Molecular Causes Of Cardiomyopathies &Modifiers Of The

Heart, Lung, And Blood Institute

Investigators

Linked publications, trials & patents

Abstract

We have identified several molecular defects associated with familial hypertrophic cardiomyopathy (FHC) and dilated cardiomyopathy (DCM) and are determining their functional consequences and clinical correlates. A mutation in the PRAKG2 gene has been reported to cause FHC associated with Wolff-Parkinson-White syndrome. A study is almost complete that examines several genetic potential modifiers of cardiac hypertrophy, such as the renin-angiotensin-system in FHC in patients in whom the molecular cause of the disease has been established. The cardiac ECM is grossly abnormal in FHC, and hence, responsible in part for the associated left ventricular diastolic and systolic dysfunction and hypertrophy. Two placebo-controlled studies are underway that examine our ability to remodel the ECM in FHC: (1) effect of ACE inhibitor and/or angiotensin receptor blockade; and (2) effect of pirfenidone, an inhibitor of several growth factors and cytokines, and a potent anti-fibrotic drug. Parameters that are monitored include cardiac hypertrophy by MRI, LV systolic and diastolic function by exercise MUGA, and arrhythmogenicity by ambulatory EKG monitoring and electrophysiology studies. A study has also been completed and is being analyzed that compared the efficacy of alcohol septal ablation and DDD pacemaker therapy in severe drug-refractory obstructive FHC.