Hypertrophic cardiomyopathy: a heart in need of an energy bar?

Styliani Vakrou,M Roselle Abraham

doi:10.3389/fphys.2014.00309

Styliani Vakrou, M Roselle Abraham

Open Access

https://doi.org/10.3389/fphys.2014.00309

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Abstract

Hypertrophic cardiomyopathy (HCM) has been recently recognized as the most common inherited cardiovascular disorder, affecting 1 in 500 adults worldwide. HCM is characterized by myocyte hypertrophy resulting in thickening of the ventricular wall, myocyte disarray, interstitial and/or replacement fibrosis, decreased ventricular cavity volume and diastolic dysfunction. HCM is also the most common cause of sudden death in the young. A large proportion of patients diagnosed with HCM have mutations in sarcomeric proteins. However, it is unclear how these mutations lead to the cardiac phenotype, which is variable even in patients carrying the same causal mutation. Abnormalities in calcium cycling, oxidative stress, mitochondrial dysfunction and energetic deficiency have been described constituting the basis of therapies in experimental models of HCM and HCM patients. This review focuses on evidence supporting the role of cellular metabolism and mitochondria in HCM.

Highlights

Hypertrophic cardiomyopathy (HCM) has been recently recognized as the most common inherited cardiovascular disorder, affecting 1 in 500 adults worldwide
Irrespective of the causal mutation, pathologically, HCM is characterized by myocyte hypertrophy, myocyte disarray and fibrosis (Ho et al, 2010)
Two studies are currently under way to test the efficacy of ranolazine on exercise tolerance and diastolic function in symptomatic HCM patients (RESTYLEHCM, Germany, Menarini) and to treat chest pain or dyspnea in patients with HCM (RHYME, USA) (Spoladore et al, 2012). It is not known whether cytosolic Na+ is increased early in the course of the disease and whether it leads to mitochondrial dysfunction in any/all HCM mutations, or whether high levels of cytosolic Na+ occur after the onset of myocyte hypertrophy and/or symptoms

Summary

Introduction

Hypertrophic cardiomyopathy (HCM) has been recently recognized as the most common inherited cardiovascular disorder, affecting 1 in 500 adults worldwide. We (Abraham et al, 2013) and others (Jung et al, 1998, 2000; Crilley et al, 2003; Timmer et al, 2011) have shown reduced PCr/ATP ratios in HCM patients with both established left ventricular hypertrophy and in the pre-hypertrophic stage, which suggests that bioenergetic deficits may be a primary cause of myocardial remodeling.

Results

Conclusion