Oxygen pulse kinetics and ventilatory inefficiency as markers of cardiovascular limitation on exercise in patients with mild pre-capillary pulmonary hypertension and exertional dyspnoea.

IntroductionCardiopulmonary exercise testing (CPET) quantifies exercise limitation and helps differentiate cardiovascular dysfunction from deconditioning in patients with exertional dyspnoea. In mild pulmonary arterial hypertension (PAH) and chronic thromboembolic pulmonary hypertension (CTEPH), traditional CPET oxygen delivery parameters may not adequately distinguish cardiac limitation. We evaluated whether oxygen pulse (O2 pulse) kinetics and the ratio of ventilation-carbon dioxide slope to peak oxygen uptake (VEVCO2/peakVO2) improve identification of cardiovascular limitation and prognostication. MethodsWe retrospectively analysed 289 consecutive patients referred for CPET. Patients were categorised into pre-capillary PH, no PH, or "unclassified" PH based on haemodynamics. O2 pulse slopes were calculated across exercise phases, and qualitative curve patterns were classified. VEVCO2/peakVO2 was derived from standard CPET parameters. Logistic regression assessed predictors of cardiac dysfunction (peak O2 pulse <65% predicted). Survival was evaluated using Kaplan-Meier and Cox regression analyses. ResultsPre-capillary PH patients demonstrated more impaired aerobic capacity and ventilatory efficiency than those without PH. Abnormal O2 pulse patterns (early plateauing or down-sloping) were associated with shallower slopes, lower peak O2 pulse, and greater chronotropic index. A work-phase O2 pulse slope < 0.40 identified impaired oxygen delivery but was not independently predictive in multivariable analysis. VEVCO2/peakVO2 independently predicted cardiac dysfunction (OR 3.9 [2.6-6.2], p < 0.001) and showed strong discrimination (AUC 0.83). VEVCO2/peakVO2 [&ge;] 2.7 independently predicted mortality (HR 13.6, 95% CI 3.8-48.5, p<0.001) outperforming peak O2 pulse and VE/VCO2 slope. ConclusionO2 pulse kinetics, particularly a work-phase slope < 0.40 and plateauing or decreasing trajectories, are associated with cardiac dysfunction in patients with pre-capillary PH. VEVCO2/peakVO2 appears to be a marker of cardiovascular limitation and mortality and may aid differentiation between cardiac dysfunction and deconditioning in this population when conventional CPET parameters are inconclusive.