Systematic review and meta-analysis of early aortic valve replacement versus conservative therapy in patients with asymptomatic aortic valve stenosis with preserved left ventricle systolic function

Abstract

Background: A quarter of patients with severe aortic stenosis (AS) were asymptomatic, and only a third of them survived at the end of 4 years. Only a select subset of these patients was recommended for aortic valve replacement (AVR) by the current American College of Cardiology/American Heart Association guidelines. We intended to study the effect of early AVR (eAVR) in this subset of asymptomatic patients with preserved left ventricle function.

Methods and results: We searched PubMed and Embase for randomised and observational studies comparing the effect of eAVR versus conservative therapy in patients with severe, asymptomatic AS and normal left ventricular function. The primary outcome was all-cause mortality. The secondary outcomes were composite major adverse cardiac events (MACE) (study defined), myocardial infarction (MI), stroke, cardiac death, sudden death, the development of symptoms, heart failure hospitalisations and major bleeding. We used GRADEPro to assess the certainty of the evidence. In the randomised controlled trial (RCT) only analysis, we found no significant difference in all-cause mortality between the early aortic intervention group versus the conservative arm (CA) (incidence rate ratio, IRR (CI): 0.5 (0.2 to 1.1), I²=31%, p=0.09). However, in the overall cohort, we found mortality benefit for eAVR over CA (IRR (CI): 0.4 (0.3 to 0.7), I²=84%, p<0.01). There were significantly lower MACE, cardiac death, sudden death, development of symptoms and heart failure hospitalisations in the eAVR group. We noticed no difference in MI, stroke and major bleeding.

Conclusion: We conclude that there is no reduction in all-cause mortality in the eAVR arm in patients with asymptomatic AS with preserved ejection fraction. However, eAVR reduces heart failure related hospitalisations and death or heart failure hospitalisations.

Prospero registration number: CRD42022306132.

Keywords: Aortic Valve Stenosis; Heart Valve Prosthesis Implantation; Outcome Assessment, Health Care; Transcatheter Aortic Valve Replacement.

Figure 1

The Preferred Reporting Items for Systematic Reviews and Meta-Analyses flowchart.

Figure 2

Comparison of early aortic valve replacement (eAVR) and conservative arm in asymptomatic patients with preserved left ventricle function. We found no reduction in all-cause mortality in the RCTs only analysis (GRADEPro high level evidence). However, when we assessed the overall cohort and the observational studies alone, eAVR reduced all-cause mortality (lower all-cause mortality with observational studies: GRADEPro very low-level evidence) separately. IRR, incidence rate ratio; PY, patient-years; RCT, randomised controlled trial; RE, random effects model.

Figure 3

Comparison of early aortic valve replacement (AVR) and conservative arm in asymptomatic patients with preserved left ventricle function on composite MACE, myocardial infarction, stroke and cardiac death. IRR incidence rate ratio; MACE, major adverse cardiac events; PY, patient-years; RCT, randomised controlled trial; RE, random effects model.

Figure 4

Comparison of early aortic valve replacement (AVR) and conservative arm in asymptomatic patients with preserved left ventricle function on sudden death, development of symptoms, heart failure hospitalisation and major bleeding. IRR, incidence rate ratio; PY, patient-years; RCT, randomised controlled trial; RE, random effects model.