Exercise-induced out-of-proportion increase in afterload and impaired right ventricular contractile reserve in HFpEF

Abstract

Aims: The pathophysiology of heart failure with preserved ejection fraction (HFpEF) includes pulmonary vascular remodelling and right ventricular (RV) involvement. We sought to investigate the significance of non-invasive cardiovascular magnetic resonance (CMR)-derived RV loading conditions. Methods: Patients with exertional dyspnoea and diastolic dysfunction [E/e′ > 8, left ventricular ejection fraction (LVEF) >50%] underwent rest and exercise-stress echocardiography, right heart catheterization and CMR. HFpEF was defined by pulmonary capillary wedge pressure [rest ≥15 mmHg (overt) or stress ≥25 mmHg (masked)]; otherwise, patients were classified as non-cardiac dyspnoea (NCD). CMR-derived RV haemodynamic indices were defined as follows: afterload Ea = end-systolic pressure (ESP)/stroke volume (SV), contractility Ees = ESP/left ventricular end-systolic volume and RV/pulmonary artery coupling as Ea/Ees. Results: HFpEF (n = 34; female 73.5%; median age 69 years) patients showed increased afterload and contractility at rest (Ea 1.20 vs. 0.85, P = 0.001, Ees 0.61 vs. 0.37, P < 0.001) and during exercise (Ea 2.48 vs. 1.53, Ees 1.00 vs. 0.74, P < 0.001) compared with NCD (n = 34; female 55.9%; median age 66 years). The relative increase of contractility from rest to stress was smallest in overt HFpEF (overt 1.40 vs. masked 1.86, P = 0.001) and highest in NCD (HFpEF 1.56 vs. NCD 1.97, P = 0.022). The out-of-proportion increase in afterload over contractility in HFpEF was reflected in a statistical trend towards increased Ea/Ees from rest to stress in HFpEF (P = 0.078) while Ea/Ees decreased in NCD (P = 0.002). Patients with resting Ea or Ees above the median showed lower exercise-induced increases in cardiac index (Ea: below: 2.8 vs. above: 2.2, P = 0.031; Ees: below: 2.9, above: 2.1, P < 0.001). Conclusions: Resting RV afterload elevation in HFpEF results in a compensatory increase in contractility. Out-of-proportion increase of afterload paralleled by inadequate increase in contractility results in failure to increase the cardiac index in HFpEF, potentially associated with exertional functional failure.