An ‘Omics’ Perspective on Cardiomyopathies and Heart Failure

Pathological enlargement of the heart, represented by hypertrophic cardiomyopathy (HCM) and dilated cardiomyopathy (DCM), occurs in response to many genetic and non-genetic factors. The clinical course of cardiac hypertrophy is remarkably variable, ranging from lifelong absence of symptoms to rapidly declining heart function and sudden cardiac death (SCD). Unbiased omics studies have begun to provide a glimpse into the molecular framework underpinning altered mechanotransduction, mitochondrial energetics, oxidative stress, and extracellular matrix in the heart undergoing physiological and pathological hypertrophy. Omics analyses indicate that post-transcriptional regulation of gene expression plays an overriding role in the normal and diseased heart. Studies to date highlight a need for more effective bioinformatics to better integrate patient omics data with their comprehensive clinical histories.

TrendsOmics have revealed that many HCM and DCM patients and asymptomatic individuals harbor multiple rare variants in their genome. This concept has been best demonstrated by the study of mutations and truncations in the TTN gene (titin) and DCM pathogenesis.Studies in experimental models have begun to uncover transcriptomic, proteomic, and metabolomic signatures of physiological and maladaptive cardiac hypertrophy. Limited information from patients’ stem cells and iPSC have also begun to shed light on the molecular consequences of primary mutations and how they are affected by modifiers.Omics technologies have emerged to provide a more detailed view of gene expression profiles that may identify DCM patients who are putatively predisposed to experience SCD.