Unraveling the Genotype-Phenotype Relationship in Hypertrophic Cardiomyopathy: Obesity-Related Cardiac Defects as a Major Disease Modifier

Edgar E Nollet, B Daan Westenbrink, Rudolf A de Boer, Diederik W D Kuster, Jolanda van der Velden*

*Bijbehorende auteur voor dit werk

OnderzoeksoutputAcademicpeer review

1 Citaat (Scopus)
8 Downloads (Pure)


Hypertrophic cardiomyopathy (HCM) is the most common inherited cardiomyopathy and is characterized by asymmetric septal thickening and diastolic dysfunction. More than 1500 mutations in genes encoding sarcomere proteins are associated with HCM. However, the genotype-phenotype relationship in HCM is incompletely understood and involves modification by additional disease hits. Recent cohort studies identify obesity as a major adverse modifier of disease penetrance, severity, and clinical course. In this review, we provide an overview of these clinical findings. Moreover, we explore putative mechanisms underlying obesity-induced sensitization and aggravation of the HCM phenotype. We hypothesize obesity-related stressors to impact on cardiomyocyte structure, metabolism, and homeostasis. These may impair cardiac function by directly acting on the primary mutation-induced myofilament defects and by independently adding to the total cardiac disease burden. Last, we address important clinical and pharmacological implications of the involvement of obesity in HCM disease modification.

Originele taal-2English
Aantal pagina's15
TijdschriftJournal of the American Heart Association
Nummer van het tijdschrift22
StatusPublished - 17-nov-2020

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