Key result
Likely pathogenic/pathogenic genetic variants independently predicted appropriate ICD interventions in dilated cardiomyopathy (OR 1.55, 95% CI 1.06-2.28; p=0.02), irrespective of LVEF.
Why the study?
Dilated cardiomyopathy carries a substantial risk of malignant ventricular arrhythmias and sudden cardiac death despite clinical risk stratification. The impact of genetic testing on primary prevention ICD decision-making and clinical outcomes after implantation needed evaluation.
Does genetic testing impact primary prevention ICD decision-making and predict appropriate ICD interventions in adult patients with dilated cardiomyopathy?
Cohort (n=699)
Does genetic testing impact primary prevention ICD decision-making and predict appropriate ICD interventions in adult patients with dilated cardiomyopathy?
In patients with dilated cardiomyopathy, genetic testing independently informs primary prevention ICD implantation—even when LVEF is >35%—and predicts appropriate device therapies, though cardiac MRI late gadolinium enhancement remains a stronger predictor when available.
May refine primary prevention ICD decisions in DCM beyond LVEF; supports extending genetic risk models but leaves open prospective validation.
Background Despite advances in clinical risk stratification, dilated cardiomyopathy (DCM) remains associated with a substantial risk of malignant ventricular arrhythmias and sudden cardiac death. Genetic testing may provide incremental value in arrhythmic risk assessment and primary prevention implantable cardioverter-defibrillator (ICD) decision-making. Objective To evaluate the impact of genetic testing on primary prevention ICD decision-making in patients with DCM and its association with clinical outcomes after implantation, including appropriate ICD interventions. Methods Between January 1, 2001, and December 1, 2025, 1,890 adult patients with DCM enrolled in our Familial Cardiomyopathy Registry were screened; those without genetic data were excluded. Genetic variants were classified according to current standards, and high-risk arrhythmogenic genes were defined per international guidelines (LMNA, FLNC, DSP, TMEM43, PLN, RBM20). Predictors of ICD implantation were evaluated using multivariable logistic regression, and associations with outcomes were assessed by time-to-event and competing-risk analyses. Results Among 699 eligible patients, 382 (55%) received an ICD, including 335 (88%) for primary prevention. Pre-implant genetic testing was performed in 36% (n=122) and increased after the introduction of exome-based panels (14% before 2018 vs 67% in 2018–2025; p<0.01). Patients tested before implantation more often carried likely pathogenic/pathogenic (LP/P) variants than those tested after (49% vs 37%; p=0.01), including variants in high-risk arrhythmogenic genes (20% vs 10%; p=0.04). LP/P variants were independently associated with primary prevention ICD implantation, together with history of syncope and persistent LVEF <35% after optimal medical therapy. Among patients with LVEF >35%, LP/P variants in high-risk arrhythmogenic genes were the only independent predictors (Table 1). During a median follow-up of 136 months (IQR 77–226), 32% (n=106) experienced appropriate device interventions. LP/P variants were associated with these interventions (p=0.01, Figure 1A) and were the sole independent predictor (OR 1.55, 95% CI 1.06–2.28; p=0.02), irrespective of LVEF. In patients with available cardiac magnetic resonance (CMR) data (n=183, 54.6%), late gadolinium enhancement (LGE) was the only independent predictor (OR 2.89, 95% CI 1.34–6.24; p=0.01). Conclusions In this large DCM cohort, genetic testing was independently associated with primary prevention ICD decision-making, including in patients with preserved or mildly reduced LVEF, and predicted appropriate ICD intervention beyond LVEF. Its incremental prognostic value was attenuated in the presence of CMR data, supporting a multimodal, guideline-consistent approach to arrhythmic risk stratification.
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Bernabei et al. (2026) conducted a cohort in Dilated cardiomyopathy (DCM) (n=699). Likely pathogenic/pathogenic (LP/P) genetic variants identified via genetic testing vs. Absence of LP/P genetic variants or post-implant testing was evaluated on Appropriate ICD interventions (OR 1.55, 95% CI 1.06-2.28, p=0.02). Likely pathogenic/pathogenic genetic variants independently predicted appropriate ICD interventions in dilated cardiomyopathy (OR 1.55, 95% CI 1.06-2.28; p=0.02), irrespective of LVEF.
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