A Good Heart Is Hard to Find: Even Early in Hypertrophic Cardiomyopathy.

Abstract

Hypertrophic cardiomyopathy (HCM) is the most common inherited cardiac disease; yet, despite several decades of research, there is no specific disease-modifying therapy. Patients most often present with reduced exercise tolerance, heart failure, and cardiac arrhythmias. The discovery of specific HCM-causing mutations, advances in molecular medicine, and improved diagnostic techniques have generated substantial interest in identifying new HCM-specific therapies and more importantly determining the optimal timing for initiation of such therapy. Research into mechanisms underlying the clinical symptoms and complications in HCM has varied from genetics to molecular and cellular pathways. For some time, there has been burgeoning evidence that cardiac metabolism may play an important role in mediating the clinical consequences of HCM.1,2 See Article by Guclu et al Decreased efficiency in adenosine triphosphate utilization is a common feature of cardiomyocytes carrying diverse mutations. Crilley et al1 reported a decreased phosphocreatine-to-adenosine triphosphate in 7 HCM carriers without left ventricular hypertrophy by the use 31P spectroscopy, suggesting that a compromised energetic state may play a role in the early manifestation of hypertrophy. We previously demonstrated that myocardial phosphocreatine was significantly decreased by 24% in HCM patients with a β-myosin heavy chain mutation compared with controls; pseudo-first-order creatine kinase rate constant was 26% lower and the forward creatine kinase flux 44% lower in HCM.3 However, in this study, myocardial strain did not correlate with the metabolic indexes. Investigations of cardiac energetics have generally used magnetic resonance spectroscopy. Positron emission tomography (PET) introduces a new level for imaging cardiac pathophysiology using physiological tracers labeled with C-11, N-13, O-15, and F-18, which allow the synthesis of naturally occurring and biologically active compounds. Use of radiolabeled compounds allow for better in vivo quantification of specific biological processes. These PET techniques have unique advantages while investigating the role of cardiac …