Clinical and Prognostic Impact of Hemodynamic Gain Index and Heart Hemodynamic Reserve in Heart Failure with Reduced and Mildly Reduced Ejection Fraction: A Multicenter Study

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.