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 cm 2 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 cm 2 and mean gradient <40 mm Hg); moderate AS (aortic valve area >1.0 cm 2 ); and high-gradient (HG) severe AS (aortic valve area ≤1.0 cm 2 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.
Invasive hemodynamic response to exercise in hemodynamically significant aortic stenosis with preserved left ventricular ejection fraction
Abstract 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 evaluating ventricular hemodynamics. No invasive studies have compared the hemodynamic response of discordant LG and severe AS during exercise. Purpose To describe exercise hemodynamics in patients with asymptomatic discordant AS and left ventricular ejection fraction ≥50%, and to identify the variables associated with the steepness of the pulmonary capillary wedge pressure (PCWP)/cardiac output (CO) slope defined as (peak exercise PCWP-rest PCWP)/(peak exercise CO-rest CO). Methods Patients with aortic valve area (AVA) ≤1.5 cm² underwent right heart catheterization at rest and during maximal exercise measuring pulmonary artery pressures, PCWP, CO and PCWP/CO slope. Patients were stratified in three groups: 1) discordant LG AS (AVA ≤1.0 cm² and mean gradient <40 mmHg); 2) moderate AS (AVA >1.0 cm²) and 3) high-gradient severe AS (AVA ≤1.0 cm² and mean gradient ≥40 mmHg). Results Among 86 patients, 17 (20%) had discordant LG, 49 (57%) moderate, and 20 (23%) high-gradient severe AS. The PCWP/CO slope was significantly steeper in discordant LG: median 3.3 mmHg/L/min (interquartile range: 2.2 mmHg/L/min) and high-gradient severe AS: 2.7 mmHg/L/min (1.5 mmHg/L/min) compared to moderate AS: 1.9 mmHg/L/min (2.0 mmHg/L/min), p=0.004. In a linear 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 and upward shift in the PCWP/CO slope. Conclusions Discordant LG and high-gradient severe AS had similar hemodynamic response 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-upward shift in PCWP/CO slope for discordant LG compared to high-gradient severe AS indicates that, this group also has latent heart failure with preserved ejection fraction physiology.