https://doi.org/10.1007/s00392-025-02625-4
1Kerckhoff Klinik GmbH Abteilung für Kardiologie Bad Nauheim, Deutschland; 2Universitätsmedizin Göttingen Herzzentrum, Klinik für Kardiologie und Pneumologie Göttingen, Deutschland; 3Johns Hopkins University School of medicine Baltimore, USA; 4Forum Medizin GbR Kardiologie Rosdorf, Deutschland; 5Universitätsklinikum Gießen und Marburg GmbH Medizinische Klinik I - Kardiologie und Angiologie Gießen, Deutschland
Background
The pathophysiology of heart failure with preserved ejection fraction (HFpEF) reaches beyond left ventricular function including pulmonary vascular remodelling and right ventricular (RV) involvement. Consequently, 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, LVEF >50%) were enrolled and underwent rest and exercise-stress echocardiography, right heart catheterisation and CMR. HFpEF was defined by pulmonary capillary wedge pressure (≥15mmHg at rest (overt) or ≥25mmHg during exercise-stress (masked)). 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
The final population consisted of n=34 HFpEF and n=34 non-cardiac dyspnoea (NCD) patients. HFpEF patients showed increased RV 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 to NCD. However, 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) (figure 1A). The out of proportion increase in afterload over contractility in HFpEF was reflected in a statistical trend towards increased coupling index Ea/Ees from rest to stress in HFpEF (p=0.078) whilst Ea/Ees decreased in NCD (p=0.002) (figure 1B). Indeed, patients with resting Ea or Ees above the median showed lower increase in cardiac index comparing rest to exercise-stress (Ea: below: 2.8 vs above: 2.2, p=0.031; Ees: below: 2.9, above: 2.1, p<0.001) (figure 1C and 1D).
Conclusion
Resting RV afterload elevation in HFpEF is compensated by increased contractility. However, out-of-proportion increase of afterload in HFpEF as opposed to inadequate response in contractility during exertion results in an inadequate increase of cardiac output. This may be a feature of HFpEF pathophysiology associated to exertional functional failure.