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

Qinghao Zhao,Zhenyan Zhao,Zhenya Duan,Yanyan Zhao,Qingrong Liu,Bincheng Wang,Weiwei Wang,Haitong Zhang,Bin Zhang,Haiyan Xu,Zikai Yu,Shuai Guo,Rui Zhao,Runlin Gao,Junxing Lv,Yunqing Ye,Yongjian Wu,Zhe Li

doi:10.3389/fcvm.2021.800961

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.

Highlights

The prevalence of aortic regurgitation (AR), a common valvular heart disease (VHD), increases sharply with age [1]
Our key findings are as follows: [1] Reduced left ventricular ejection fraction (LVEF) is the most contributive independent predictor of death or hospitalization for heart failure (HHF) in patients with moderate AR; [2] LVEF ≤55% was the optimal threshold for predicting poor prognosis under medical treatment (MT), with excellent performance in risk stratification and substantial incremental value; [3] At an LVEF of 35–55%, early aortic valve intervention (AVI) within 6 months of diagnosis was
Associated with a reduced risk of death or HHF vs. MT alone, whereas this prognostic benefit was markedly attenuated when LVEF decreased to ≤35% or increased to >55%. These findings suggest that LVEF, as a routine echocardiographic measure of left ventricle (LV) systolic function, is crucial in risk stratification and provides potential implications for treatment decision-making in patients with moderate AR

Summary

Introduction

The prevalence of aortic regurgitation (AR), a common valvular heart disease (VHD), increases sharply with age [1]. Left ventricular systolic dysfunction (LVSD) is highly prevalent in older adults, affecting up to 11% of the community-dwelling elderly population [3]. Whether as a direct cause or a comorbid condition of LVSD, AR imposes a significant preload and afterload burden on the left ventricle (LV), thereby exacerbating systolic dysfunction [5]. In this case, the presence of moderate AR may not be as benign in patients with LVSD as in those with normal LV systolic function; relevant data are still lacking. 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)

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Discussion

Conclusion