Elena Bacigalupi, Marco Merlo, Giulia Barbati, Andrea Villatore, Luciano Molinari, Matteo Dal Ferro, Alessia Paldino, Cinzia Radesich, Giulia Bassetto, Lina Manzi, Chiara Di Resta, Maria Perotto, Carola Pio Loco Detto Gava, Simone Sala, Antonio Esposito, Paolo Della Bella, Gianfranco Sinagra, Giovanni Peretto
BACKGROUND: Nondilated left ventricular cardiomyopathy (NDLVC) is a highly heterogeneous and unexplored category of cardiomyopathies introduced in the 2023 European Society of Cardiology (ESC) guidelines. This study aims to identify factors associated with adverse remodeling in a large multicentre cohort of patients with NDLVC. METHODS: A total of 432 patients with NDLVC (63.4% male, mean age 39.4 ± 14.6 years) with multiparametric characterization were enrolled from January 2010 to May 2023 in 2 high-volume Italian centres. Diagnosis followed ESC criteria. Endpoints were worsening of left ventricular ejection fraction (LVEF) ≥ 10% from the baseline value (or group W), evolution to dilated cardiomyopathy (DCM) (or group E), and the concomitant occurrence of both (or group W + E), assessed at the latest available echocardiographic evaluation. RESULTS: During a median follow-up of 77 months (interquartile range [IQR]: 48-109), 27.3% of patients experienced worsening LVEF, 28.9% progressed to DCM, and 18.3% reached the combined W + E endpoint. A multivariable model including positive genetic testing associated to myocardial inflammation, family history of cardiomyopathies or sudden cardiac death, intraventricular conduction delay, baseline echocardiographic LVEF < 45%, a ring-like late gadolinium enhancement on cardiac magnetic resonance, and nonsustained ventricular tachycardia at baseline had the strongest discrimination power for predicting worsening LVEF (area under the curve [AUC] of 0.8; 95% confidence interval [CI], 0.75-0.86), evolution to DCM (AUC 0.78; 95% CI, 0.73-0.84) and the combined W + E (AUC 0.84; 95% CI, 0.79-0.89). Negative genetic testing reduced the risk across all the endpoints (odds ratio [OR], 0.2; 95% CI, 0.1-0.4; P < 0.001; OR, 0.2; 95% CI, 0.1-0.4; P < 0.001 and OR, 0.1; 95% CI, 0.04-0.3; P < 0.001, respectively). CONCLUSIONS: In this large NDLVC cohort, in which 38% of patients showed an adverse remodelling over long-term follow-up, a multiparametric approach integrating deep phenotyping and genetics effectively identified high-risk patients.