Decreased exercise capacity portends a poor prognosis in heart failure with preserved
ejection fraction (HFpEF). The hemodynamic gain index (HGI) is an integrated marker
of hemodynamic reserve measured during exercise stress testing and is associated with
survival. The goal of this study was to establish the association of HGI with exercise
capacity, serum biomarkers, and echocardiography features in subjects with HFpEF.
In 209 subjects with HFpEF enrolled in the RELAX (Phosphodiesterase-5 Inhibition to
Improve Clinical Status and Exercise Capacity in Diastolic Heart Failure) trial who
underwent cardiopulmonary exercise testing, we calculated the HGI ([peak heart rate
[HR] × peak systolic blood pressure [SBP]–[HR at rest × SBP at rest])/(HR at rest × SBP
at rest) and tested associations with outcomes of interest. The median (interquartile
range) HGI was 0.94 (0.5 to 1.3) beats per min/mm Hg. In multivariable-adjusted linear
regression, higher HGI was associated with greater peak oxygen consumption (VO2), VO2 at anaerobic threshold, peak minute ventilation, and 6-minute walk distance (all
p <0.001). Higher HGI was associated with lower serum high-sensitivity troponin I,
pro-collagen III, N-terminal pro-B-type natriuretic peptide, and creatinine (all p <0.05)
and with longer deceleration time, lower E/A ratio, and lower left atrial volume index
by echocardiography (all p <0.05). In conclusion, higher HGI in stable HFpEF was associated
with greater exercise capacity, a biomarker profile indicating less myocardial injury
and fibrosis and less kidney dysfunction, and with less severe diastolic dysfunction.
These results suggest that HGI, an easily calculated metric from routine exercise
testing, is a marker of functional capacity and disease severity in HFpEF and may
serve as a surrogate for VO2 parameters for use in treadmill testing without gas exchange capability.
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Article info
Publication history
Published online: December 20, 2022
Received in revised form:
November 7,
2022
Received:
August 5,
2022
Footnotes
Funding: Research reported in this publication was supported by: Dr. Grodin receives research funding from the Texas Health Resources Clinical Scholarship (Arlington, Texas), Eidos (San Francisco, California), and the National Heart, Lung, and Blood Institute of the National Institutes of Health (Bethesda, Maryland) under award number R01HL160892.
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