Cardiopulmonary Exercise Testing in the Prognostic Assessment of Heart Failure: From a Standardized Approach to Tailored Therapeutic Strategies

Cardiopulmonary Exercise Testing (CPET) is the gold standard for the functional assess- ment in patients with heart failure (HF), providing objective parameters that reflect the integrated response of the cardiovascular, respiratory, and muscular systems, in addition several CPET-derived variables have shown independent prognostic value in patients with both reduced (HFrEF) and preserved ejection fraction (HFpEF) HF. This review aims to critically analyze the main CPET prognostic variables in heart failure, highlighting their underlying pathophysiological mechanisms, their predictive capacity for mortality and hospitalizations, and their integration into clinical decision-making models. Param- eters such as peak oxygen uptake (VO2), minute ventilation/carbon dioxide production (VE/VCO2) slope, periodic breathing (or exercise oscillatory ventilation—EOV), anaero- bic threshold (AT), oxygen pulse, and VO2/work slope provide complementary insights into clinical risk; moreover, the combination of multiple CPET variables allows for more accurate risk stratification compared to the isolated use of each parameter. Multiparametric prognostic models such as the Metabolic Exercise Cardiac Kidney Index (MECKI) score, the Seattle Heart Failure Model, and the Heart Failure Survival Score (HFSS) incorporate these variables alongside clinical and laboratory data to guide advanced management and therapeutic decisions, including heart transplantation or left ventricular assistant device (LVAD) implantation. For these reasons, CPET-derived variables are essential prognostic tools in heart failure. Beyond improving risk stratification, their integration into multi- parametric models supports a more personalized therapeutic approach, including tailored pharmacological management.