.3 ± 30.8, P < 0.0001). Atrial premature beat counts were significantly greater in DDDR than in APP (30689 ± 42534 versus 7717 ± 10700, P < 0.005). There was no significant difference in mode switch episode counts between DDIR and APP (2.6 ± 5.5 versus 8.4 ± 19.2, NS).
Although there was no significant difference in mode switch episode counts between DDDR and APP, APP algorithm can successfully prevent atrial premature beats in patients with tachycardia-bradycardia syndrome.

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In the treatment of arrhythmia, β-blockers are mainly used to regulate the heart rate. However, β-blockers are also known as drugs with an antiarrhythmic effect due to the suppression of sympathetic activity. We evaluated the antiarrhythmic effects of a highly selective β₁-blocker, bisoprolol, in patients with diurnal paroxysmal atrial fibrillation (P-AF).
A total of 136 patients with symptomatic diurnal P-AF were enrolled. Patients were divided into a diurnal-specific P-AF group and a diurnal & nocturnal P-AF group, as well as into a bisoprolol single use group and a combined use group with an antiarrhythmic drug. The effects of bisoprolol were evaluated in 3 categories: subjective symptom improvement, quality of life (QOL) improvement, and elimination of P-AF episode in Holter electrocardiograms (ECGs). For patients with effective treatment, a long-term effect up to 24 months was evaluated.
Five patients (3.7%) discontinued bisoprolol due to side effects. Following administration of bisoprolol, 109 patients (80%) experienced subjective symptom improvement, 103 patients (76%) experienced QOL improvement, and elimination of P-AF episodes in ECGs was observed in 84 patients (62%). The elimination rate of P-AF episodes in ECGs was higher in the diurnal P-AF group than in the diurnal & nocturnal P-AF group (P = 0.042). There was no significant difference between the bisoprolol single use group and the combined use group. A long-term suppressive effect by bisoprolol was observed in 70 of 83 patients (84%).
The results demonstrate that bisoprolol has an antiarrhythmic effect against sympathetic diurnal P-AF, improving subjective symptoms and QOL and eliminating P-AF episodes in ECGs.

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Few studies have examined predictors of poor blood pressure (BP) control. The aim of this study was to observe the relationship between the pulsatility of brachial artery pressure characterized as pulse pressure/diastolic pressure (PP/DP), suggesting aortic input impedance, and poor BP control.
We obtained office BP measurements for 94 patients aged 40-75 years with either office systolic BP (SBP) ≥ 140 mmHg or diastolic BP (DBP) ≥ 90 mmHg. Patients were given a single antihypertensive agent or were untreated at baseline. The angiotensin II receptor blocker valsartan (80 mg) was administered to all patients. Patients were treated with 1 to 2 antihypertensive drugs (valsartan only or valsartan + Ca antagonist) for 6 months to achieve an office BP of less than 140/90 mmHg.
At follow-up, 32 patients were taking a single drug (valsartan) with good BP control, 24 were receiving two drugs with good BP control, and 38 were on two drugs with poor BP control. SBP and DBP at baseline were similar in the 3 groups. PP/DP at baseline differed in the 3 groups (P < 0.01). In multivariate analysis, only PP/DP at baseline correlated with lack of BP control.
The pulsatility of brachial artery pressure is associated with achieving adequate BP control.

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Elevated concentrations of asymmetric dimethylarginine (ADMA), an endogenous inhibitor of nitric oxide synthase, are associated with endothelial dysfunction. Metabolic syndrome (MetS) is also a condition associated with impaired endothelial function. To test the hypothesis that lipid lowering treatment with a statin lowers ADMA levels, we investigated the effect of fluvastatin treatment on serum ADMA levels in patients with MetS.
A total of 85 hypercholesterolemic MetS patients (53 females, 32 males; mean age, 55.8 ± 9.1 years) were included in this prospective, randomized, controlled study. Patients were randomly assigned to either the treatment (n = 42) or control group (n = 43). Recommendations for lifestyle modification were provided to both groups. In addition, the patients in the treatment group received fluvastatin, extended release tablets, 80 mg/day, orally for 6 weeks. Serum levels of ADMA and lipids were assessed at baseline and at the completion of treatment. High performance liquid chromatography was used to measure serum ADMA concentrations.
In the fluvastatin group, there was a significant reduction in serum ADMA levels compared to baseline (from 1.57 ± 1.07 μmol/L to 1.17 ± 1.41 μmol/L, P < 0.05), whereas in the control group no significant change was observed (from 1.06 ± 0.46 μmol/L to 1.24 ± 1.38 μmol/L, P > 0.05). There was a statistically significant difference between the groups in terms of mean percent change from baseline (P = 0.047).
Fluvastatin treatment for hypercholesterolemia in patients with MetS is associated with a decrease in serum ADMA levels at 6 weeks. This finding is consistent with known beneficial effects of statin treatment on endothelial function in hypercholesterolemic patients.

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A phenotypic change of smooth muscle cells (SMCs) is considered to be critical in the pathogenesis of atherosclerotic lesions such as coronary artery disease (CAD). Mrf-2/ARID5B, a member of the AT-rich interaction domain family of transcription factors, is highly expressed in the cardiovascular system and is believed to play essential roles in the phenotypic change of SMCs through its regulation of SMC differentiation. In addition, recent studies on gene-engineered mice suggested that this transcriptional factor is involved in obesity and adipogenesis, which are critical aspects for the pathogenesis of atherosclerosis. Thus, we hypothesized that genetic variations of the Mrf-2 gene might be associated with susceptibility to CAD.
We investigated 11 common genetic variations of Mrf-2 to determine whether they were associated with susceptibility to CAD in 475 CAD subjects and 310 control subjects. The prevalence of homozygotes for the minor allele G of SNP4 (rs2893880) and minor allele G of SNP6 (rs7087507) were significantly more frequent in the control subjects than in patients with CAD (P = 0.0002, rs2893880, P = 0.0058, rs7087507). Four nearby SNPs (SNP4 to SNP7) (rs2893880, rs10740055, rs7087507 and rs10761600) showed almost complete linkage disequilibrium, and haplotype analysis revealed that the haplotype G (rs2893880)-C (rs10740055)-G (rs7087507)-A (rs10761600) was also significantly negatively associated with susceptibility to CAD (P = 0.049). Moreover, these negative disease associations still existed after logistic regression analysis was taken into account to eliminate confounding conventional coronary risk factors.
The results implicate possible disease relevance of the polymorphisms in the Mrf-2 gene with susceptibility to CAD. However, a larger scale prospective study is needed to clarify these findings.

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Prostaglandin F_2α (PGF_2α) stimulates hypertrophic growth of neonatal rat cardiac myocytes, a feature of which includes downregulation of the Ca²⁺-ATPase (SERCA2), a major Ca²⁺ transport protein in SR. The molecular mechanisms by which PGF_2α inhibits SERCA2 gene expression remain unknown. We determined the cis-regulatory elements responsible for the regulation of the SERCA2 gene expression in cultured neonatal rat cardiac myocytes exposed to PGF_2α. The role of Egr-1 was evaluated by transient transfection of its expression vector and antisense oligonucleotide. Signaling pathways were determined by using the pharmacological inhibitors or cDNA expression plasmids coding for dominant negative forms of Ras and Rac. PGF_2α reduced the SERCA2 mRNA levels in a time- and dose-dependent manner in cultured rat cardiac myocytes. Transient transfection analyses showed that PGF_2α -responsive elements are located between -284 and -72 of the SERCA2 promoter, which contains G+C-rich sequences homologous to Sp1, Egr-1 and AP2-binding sites. PGF_2α significantly increased Egr-1 expression, and overexpression of Egr-1 largely reduced the transcription of the SERCA2 gene. Egr-1 antisense oligonucleotides blocked the PGF_2α -mediated decrease in SERCA2 mRNA expression. Furthermore, inhibitors for either genistein-sensitive tyrosine kinase or p38 MAPK, and dominant negative forms of either Ras or Rac, prevented PGF_2α -induced repression of SERCA2 mRNA levels. These results suggest that Egr-1, as well as Ras, Rac, and p38 MAPK, plays a crucial role in the repression of SERCA2 gene expression during PGF_2α -induced cardiac hypertrophy.

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The combined effect of creatine (Cr) or estrogen (E₂) with exercise training on cardiac reserve function and antioxidant reservation against oxidative stress were investigated in ovariectomized female Golden Syrian hamsters. One hundred animals were divided into nonexercise and exercise-trained groups, in which each group was separated into the control and 4 treatments of Cr depletion (Cr-), Cr supplementation (Cr+), E₂ replacement (E₂), and Cr supplementation combined with E₂ replacement (Cr+E ₂). In the exercise-trained group, wheel-running exercise (10 minutes a day, 5 days a week) was imposed for 9 weeks. After the animals were sacrificed, several indicators of cardiac function, specifically the corrected QT interval, left ventricular developed pressure (LVDP), and maximum rate of rise (dP/dt_max) against a hydrogen peroxide (H₂O₂) stress test were measured in isolated hearts using the Langendorff apparatus. Markers of oxidative stress, in other words, reduced glutathione (GSH), oxidized glutathione (GSSG), and an antioxidant enzyme, glutathione peroxidase (GPx) were determined. Exercise-trained animals could restore cardiac reserve function and antioxidant levels against oxidative damage (P < 0.05). Cr+, E₂ , and Cr+E₂ combined with exercise training showed highly protected cardiac reserve function against oxidative stress compared to Cr+, E₂ , and Cr+E₂ without exercise (P < 0.05). The myocardial antioxidant levels were improved greatly in E₂ and Cr+E₂ combined with exercise training (P < 0.05). In conclusion, estrogen replacement and creatine supplementation plus estrogen replacement when combined with exercise training show significant protective effects for cardiac reserve function and antioxidant reservation against oxidative stress in estrogen-deficient hamsters.

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This study attempts to compare the risks and benefits of provisional stenting with drug eluting stents and bypass surgery for left main coronary artery (LMCA) stenosis.
Recent improvements in interventional technologies have increased interest in percutaneous treatment of LMCA stenosis. However, application of percutaneous techniques to LMCA has been sporadic and controversial.
In-hospital and one year outcomes of coronary artery bypass graft (CABG) and percutaneous coronary intervention (PCI) cases were compared. From September, 2003 to June, 2005, a total of 59 consecutive patients with de novo unprotected LMCA stenosis were treated with either CABG or PCI. Twenty patients received non-intravascular ultrasound-guided PCI with a stent in the LMCA. Thirty-nine patients underwent CABG.
At 30-day follow-up, the major adverse cardiac and cerebrovascular event (MACE) rates of mortality, myocardial infarction, cerebral vascular accident, and target vessel revascularization were 25.6% in the CABG group and 5% in the PCI group (P = 0.054).
At one year follow-up, the MACE rates were 33.3% in the CABG group and 5% in the PCI group. One year MACE for the CABG group significantly differed from that of the PCI group (P = 0.015). The odds ratio (OR) of one year MACE-free survival was 0.75 (P < 0.001) in the CABG group versus the PCI group. Further analysis demonstrated there was a significant difference in in-hospital MACE and one year MACE between the elective CABG group and elective PCI group (P = 0.045). However, there was no significant difference between the emergent CABG group and emergent PCI group (P = 1.000 for in-hospital MACE; P = 0.486 for one year MACE).
PCI on unprotected LM offers an alternative option in patients with high surgical risk and appropriate lesion morphology.

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Infective endocarditis (IE) is a relatively rare but serious complication of hypertrophic obstructive cardiomyopathy. Currently, antibiotic prophylaxis is not generally recommended in these patients. We report a case of infective endocarditis in a patient after alcohol septal ablation for hypertrophic obstructive cardiomyopathy with residual left ventricle outflow tract obstruction. To the best of our knowledge, this is the first case in the medical literature demonstrating this complication in the late postprocedural period following alcohol septal ablation.

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A 32 year-old woman with bilateral hilar lymphadenopathy suffered from syncopal attacks after her first delivery. Electrocardiograms showed complete atrioventricular block (AVB) and myocardial scintigrams demonstrated a decreased uptake in the anteroseptal area. She was diagnosed as having postpartal cardiac acceleration of sarcoidosis. Because she rejected permanent pacemaker implantation, we started steroid therapy under temporary pacing. Fortunately, the treatment was very effective. Even after tapering-off of the steroid, the AVB has never reappeared. Permanent pacemaker implantation with subsequent steroid therapy is generally recommended for complete AVB due to cardiac sarcoidosis. However, steroid therapy alone can be considered for some selected cases.

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