Title : Myocarditis in desmoplakin cardiomyopathy: A misdiagnosed entity or a distinct phenotype?
Abstract:
Background: Desmoplakin (DSP) cardiomyopathy is a distinct form of arrhythmogenic cardiomyopathy (ACM), often presenting with left-dominant or biventricular involvement. A subset of these patients exhibits a myocarditis-like phenotype, characterized by acute chest pain, troponin elevation, and ventricular arrhythmias, mimicking viral or autoimmune myocarditis. However, recent studies suggest that these episodes may represent an inflammatory disease phase rather than true infectious myocarditis. Distinguishing these entities is crucial for appropriate risk stratification and management, as DSP mutation carriers have a higher incidence of ventricular arrhythmias and progressive left ventricular dysfunction compared to classic myocarditis patients.
Objective: To analyze the clinical and imaging characteristics of myocarditis-like presentations in DSP cardiomyopathy, and to highlight the role of multimodal diagnostics, particularly cardiac MRI and genetic testing, in differentiating inflammatory myocardial injury from an underlying genetic cardiomyopathic process.
Methods: This narrative review synthesizes existing literature and case reports evaluating myocarditis-like presentations in DSP cardiomyopathy. A structured literature search was conducted, including studies on cardiac MRI findings, histopathology, and genetic correlations in myocarditis and DSP-associated cardiomyopathy. Additionally, clinical cases were reviewed where initial myocarditis diagnosis was later linked to DSP mutations.
Results: Patients with DSP cardiomyopathy and myocarditis-like presentations frequently exhibited acute chest pain (85–90%), troponin elevation (75–85%), and ventricular arrhythmias (30–50%), closely resembling viral myocarditis. However, cardiac MRI findings were distinct, with subepicardial and mid-myocardial late gadolinium enhancement (LGE) in 80–90% of cases, particularly in the inferolateral wall, but minimal to absent myocardial edema on T2-weighted imaging. This contrasts with classic viral myocarditis, which typically exhibits extensive transient myocardial edema. Histopathological analysis from endomyocardial biopsies, when performed, demonstrated variable inflammatory infiltrates but was often dominated by fibrosis and fibrofatty replacement, suggesting a genetic rather than infectious etiology. Genetic testing confirmed DSP mutations in 30–40% of suspected myocarditis cases, reinforcing the hypothesis that these episodes represent an inflammatory phase of DSP cardiomyopathy. Clinically, DSP mutation carriers had a two- to three-fold higher risk of recurrent ventricular arrhythmias and progressive systolic dysfunction compared to non-genetic myocarditis cases. These findings highlight the need for close follow-up, arrhythmic risk assessment, and early implantable cardioverter-defibrillator consideration. Emerging evidence suggests a potential role for anti-inflammatory or immunomodulatory therapies, though further studies are needed to validate these approaches.
Conclusion: Myocarditis-like presentations in DSP cardiomyopathy likely represent an inflammatory disease phase rather than true infectious myocarditis. Differentiation using cardiac MRI and genetic testing is essential for accurate diagnosis, appropriate risk stratification, and long-term management. Early identification of DSP mutations in suspected myocarditis cases can alter clinical decision-making, emphasizing the need for early arrhythmic risk assessment and implantable cardioverter-defibrillator consideration.
Future directions: Prospective studies are needed to determine the prevalence and prognostic impact of myocarditis-like episodes in DSP cardiomyopathy. Further research should explore biomarkers and inflammatory pathways involved in DSP-related myocardial injury. The role of targeted anti-inflammatory and immunomodulatory therapies in DSP cardiomyopathy should be investigated.
