- Desmoplakin (DSP) mutations cause a unique form of cardiomyopathy with a high prevalence of LV inflammation, fibrosis, and systolic dysfunction, and DSP cardiomyopathy should be considered in the differential diagnosis for myocarditis and sarcoidosis.
- The presence of any LV systolic dysfunction in DSP cardiomyopathy, particularly when associated with ventricular ectopy and late gadolinium enhancement, indicates a substantial risk for severe ventricular arrhythmias.
What are the key clinical phenotypes and diagnostic features that distinguish desmoplakin (DSP) cardiomyopathy from typical dilated cardiomyopathy (DCM) or arrhythmogenic right ventricular cardiomyopathy (ARVC)?
The authors collected clinical and genetic data on 107 patients with pathogenic DSP mutations and 81 patients with pathogenic plakophilin 2 (PKP2) mutations as a comparison cohort. A composite outcome of severe ventricular arrhythmia was assessed.
Primary left ventricular (LV) involvement was exclusively present among patients with DSP (55% vs. 0% for PKP2, p < 0.001), whereas RV cardiomyopathy was present in only 14% of patients with DSP versus 40% for PKP2 (p < 0.001). LV late gadolinium enhancement was present in a primarily subepicardial distribution in 40% of patients with DSP, and one third of those occurred despite normal LV function. Episodes of acute myocardial injury occurred in 15% of patients with DSP and were strongly associated with LV late gadolinium enhancement (90%). In four DSP cases with 18F-fluorodeoxyglucose positron emission tomography scans, acute LV myocardial injury was associated with myocardial inflammation misdiagnosed initially as cardiac sarcoidosis or myocarditis. LV ejection fraction (LVEF) <55% was strongly associated with severe ventricular arrhythmias for DSP cases. RVEF <45% was associated with severe arrhythmias for PKP2 cases. Frequent premature ventricular contractions (PVCs) were common among patients with severe arrhythmias for both DSP (80%) and PKP2 (91%) groups.
The authors concluded that DSP cardiomyopathy is a distinct form of arrhythmogenic cardiomyopathy and it is characterized by episodic myocardial injury, LV fibrosis that precedes systolic dysfunction, and a high incidence of ventricular arrhythmias.
Mutations in the DSP gene encoding desmoplakin were first identified in an autosomal recessive form of arrhythmogenic cardiomyopathy. The present study makes a case for DSP cardiomyopathy being a distinct form of cardiomyopathy. DSP cardiomyopathy results in episodic inflammation, which precedes the development of fibrosis. Frequent PVCs occurring before LV systolic dysfunction or LV enlargement is also a key distinction from most cases of DCM. In DSP patients, late gadolinium enhancement was found in the LV subepicardium rather than mid-myocardial as is often seen with nonischemic cardiomyopathy. The correct diagnosis must include the identification of the DSP mutation. This paper is likely to be very impactful, as it suggests that some of the patients suspected of myocarditis and cardiac sarcoidosis may actually have DSP cardiomyopathy.
Clinical Topics: Arrhythmias and Clinical EP, Heart Failure and Cardiomyopathies, Noninvasive Imaging, Implantable Devices, EP Basic Science, Genetic Arrhythmic Conditions, SCD/Ventricular Arrhythmias, Atrial Fibrillation/Supraventricular Arrhythmias, Acute Heart Failure
Keywords: Arrhythmias, Cardiac, Arrhythmogenic Right Ventricular Dysplasia, Cardiomyopathies, Cardiomyopathy, Dilated, Desmoplakins, Diagnostic Imaging, Fluorodeoxyglucose F18, Gadolinium, Heart Failure, Hypertrophy, Left Ventricular, Inflammation, Myocarditis, Myocardium, Plakophilins, Stroke Volume, Ventricular Dysfunction, Ventricular Premature Complexes
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