Prediction and prognostic role of left ventricular systolic dysfunction in family screening for dilated cardiomyopathy and non-dilated left ventricular cardiomyopathy

Aims: The prognostic significance of detecting left ventricular (LV) systolic dysfunction during family screening programmes (FSPs) in relatives of probands affected by dilated (DCM) and non-dilated left ventricular (NDLVC) cardiomyopathies remain unclear. This study sought to evaluate the prognostic role of LV systolic dysfunction detection in relatives of DCM/NDLVC probands and to define the most accurate FSP. Methods and results: Baseline and follow-up data of first-degree relatives of probands affected by DCM/NDLVC were collected. The primary outcome was all-cause death and heart transplantation. Secondary heart failure (HF) and arrhythmic outcomes were also included. A total of 492 first degree relatives were enrolled. During a median follow-up of 110 months (interquartile range 57–188 months), only subjects that previously developed LV systolic dysfunction had primary outcomes (19 vs. 0, p < 0.001) and secondary outcomes (HF: 12 vs. 0, p = 0.005; arrhythmic: 30 vs. 0, p < 0.001). Subjects with LV systolic dysfunction detected by FSP showed lower rate of primary outcomes (FSP: n = 19 [14%]; no-FSP: n = 40 [37%]; p < 0.001) and secondary arrhythmic outcomes (FSP: n = 18 [13%]; no-FSP: n = 41 [38%]; p < 0.001). In this setting, family history of arrhythmia and being carrier of a pathogenic/likely pathogenic variant are the main risk factors for LV systolic dysfunction, while LV global longitudinal strain (LV-GLS) and Holter electrocardiogram (ECG) showed a relevant role in terms of prediction of LV systolic dysfunction and outcomes. Conclusion: Relatives of DCM/NDLVC probands who developed LV systolic dysfunction during a long follow-up had a significant increased risk of major adverse cardiovascular outcomes. However, LV systolic dysfunction detected by FSP showed a better prognosis. In this context, genetics, Holter ECG and LV-GLS demonstrated their functional role for disease and event prediction.