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 ...