Integrated evaluation of functional recovery and cardiac remodeling after an acute heart failure episode during full optimization of gdmt in hfref: a monocentric prospective pilot study
N Bonini, M Vitolo, E Tartaglia, M Mantovani, P Trapanese, M Paolini, F Tritto, M Izzi, G Procaccia, J Galloni, A Russo, F Baldisserri, D A Mei, J F Imberti, G BorianiAbstract
Background and Aim of the study
Short-term functional recovery and cardiac reverse remodeling after an acute heart failure episode (AHF) in patients with reduced ejection fraction (HFrEF) undergoing guideline-directed medical therapy (GDMT) optimization remain poorly characterized. The study prospectively evaluated the early and serial changes of cardiopulmonary exercise testing (CPET), the six-minute walking test (6MWT), the echocardiographic parameters and the and B-type natriuretic peptide (BNP) levels.
Methods
Patients hospitalized for AHF episode between December 2022 and August 2025 were enrolled in a monocentric prospective dataset of HFrEF patients (PILLARS project). We assessed patients at discharge, 1 month, and 3 months with a comprehensive functional evaluation. A predefined sub-analysis compared de novo HF (newHF) and worsened HF (wHF). Based on VO2/Kg recovery, patients were defined as "improved" (VO2/Kg follow-up >1 ml/Kg/min from the baseline values) or "Tx referral" if were improved with a VO2/Kg <14ml/Kg/min.
Results
We enrolled 33 patients (12% female, median NYHA II [II-III], figure 1). During follow-up, peak VO₂/kg improved from 11.5 [10.2–14.2] to 14.2 ml/kg/min [12.5–16.6] at three months (p<0.001), while VE/VCO₂ slope showed a non-significant decrease from 33.0 [27.1–40.5] to 28.5 [25.4–39.7]. Echocardiography revealed significant reverse remodeling with LVEF increasing from 30% to 41% (p<0.001), LVEDV decreasing from 187 to 160 mL (p=0.002), and LAV reduction (p=0.005). Median 6MWT distance increased from 440.0 to 487.5 m (p=0.140), and BNP significantly declined from 345.5 to 94.0 pg/mL (Figure 1). In the sub-analysis, new HF (n= 18) patients attained higher peak VO₂/kg (14.8 vs 13.1 ml/kg/min, p=0.016) and lower VE/VCO₂ slope (29.5 vs 33.1, p=0.04) compared with wHF (n=15) at three months. Among the two groups, no difference was found in terms of "improved" patients, but wHF had a higher proportion of patients reaching a VO₂/kg qualifying them as "Tx referral" (Figure 2).
Conclusion
In a contemporary cohort of HFrEF patients receiving optimized GDMT after an AHF hospitalization, multiparametric evaluation during a short-term follow-up revealed consistent and early improvements in both functional and structural parameters. Although main parameters in new HF and wHF groups improved over time, wHF patients attained lower peak VO₂/kg values and were more likely to meet VO₂/kg thresholds suggestive of early referral for advanced therapies compared with those with de novo heart failure, despite GDMT full optimization.Figure 1For image description, please refer to the figure legend and surrounding text.Figure 2For image description, please refer to the figure legend and surrounding text.