Related Experiment Video
Updated: Feb 25, 2026

Lumped-Parameter and Finite Element Modeling of Heart Failure with Preserved Ejection Fraction
Published on: February 13, 2021
Invasive Hemodynamic Exercise Response in Hemodynamically Significant Aortic Stenosis With Preserved Left Ventricular
Mulham Ali1,2,3, Peter Hartmund Frederiksen1,2, Jacob Eifer Møller1,2,4
1Department of Cardiology, Odense University Hospital, Denmark (M.A., P.H.F., J.E.M., N.S.B.M., A.C., A.H., M.K.P., K.A.Ø., J.S.D.).
Background:
Guidelines acknowledge that discordant low-gradient (LG) aortic stenosis (AS) may be severe, but verifying this can be challenging. Right heart catheterization during exercise is considered the gold standard for evaluating ventricular hemodynamics. No invasive studies have compared the hemodynamic response of discordant LG and severe AS during exercise. The aim of this observational study was to describe exercise hemodynamics in patients with asymptomatic discordant AS and left ventricular ejection fraction ≥50%.
Methods:
Patients with aortic valve area ≤1.5 cm2 underwent right heart catheterization at rest and during maximal exercise, measuring pulmonary capillary wedge pressure (PCWP), cardiac output (CO), and the PCWP/CO-slope. Patients were stratified into 3 groups: discordant LG AS (aortic valve area ≤1.0 cm2 and mean gradient <40 mm Hg); moderate AS (aortic valve area >1.0 cm2); and high-gradient (HG) severe AS (aortic valve area ≤1.0 cm2 and mean gradient ≥40 mm Hg).
Results:
Among 86 patients, 17 (20%) had discordant LG, 49 (57%) moderate, and 20 (23%) HG severe AS. The median PCWP/CO-slope was significantly steeper in discordant LG (3.3 [interquartile range, 2.1-4.3] mm Hg/L/min) and HG severe AS (2.7 [1.9-3.4] mm Hg/L per minute) compared with moderate AS (1.9 [0.7-2.8] mm Hg/L per minute), P=0.004. In a regression model adjusted for age, sex, and rest PCWP, systemic arterial compliance and AS severity were significantly associated with the PCWP/CO-slope. Furthermore, patients with discordant LG AS had a leftward-upward shift in the PCWP/CO-curve.
Conclusions:
Discordant LG and HG severe AS had similar hemodynamic responses to exercise with steeper PCWP/CO-slope than in moderate AS, suggesting that discordant LG AS is a severe form of AS. In addition, the left upwards shift in PCWP/CO-curve for discordant LG compared with HG severe AS indicates that this group also has heart failure with preserved ejection fraction physiology.
Registration:
URL: https://www.clinicaltrials.gov; Unique identifier: NCT04913870 and NCT02395107.
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