Patients with unexplained sudden cardiac arrest (SCA) require deep phenotyping, genotyping, and cascade screening to inform personalised management.

The clinical significance of left ventricular non-compaction (LVNC) remains unclear. We sought to assess the genetic testing yield in adults with LVNC without a family history, with a focus on those with isolated LV trabeculations. Adults diagnosed with LVNC, who attended the Genetic Heart Disease Clinic in Sydney (2002-2018) were included. Cohort 1 included patients with LVNC with other clinical features such as cardiac dysfunction, ECG abnormalities, cardiovascular malformations, or syndromic features. Cohort 2 included patients with LVNC alone. Exome sequencing was performed with targeted analysis of 195 genes included on commercial panels. Cohort 1 (n=25) patients were 52% male with mean age at diagnosis of 42±13 years. The majority of patients (76%) had LV dysfunction (mean LVEF 50±14) or ECG abnormalities (28% had non-sustained ventricular tachycardia and 44% had atrial fibrillation). Pathogenic or likely pathogenic variants in NKX2-5 and TBX-5 were identified in 3 patients (12%). Cohort 2 (n=10) patients were majority female (70%) with mean age at diagnosis of 48±11 years. No pathogenic or likely pathogenic variants were identified. No likely pathogenic or pathogenic variants were identified in adults with isolated LV trabeculations (“isolated LVNC”) without a family history or additional features. This likely reflects a cohort of individuals with physiological trabeculations where genetic testing has little utility. Genetic testing may be helpful in those with associated features.