Prognostic utility of cardiopulmonary exercise testing with simultaneous exercise echocardiography in heart failure with preserved ejection fraction

Aims: Cardiopulmonary exercise testing (CPET) combined with exercise echocardiography (CPETecho) allows simultaneous assessments of cardiac, pulmonary, and ventilation in heart failure (HF) with preserved ejection fraction (HFpEF). This study sought to determine whether simultaneous assessment of CPET variables could provide additive predictive value over exercise stress echocardiography in patients with dyspnoea. Methods and results: CPETecho was performed in 443 patients with suspected HFpEF (240 HFpEF and 203 controls without HF). Patients with HFpEF were divided based on peak oxygen consumption (VO₂, ≥10 or <10 ml/min/kg) or the slope of minute ventilation to carbon dioxide production (V_E vs. VCO₂ slope ≥45.0 or <45.0). The primary endpoint was defined as a composite of all-cause mortality, HF hospitalization, unplanned hospital visits requiring intravenous diuretics, or intensification of oral diuretics. During a median follow-up of 399 days, the composite outcome occurred in 57 patients. E/e' ratio during peak exercise was associated with adverse outcomes. Patients with HFpEF and lower peak VO₂ had increased risks of the composite event (hazard ratio [HR] 5.05, 95% confidence interval [CI] 2.65–9.62, p < 0.0001 vs. controls; HR 3.14, 95% CI 1.69–5.84, p = 0.0003 vs. HFpEF with higher peak VO₂). Elevated V_E versus VCO₂ slope was also associated with adverse events in HFpEF. The addition of either the presence of abnormal peak VO₂ or V_E versus VCO₂ slope increased the predictive ability over the model based on age, sex, atrial fibrillation, left atrial volume index, and exercise E/e' (p < 0.05). Conclusion: These data provide new insights into the role of CPETecho in patients with HFpEF.