PO62 The Missing Piece: The Crucial Role of Genetics

Abstract Genetic characterization in dilated cardiomyopathy (DCM) can be decisive for therapeutic management and prognosis definition. We report a case of a 54-year-old woman with a history of complete left bundle branch block (LBBB, QRS 160ms), identified in 2016. At that time, a transthoracic echocardiogram (TTE) revealed mild left ventricular (LV) dysfunction, and bisoprolol 2.5mg/day was initiated. In 2019, she underwent a myocardial perfusion scintigraphy, which was negative for myocardial ischemia. In January 2021, she presented to the emergency department (ED) with palpitations. The initial ECG showed regular wide-complex tachycardia with LBBB pattern and a heart rate of 202 bpm, interpreted as supraventricular tachycardia (SVT) with aberrant conduction. Pharmacological cardioversion was performed, restoring sinus rhythm (SR), and she was referred to the Arrhythmology Consultation At the consultation in March 2021 , the family history was revealed: her mother had LV dilation, and her mother, maternal aunt, and maternal cousin had pacemaker implantation at ages 44, 60, and 54, respectively. The ECG showed SR with LBBB (QRS 200ms), and the TTE showed mild LV dilation, intraventricular (IV) dyssynchrony, and a left ventricular ejection fraction (LVEF) of 45–50%. Prognosis-modifying therapy was initiated, and an electrophysiological study was performed, which did not induce any supraventricular or ventricular arrhythmias. A cardiac magnetic resonance imaging (CMR) performed in 2022 showed mild LV dilation, global hypokinesia, and IV dyssynchrony, with LVEF of 40% and no late gadolinium enhancement. Follow-up showed recovery of LVEF and absence of arrhythmic events. In November 2024, genetic testing was requested when she began follow-up in the Cardiomyopathies Consultation. In January 2025, she returned to the ED with palpitations. A regular SVT with aberrant conduction was identified and chemically cardioverted to SR. Over the following 48 hours, she had paroxysmal episodes of atrial fibrillation and atrial tachycardia. Initial treatment with amiodarone was chosen. At discharge, LVEF was estimated at 50–55%, and a CMR was requested (pending). Genetic testing identified a likely pathogenic variant, c.3010_3022delTGCATTGCCACCC; p.(Cys1004Profs*136), in heterozygosity, in the SCN5A gene, previously reported in the ClinVar database. This genetic variant leads to the formation of a premature termination codon, which may result in a truncated, non-functional protein. This clinical case highlights the relevance of an integrative approach in DCM, emphasizing the critical role of genetic testing in understanding clinical manifestations. Variants in the SCN5A gene, classically associated with supraventricular arrhythmias, conduction system disease, and Brugada syndrome, were first linked to DCM in 2004. Subsequent studies identified these variants in approximately 1.7% of cases, often associated with SV arrhythmias and conduction system disturbances.