Cell therapy is a promising approach to improve cardiac function in patients with ischemic heart disease. Beneficial effects of cell therapy have been shown in experimental studies and clinical trials. However, with current treatment strategies the therapeutic effect is limited. In the current article, critical aspects of cell therapy are discussed: cell type, the state of ischemic heart disease and the condition of cells at the time of treatment. Because treatment options of native cells by systemic pharmacotherapy are limited, we propose a concept of ex vivo preconditioning to overcome functional cell impairment and to enhance cell-based regenerative approaches. (Circ J 2009; 73: 2179-2182)

View full abstract

Development of blood vessels is coordinated by angiogenesis and stabilization of vascular endothelial cells (ECs). The vascular network is established during embryogenesis to supply oxygen and nutrients to the tissues and organs. However, after cardiac or peripheral ischemia is caused by occlusion of the vessels, new vessels must be formed to rescue the ischemic tissues. Many angiogenic growth factors and chemokines are produced in the ischemic tissue to induce angiogenic sprouting of preexisting vessels. Branched vessels must be again restabilized to form mature vessels that deliver blood to the tissues. To this end, vascular EC-cell adhesion is tightly regulated by cell-cell adhesion molecules and extracellular stimuli that activate G protein-coupled receptors and receptor tyrosine kinases exclusively expressed on vascular ECs. This review spotlights the recent studies of vascular endothelial cadherin and of sphingosine 1-phosphate signaling and angiopoietin-Tie signaling. (Circ J 2009; 73: 2183-2191)

View full abstract

Recent major increases in obesity and related metabolic diseases (known as the metabolic syndrome (MetS)) because of sedentary lifestyles and overnutrition in developed and developing countries, are an exploding medical and social problem. These conditions are associated with increased risk of cardiovascular disease (CVD), the leading cause of death. Thus, it is necessary to understand the molecular basis underlying MetS and develop effective preventive and therapeutic approaches against CVD. To date, 7 angiopoietin-like proteins (Angptls) that are structurally similar to angiopoietins have been identified. However, none binds to the angiopoietin receptor, Tie2, or to the closely related Tie1 receptor, suggesting that these ligands function differently from angiopoietins. Some Angptls potently regulate angiogenesis, similar to angiopoietins, whereas others have pleiotropic activity other than angiogenesis and function in lipid and energy metabolism. In this review, we focus on the roles of Angptl2 and Angptl6/angiopoietin-like growth factor (AGF) in the development of MetS and CVD, and discuss the potential for Angptl2 and Angptl6/AGF to function as molecular targets for the prevention and treatment of both conditions. (Circ J 2009; 73: 2192-2197)

View full abstract

An increase in short-term blood pressure (BP) variability is a characteristic feature of hypertensive patients, especially in elderly patients. There is increasing evidence that large BP variability aggravates hypertensive target organ damage and is an independent risk factor for the cardiovascular events in elderly hypertensive patients. However, little is known about the underlying mechanism. We have created a rat model of a combination of hypertension and large BP variability by performing sinoaortic denervation (SAD) in spontaneously hypertensive rats (SHRs). SAD aggravates left ventricular (LV)/myocyte hypertrophy and myocardial fibrosis to a greater extent and impairs LV systolic function without changing mean BP in SHR. SAD upregulates cardiac monocyte chemoattractant protein-1 and transforming growth factor-β, and induces macrophage infiltration. Cardiac angiotensinogen expression is increased and the angiotensin II type 1 receptor is activated by SAD. A subdepressor dose of angiotensin receptor blocker abolishes SAD-induced inflammatory changes and cardiac remodeling and subsequently prevents systolic dysfunction in SHR+SAD. Accordingly, it is suggested that cardiac inflammation via activation of the cardiac angiotensin II system would play a role in the aggravation of cardiac remodeling and dysfunction in hypertensives with large BP variability. (Circ J 2009; 73: 2198-2203)

View full abstract

Background: Therapeutic hypothermia (TH, 30°C) protects the brain from hypoxic injury. However, TH may potentiate the occurrence of lethal ventricular fibrillation (VF), although the mechanism remains unclear. The present study explored the hypothesis that TH enhances wavebreaks during VF and S₁ pacing, facilitates pacing-induced spatially discordant alternans (SDA), and increases the vulnerability of pacing-induced VF. Methods and Results: Using an optical mapping system, epicardial activations of VF were studied in 7 Langendorff-perfused isolated rabbit hearts at baseline (37°C), TH (30°C), and rewarming (37°C). Action potential duration (APD)/conduction velocity (CV) restitution and APD alternans (n=6 hearts) were determined by S₁ pacing at these 3 stages. During TH, there was a higher percentage of VF duration containing epicardial repetitive activities (spatiotemporal periodicity) (P<0.001). However, TH increased phase singularity number (wavebreaks) during VF (P<0.05) and S₁ pacing (P<0.05). TH resulted in earlier onset of APD alternans (P<0.001), which was predominantly SDA (P<0.05), and increased pacing-induced VF episodes (P<0.05). TH also decreased CV, shortened wavelength, and enhanced APD dispersion and the spatial heterogeneity of CV restitution. Conclusions: TH (30°C) increased the vulnerability of pacing-induced VF by (1)facilitating wavebreaks during VF and S₁ pacing, and (2)enhancing proarrhythmic electrophysiological parameters, including promoting earlier onset of APD alternans (predominantly SDA) during S₁ pacing. (Circ J 2009; 73: 2214-2222)

View full abstract

Background: Few studies have explored risk stratification of arrhythmic events in patients with ischemic heart diseases according to T-wave alternans (TWA) using modified moving average (MMA) method and heart rate turbulence (HRT). Methods and Results: A retrospective analysis of 63 patients who underwent MMA-based TWA and HRT divided the patients into 3 groups: group-C of 21 controls, group-O of 21 patients with old myocardial infarction (OMI) showing no episodes of sustained ventricular tachyarrhythmia (SVT), and group-V of 21 OMI patients with episodes of SVT who received an implantable cardioverter-defibrillator. Among the 3 groups, positive TWA (≥65 μV) and impaired HRT were observed most frequently in group-V (P<0.05). Using a logistic regression model, TWA yielded an odds ratio of 4.9 (95% confidence interval: 1.2-19.6, P<0.05), which was the only significant covariate for the incidence of life-threatening ventricular arrhythmias during a mean follow-up of 72 months. Conclusions: Patients with OMI showing episodes of SVT have a high risk for cardiac death because of abnormal repolarization and autonomic regulation. The analysis of MMA-based TWA and HRT can be a useful tool for predicting OMI patients at high risk of arrhythmic events. (Circ J 2009; 73: 2223-2228)

View full abstract

Background: There is limited information regarding the angiographic and clinical outcomes among the different drug-eluting stents (DESs) in patients with acute myocardial infarction (AMI) undergoing percutaneous coronary intervention (PCI). Methods and Results: A total 355 consecutive AMI patients who underwent PCI with a sirolimus- (SES, n=116) or paclitaxel- (PES, n=153) or zotarolimus-eluting stent (ZES, n=86) were enrolled. The 6-month angiographic and 1-year clinical outcomes were compared among the 3 groups. At 6 months, there was a trend toward a higher incidence of binary restenosis in the PES group (SES: 8.6%, PES: 19.8%, ZES: 8.3%, P=0.052). Percentage of restenosis was higher in the PES group compared with SES, but was similar to ZES (SES: 18.75 ±18.16%, PES: 29.32 ±24.16%, ZES: 23.91 ±17.03%, P=0.006). Late loss was lower in the SES group compared with PES and ZES (SES: 0.44 ±0.52, PES: 0.83 ±0.87, ZES: 0.75 ±0.63, P<0.001). However, clinical outcomes, including mortality, MI, repeat PCI and major adverse cardiac events, were not different among the 3 groups. Conclusions: The angiographic benefit of SES did not translate into a clinical benefit for up to 1 year in AMI patients. (Circ J 2009; 73: 2229-2235)

View full abstract

Background: The efficacy of partial vs full coverage for tandem lesions in the culprit vessel during primary percutaneous coronary intervention (PCI) after ST-elevation myocardial infarction (STEMI) was compared in the present study. Methods and Results: The 76 patients with STEMI and tandem lesions in the culprit vessel were randomized to receive stent implantation for an occluded/culprit lesion only (partial group) or complete coverage of lesions (full group). After PCI, patients in the partial group had more complete ST-segment resolution (STR) at 90 min (60.5% vs 28.9%, P=0.006), Thrombosis In Myocardial Infarction (TIMI) flow grade 3 (68.4% vs 28.9%, P=0.001), and myocardial blush grade 3 (42.1% vs 15.8%, P=0.04) than those in the full group. At 6 months, the major adverse cardiac events-free survival rate did not differ significantly between groups, but left ventricular (LV) ejection fraction was improved in the partial group. Multivariate analysis revealed pre-procedural TIMI flow grade >1 and door-to-balloon time <90 min were positively associated with complete STR at 90 min, whereas full coverage for tandem lesions was an independent factor for poor STR (odds ratio 2.58, 95% confidence interval 1.08-5.42, P=0.03). Conclusions: For acute STEMI patients with tandem lesions in the culprit vessel, primary stenting for the occluded lesion only is beneficial in improving myocardial perfusion and LV function. (Circ J 2009; 73: 2236-2243)

View full abstract

Background: Atrial fibrillation (AF) after coronary artery bypass grafting (CABG) is still the most common postoperative arrhythmic complication. Previous studies report that patients undergoing preoperative statin therapy had a lower incidence of postoperative AF. This study aimed to assess the effect of preoperative atorvastatin therapy on preventing AF following off-pump CABG in a randomized, controlled trial. Methods and Results: The 140 consecutive patients undergoing elective off-pump CABG, without a history of AF or previous statin treatment, were enrolled and randomly assigned to a statin (atorvastatin 20 mg/day, n=71) or a control group (placebo, n=69) starting 7 days preoperatively. The primary endpoint was the occurrence of postoperative AF; secondary endpoints were major adverse in-hospital cardiac and cerebrovascular events and identification of variables predicting postoperative AF. Atorvastatin significantly reduced the incidence of postoperative AF and the postoperative peak C-reactive protein (CRP) level vs placebo (14% vs 34%, P=0.009; 126.5 ±22.3 vs 145.2 ±31.6 mg/L, P<0.0001). Logistic regression analysis showed preoperative atorvastatin treatment was an independent factor associated with a significant reduction in postoperative AF (odds ratio (OR) 0.219, P=0.005), whereas a high postoperative CRP level was associated with increased risk (OR 2.011, P=0.013). Conclusions: Administration of atorvastatin 20 mg/day, initiated 1 week before elective off-pump CABG and continued in the postoperative period, significantly decreases postoperative AF. (Circ J 2009; 73: 2244-2249)

View full abstract

Background: Although ω-3 polyunsaturated fatty acids are known to have beneficial effects on cardiovascular diseases, their prognostic value has not been studied prospectively in patients with acute myocardial infarction (AMI). Methods and Results: The plasma levels of phospholipids, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) (% of total fatty acids), were measured in 508 patients (365 males; mean age, 63 years) with AMI. Clinical and biomarker predictors of all-cause and cardiovascular mortality were identified by stepwise Cox regression model. During a mean follow-up of 16.1 months, 36 (7.1%) patients died. After controlling for confounding variables, age (hazard ratio (HR): 1.09, P<0.001), renal insufficiency (HR: 2.84, P=0.01) and EPA level (HR: 0.29, P=0.004) were identified as independent predictors of all cause-mortality. When stratified by gender, age (HR: 1.08, P=0.001) and renal insufficiency (HR: 4.49, P=0.003) were predictors of all-cause-mortality in males, whereas EPA level (HR: 0.18, P=0.009) and angiotensin-converting enzyme inhibitor use (HR: 0.24, P=0.03) were identified as predictive of all-cause-mortality in females. Conclusions: Lower plasma level of EPA, but not DHA, was an independent predictor for all-cause-mortality in patients with AMI, but this relationship was significant only in female patients. (Circ J 2009; 73: 2250-2257)

View full abstract

Background: Risk factor clustering, the so-called metabolic syndrome (MetS), is an important risk factor for cardiovascular disease (CVD). Smoking is also an important CVD risk factor with still a high prevalence. However, few previous studies have compared the risk for CVD or the population-attributable fraction (PAF) of smoking, MetS, and both. Methods and Results: The present study was an 11.9-year cohort study of 1,822 men and 2,089 women, aged 40-74 years, selected randomly from an urban general population in Japan. MetS was defined according to the National Cholesterol Education Program on Adult Treatment Panel III (NCEP-ATPIII) guideline modified by the Asian criteria for waist circumference. The prevalence of smoking was 49.5% in men and 11.1% in women, and that of MetS was 19.8% and 23.5%, respectively. In men, the multivariate-adjusted hazard ratio for CVD incidence, compared with non-smoking participants without MetS, was 2.07 (1.26-3.40) in those who smoked, 2.09 (1.08-4.04) in those with MetS, and 3.56 (1.89-6.72) in those with both. In men the PAF for CVD incidence was 21.8% because of smoking, 7.5% because of MetS, and 11.9% because of both. Conclusions: Although countermeasures for MetS are important, smoking should continue to be considered an important public health problem and antismoking campaigns should be promoted, especially for men, to prevent CVD. (Circ J 2009; 73: 2258-2263)

View full abstract

Background: It is reported that adiponectin has a cardioprotective effect and is decreased in type 2 diabetes mellitus (DM). Methods and Results: The effect of carperitide (atrial natriuretic peptide: ANP) on plasma adiponectin levels was evaluated in acute decompensated heart failure (ADHF) patients with and without DM. In 47 patients (DM: n=11) who were admitted with ADHF, blood samples were collected before and 7 days after administration of carperitide. The plasma levels of ANP, brain natriuretic peptide (BNP), aldosterone and adiponectin were measured. Plasma adiponectin levels were significantly increased (17.6 ±1.5 to 19.6 ±1.8 μg/ml, P=0.0003) concomitant with the increase in ANP and decrease in BNP 7 days after carperitide infusion. Although adiponectin levels before treatment were slightly lower in ADHF patients with DM, the % increase in adiponectin levels was significantly greater in ADHF patients with DM than in those without DM (26.7 vs 6.6%, P=0.007). In the stepwise multivariate analyses, a higher plasma aldosterone levels before treatment (P=0.04) and DM (P=0.01) were significant independent predictors of a greater % increase in adiponectin levels after treatment with carperitide. Conclusions: Carperitide infusion increases the plasma adiponectin level, especially in ADHF patients with DM. (Circ J 2009; 73: 2264-2269)

View full abstract

Background: The effect of the dose of carvedilol on cardiac sympathetic nerve activity (CSA) and mortality remain uncertain in patients with chronic heart failure (CHF). Methods and Results: To compare the dose of carvedilol and the transcardiac gradient of norepinephrine (NE), a biomarker of CSA, and prognosis in patients with CHF, hemodynamic parameters and plasma levels of NE, N-terminal brain natriuretic peptide (NT-proBNP) in the aortic root and coronary sinus were measured in 107 patients with systolic CHF who received carvedilol. Patients were divided into 2 groups [group I: low dose (<10 mg/day, n=41) and group II: high dose (≥10 mg/day, n=66)]. There was no difference between the 2 groups for the hemodynamic parameters. The dose of carvedilol did not correlate with plasma NE, but was significantly correlated with the transcardiac increase in NE. During a median follow-up of 4.3 years, 13 patients died of cardiac disease. In the Cox stepwise multivariate analyses, a high level of transcardiac increase in NE (P<0.001), high level of plasma log NT-proBNP (P=0.004) and low dose of carvedilol (P=0.012) were significant independent predictors. Conclusion: The carvedilol dose is important for the management of CSA and prognosis in patients with systolic CHF. (Circ J 2009; 73: 2270-2275)

View full abstract

Background: Risk stratification for elderly patients with acute decompensated heart failure (ADHF) may help clinicians to select the appropriate therapy and raise the quality of care. Methods and Results: The present study enrolled 349 patients aged over 65 years who were hospitalized with ADHF from January 2004 to October 2008. Five independent prognostic factors were identified by multivariate logistic regression analysis, and each factor was assigned a number of points proportional to its regression coefficient: prior heart failure hospitalization (2points), sodium ≤138 mmol/L (2points), BUN ≥35 mg/dl (2points), albumin ≤3.2 g/dl (3points), and BNP ≥980 pg/ml (2points); in particular, hypoalbuminemia was identified as the strongest prognostic factor. The patients were stratified into 3 groups: low risk (0-4points), moderate risk (5-7points), and high risk (8-11points). The respective in-hospital mortality rates were 1.6%, 15.8%, and 42.1% (P<0.05). Conclusions: In addition to known prognostic factors, hypoalbuminemia may provide important information for elderly patients with ADHF. A simple risk score may help to stratify the risk of in-hospital mortality and contribute to better clinical management of these elderly patients. (Circ J 2009; 73: 2276-2281)

View full abstract

Background: Antihypertensive agents differentially influence the plasma adiponectin concentration and the effects of fixed-dose combination regimens remain unclear. The influence of a combination of an angiotensin-converting enzyme inhibitor (ACEI) and a thiazide-type diuretic or an ACEI alone on plasma adiponectin concentrations in patients with essential hypertension was evaluated in the present study. Methods and Results: After a 2-week placebo run-in phase, 30 patients with essential hypertension were randomized to receive preterax (2 mg perindopril/0.625 mg indapamide) or cilazapril (2.5 mg) once daily for 12 weeks. Plasma adiponectin and insulin concentrations were measured before and after treatment. Insulin resistance was measured by homeostasis assessment index (HOMA-IR). Treatment with preterax (P=0.003) and cilazapril (P=0.031) significantly reduced systolic blood pressure (BP), but only preterax reduced diastolic BP (P=0.024). Cilazapril treatment significantly increased the plasma adiponectin concentration (P=0.025) and reduced plasma triglycerides (P=0.041), whereas preterax treatment increased the plasma insulin concentration (P=0.041) and tended to increase HOMA-IR. Conclusions: The combination of an ACEI and indapamide improved BP control, but attenuated the beneficial effects of ACE inhibition on plasma adiponectin in patients with essential hypertension. Such a combination may be best reserved for improved BP control rather than for metabolic protection in clinical hypertension. (Circ J 2009; 73: 2282-2287)

View full abstract

Background: This study aimed to reveal the incremental prognostic implications of perfusion/function variables by stress/rest gated single-photon emission computed tomography (SPECT) over clinical risks in patients with known coronary artery disease (CAD). Methods and Results: Using the Japanese Assessment of Cardiac Events and Survival Study by Quantitative Gated SPECT (J-ACCESS) database, the 3-year follow-up data of 2,200 patients who had established CAD were analyzed. Major cardiac events (cardiac death, myocardial infarction, heart failure, and unstable angina) were observed in 167 (7.6%) patients. Multivariate logistic regression analysis identified peripheral artery disease, diabetes mellitus, no use of statins, typical chest pain, pharmacological stress test, heart rate at rest, left ventricular end-systolic volume index derived from gated SPECT (LVESVI), and summed difference score (SDS) as independent significant predictors of the major cardiac events, with odds ratios of 1.025 to 2.291 (P=0.0309-0.0008). Global chi-square values increased by combining the independent predictors, and the greatest values (nearly 110) were observed when LVESVI or SDS was added to the pre-scan clinical information. Conclusions: Perfusion/function measures by stress/rest gated SPECT contribute to a significant improvement in risk stratification and secondary prevention strategy in combination with pre-scan clinical risks in patients with known CAD. (Circ J 2009; 73: 2288-2293)

View full abstract

Background: Asymmetrical septal hypertrophy and impaired left ventricular (LV) diastolic function are common echocardiographic features of hypertrophic cardiomyopathy (HCM). However, it is difficult to differentiate nonobstructive HCM from hypertensive LV hypertrophy (H-LVH). Methods and Results: Standard echocardiography and tissue Doppler imaging were performed in 14 patients with HCM, 16 patients with H-LVH, and 21 control subjects. Endomyocardial radial strain, systolic strain rate (SR), and the early diastolic SR at the posterior and septal segments of the LV short axis were calculated. Endomyocardial peak strain (ε) and the absolute value of peak early diastolic SR at the posterior segment were significantly smaller in patients with HCM than in those with H-LVH, whereas the thickness of the LV posterior wall did not differ between these 2 groups. Multivariate analysis of discrimination, including the ratio of interventricular septal thickness and posterior wall thickness (IVST/PWT), ε, and SR parameters, between HCM and H-LVH patients revealed that ε at the LV posterior segment was the highest discriminant parameter (discriminant coefficient: -14.6, P=0.012). The ε at the posterior segment significantly correlated with early diastolic mitral annular velocity. Conclusions: Endomyocardial radial strain imaging may prove informative for discriminating between HCM and H-LVH. (Circ J 2009; 73: 2294-2299)

View full abstract

Background: Late stent thrombosis related to delayed neointimal growth is a major concern after drug-eluting stent (DES) implantation. The time course of neointimal growth and risk factors of uncovered stent struts after sirolimus-eluting stent (SES) was studied using optical coherence tomography (OCT). Methods and Results: The 60 patients were enrolled and classified into G1 (follow-up period <9 months, n=27), G2 (9-24 months, n=18), and G3 (>25 months, n=15). The time elapsed since SES implantation was associated with a significant increase in mean neointimal area and neointimal thickness, and also with a significant decrease in the number of uncovered stent struts (G1: 14.8%, G2: 11.7%, and G3: 4.1%, P<0.001). However, only 17.6% of implanted SES was completely covered by neointima, even in the G3 period. Small-diameter SES, complex coronary lesions with lipid and calcium content adjacent to stent struts, and diabetes predicted delayed neointimal coverage of SES struts in G1. Conclusions: Neointima inside SES progressively increases after the routine follow-up period, but only a few SES were completely covered at 3 years after implantation. OCT is a useful modality for assessing neointimal formation after SES implantation, and may give important information about the strategy of antiplatelet therapy after DES implantation. (Circ J 2009; 73: 2300-2307)

View full abstract

Background: Some stable angina patients with significant coronary function have low exercise capacity, whereas some have high exercise capacity. The aim of the present study was to determine whether coronary pressure-derived fractional flow reserve (FFRmyo), a functional index of coronary stenosis, is a better indicator of exercise capacity than angiographic stenosis. Methods and Results: The 15 male (65.8 ±8.9 years old) subjects with stable angina and 75% angiographic stenosis underwent a cardiopulmonary exercise test (CPX), and peak oxygen uptake (PeakVO₂) and oxygen uptake at anaerobic threshold (AT) were measured. The relationship between FFRmyo and CPX values was assessed. The left anterior descending artery was affected in 8 patients, the left circumflex artery in 5, and the right coronary artery in 2. Percent diameter stenosis (%DS) was 61.7 ±9.1% by quantitative coronary angiography. Mean FFRmyo, PeakVO₂, and AT was 0.84 ±0.66, 17.1 ±3.2 ml · kg^-1 · min^-1, and 11.1 ±2.0 ml · kg^-1 · min^-1, respectively. There was no significant correlation between %DS and FFRmyo, PeakVO₂, or AT (r=0.12, 0.051, and 0.013, respectively; P=NS), but FFRmyo had a significant positive correlation with PeakVO₂ and AT (r=0.534 and 0.542, respectively; P<0.05). Conclusions: Exercise capacity reflects functional stenosis in stable angina patients. (Circ J 2009; 73: 2308-2314)

View full abstract

Background: The present study investigated whether administration of controlled release matrix metalloproteinase-1 (MMP-1) plasmid DNA prevents left ventricular (LV) remodeling in a rat chronic myocardial infarction (MI) model. Methods and Results: Rats with a moderate-sized MI were randomized to 2 groups: injection of phosphate buffered saline (PBS) containing microspheres into the peri-infarct area (MI group, n=14) and injection of cationized gelatin microspheres incorporating MMP-1 plasmid DNA (MI+MMP-1 group, 50 μg MMP-1/20 μl; n=14). As a control group (n=14), rats received neither the coronary artery ligation nor the injection of PBS. Echocardiography, cardiac catheterization and histological studies were performed. At 2 and 4 weeks after the treatment, the MI+MMP-1 group had smaller LV end-diastolic and end-systolic dimensions, better fractional area change and smaller akinetic areas than the MI group. The LV end-systolic elastance and time constant of isovolumic relaxation were also better in the MI+MMP-1 group compared with the MI group 4 weeks after the treatment. Fibrosis evaluated with Masson's trichrome staining was less in the MI+MMP-1 group than the MI group. Conclusions: Gelatin microspheres for the controlled release of MMP-1 plasmid DNA are promising for improving cardiac remodeling and function when they are administered during the chronic phase of MI. (Circ J 2009; 73: 2315-2321)

View full abstract

Background: Atherosclerosis leads to myocardial infarction (MI) and P2RY2 plays an important role in this process. The aim of the present study was to investigate the association between human P2RY2 and MI via a haplotype-based case-control study that additionally analyzed the group by sex. Methods and Results: The 310 MI patients and 254 controls were genotyped for 5 single-nucleotide polymorphisms (SNPs) of the human P2RY2 gene (rs4944831, rs1783596, rs4944832, rs4382936, rs10898909). Data were separately analyzed for the total, male, and female subjects. For men, the GA+AA genotype of rs10898909 was significantly higher in MI patients as compared with controls (P=0.040). Logistic regression analysis found a significant difference for the genotype (P=0.016). As compared with controls, the frequencies of the C-A and T-C-A haplotypes were significantly higher (P=0.016, and P=0.045, respectively) in men, whereas the frequencies of the C-G and T-A-A haplotypes were significantly lower (P=0.023, and P=0.025, respectively) in MI patients. Conclusions: The GA+AA genotype, as well as the C-A and T-C-A haplotypes, of human P2RY2 could be genetic markers for MI in Japanese men. (Circ J 2009; 73: 2322-2329)

View full abstract

Background: Hypertrophic cardiomyopathy (HCM) with an apical phenotype, in which hypertrophy of the myocardium predominantly involves the apex of the left ventricle, is not uncommon in Japan, but its morphologic variations are not well recognized. The aim of this study was to investigate if these variations have different clinical characteristics although they are still confused to be the same. Methods and Results: Patients with the apical phenotype were divided into 2 groups, the "pure-apical" form and the "distal-dominant" form, and their clinical profiles were compared. From the study cohort of 264 patients with HCM, 80 (30%) were classified as having the apical phenotype: 51 with the pure-apical form and 29 with the distal-dominant form. The age at diagnosis was approximately 60 years, and in both groups the majority were male. The distal-dominant group had a significantly larger left atrial diameter (43 vs 39 mm) and higher ratio of proven familial HCM (28 vs 6%), and were more symptomatic (New York Heart Association ≥3) at presentation (17 vs 0%). The event-free rate of cardiovascular events in patients with the distal-dominant form was significantly worse (log-rank P=0.012) than that in patients with the pure-apical form (follow-up period: ≈5 years). Conclusions: The 2 phenotypes of apical HCM should be recognized and distinguished clinically. (Circ J 2009; 73: 2330-2336)

View full abstract

Background: It is unclear how much the sympathetic nervous system is involved in the development of pulmonary arterial hypertension (PAH). The present study examined whether or not a pure α/β-adrenergic receptor blocker (arotinolol) could prevent the development of PAH and right ventricular hypertrophy (RVH) in a rat model of monocrotaline (MCT)-induced PAH. Methods and Results: The heart rate, arterial blood pressure (BP), left ventricular pressure, pulmonary artery pressure (PAP), and right ventricular pressure (RVP) were measured after administration of arotinolol or saline for 2 weeks. Ventricular weight and myocyte size were also measured. Mean PAP was increased less in the arotinolol group (n=6), (53 ±9 vs 21 ±2 mmHg in the control (n=6); P<0.01). Systolic RVP was also less in the arotinolol group (41 ±3 vs 91 ±14 mmHg in the control, P<0.05) without differences in BP. It also significantly reduced the RV/body weight ratio (0.58 ±0.01 vs 0.77 ±0.04 mg/g; P<0.01). Furthermore, the myocyte width was significantly decreased in the arotinolol group. Conclusions: The pure α/β-blocker arotinolol prevented the progression of MCT-induced PAH and RVH in rats, suggesting that sympathetic nervous activation might play a role in the development of PAH. (Circ J 2009; 73: 2337-2341)

View full abstract

Background: Evidence of the beneficial effects of antiplatelet therapy after ischemic stroke is currently lacking in China. Methods and Results: Demographic data, pre-stroke risk factors, severity of neurological deficit, and disability graded by the National Institutes of Health Stroke Scale (NIHSS) and Modified Rankin Scale (MRS) of 1,951 patients were measured and recorded at baseline. Regular follow-up by interview was performed for 12 months post-recruitment. The all-cause mortality was 1.88 per 100 person-years during the follow-up period. Recurrent fatal and nonfatal cerebrovascular events occurred in 90 patients, accounting for 4.24 per 100 person-years of cumulative incidence. After adjustment by other variables, antiplatelet therapy was identified as an independent protective predictor of all-cause death (hazard ratio (HR) 0.42; 95% confidence interval (CI) 0.21-0.86; P=0.017) and recurrent cerebrovascular events (HR 0.58; 95%CI 0.36-0.92; P=0.021). Among survivors, antiplatelet therapy was also an independent predictor for improvement in the NIHSS (HR 1.27; 95%CI 1.07-1.51; P=0.006) and the MRS (HR 1.25; 95%CI 1.02-1.52; P=0.031). Conclusions: The data from this multicenter, prospective study confirmed the association between antiplatelet therapy and decreased risk of all-cause mortality and recurrent cerebrovascular events after ischemic stroke in Chinese patients. (Circ J 2009; 73: 2342-2347)

View full abstract

An enlarged thymus adversely affected pulmonary artery development and perfusion in a 4-month-old boy with asplenia syndrome and a single ventricular circulation with aorto-pulmonary shunt. Steroid administration for 4 weeks successfully reduced thymus volume, concomitant with improvement of pulmonary vasculature and perfusion. Given the importance of pulmonary physiology in the Fontan circulation, the effects of thymic hyperplasia on pulmonary circulation should be taken into consideration in the overall management of candidates for Fontan surgery. (Circ J 2009; 73: 2348-2351)

View full abstract

A case of a 2-month-old Down syndrome infant without structural cardiac anomaly is reported in whom management of gastroesophageal reflux (GER) using duodenal-tube feeding successfully treated pulmonary arterial hypertension (PAH). Based on this case, examination for GER is recommended for infants who present with PAH, especially those with Down syndrome who have no cardiac anomalies. (Circ J 2009; 73: 2352-2354)

View full abstract

A 60-year-old man who had serious chest and arm pain died suddenly during hospitalization. He suffered from coronary vasospastic angina complicated by a fatal acute fulminant-type of myocarditis associated with Churg-Strauss syndrome (CSS). The diagnosis at autopsy was acute progressive eosinophilic myocarditis associated with CSS. (Circ J 2009; 73: 2355-2359)

View full abstract

Congenital atresia of the left main coronary ostium is a rare coronary artery anomaly. A 3-year-old boy who was asymptomatic had a heart murmur because of mitral regurgitation. He underwent reconstruction of the left main coronary artery, but stenosis occurred in the early postoperative period. Although the patient underwent repair of the coronary artery stenosis, the distal portion of the left coronary artery re-stenosed. Percutaneous transluminal coronary angioplasty for the stenosis was performed successfully and there has not been any sign of re-stenosis for 30 months to date. (Circ J 2009; 73: 2360-2362)

View full abstract

(Circ J 2009; 73: 1893 - 1900)

View full abstract