Unexpected Genetic Twists in Patients with Cardiac Devices

Abstract

Objective: To assess the frequency and types of genetic mutations in patients with arrhythmias who underwent cardiac device implantation. Methods: Retrospective observational study, including 38 patients with different arrhythmias and cardiac arrest as a first cardiac event. Treatment modalities encompass pacemakers, transvenous defibrillators, loop recorders, subcutaneous defibrillators, and cardiac resynchronization therapy. All patients underwent genetic testing, using commercially available panels (106–174 genes). Outcome measures include mortality, arrhythmia recurrence, and device-related complications. Results: Clinical parameters revealed a family history of sudden cardiac death in 19 patients (50%), who were predominantly male (58%) and had a mean age of 44.5 years and a mean left ventricle ejection fraction of 40.3%. Genetic testing identified mutations in various genes, predominantly TMEM43 (11%). In two patients (3%) with arrhythmogenic cardiomyopathy, complete subcutaneous defibrillator extraction with de novo transvenous implantable cardioverter-defibrillator implantation was needed. The absence of multiple associations among severe gene mutations was crucial for cardiac resynchronization therapy response. Mortality in this group was around 3% in titin dilated cardiomyopathy patients. Conclusions: Integration of genetic testing into the decision-making process for patients with electronic devices represents a paradigm shift in personalized medicine. By identifying genetic markers associated with arrhythmia susceptibility, heart failure etiology, and cardiac resynchronization therapy response, clinicians can tailor device choices to optimize patient outcomes.