Genetic insights into non-ischemic arrhythmogenic cardiomyopathy: a case report of desmoplakin mutation

We aim to describe a unique case of a desmoplakin gene mutation with refractory ventricular arrhythmia and cardiomyopathy. We describe a 29-year-old man hospitalized for chest pain and cardiomyopathy, who subsequently developed ventricular arrhythmia that was refractory to multiple antiarrhythmic agents, ablation, immunotherapy, and sympathectomy. Diagnostic studies included coronary catheterization, cardiac MRI, and endomyocardial biopsy. He underwent placement of an Impella 5.5 temporary mechanical support device for multi-organ failure; eventually requiring a Heartmate 3 left ventricular assist device. This report details how cardiac MRI, endomyocardial biopsy, and genetic testing are crucial diagnostic modalities when assessing patients with refractory arrhythmias or myocarditis. Pathogenic variants in the desmoplakin gene can be associated with significant morbidity in patients and require multidisciplinary care from cardiology, electrophysiology, advanced heart failure, and cardiac surgery. Arrhythmogenic cardiomyopathies should be considered for patients suffering repeated episodes of myocarditis or refractory ventricular arrhythmias. We utilized various criteria of functional, electrocardiographic, arrhythmic, tissue characterization, and genetic findings to establish the diagnosis of arrhythmogenic cardiomyopathy, which will be discussed later in this paper.