*Article* **Sex-Specific Prognostic Implications in Dilated Cardiomyopathy after Left Ventricular Reverse Remodeling**

**Antonio Cannata 1,2,**†**, Paolo Manca 1,**†**, Vincenzo Nuzzi 1, Caterina Gregorio 3, Jessica Artico 1, Piero Gentile 1, Carola Pio Loco 1, Federica Ramani 1, Giulia Barbati 3, Marco Merlo 1,\* and Gianfranco Sinagra <sup>1</sup>**


Received: 2 July 2020; Accepted: 27 July 2020; Published: 29 July 2020

**Abstract:** Background. Women affected by Dilated Cardiomyopathy (DCM) experience better outcomes compared to men. Whether a more pronounced Left Ventricular Reverse Remodelling (LVRR) might explain this is still unknown. Aim. We investigated the relationship between LVRR and sex and its long-term outcomes. Methods. A cohort of 605 DCM patients with available follow-up data was consecutively enrolled. LVRR was defined, at 24-month follow-up evaluation, as an increase in left ventricular ejection fraction (LVEF) ≥ 10% or a LVEF > 50% and a decrease ≥ 10% in indexed left ventricular end-diastolic diameter (LVEDDi) or an LVEDDi <sup>≤</sup> 33 mm/m2. Outcome measures were a composite of all-cause mortality/heart transplantation (HTx) or ventricular assist device (VAD) and a composite of Sudden Cardiac Death (SCD) or Major Ventricular Arrhythmias (MVA). Results. 181 patients (30%) experienced LVRR. The cumulative incidence of LVRR at 24-months evaluation was comparable between sexes (33% vs. 29%; *p* = 0.26). During a median follow-up of 149 months, women experiencing LVRR had the lowest rate of main outcome measure (global *p* = 0.03) with a 71% relative risk reduction compared to men with LVRR, without significant difference between women without LVRR and males. A trend towards the same results was found regarding SCD/MVA (global *p* = 0.06). Applying a multi-state model, male sex emerged as an independent adverse prognostic factor even after LVRR completion. Conclusions. Although the rate of LVRR was comparable between sexes, females experiencing LVRR showed the best outcomes in the long term follow up compared to males and females without LVRR. Further studies are advocated to explain this difference in outcomes between sexes.

**Keywords:** sex differences; dilated cardiomyopathy; left ventricular reverse remodelling; longterm outcomes
