Ventilatory inefficiency, mitral regurgitation and pulmonary hypertension during exercise: the culprit interaction in heart failure reduced ejection fraction

Introduction: Dyspnea and exercise intolerance are landmark manifestations of heart failure (HF). An impaired efficiency in ventilation (VE) as indicated by a steep increase in VE vs CO2 output during exercise provides remarkable prognostic indications. Hypothesis: We aimed at defining the role of different hemodynamic components that may determine the most unfavorable ventilatory phenotype and worse clinical status. Methods: 71 HF reduced ejection fraction patients (mean age 67±11; male 72%; ischemic etiology 61%; NYHA class I, II, III and IV 13%, 36%, 39% and 12%, mean ejection fraction 33±9%) underwent cardiopulmonary exercise test evaluation on tiltable cycle-ergometer combined with simultaneous echocardiographic assessment. Results: Patients were divided in 4 ventilatory classes (VC) according to the VE/VCO2 slope classification focusing on peak exercise variables. We observed a VC related increase in E/e’ ratio, mitral regurgitation and pulmonary artery systolic pressure and a progressive reduction in TAPSE and peak VO2. The best correlation with VC groups was found for E/e’ ratio and peak VO2. Conclusions: A remarkable culprit interaction emerged between the degree of diastolic dysfunction, mitral regurgitation, pulmonary hypertension and right heart dysfunction with inefficient VE during exercise. A systematic analysis of these hemodynamic determinants by stress echo combined with gas exchange analysis may become a valuable addition for appropriately refining therapeutic interventions.