Cardiovascular disease (CVD) is the leading cause of death in the world and half of the cases of CVD are estimated to occur in Asia. Compared with Western countries, most Asian countries, except for Japan, South Korea, Singapore and Thailand, have higher age-adjusted mortality from CVD. In Japan, the mortality from CVD, especially stroke, has declined continuously from the 1960s to the 2000s, which has contributed to making Japan into the top-ranking country for longevity in the world. Hypertension and smoking are the most notable risk factors for stroke and coronary artery disease, whereas dyslipidemia and diabetes mellitus are risk factors for ischemic heart disease and ischemic stroke. The nationwide approach to hypertension prevention and control has contributed to a substantial decline in stroke mortality in Japan. Recent antismoking campaigns have contributed to a decline in the smoking rate among men. Conversely, the prevalence of dyslipidemia and diabetes mellitus increased from the 1980s to the 2000s and, therefore, the population-attributable risks of CVD for dyslipidemia and diabetes mellitus have increased moderately. To prevent future CVD in Asia, the intensive prevention programs for hypertension and smoking should be continued and that for emerging metabolic risk factors should be intensified in Japan. The successful intervention programs in Japan can be applied to other Asian countries.  (Circ J 2013; 77: 1646–1652)

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Cardiac troponins (cTns) T and I are exclusively expressed at high concentrations in cardiac muscle and have emerged as the preferred biomarker in the universal definition of myocardial infarction (MI). With the recent introduction of high-sensitivity (hs) assays, diagnostic sensitivity for earlier detection of MI has substantially improved. However, lowering the diagnostic cut-off has increased the detection of myocardial injuries in various non-acute coronary syndrome (ACS) conditions, which are not related to myocardial ischemia, leading to rising difficulties in diagnosing MI in clinical situations. Several approaches, such as serial sampling and incorporation of relative or absolute δ-changes, have been proposed to overcome the limitation of decreased sensitivity for MI diagnosis with hs-cTn assays. Current consensus for rapid rule-in proposes a 20% increase within 3 or 6h when baseline cTn levels are elevated. In the case of negative baseline values, relative increases ≥50% above the 99^th percentile were found to be adequate to improve accuracy of MI diagnosis. Besides improved diagnostic accuracy for myocardial injury, even minor cTn elevations provide important prognostic information, and increased levels of cTn are associated with adverse outcomes in both the ACS and non-ACS condition, irrespective of whether the underlying cause is an acute or chronic illness. Thus, it is highly likely that lowering the diagnostic cut-off with even more sensitive assays might improve risk stratification in both conditions.  (Circ J 2013; 77: 1653–1661)

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Myocardial perfusion imaging (MPI) has played an important role in the diagnosis and risk assessment of coronary artery disease (CAD) since the early 1970s. Positron emission tomography (PET) MPI has high diagnostic accuracy and prognostic value. PET MPI can also be used to quantitatively evaluate regional myocardial blood flow (MBF) through a mathematical model. PET MBF measurements can be used in evaluating early-stage atherosclerosis with endothelial dysfunction right through to diagnosing CAD. PET/computed tomography scanners are now found in many facilities across North America, Europe, and Asia, and PET MBF quantification is expected to move from strictly research to more clinical applications. Nuclear cardiology has been a leader in quantification approaches that can be applied to other new imaging modalities. Therefore, it would be valuable to understand the basic aspects of quantification approaches. This review will address the basic aspects of MBF quantification and the additional value of quantification approaches in the clinical setting.  (Circ J 2013; 77: 1662–1671)

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Transthoracic epicardial catheter ablation is a useful supplemental or even preferred strategy to eliminate cardiac arrhythmias in the electrophysiology laboratory. The indication for this technique has extended to a diverse range of cardiac arrhythmias, including scar-related ventricular tachycardia (VT), idiopathic VTs, accessory pathways, atrial tachycardias, inappropriate sinus tachycardia, and atrial fibrillation, as the epicardial substrates of these tachyarrhythmias have become increasingly recognized. When endocardial ablation and epicardial ablation through the cardiac veins are unsuccessful, transthoracic epicardial ablation should be the next option. Intrapericardial access is usually obtained through a subxiphoidal pericardial puncture. This approach might not be possible in patients with pericardial adhesions caused by prior cardiac surgery or pericarditis. In such cases, a hybrid procedure involving surgical access with a subxiphoid pericardial window and limited anterior or lateral thoracotomy might be a feasible and safe method of performing epicardial catheter ablation in the electrophysiology laboratory. Potential complications associated with this technique include bleeding and collateral damage to the coronary artery and phrenic nerve. Although the risk of these complications is low, electrophysiologists who attempt epicardial catheter ablation should know the complications associated with this technique, how to minimize their occurrence, and how to rapidly recognize and treat the complications that they encounter. This review discusses the indications, techniques, and complications of transthoracic epicardial catheter ablation.  (Circ J 2013; 77: 1672–1680)

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Background: The long-term effects of catheter ablation (CA) on the left atrium and left atrial appendage (LAA) are unknown in persistent atrial fibrillation (AF). This study investigated left atrial (LA) reverse remodeling and evolution of LA/LAA function after successful CA for persistent AF and identified predictors for maintenance of sinus rhythm (SR) and LA reverse remodeling. Methods and Results: CA was performed in 123 patients with persistent AF. LA volumes, LA strain and LAA wall velocity were assessed both at baseline and at 12 months after ablation. Patients who maintained SR were divided into 2 groups according to whether LA volume decreased by ≥15% at follow-up (responders) or not (non-responders). During a follow-up period of 18±2 months, AF recurred in 45 patients (37%). Of the remaining 78 patients (63%) without recurrent AF, 62 patients (79%) were classified as responders. LA/LAA function significantly improved and the prevalence of spontaneous echo contrast decreased only in responders at follow-up. LA systolic strain and LAA wall velocity were independent predictors of both maintenance of SR (odds ratio [OR], 2.57; P=0.003; OR, 3.02; P=0.002, respectively) and LA reverse remodeling (OR, 4.44; P=0.007; OR, 3.52; P=0.01, respectively). Conclusions: Successful CA is associated with LA reverse remodeling and LA/LAA functional recovery in patients with persistent AF. LA systolic strain and LAA wall velocity at baseline predicted both maintenance of SR and LA reverse remodeling.  (Circ J 2013; 77: 1695–1704)

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Background: The genetic background of catecholaminergic polymorphic ventricular tachycardia (CPVT) has been extensively investigated for the last decade in Western countries, but it remains unstudied in the Asian population. Methods and Results: In 50 Japanese probands from unrelated families who satisfied clinical criteria for CPVT, genetic testing was conducted in all exons on 3 CPVT-related genes: cardiac ryanodine receptor 2 (RYR2), calsequestrin 2 (CASQ2) and inward rectifier potassium channel 2 (KCNJ2), and the clinical features between RYR2-genotyped and -non-genotyped patient groups were compared. Genetic and clinical evaluation was also done in 46 family members. In the genetic screening, 28 (18 novel) RYR2 (56.0%), 1 compound heterozygous CASQ2 (2.0%) and 1 KCNJ2 (2.0%) mutation carriers were identified. In the RYR2 mutation-positive group, the frequency of bidirectional ventricular tachycardia and the use of β-blockers were significantly higher than in the mutation-negative group. In contrast, there was no significant difference in supraventricular arrhythmias between the 2 groups. With regard to disease penetrance, the number of family members of RYR2-genotyped probands with a clinical diagnosis of CPVT was high. Conclusions: Thirty gene mutation carriers were found for 3 genes in 50 probands clinically diagnosed as having CPVT. The penetrance of CPVT phenotype was significantly higher in RYR2 mutation carriers, thus RYR2 gene screening in CPVT patients would be indispensable to prevent unexpected cardiac sudden death of young family members.  (Circ J 2013; 77: 1705–1713)

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Background: Global medical devices have become more popular, but investment money for medical device development is not easily available in the market. Worldwide health-care budget constraints mean that efficient medical device development has become essential. To achieve efficient development, globalization is a key to success. Spending large amounts of money in different regions for medical device development is no longer feasible. Methods and Results: In order to streamline processes of global medical device development, an academic, governmental, and industrial consortium, called the Harmonization by Doing program, has been set up. The program has been operating between Japan and the USA since 2003. The program has 4 working groups: (1) Global Cardiovascular Device Trials; (2) Study on Post-Market Registry; (3) Clinical Trials; and (4) Infrastructure and Methodology Regulatory Convergence and Communication. Each working group has as its goals the achievement of speedy and efficient medical device development in Japan and the USA. The program has held multiple international meetings to deal with obstacles against efficient medical device development. Conclusions: This kind of program is very important to deliver novel medical devices. Involvement of physicians in this type of activity is also very helpful to achieve these goals.  (Circ J 2013; 77: 1714–1718)

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Background: Bleeding is a potentially catastrophic complication after primary percutaneous coronary intervention (PPCI). It occurs most frequently within the first 30 days following the intervention. The aim of this study was to generate a simple and accurate risk model for the prediction of bleeding after PPCI. Methods and Results: The training set included 2,096 patients enrolled in the RISK-PCI trial. The model was validated using a database of 961 patients enrolled in the ART-PCI trial. Bleeding was defined as type ≥3a bleeding according to the Bleeding Academic Research Consortium definition. Multivariate logistic regression was used to evaluate the predictors of outcome. A sum of weighted points for specific predictors was calculated to determine the final score. The model included 5 independent predictors of 30-day bleeding: gender (female); history of peptic ulcer; creatinine clearance at admission (<60ml/min); hemoglobin at presentation (<125g/dl); and Killip class >1 heart failure at admission. The model showed good discrimination and calibration for the prediction of bleeding in the derivation set (C-statistic, 0.79; goodness of fit, P=0.12) and in the validation set (C-statistic, 0.76; goodness of fit, P=0.37). Patients were classified into 3 risk classes and the observed incidence of 30-day bleeding of 1.0%, 3.5% and 10.7% corresponded to the low-, intermediate- and high-risk classes, respectively. Conclusions: A simple risk model was developed that has a reasonably good capacity for the prediction of 30-day bleeding after PPCI.  (Circ J 2013; 77: 1719–1727)

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Background: The association between endothelial progenitor cells (EPCs) at the time of percutaneous coronary intervention (PCI) and the subsequent long-term clinical outcome remains undefined. To address this issue, a pre-specified analysis of the PROgenitor Cells role in Restenosis and progression of coronary ATherosclerosis after percutaneous coronary intervention (PROCREATION) study was done. Methods and Results: A total of 155 patients with stable angina treated with PCI had flow cytometry before PCI. Patients had a 5-year follow-up. Primary outcome was the composite of major adverse cardiac or cerebrovascular events (MACCE), that is, death, stroke, myocardial infarction, and revascularization. During follow-up, MACCE occurred in 65 of 155 patients (42%). There were no significant differences in clinical and angiographic variables between patients with or without MACCE, apart from a different extent of coronary atherosclerosis. The incidence of MACCE increased significantly over tertiles of CD34+/KDR+/CD45– cells and CD133+/KDR+/CD45– cells, with rates of 25%, 39%, and 69% (P=0.0001), and 26%, 44%, and 59% (P=0.003), respectively. On multivariate analysis it was estimated that the increase in CD34+/KDR+/CD45– cells was associated with a 35% higher risk for MACCE (hazard ratio [HR], 1.75; 95% confidence interval [CI]: 1.07–1.99; P=0.001), and the increase in CD133+/KDR+/CD45– cells was associated with a 25% higher risk for MACCE (HR, 1.35; 95% CI: 1.01–1.74; P=0.03). Conclusions: Assessment of subpopulations of circulating EPCs in patients with stable angina treated with PCI can improve characterization of long-term prognosis (ClinicalTrials.gov: NCT01575431).  (Circ J 2013; 77: 1728–1735)

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Background: The DuraHeart left ventricular assist device (LVAD) is the world’s first approved magnetically levitated implantable centrifugal pump. We report our initial experience with the DuraHeart as a bridge to heart transplantation. Methods and Results: Between 2008 and 2011, 23 patients (17 males; mean age 35 years, range 16–53 years) with endstage heart failure underwent implantation with the DuraHeart LVAD at Osaka University Hospital. Of those, 7 underwent conversion surgery from a Nipro paracorporeal LVAD to the DuraHeart. There were no deaths during the mean support period of 559±241 days (176–999 days). In total, 17 patients (74%) remain with the LVAD and 5 (22%) underwent heart transplantation after 580±302 days (176–982 days) of support. Major adverse events included 8 (34%) driveline/pocket infections, 4 (17%) cerebrovascular accidents, 4 (17%) right heart failures requiring mechanical support, and 3 (13%) mechanical device failures (magnetic levitation failure caused by driveline fracture). Of the 5 patients who developed pump pocket infection, 3 underwent previous conversion surgery from the Nipro LVAD. Conclusions: Our initial experience with the DuraHeart LVAD in Japan demonstrated excellent long-term survival with acceptable rates of adverse events. With refinement of the system, including mechanical durability, this pump will further enhance the quality of life for patients who require long-term mechanical circulatory support.  (Circ J 2013; 77: 1736–1741)

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Background: The aim of this study was to investigate whether the extent of late gadolinium e