Abstract 4371939: Primary prevention of arrhythmic events in dilated cardiomyopathy: the role of genetic testing

Abstract

Background: Dilated cardiomyopathy (DCM) is a genetically heterogeneous disease with variable arrhythmic risk. Implantable cardioverter-defibrillators (ICD) are used to prevent sudden cardiac death, but current indications do not routinely consider genetic findings. Hypothesis: To assess the clinical impact of genetic testing in patients with DCM, focusing on how genotype classification and timing of testing influence the incidence of appropriate ICD interventions. Methods: We retrospectively evaluated 1124 DCM patients who underwent genetic testing. Based on established prognostic evidence, a composite genotype variable was created to classify variants as “favorable” (TTN, sarcomeric variants) or “unfavorable” (LMNA, FLNC, DSP, RBM20, SCN5A, BAG3). Results: Most patients (64.5%) were male. A total of 469 (41.7%) patients carried pathogenic or likely pathogenic (P/LP) variants, the others were genotype-negative or carried variants of uncertain significance (VUS). Among them, 238 (50.7%) carried favorable genes and 167 (35.6%) carried variants associated with poor prognosis. ICD were implanted in 424 patients (37.7%), including 361 (85.1%) for primary prevention. In these last subjects, genetic testing was performed before ICD implantation in 86 cases (23.8%) (vs n=276, 76.4%, post-genetic testing). The incidence of unfavorable genotype did not differ between patients who underwent genetic testing before versus after ICD treatment (26.7% vs. 26.1%, respectively, p=0.56) Moreover, during the subsequent follow-up of 10 years, appropriate ICD interventions occurred in 104 of these patients (28.8%), with a mean time of 3 months after implantation. A trend toward more frequent arrhythmic events in patients tested after ICD implantation than in those tested before (31.1% Vs. 20.9%, respectively, p=0.07). Among P/LP carriers (n=153, 42.4%), those tested after ICD implantation had significantly more arrhythmic events than those tested earlier (39.6% Vs. 21%, respectively p=0.03). No significant difference was observed among carriers of VUS or genotype-negative based on testing timing (before ICD 25.5% Vs. after ICD 29.3%, p=0.6). Conclusion: In DCM, pre-implant genetic testing helps target ICD therapy to high-risk individuals while sparing low-risk patients from unnecessary interventions. Integrating genetics into routine care enables more precise and effective decision-making.