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. 2023 Oct;11(10):1427-1438.
doi: 10.1016/j.jchf.2023.03.003. Epub 2023 Apr 26.

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

Sergio Caravita  1 , Claudia Baratto  2 , Aurora Filippo  3 , Davide Soranna  4 , Céline Dewachter  5 , Antonella Zambon  6 , Giovanni Battista Perego  7 , Denisa Muraru  8 , Michele Senni  9 , Luigi P Badano  8 , Gianfranco Parati  8 , Jean-Luc Vachiéry  5 , Marat Fudim  10
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Free article

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

Sergio Caravita et al. JACC Heart Fail. 2023 Oct.
Free article

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 (Pinteraction = 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.

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Conflict of interest statement

Funding Support and Author Disclosures This study was funded by the Italian Ministry of Health 5 x 1000. Dr Baratto is the recipient of a research grant from the European Society of Cardiology. Dr Vachiéry is the holder of the Actelion Research Chair on Pulmonary Hypertension in his department. Dr Fudim was supported by the National Heart, Lung, and Blood Institute (K23HL151744), the American Heart Association (20IPA35310955), Doris Duke, Bayer, Bodyport, and Verily; and has been the recipient of consulting fees from Abbott, Alio Health, Alleviant, Audicor, AxonTherapies, Bayer, Bodyguide, Bodyport, Boston Scientific, Cadence, Coridea, CVRx, Daxor, Deerfield Catalyst, Edwards LifeSciences, EKO, Feldschuh Foundation, Fire1, Gradient, Impulse Dynamics, Intershunt, Medtronic, NIMedical, NXT Biomedical, Pharmacosmos, PreHealth, ReCor, Shifamed, Splendo, Sumacor, SyMap, Verily, Vironix, Viscardia, and Zoll. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.

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