The Oxygen Cascade According To HFpEF Likelihood: A Focus on Sex Differences

Overview

Journal JACC Adv

Specialty Cardiology & Vascular Diseases

Date 2024 Aug 12

PMID 39130052

Authors

Jan Verwerft

Stephen Foulkes

Youri Bekhuis

Sara Moura-Ferreira

Maarten Falter

Sarah Hoedemakers

Ruta Jasaityte

Jan Stassen

Lieven Herbots

Andre La Gerche

Mark J Haykowsky

Guido Claessen

Affiliations

Soon will be listed here.

Abstract

Background: Women are at greater risk for heart failure with preserved ejection fraction (HFpEF).

Objectives: The aim of the study was to compare sex differences in the pathophysiology of exertional breathlessness in patients with high vs low HFpEF likelihood.

Methods: This cohort study evaluated consecutive patients (n = 1,936) with unexplained dyspnea using cardiopulmonary exercise testing and simultaneous echocardiography and quantified peak oxygen uptake (peak VO) and its determinants. HFpEF was considered likely when the HFPEF or HFA-PEFF score was ≥6 or ≥5, respectively. Sex differences were evaluated with the Student's -test or Mann-Whitney test and determinants of exercise capacity with a multivariable linear regression.

Results: The cohort included 1,963 patients (49% women and 28% [n = 555] with a high HFpEF likelihood). HFpEF likelihood did not impact the magnitude of sex differences in peak VO and its determinants. Overall, women had lower peak VO (mean difference -4.4 mL/kg/min [95% CI: -3.7 to -5.1 mL/kg/min]) secondary to a reduced O delivery (-0.5 L/min [95% CI: -0.4 to -0.6 L/min]) and less oxygen extraction (-2.9 mL/dL [95% CI: -2.5 to -3.2 mL/dL]). Reduced O delivery was due to lower hemoglobin (-1.2 g/dL [95% CI: -0.9 to -1.5 g/dL]) and smaller stroke volume (-15 mL [95% CI: -14 to -17 mL]). Women demonstrated increased mean pulmonary artery pressure/cardiac output slope (+0.5 mm Hg/L/min [95% CI: 0.3-0.7 mm Hg/L/min]) and left ventricular ejection fraction (+1% [95% CI: 1%-2%]), while they had smaller left ventricular end-diastolic volumes (-9 mL/m [95% CI: -8 to -11 mL/m]) and mass (-12 g/m [95% CI: -9 to -14 g/m]) and more often iron deficiency (55% vs 33%; < 0.001).

Conclusions: Women with unexplained dyspnea had significantly lower peak VO, regardless of HFpEF likelihood, attributed to both lower peak exercise O delivery and extraction. This suggests that physiologic sex differences, and not HFpEF likelihood, are an important factor contributing to functional limitations in females with exertional breathlessness.

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