Genetic Cardiomyopathies Causing Heart Failure

Abstract

Despite the striking advances in medical and surgical therapy, the morbidity, mortality, and economic burden of heart failure (HF) remain unacceptably high. There is increasing evidence that the risk and course of HF depend on genetic predisposition; however, the genetic contribution to HF is heterogeneous and complex. At one end of the spectrum are the familial monogenic HF syndromes in which causative mutations are rare but highly penetrant. At the other, HF susceptibility and course may be influenced by more common, less penetrant genetic variants. As detailed in this review, efforts to unravel the basis of the familial cardiomyopathies at the mendelian end of the spectrum already have begun to deliver on the promise of informative mechanisms, novel gene-based diagnostics, and therapies for distinct subtypes of HF. However, continued progress requires the differentiation of pathogenic mutations, disease modifiers, and rare, benign variants in the deluge of data emerging from increasingly accessible novel sequencing technologies. This represents a significant challenge and demands a sustained effort in analysis of extended family pedigrees, diligent clinical phenotyping, and systematic annotation of human genetic variation. (Circ Res. 2013;113:660-675.)

Resistance of Dynamin-related Protein 1 Oligomers to Disassembly Impairs Mitophagy, Resulting in Myocardial Inflammation and Heart Failure

“…Its etiology is diverse, including ischemia, inflammation, and genetic disease (1). Rare monogenic forms of DCM are mechanistically tractable models, yielding insights into disease pathogenesis.…”

Myoscape controls cardiac calcium cycling and contractility via regulation of L-type calcium channel surface expression

“…Despite decades of research, heart failure remains a major cause of death and mortality32333435363738. Therefore, improved understanding of the molecular mechanisms underlying heart failure is still urgently needed to develop novel targeted treatment strategies.…”

Research Advances in Heart Failure

“…17 Three decades after these clinical and pathological observations, the modern study of the genetics of the cardiomyopathies was launched by the discovery by the Seidmans and their associates that a missense mutation in the β-myosin gene was the cause of HCM in some families. 18 In this Compendium, Cahill et al 19 provide an excellent update on the several primary genetic cardiomyopathies causing HF. As they point out, HCM is recognized to be the most common monogenic cardiomyopathy, present in 1 of every 500 births, and it is associated with HF in about one sixth of cases.…”

“…18 In this Compendium, Cahill et al 19 provide an excellent update on the several primary genetic cardiomyopathies causing HF. As they point out, HCM is recognized to be the most common monogenic cardiomyopathy, present in 1 of every 500 births, and it is associated with HF in about one sixth of cases.…”