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Arrhythmogenic Cardiomyopathy: Mechanisms, Genetics, and Their Clinical Implications

  • Genetics (A.T. Owens and N. Reza, Section Editors)
  • Published:
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Abstract

Purpose of Review

Arrhythmogenic cardiomyopathy (ACM) represents a collection of cardiomyopathies with etiologies convergent upon highly arrhythmogenic clinical presentations not explained by ischemic, hypertensive, or valvular heart disease. This review describes the current state of knowledge regarding molecular mechanisms and genetic diagnosis in ACM.

Recent Findings

Clinical manifestations, specifically structural presentations, of ACM may span the right and left side of the heart. The umbrella definition of ACM encompasses disease mechanisms involving disruption of cell-cell adhesion, mechanotransduction, transcription, calcium handling, and post-transcriptional regulators. As such, the underlying genetics are themselves wide ranging but generally map to perturbations of proteins comprising the desmosome and regulating downstream cellular signaling. The recognition that many genetic forms of ACM share the feared outcomes of life-threatening ventricular arrhythmia and heart failure motivates the identification of causative genetic variants for family screening and in some cases precision therapy. In turn, contemporary clinical practice has shifted towards broadened genetic testing strategy and the discovery of complex gene-specific clinical ramifications.

Summary

The molecular mechanisms of ACM are complex, and the genetic architecture is ever evolving. Given this, multidisciplinary patient care for the incorporation of genetics and family cardiovascular care is critical. Future work will refine the understanding of gene-specific outcomes in ACM and implications for tailored therapy.

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Funding

This work was supported by the Boring Trust Research Award (to AMD), the John Taylor Babbitt Foundation, the Sarnoff Cardiovascular Research Foundation, and NIH National Heart Lung and Blood Institute K08 HL143185 (to VNP).

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  1. Stanford Center for Inherited Cardiovascular Disease, Stanford University School of Medicine, 300 Pasteur Drive, Falk CVRB room 187, Palo Alto, Stanford, CA, 94305, USA

    Chloe M. Reuter, Annika M. Dries & Victoria N. Parikh

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Annika M. Dries and Victoria N. Parikh declare that they have no conflict of interest. Chloe M. Reuter is a consultant for My Gene Counsel.

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Reuter, C.M., Dries, A.M. & Parikh, V.N. Arrhythmogenic Cardiomyopathy: Mechanisms, Genetics, and Their Clinical Implications. Curr Cardiovasc Risk Rep 15, 7 (2021). https://doi.org/10.1007/s12170-021-00669-5

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