Real-world outcomes and predictors of arrhythmic events in patients with Inherited Cardiac Conditions and Intermediate SCD risk

Abstract Background Sudden cardiac death (SCD) remains a critical concern for patients with inherited cardiac conditions (ICCs), presenting considerable challenges in risk stratification. Methods We conducted a retrospective analysis of 193 patients evaluated at a ICC multidisciplinary team (MDT) meetings (2021 - 2024) for SCD risk assessment in an intermediate risk group. Results The cohort (48 ± 16 years, 37% female) included patients from varied ethnic backgrounds and various underlying inherited cardiac conditions (see Figure 1). Available scores in 68% of patients indicated a 5-year annualized risk of SCD in HCM of 4.1 ± 2.1, in ARVC risk score of 2.1 ± 1.6, and 7.0 ± 4.1. in LMNA. 12.4 ± 6.6. Median follow-up duration post-MDT was 983 days (246; 1539). An ICD was recommended for 121 patients (63%); of these, 88 patients received an ICD, 20 declined, and 13 are awaiting the procedure. Thirteen additional patients received ICDs during follow-up due to changes in clinical status or diagnosis. The median time to ICD implantation post-MDT was 3 months (0; 35). Fifteen patients (8%) experienced malignant VA, with a median age of 35 years. Diagnoses in this subgroup included ACM (7), HCM (5), DCM (2), and LMNA-related cardiomyopathy (1), and nine had confirmed genetic diagnoses. HCM, ARVC, and LMNA risk scores in these patients were 2.3% (2.0; 6.5), 2.6 (0.9; 8.5), and 9%, respectively. Among patients with already implanted ICDs, nine experienced arrhythmias treated effectively by the device; one patient required additional antiarrhythmic therapy for sustained VT. Electrical storms occurred in two patients, and three suffered SCA, resulting in two fatalities. During follow-up, three patients died from end-stage heart failure, one patient died of a non-cardiac cause, and in two patients no further information was available. Female (p=0.01) and younger (mean age 39 vs. 48 years, p=0.029) patients were more likely to experience an arrhythmic event. Neither ethnicity, underlying disease, nor MDT ICD recommendations correlated significantly with arrhythmic outcomes. Female gender emerged as the strongest predictor of arrhythmic events, yet females were marginally less likely to receive an ICD recommendation (57% vs. 65%), though this difference was not statistically significant (p=0.538). Conclusion Current risk scores for predicting SCD risk in patients with inherited cardiomyopathies perform imperfectly in the intermediate risk group, underscoring the need for improved stratification strategies. Identification of particular subgroups at higher risk could be improved and in particular gender related differences in SCD risk represent a priority for future research.Distribution of underlying condition