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Evidence-Based Supplement Research
Evidence-Based Supplement Research

Natural history of asymptomatic moderate or severe aortic regurgitation: a systematic review and meta-analysis.

  • 2025-11-17
  • Heart (British Cardiac Society) 112(12)
    • Jwan A Naser
    • Faysal Massad
    • Abdullah Al-Abcha
    • Dana Gerberi
    • Sorin V Pislaru
    • Vuyisile T Nkomo
    • Jeremy J Thaden
    • Zhen Wang
    • Joao L Cavalcante
    • Patricia A Pellikka
    • Hector I Michelena
    • Maurice Enriquez-Sarano

Study Design

Type
Meta-Analysis
Sample size
n = 4,720
Population
asymptomatic moderate or severe aortic regurgitation (4720 patients; mean age 49 years)
Methods
Systematic searches (inception-July 2025) identified cohort studies; random-effects models estimated pooled incidence rates; fixed-effects models for hazard ratios of AVR vs conservative management
Duration
mean follow-up 3.9 years

Background

The natural history of asymptomatic moderate or severe aortic regurgitation (AR) remains uncertain, with conflicting reports about its progression and surgical timing. We aimed to quantify adverse outcomes under conservative management and evaluate the association of aortic valve replacement/repair (AVR) with mortality.

Methods

Systematic searches (inception-July 2025) identified cohort studies of asymptomatic moderate/severe AR. Random-effects models estimated pooled incidence rates of adverse events; fixed-effects models were used for hazard ratios (HRs) of AVR vs conservative management.

Results

Twenty-seven studies (4720 patients; mean age 49 years; mean follow-up 3.9 years) were included. Pooled incidence rates per 100 person-years were 1.75 (95% CI 1.27 to 2.41) for all-cause mortality, 1.29 for cardiac death, 0.29 for sudden death, 4.30 for new symptoms and 7.01 for AVR. Asymptomatic low left ventricular ejection fraction occurred in only 0.9 per 100 person-years. Mortality rates were more than double those of the general population across age groups-2.45 (1.90 to 3.18) per 100 person-years for cohorts with mean age ≥50 years versus 0.59 (0.29 to 1.21) for younger cohorts. Early AVR was associated with lower mortality (pooled HR 0.33; 95% CI 0.30 to 0.37).

Conclusion

Asymptomatic moderate/severe AR carries significant excess mortality irrespective of age, contradicting its historically benign reputation. Given the rarity of asymptomatic LV dysfunction, earlier intervention guided by more sensitive markers of LV damage may improve outcomes, although heterogeneity and study quality warrant cautious interpretation.

Prospero registration number

CRD42024522683.

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