Prognostic Impact of Left Ventricular Ejection Fraction in Patients With Moderate Aortic Regurgitation: Potential Implications for Treatment Decision-Making

Abstract

Background: The prognostic impact and optimal treatment of left ventricular systolic dysfunction in patients with moderate aortic regurgitation (AR) remain unknown. We aimed to assess the prognostic value of left ventricular ejection fraction (LVEF) in patients with moderate AR and explore the potential benefits of aortic valve intervention (AVI).

Methods: In total, 1,211 consecutive patients with moderate AR (jet width, 25-64% of LV outflow tract; vena contracta, 0.3-0.6 cm; regurgitant volume, 30-59 mL/beat; regurgitant fraction, 30-49%; effective regurgitation orifice, 0.10-0.29 cm2) prospectively registered between April and June 2018 at 46 academic hospitals were included. The primary outcome was a composite of death or hospitalization for heart failure (HHF). The optimal LVEF threshold for predicting the primary outcome was determined through the penalized spline shape and maximally selected rank statistics.

Results: During the 2-year follow-up, 125 deaths or HHF occurred. In the penalized splines, the relative hazard of death or HHF monotonically increased with decreasing LVEF. In the multivariate analysis, LVEF ≤55% was identified as the best threshold for independently predicting death or HHF under medical treatment (adjusted hazard ratio [HR]: 2.18; 95% confidence interval [CI] 1.38-3.42; P = 0.001), with substantial incremental values (integrated discrimination improvement index = 0.018, P = 0.030; net reclassification improvement index = 0.225, P = 0.006; likelihood ratio test P < 0.001). Among patients with LVEF 35-55%, AVI within 6 months of diagnosis was associated with a reduced risk of death or HHF compared with medical treatment alone (adjusted HR: 0.15; 95% CI: 0.04-0.50; P = 0.002), whereas this benefit was markedly attenuated when LVEF was ≤35% (adjusted HR: 0.65; 95% CI: 0.21-1.97; P = 0.441, P-interaction = 0.010) or >55% (adjusted HR: 0.40; 95% CI: 0.14-1.15; P = 0.089, P-interaction = 0.723).

Conclusions: LVEF is an independent and incremental prognostic factor in patients with moderate AR, with LVEF ≤55% being a robust marker of poor prognosis. Patients with LVEF 35-55% may benefit from early surgical correction of moderate AR. Further studies are warranted to validate our findings in a randomized setting.

Registration: China Valvular Heart Disease Study (China-VHD study, NCT03484806); clinicaltrials.gov/ct2/show/NCT03484806.

Keywords: aortic regurgitation; heart failure; intervention; left ventricular systolic dysfunction; mortality.

Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflictof interest.

Copyright © 2022 Zhao, Zhang, Ye, Li, Liu, Zhao, Zhao, Wang, Yu, Zhang, Duan, Wang, Lv, Guo, Zhao, Gao, Xu and Wu.

Figures

Figure 1

Association between baseline LVEF and relative hazard of 2-year death or HHF. Penalized spline curves demonstrate the shape of the association in overall (A), medically and AVI managed patients (B), with 95% confidence interval. The gray area underneath the curve indicates the density of the population. The horizontal line at HR = 1 represents the mean risk of the cohort. AVI, aortic valve intervention; HHF, hospitalization for heart failure; LVEF, left ventricular ejection fraction.

Figure 2

Kaplan-Meier curves of event-free survival under medical treatment according to the selected LVEF threshold. Kaplan-Meier curves of freedom from the composite of death or HHF (A), death (B), and HHF (C) under medical treatment were plotted according to the selected LVEF threshold (≤55 and >55%). AVI, aortic valve intervention; HHF, hospitalization for heart failure; LVEF, left ventricular ejection fraction.

Figure 3

Impact of AVI on the composite of death or HHF according to baseline LVEF. (A) The unadjusted relative risk of death or HHF after AVI vs. under medical treatment alone according to LVEF, with 95% confidence interval. The shaded area entirely below the horizontal line (HR = 1) denotes the upper bound of the 95% confidence interval is <1, indicating AVI is prognostically more favorable at this LVEF. (B) Kaplan-Meier curves of event-free survival after early AVI (within 6 months) and under medical treatment alone according to the LVEF ranges, with (solid line) and without (dashed line) inverse probability treatment weighting adjustment. AVI, aortic valve intervention; HHF, hospitalization for heart failure; LVEF, left ventricular ejection fraction.

Figure 4

Temporal course of symptom status in patients with moderate AR and LVSD (LVEF ≤55%) under different treatment strategies. The river plots show the changes in New York Heart Association (NYHA) functional classification for patients under medical treatment who at least survived and were followed up for 15 days and for patients undergoing early aortic valve intervention (AVI) within 6 months of the baseline echocardiography.