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

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.

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.

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).

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.