Glycation of ryanodine receptor in circulating lymphocytes predicts the response to cardiac resynchronization therapy

Finding reliable parameters to identify patients with heart failure (HF) that will respond to cardiac resynchronization therapy (CRT) represents a major challenge. We and others have observed post-translational modifications of Ryanodine Receptor (RyR) in several tissues (including skeletal muscle and circulating lymphocytes) of patients with advanced HF. We designed a prospective study to test the hypothesis that RyR1 glycation in circulating lymphocytes could predict CRT responsiveness in patients with non-ischemic HF. We enrolled 94 patients who underwent CRT and 30 individuals without HF, examining RyR1 glycation in peripheral lymphocytes at enrollment and after 1 year. We found that baseline RyR1 glycation independently predicts CRT response at 1 year after adjusting for age, diabetes, QRS duration and morphology, echocardiographic dyssynchrony, and hypertension. Moreover, RyR1 glycation in circulating lymphocytes significantly correlated with pathologic intracellular calcium leak. Taken together, our data show for the first time that RyR1 glycation in circulating lymphocytes represents a novel biomarker to predict CRT responsiveness.