Sympatho-adrenergic mechanisms in heart failure: new insights into pathophysiology

The sympathetic nervous system is activated in the setting of heart failure(HF)to compensate for hemodynamic instability.However,acute sympathetic surge or sustained high neuronal firing rates activatesβ-adrenergic receptor(βAR)signaling contributing to myocardial remodeling,dysfunction and electrical instability.Thus,sympathoβAR activation is regarded as a hallmark of HF and forms pathophysiological basis forβ-blocking therapy.Building upon earlier research findings,studies conducted in the recent decades have significantly advanced our understanding on the sympatho-adrenergic mechanism in HF,which forms the focus of this article.This review notes recent research progress regarding the roles of cardiacβ2AR orα1AR in the failing heart,significance ofβ1AR-autoantibodies,andβAR signaling through G-protein independent signaling pathways.Sympatho-βAR regulation of immune cells or fibroblasts is specifically discussed.On the neuronal aspects,knowledge is assembled on the remodeling of sympathetic nerves of the failing heart,regulation by presynapticα2AR of NE release,and findings on device-based neuromodulation of the sympathetic nervous system.The review ends with highlighting areas where significant knowledge gaps exist but hold promise for new breakthroughs.