Plasma MicroRNA Clusters in Human Left Ventricular Remodeling
A Biomarker and Discovery Platform
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See Article by Shah et al
Impaired cardiac function results in increased neurohormonal activity, a stress response initially mounted to augment cardiac output. However, chronic or excessive activity of the neurohormonal response contributes to progressive myocardial damage and the clinical manifestations of the heart failure (HF) syndrome.1 This myocardial injury leads to a vicious cycle of organ remodeling, wherein the shape, thickness, volume of the ventricular cavity, and the functional state of the cells populating the stressed heart are adversely altered in a manner that further compromises cardiac performance.1,2 Early work in animal models of myocardial infarction demonstrated the pathophysiologic significance of cardiac remodeling and a role for neurohormonal blockade in its prevention and reversal.2 These findings were subsequently extended to humans with myocardial infarction–associated HF and cardiac dilation in the absence of HF, with the severity of remodeling serving as a poor prognostic indicator.3,4 Current guideline-directed medical therapy for HF is associated with regression of ventricular dilation and improvement of ejection fraction in a subset of patients, a process called left ventricular reverse remodeling (LVRR). As LVRR has emerged as a strong predictor of improved outcomes in HF patients,5,6 understanding the molecular determinants of LVRR in humans and developing improved molecular biomarkers that predict LVRR are of great clinical interest. In this issue of Circulation: Heart Failure, Shah et al7 implicate a panel of plasma microRNAs (miRNAs) as predictors of LVRR in a cohort of patients with HF with reduced ejection fraction, findings which may point to novel …