Key Points
- To evaluate the clinical, genetic, and imaging characteristics of desmoplakin (DSP) variant carriers to determine whether DSP-related cardiomyopathy constitutes a distinct disease entity.
- Retrospectively analyzed clinical, genetic, and imaging data from 18 heterozygous DSP variant probands identified using a targeted next-generation sequencing cardiomyopathy panel in Italy.
- Assessed cardiac magnetic resonance imaging (CMRI), left ventricular enlargement, NYHA functional class, implantable cardioverter defibrillator (ICD) use, and episodes of presumed myocarditis.
- Identified 16 pathogenic/likely pathogenic DSP variants (75% truncating); 39% of patients (n=7) presented with myocarditis-like episodes (57% recurrent), and 55% (n=10) showed left ventricular enlargement.
- CMRI demonstrated delayed enhancement indicating left ventricular myocardial fibrosis in 100% of patients (n=18), with greater extent in recurrent injury cases, and 61% (n=11) received an ICD.
Structured PICO
PPopulation18 probands characterized as heterozygotes for desmoplakin (DSP) variants by a target Next Generation Sequencing (NGS) cardiomyopathy panel, mean age at diagnosis 40.61 years, from an Italian cohort.
OOutcomeCardiological, genetic data, and imaging features
DSP-related cardiomyopathy emerges as a distinct clinical entity characterized by a high arrhythmic burden, variable left ventricular enlargement, subepicardial late gadolinium enhancement, and recurrent myocarditis-like episodes.