Metabolic changes in hypertrophic cardiomyopathies: scientific update from the Working Group of Myocardial Function of the European Society of Cardiology

Abstract

Disturbed metabolism as a consequence of obesity and diabetes may cause cardiac diseases (recently highlighted in the cardiovascular research spotlight issue on metabolic cardiomyopathies).1 In turn, the metabolism of the heart may also be disturbed in genetic and acquired forms of hypertrophic cardiac disease. Herein, we provide an overview of recent insights on metabolic changes in genetic hypertrophic cardiomyopathy and discuss several therapies, which may be explored to target disturbed metabolism and prevent onset of cardiac hypertrophy.This article is part of the Mini Review Series from the Varenna 2017 meeting of the Working Group of Myocardial Function of the European Society of Cardiology.

Figure 1

Excitation-contraction coupling in a healthy heart. Contraction is initiated upon Ca²⁺ entry in the muscle cell, which activates Ca²⁺ release from the SR. Ca²⁺ binds to the myofilaments, which causes contraction. To relax Ca²⁺ detaches from myofilaments and is pumped back into the SR. A small fraction of Ca²⁺ is removed out of the cell via the Na⁺-Ca²⁺ exchanger (NCX). Mitochondria take care of sufficient ATP needed for proper contraction and relaxation of cardiomyocytes. In the healthy heart, CK catalyses the transfer of phosphate from phosphocreatine to ADP, thereby regenerating ATP, while preventing accumulation of cytosolic ADP.

Figure 2

Excitation-contraction coupling in diseased heart and possible targets for therapy. Mutation-induced changes in myofilament properties increase ATP utilization. Cellular metabolism changes as a consequences of mutation-induced and ADP-mediated increases in myofilament Ca²⁺-sensitivity, impaired mitochondrial function and reduced creatine kinase activity. Different therapies may target impaired metabolism in HCM.