Shedding Light on Latent Pulmonary Vascular Disease in Heart Failure With Preserved Ejection Fraction

Abstract

Background: Among patients with heart failure with preserved ejection fraction (HFpEF), a distinct hemodynamic phenotype has been recently described, ie, latent pulmonary vascular disease (HFpEF-latentPVD), defined by exercise pulmonary vascular resistance (PVR) >1.74 WU.

Objectives: This study aims to explore the pathophysiological significance of HFpEF-latentPVD.

Methods: The authors analyzed a cohort of patients who had undergone supine exercise right heart catheterization with cardiac output (CO) measured by direct Fick method, between 2016 and 2021. HFpEF-latentPVD patients were compared with HFpEF control patients.

Results: Out of 86 HFpEF patients, 21% qualified as having HFpEF-latentPVD, 78% of whom had PVR >2 WU at rest. Patients with HFpEF-latentPVD were older, with a higher pretest probability of HFpEF, and more frequently experienced atrial fibrillation and at least moderate tricuspid regurgitation (P < 0.05). PVR trajectories differed between HFpEF-latentPVD patients and HFpEF control patients (P_interaction = 0.008), slightly increasing in the former and reducing in the latter. HFpEF-latentPVD patients displayed more frequent hemodynamically significant tricuspid regurgitation during exercise (P = 0.002) and had more impaired CO and stroke volume reserve (P < 0.05). Exercise PVR was correlated with mixed venous O₂ tension (R² = 0.33) and stroke volume (R² = 0.31) in HFpEF-latentPVD patients. The HFpEF-latentPVD patients had had higher dead space ventilation during exercise and higher PaCO₂ (P < 0.05), which correlated with resting PVR (R² = 0.21). Event-free survival was reduced in HFpEF-latentPVD patients (P < 0.05).

Conclusions: The results suggest that when CO is measured by direct Fick, few HFpEF patients have isolated latent PVD (ie, normal PVR at rest, becoming abnormal during exercise). HFpEF-latentPVD patients present with CO limitation to exercise, associated with dynamic tricuspid regurgitation, altered ventilatory control, and pulmonary vascular hyperreactivity, portending a poor prognosis.

Keywords: exercise; heart failure; pulmonary hypertension; right heart catheterization; tricuspid regurgitation.