Accurate prognostic stratification in patients with chronic heart failure and reduced ejection fraction (HFrEF) remains a significant clinical challenge. Many different parameters, including left ventricular (LV) and right ventricular (RV) function and cardiopulmonary exercise testing (CPET) parameters, are available in the literature. LV ejection fraction (LVEF) is the most used parameter in clinical practice. This study aimed to analyze CPET and echocardiographic data in patients under evaluation for heart transplantation (HTx) to identify the parameter that best correlates with cardiac events. Methods and Results. Echocardiography and CPET were performed in patients with HFrEF under evaluation for HTx. The population comprised 170 patients (mean age: 55 ± 9 years; 88% male; non-ischemic etiology: 63%). LVEF was 30.4 ± 7.6%, peak oxygen uptake (Vo_2peak) was 17.08 ± 4.6 mL/Kg/min; minute ventilation (VE)/carbon dioxide production (Vco₂) slope was 34.8 ± 8.7. During a follow-up of 4 ± 1 years, 37 hospitalizations, 4 deaths, 14 HTx, and 5 LV assist device implantation occurred. Patients who experienced major events had a lower Vo_2peak (p < 0.005), higher VE/Vco₂ slope (p < 0.005), greater LV end-systolic diameter (p < 0.005), and RV end-diastolic diameter (p < 0.005) than patients without events. Conversely, LVEF did not differ between these two groups. VE/Vco₂ slope and RV dimensions significantly correlated with hard cardiac events (p = 0.019 and p = 0.008, respectively). Conclusions. In patients with HFrEF, parameters quantifying the system reserve (i.e., Vo_2peak and VE/Vco₂ slope) and those demonstrating advanced biventricular remodeling may help stratify the risk of cardiac events. Conversely, LVEF showed a limited prognostic value in this setting.

Background/Objectives: Cardiopulmonary exercise testing (CPET) is a well-established tool for risk stratification in patients with heart failure (HF); however, its utility is limited in routine clinical practice due to the associated cost and technical demands. The hemodynamic gain index (HGI), a non-metabolic parameter derived from systolic blood pressure and heart rate changes during exercise, has been demonstrated to play a promising role in HF populations. In this study, we aimed both to validate the prognostic value of the HGI and to evaluate a novel metric, heart hemodynamic reserve (HHR), in patients with HF and left ventricular ejection fraction (LVEF) below 50%. Methods: We retrospectively enrolled 479 consecutive patients with HF and reduced or mildly reduced LVEF who underwent maximal, symptom-limited CPET at three Italian university hospitals between 2012 and 2024. The HGI and HHR were computed using resting and peak exercise hemodynamic data. HHR is defined as the product of systolic blood pressure and heart rate reserve with exercise, normalized for the age-predicted maximum heart rate. The primary endpoint was a composite of cardiovascular death, urgent heart transplantation (HTx), or left ventricular assist device (LVAD) implantation. Prognostic associations were assessed using multivariable Cox regression and area under the receiver operating characteristic curves (AUCs). Results: During a median follow-up of 3.25 years, the composite outcome occurred in 56 patients (11.5%). Both the HGI and HHR were independently associated with the prespecified endpoint (HGI HR: 0.41, 95% CI: 0.20–0.83, p = 0.013; HHR HR: 0.89, 95% CI: 0.83–0.96, p = 0.004), with HHR showing a slightly higher prognostic accuracy than the HGI (AUC 0.78 vs. 0.74; p = 0.033). Conclusions: Both the HGI and HHR are independent prognostic markers in HF patients with LVEF < 50%. Their non-metabolic derivation makes them valuable tools for risk stratification in settings where CPET is unavailable.