April 10, 2026Open Access

Red Flags for Differentiating Desmosomal “Hot‐Phase” Cardiomyopathy From Acute Myocarditis

Q: What does this research mean for the field?

A red flag-based approach improves the clinical recognition and differentiation of desmosomal hot-phase cardiomyopathy from classic acute myocarditis. Novelty: ClaimNovelty.INCREMENTAL. Consensus alignment: ConsensusAlignment.NEUTRAL.

Key Result

A red flag-based approach improves the recognition of desmosomal hot-phase cardiomyopathy over classic acute myocarditis.

Key Points

The research aims to distinguish desmosomal 'hot-phase' cardiomyopathy from acute myocarditis using specific diagnostic flags.
Retrospective analysis of patients diagnosed with acute myocarditis using biopsy and cardiac imaging.
Comparison of clinical and imaging features between cases of desmosomal cardiomyopathy and controls.
Development and testing of diagnostic algorithms in an external cohort.
Desmosomal cardiomyopathy was more common in younger females, with distinctive clinical red flags identified.
A first-contact algorithm demonstrated 77% accuracy in identifying desmosomal gene variant carriers.
An alternative algorithm reached 93% accuracy by incorporating key clinical features.

Structured PICO

Do specific clinical, imaging, and electrical red flags differentiate desmosomal hot-phase cardiomyopathy from acute myocarditis?

Population

134 patients receiving a first diagnosis of acute myocarditis (AM) proven by endomyocardial biopsy or cardiac magnetic resonance plus troponin elevation, and an external multicenter cohort of 30 desmosomal gene variant (DGV) carriers.

Intervention

Desmosomal hot-phase cardiomyopathy (HPC) defined by presence of pathogenic desmosomal gene variants (DGVs)

Comparator

Gene-negative acute myocarditis (AM) controls

Outcome

Diagnostic 'red flags' favoring HPC over AM and accuracy of diagnostic algorithms

A red flag-based diagnostic algorithm incorporating clinical and CMR features accurately differentiates desmosomal hot-phase cardiomyopathy from classic acute myocarditis.

Main Result

Absolute Event Rate: 0% vs 0%

Abstract

Background: Desmosomal “hot‐phase” cardiomyopathy (HPC), characterized by bursts of myocardial inflammation mimicking acute myocarditis (AM), carries relevant risks of adverse outcomes. This study aimed to identify diagnostic “red flags” favoring HPC over AM. Methods: Patients (n=134) receiving a first diagnosis of AM, proven by endomyocardial biopsy or cardiac magnetic resonance plus troponin elevation, were retrospectively identified at a referral center. HPC was defined by presence of pathogenic desmosomal gene variants (DGVs). Clinical, imaging, and electrical features were compared between HPC cases and controls with gene‐negative AM to identify red flags. Diagnostic algorithms were derived and tested in an external multicenter cohort of DGV carriers (n=30). Results: Patients with HPC (n=22; 91% DSP +) were more frequently female (73% versus 24%, P 1000/24 hours ventricular ectopy; and recurrent nonsustained ventricular tachycardia. A “first‐contact” algorithm based on female sex and age <30 years achieved 77% accuracy, identifying 63% of DGV carriers in the external cohort. An alternative algorithm incorporating ring‐like late gadolinium enhancement, right ventricular involvement, and family history showed higher accuracy (93%) and yield (93%). Conclusions: Myocarditis in DGV carriers predominantly affects young women. A red flag‐based approach improves recognition of desmosomal HPC over classic AM.