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Randomized Controlled Trial
. 2025 Aug;13(8):102523.
doi: 10.1016/j.jchf.2025.102523. Epub 2025 Jun 26.

Heart-Lung Interactions in HFpEF: Dynamic Hyperinflation and Exercise PCWP

Michael G Leahy  1 , Denis J Wakeham  1 , James P MacNamara  1 , Tiffany Brazile  1 , Abidan Abulimiti  1 , Christopher M Hearon Jr  1 , Mitchel Samels  2 , Andrew R Tomlinson  1 , Bryce N Balmain  1 , Tony G Babb  1 , Benjamin D Levine  1 , Satyam Sarma  3
Affiliations
Randomized Controlled Trial

Heart-Lung Interactions in HFpEF: Dynamic Hyperinflation and Exercise PCWP

Michael G Leahy et al. JACC Heart Fail. 2025 Aug.

Abstract

Background: Patients with heart failure with preserved ejection fraction (HFpEF) are characterized by an exaggerated rise in pulmonary capillary wedge pressure (PCWP) with exercise compared with healthy similar-aged adults. Due to the multisystemic effects of the disease, patients with HFpEF often experience expiratory flow limitation (EFL), thereby perpetuating dynamic hyperinflation (DH) and ventilation at a higher percentage of total lung volume. How lung mechanics and operational lung volume affect central hemodynamics in patients with HFpEF is not fully understood.

Objectives: The authors sought to characterize the association and correlation of DH and EFL on PCWP in adults with HFpEF during exercise.

Methods: A total of 55 patients with HFpEF (71 ± 7 years of age, 70% female) were studied at rest and during 20-W and peak exercise on an upright semirecumbent cycle ergometer. Right atrial and mean pulmonary artery (mPAP) pressures as well as PCWP (via right heart catheterization), oxygen uptake (indirect calorimetry), cardiac output (direct Fick), and ventilation (flow-volume parameters) were measured at each timepoint. DH was defined as an increase in end-expiratory lung volume of ≥150 mL from rest as determined by repeated inspiratory capacity maneuvers.

Results: PCWP was greater in those with DH at 20-W exercise (DH 24 ± 6 mm Hg vs typical 18 ± 6; P = 0.033) and peak exercise (DH 44 ± 9 vs typical 31 ± 6 mm Hg; P = 0.002). The degree of dynamic inflation was modestly, but significantly associated with a greater PCWP at 20-W (r2 = 0.196; P = 0.001) and peak (r2 = 0.204; P < 0.001) exercise, as was mPAP (both P < 0.001).

Conclusions: Patients with HFpEF that dynamically hyperinflate during exercise have greater PCWP as measured with reference to atmospheric pressure. The severity of hyperinflation scaled proportionally to higher exercise PCWP. Our findings suggest that the augmented exercise PCWP in patients with HFpEF may not be entirely attributed to ventricular stiffness, but also a consequence of increased intrathoracic pressure from dysfunctional ventilatory mechanics. (Mechanisms of Exercise Intolerance in Heart Failure With Preserved Ejection Fraction; NCT04068844).

Keywords: dynamic hyperinflation; heart failure with preserved ejection fraction; pulmonary capillary wedge pressure; pulmonary vascular pressure.

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Conflict of interest statement

Funding Support and Author Disclosures This study was supported through funding from the National Institutes of Health (P01HL137630). Dr Sarma has received support from an American Heart Association career development award. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.

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