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

Clinical Snapshot

Key Findings

• P Value: Not specified in abstract

• Effect Size: Early AVR associated with 67% mortality reduction (HR 0.33)

• Primary Outcome: All-cause mortality rate 1.75 per 100 person-years (95% CI 1.27-2.41)

• Nnt Or Sensitivity: Excess mortality >2-fold higher than general population in patients ≥50 years

• Confidence Interval: 95% CI 0.30-0.37 for AVR mortality benefit

Clinical Application

Findings support earlier intervention strategies, requiring multidisciplinary heart team approach available in Australian tertiary centres Relevant to CSANZ guidelines and PBS-funded cardiac surgery programs; supports earlier referral to cardiothoracic surgery in appropriate candidates Australian adults with asymptomatic moderate-severe AR under cardiology care

Abstract

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.

References

1. 1.Naser, J. A., Massad, F., Al-Abcha, A., Gerberi, D., Pislaru, S. V., Nkomo, V. T., Thaden, J. J., Wang, Z., Cavalcante, J. L., Pellikka, P. A., Michelena, H. I., & Enriquez-Sarano, M. (2026). Natural history of asymptomatic moderate or severe aortic regurgitation: a systematic review and meta-analysis. Heart. https://doi.org/10.1136/heartjnl-2025-326643