PO81
Genotype-Driven Primary Prevention: A Case of Extravascular ICD Implantation in a Young Hispanic Male with Pathogenic DSP Mutation

Pathogenic variants in the desmoplakin (DSP) gene disrupt cardiac desmosomes, leading to myocardial fibrosis, ventricular dysfunction, and an increased risk of malignant arrhythmias, collectively referred to as DSP cardiomyopathy. These mutations can cause arrhythmogenic and dilated cardiomyopathies with variable expression and significant arrhythmic burden. Management often involves primary prevention with an implantable cardioverter-defibrillator (ICD). Extravascular ICDs (EV-ICDs) have emerged as a promising alternative, offering effective defibrillation and antitachycardia pacing while minimizing complications associated with transvenous leads.

A 42-year-old Hispanic male with dyslipidemia and a family history of premature coronary disease presented to cardiology clinic with complaints of recurrent retrosternal chest pressure. Electrocardiogram showed sinus rhythm with nonspecific lateral T-wave abnormalities. Stress echocardiogram demonstrated a left ventricular ejection fraction (LVEF) of 30% and wall motion abnormalities suggestive of ischemia. Guideline-directed medical therapy (GDMT) for HFrEF was initiated. Coronary angiography revealed nonobstructive LAD disease without atherosclerosis. Cardiac MRI showed LV Transmural Late Gadolinium Enhancement (LGE) in a classic "ring-like pattern." Patient underwent genetic testing, which revealed a heterozygous pathogenic Desmoplakin gene variant (c.3707dup (p.Asn1237Lysfs4)), confirming DSP Cardiomyopathy.

His DSP cardiomyopathy and LGE on cardiac MRI prompted electrophysiology evaluation for ICD placement for primary prevention. Options of transvenous versus extravascular ICDs were discussed. Given his young age, a subcutaneous extravascular (EV) ICD was recommended to preserve his vasculature. A single-chamber EV-ICD was successfully implanted. He continued GDMT with scheduled device checks. Family cascade screening and genetic counseling were advised, especially given that he has two young children. At patient's most recent follow-up, he reported controlled cardiovascular symptoms.

This case underscores the critical importance of early genetic testing for unexplained cardiomyopathies, as prompt identification of pathogenic variants can inform both familial risk and clinical management. Extensive LGE on cardiac MRI in DSP cardiomyopathy is a robust marker of arrhythmic risk, supporting its integration into risk stratification algorithms and justifying ICD placement for primary prevention, even with LVEF above traditional thresholds. The use of an EV-ICD illustrates a contemporary, evidence-based approach to mitigate sudden cardiac death risk while minimizing transvenous lead-related complications. Collectively, this case highlights the evolving paradigm of precision risk assessment and device therapy in nonischemic cardiomyopathy, advocating for a multiparametric approach that integrates genetic testing, advanced imaging, and innovative device technologies to optimize patient outcomes.