Reduction of lymphocyte G-protein coupled receptor kinase-2 (GRK2) after exercise training predicts survival in patients with heart failure

Abstract

Background: Increased cardiac G-protein coupled receptor kinase-2 (GRK2) expression has a pivotal role at inducing heart failure (HF)-related β-adrenergic receptor (βAR) dysfunction. Importantly, abnormalities of βAR signaling in the failing heart, including GRK2 protein levels, are mirrored in circulating lymphocytes and are directly correlated with HF severity. Exercise training has been demonstrated to exert several beneficial effects on the failing heart, including normalization of cardiac βAR function and GRK2 protein levels. In the present study we evaluated whether lymphocyte GRK2 and its changes after an exercise training program can predict long-term survival in HF patients. Methods and results: At this aim, we prospectively studied 193 HF patients who underwent a 3-month exercise training program. Lymphocyte GRK2 protein levels, plasma N-terminal pro-brain natriuretic peptide (NT-proBNP) and norepinephrine were measured at baseline and after training along with clinical and functional parameters (left ventricular ejection fraction, NYHA class, and peak-VO2). Cardiac-related mortality was evaluated during a mean follow up period of 37±20 months. Exercise induced a significant reduction of lymphocyte GRK2 protein levels. Importantly, exercise related changes of GRK2 (delta values) robustly predicted survival in our study population. Interestingly, the lack of any significant effect of exercise to reduce lymphocyte GRK2 protein levels identified those HF patients with the poorest outcome. ![Figure][1] Conclusions: Our data offer the first demonstration that changes of lymphocyte GRK2 induced by exercise can strongly predict outcome in patients with advanced HF. [1]: pending:yes