A lthough recent advances in the management of acute myocardial infarction (AMI), including primary percutaneous coronary intervention strategies and evidence-based therapies, have resulted in a substantial decline in mortality, the number of post-AMI patients who survive AMI but experience development of ischemic heart failure (HF) is increasing worldwide.1 Therefore, the identification of biomarkers that can predict risk of HF development in post-AMI patients is needed for optimizing management and treatment strategies. To date, several types of biomarkers, such as N-terminal probrain natriuretic peptide and cardiac troponin T, have been shown to predict cardiovascular events after AMI; however, it remains inconclusive whether these biomarkers can predict future HF in post-AMI patients. Rationale: Despite a recent decline of in-hospital mortality attributable to acute myocardial infarction (AMI), the incidence of ischemic heart failure (HF) in post-AMI patients is increasing. Correspondence to Yukio Kawahara, Laboratory of RNA Function, Graduate School of Medicine, Osaka University, 2-2 Yamada-oka, Suita, Osaka 565-0871, Japan (e-mail ykawahara@rna.med.osaka-u.ac.jp); or Issei Komuro, Department of Cardiovascular Medicine, Graduate School of Medicine, Osaka University, 2-2 Yamada-oka, Suita, Osaka 565-0871, Japan (e-mail komuro-tky@umin.ac.jp). Matsumoto et al Circulating MicroRNAs Predict Heart Failure 323membrane-bound vesicles termed exosomes, which circulate stably in the bloodstream. [3][4][5] Although the physiological significance of circulating microRNAs is not fully understood, they have attracted attention as potential diagnostic and prognostic biomarkers for various diseases, particularly cancer. 3,4 With respect to cardiovascular disease, several cardiac microRNAs, including miR-1, miR-133a, and miR-208a, have been detected in the serum in the acute phase of AMI and thus represent potentially useful diagnostic markers for AMI. 5,6 However, these microRNAs are most likely released from necrotic heart tissue into the blood directly and are not encapsulated within exosomes and, therefore, have short half-lives. For this reason, these cardiac microRNAs are unlikely to be predictive of future HF development in post-AMI patients. 6 The aim of the present study was to identify circulating microRNAs that can serve as predictors of HF development in patients who survive the acute stage of AMI. MethodsWe retrospectively analyzed the records of patients registered in the Osaka Acute Coronary Insufficiency Study, which has been described elsewhere. 7 The study protocol was approved by the ethics committee of each participating hospital, and written informed consent was provided by each patient at the time of registration. On the basis of the results of an initial screening (Online Table I), we performed a second screening to examine the microRNA profiles of an increased number of matched patients (HF group, n=21; control group, n=65; Online Table II ResultsTo identify microRNAs with altered expression ...

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IntroductionNeither the pathophysiology nor an effective treatment for heart failure with preserved ejection fraction (HFpEF) has been elucidated to date. The purpose of this ongoing study is to elucidate the pathophysiology and prognostic factors for patients with HFpEF admitted to participating institutes. We also aim to obtain insights into the development of new diagnostic and treatment methods by analysing patient background factors, clinical data and follow-up information.Methods and analysisThis study is a prospective, multicentre, observational study of patients aged ≥20 years admitted due to acute decompensated heart failure with preserved left ventricular ejection fraction (≥50%) and elevated N-terminal-pro brain natriuretic peptide (NT-proBNP) (≥400 pg/mL). The study began in June 2016, with the participation of Osaka University Hospital and 31 affiliated facilities. We will collect data on history in detail, accompanying diseases, quality of life, frailty score, medication history, and laboratory and echocardiographic data. We will follow-up each patient for 5 years, and collect outcome data on mortality, cause of death, and the number and cause of hospitalisation. The target number of registered cases is 1500 cases in 5 years.Ethics and disseminationThe protocol was approved by the Institutional Review Board (IRB) of Osaka University Hospital on 24 February 2016 (ID: 15471), and by the IRBs of the all participating facilities. The findings will be disseminated through peer-reviewed publications and conference presentations.

Background: Genome-wide association studies provided many biological insights into coronary artery disease (CAD), but these studies were mainly performed in Europeans. Genome-wide association studies in diverse populations have the potential to advance our understanding of CAD. Methods: We conducted 2 genome-wide association studies for CAD in the Japanese population, which included 12 494 cases and 28 879 controls and 2808 cases and 7261 controls, respectively. Then, we performed transethnic meta-analysis using the results of the coronary artery disease genome-wide replication and meta-analysis plus the coronary artery disease 1000 Genomes meta-analysis with UK Biobank. We then explored the pathophysiological significance of these novel loci and examined the differences in CAD-susceptibility loci between Japanese and Europeans. Results: We identified 3 new loci on chromosome 1q21 ( CTSS ), 10q26 ( WDR11-FGFR2 ), and 11q22 ( RDX - FDX1 ). Quantitative trait locus analyses suggested the association of CTSS and RDX - FDX1 with atherosclerotic immune cells. Tissue/cell type enrichment analysis showed the involvement of arteries, adrenal glands, and fat tissues in the development of CAD. We next compared the odds ratios of lead variants for myocardial infarction at 76 genome-wide significant loci in the transethnic meta-analysis and a moderate correlation between Japanese and Europeans, where 8 loci showed a difference. Finally, we performed tissue/cell type enrichment analysis using East Asian-frequent and European-frequent variants according to the risk allele frequencies and identified significant enrichment of adrenal glands in the East Asian-frequent group while the enrichment of arteries and fat tissues was found in the European-frequent group. These findings indicate biological differences in CAD susceptibility between Japanese and Europeans. Conclusions: We identified 3 new loci for CAD and highlighted the genetic differences between the Japanese and European populations. Moreover, our transethnic analyses showed both shared and unique genetic architectures between the Japanese and Europeans. While most of the underlying genetic bases for CAD are shared, further analyses in diverse populations will be needed to elucidate variations fully.

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