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Area of Science:

  • Cardiology
  • Genetics
  • Pathology

Background:

  • Desmosomal hot-phase cardiomyopathy (HPC) presents with myocardial inflammation mimicking acute myocarditis (AM).
  • HPC carries significant risks of adverse cardiovascular outcomes.
  • Distinguishing HPC from AM is crucial for appropriate management.

Purpose of the Study:

  • To identify diagnostic red flags that differentiate desmosomal hot-phase cardiomyopathy (HPC) from acute myocarditis (AM).
  • To develop and validate diagnostic algorithms for HPC detection.

Main Methods:

  • Retrospective analysis of 134 patients with initial AM diagnosis.
  • HPC defined by pathogenic desmosomal gene variants (DGVs); controls were gene-negative AM.
  • Comparison of clinical, imaging, and electrical features to identify red flags.
  • Validation of diagnostic algorithms in an external cohort of DGV carriers.

Main Results:

  • HPC patients (22/134) were younger and more frequently female than AM controls.
  • Distinctive red flags in DGV carriers included family history, recurrent troponin peaks, ventricular dysfunction/arrhythmias, and specific MRI findings.
  • A 'first-contact' algorithm (female sex, age <30) showed 77% accuracy.
  • An algorithm using MRI (ring-like LGE, RV involvement) and family history achieved 93% accuracy.

Conclusions:

  • Myocarditis in desmosomal gene variant carriers predominantly affects young women.
  • A red flag-based diagnostic approach enhances the recognition of desmosomal HPC compared to classic AM.
  • Improved diagnostic strategies can lead to better patient management and outcomes.