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

Eva Del Mestre; Alessia Paldino; Carola Pio Loco Detto Gava; Ilaria Gandin; Marta Gigli; Davide Stolfo; Martina Setti; Giovanni Maria Severini; Beatrice Spedicati; Stefania Lenarduzzi; Giorgia Girotto; Alessandro Folgheraiter; Jacopo Giulio Rizzi; Renata Korcova; Luisa Mestroni; Marco Merlo; Matteo Dal Ferro; Gianfranco Sinagra

doi:10.1002/ejhf.3657

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

Eur J Heart Fail. 2025 Apr 13. doi: 10.1002/ejhf.3657. Online ahead of print.

Authors

Eva Del Mestre^#^{1

2}, Alessia Paldino^#^{1

2}, Carola Pio Loco Detto Gava^{1

2}, Ilaria Gandin³, Marta Gigli^{1

2}, Davide Stolfo^{1

2}, Martina Setti⁴, Giovanni Maria Severini⁵, Beatrice Spedicati⁵, Stefania Lenarduzzi⁵, Giorgia Girotto^{5

6}, Alessandro Folgheraiter^{1

2}, Jacopo Giulio Rizzi^{1

2}, Renata Korcova^{1

2}, Luisa Mestroni⁷, Marco Merlo^{1

2

6}, Matteo Dal Ferro^{1

2}, Gianfranco Sinagra^{1

2

6}

Affiliations

¹ Cardiovascular Department, Azienda Sanitaria Universitaria Giuliano Isontina (ASUGI), University of Trieste, Trieste, Italy.
² European Reference Network for rare, low-prevalence, or complex diseases of the Heart (ERN GUARD-Heart).
³ Biostatistics Unit, Department of Medicine, Surgery and Health Science, University of Trieste, Trieste, Italy.
⁴ Department of Cardiology, Cardio-Thoracic Department, University Hospital of Verona, Verona, Italy.
⁵ Institute for Maternal and Child Health - IRCCS 'Burlo Garofolo', Trieste, Italy.
⁶ Department of Medicine, Surgery and Health Sciences, University of Trieste, Trieste, Italy.
⁷ Molecular Genetics, Cardiovascular Institute, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.

^# Contributed equally.

PMID: 40222818
DOI: 10.1002/ejhf.3657

Abstract

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.

Keywords: Dilated cardiomyopathy; Family screening; Genetics; Non‐dilated left ventricular cardiomyopathy; Relatives.