Natural History of Asymptomatic Severe Aortic Stenosis and the Association of Early Intervention With Outcomes: A Systematic Review and Meta-Analysis.

Gahl, Brigitta; Çelik, Mevlüt; Head, Stuart J; Vanoverschelde, Jean-Louis; Pibarot, Philippe; Reardon, Michael J; van Mieghem, Nicolas M; Kappetein, A Pieter; Jüni, Peter; Da Costa, Bruno R (2020). Natural History of Asymptomatic Severe Aortic Stenosis and the Association of Early Intervention With Outcomes: A Systematic Review and Meta-Analysis. JAMA cardiology, 5(10), pp. 1102-1112. American Medical Association 10.1001/jamacardio.2020.2497

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Whether intervention should be performed in patients with asymptomatic severe aortic stenosis (AS) remains debated.


To meta-analyze the natural history of asymptomatic severe AS and examine the association of early intervention with survival.

Data Sources

PubMed, Embase, and Cochrane databases were searched from inception to February 1, 2020.

Study Selection

Observational studies of adult patients with asymptomatic severe AS.

Data Extraction and Synthesis

Two investigators independently extracted study and patient characteristics, follow-up time, events, and prognostic indicators of events. Random-effects models were used to derive pooled estimates.

Main Outcomes and Measures

The meta-analysis on natural history was performed on the primary end point of all-cause death occurring during a conservative treatment period, with secondary end points consisting of cardiac death, death due to heart failure, sudden death, development of symptoms, development of an indication for aortic valve intervention, and aortic valve intervention. The primary end point for the meta-analysis of early intervention vs a conservative strategy was all-cause death during long-term follow-up. Finally, meta-analysis was performed on the association of prognostic indicators with the composite of death or aortic valve intervention found in multivariable models.


A total of 29 studies with 4075 patients with 11 901 years of follow-up were included. Pooled rates per 100 patients per year were 4.8 (95% CI, 3.6-6.4) for all-cause death, 3.0 (95% CI, 2.2-4.1) for cardiac death, 2.0 (95% CI, 1.3-3.1) for death due to heart failure, 1.1 (95% CI, 0.6-2.1) for sudden death, 18.1 (95% CI, 12.8-25.4) for an indication for aortic valve intervention, 18.5 (95% CI, 13.4-25.5) for development of symptoms, and 19.2 (95% CI, 15.5-23.8) for aortic valve intervention. Early intervention was associated with a significant reduction in long-term mortality (hazard ratio, 0.38; 95% CI, 0.25-0.58). Factors associated with worse prognosis were severity of AS, low-flow AS, left ventricular damage, and atherosclerotic risk factors.

Conclusions and Relevance

Data from observational studies and a recent randomized clinical trial suggest that many patients with asymptomatic severe AS develop an indication for aortic valve intervention, and their deaths are mostly cardiac but not only sudden. Other end points besides sudden death should be considered during the decision to perform early intervention that are associated with improved survival.

Item Type:

Journal Article (Original Article)


04 Faculty of Medicine > Medical Education > Institute of General Practice and Primary Care (BIHAM)
04 Faculty of Medicine > Pre-clinic Human Medicine > Department of Clinical Research (DCR)

UniBE Contributor:

Gahl, Brigitta, Da Costa, Bruno


600 Technology > 610 Medicine & health
300 Social sciences, sociology & anthropology > 360 Social problems & social services




American Medical Association




Andrea Flükiger-Flückiger

Date Deposited:

22 Jul 2020 19:32

Last Modified:

20 Feb 2024 14:16

Publisher DOI:


PubMed ID:





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