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Publications

Case Reports Journal Article Ahead of print

PubMed: 42283673 DOI: 10.1016/j.jaccas.2026.108583

Reclassification of Exercise-Induced Arrhythmogenic Cardiomyopathy: Detection of a Pathogenic PKP2 Variant in a Male Athlete.

JACC Case Rep

Authors: Lucas Tramèr, Firat Erdogan, Argelia Medeiros-Domingo, Ron N Hille, Robert Manka, Felix C Tanner, Corinna Brunckhorst, Firat Duru, Ardan M Saguner

Affiliations

  • Department of Cardiology, University Heart Center, University Hospital Zurich, University of Zurich, Zurich, Switzerland.
  • SwissDNAlysis, Duebendorf, Switzerland.
  • Cardiance Clinic AG, Pfaeffikon, Switzerland.
  • Department of Cardiology, University Heart Center, University Hospital Zurich, University of Zurich, Zurich, Switzerland; Diagnostic and Inverventional Radiology, University Hospital Zurich, Zurich, Switzerland.
  • Department of Cardiology, University Heart Center, University Hospital Zurich, University of Zurich, Zurich, Switzerland; Center for Translational and Experimental Cardiology (CTEC), Department of Cardiology, University Hospital Zurich, University of Zurich, Zurich, Switzerland.
  • Department of Cardiology, University Heart Center, University Hospital Zurich, University of Zurich, Zurich, Switzerland; Center for Translational and Experimental Cardiology (CTEC), Department of Cardiology, University Hospital Zurich, University of Zurich, Zurich, Switzerland.

Abstract

BACKGROUND

Arrhythmogenic cardiomyopathy (ACM) is predominantly a genetic disease. Endurance exercise acts as a disproportionate trigger in gene-elusive ACM.

CASE SUMMARY

A 52-year-old male endurance athlete with stable coronary artery disease and no family history of ACM presented with premature ventricular contractions, right ventricular dilatation, and subtricuspid dyskinesia. After multimodality evaluation, "borderline" biventricular ACM was diagnosed. Genetic testing was negative, leading to a working diagnosis of exercise-induced ACM. Repeat genetic testing after 3 years using novel analytical methods identified a deep intronic pathogenic variant of PKP2.

DISCUSSION

The identification of a pathogenic variant is relevant for family screening, risk stratification, and exercise counseling because most available outcome data apply to desmosomal ACM. Periodic genetic retesting is advised in gene-elusive ACM.

TAKE-HOME MESSAGES

Periodic genetic retesting and readjudication is crucial for the management of gene-elusive ACM. Robust evidence-based data to guide personalized exercise recommendations in ACM are lacking.

MeSH

Exercise, Research Design, Genes, Genetic Testing, Athletes, Cardiomyopathies