What is the clinical evidence from this study?

Study design: Cohort. Population: subvalvular aortic stenosis (SAS) (n=312). Intervention: Operative state at baseline and sex vs. Unoperated cohort and matched general population. Primary outcome: 15-year survival (95% CI 89.6-96.3).

What does this research mean for the field?

Female sex is associated with a higher risk of arrhythmic events in adult patients with subvalvular aortic stenosis. Novelty: ClaimNovelty.NOVEL_FINDING. Consensus alignment: ConsensusAlignment.NEUTRAL.

What question did this study set out to answer?

To explore the clinical outcomes and differences between males and females with subvalvular aortic stenosis in adults.

February 6, 2026

Subvalvular aortic stenosis in adults, focussing on male-female differences

Key Result

Prior operation for subvalvular aortic stenosis was associated with lower survival compared to unoperated patients (p=0.009), though overall 15-year survival was 92.9% (95% CI 89.6-96.3%).

Key Points

To explore the clinical outcomes and differences between males and females with subvalvular aortic stenosis in adults.
Analysed patients registered from 2001-2019 in the Dutch Congenital Cor Vitia registry.
Assessed survival rates and event-free survival over a follow-up period of 4,423 years.
Used Poisson regression to identify risk factors for cardiovascular events.
Evaluated longitudinal changes in echocardiographic peak velocity using linear mixed models.
Fifteen-year survival rate was 92.9%, indicating comparable survival to the general population.
Significantly lower survival in patients previously operated compared to unoperated patients.
Found increased risk of arrhythmic events associated with female sex and prior myectomy.
Cumulative incidence of aortic valve surgery due to aortic regurgitation was 7.6% at 15 years.

Study Design

Type

Cohort (n=312)

Multicenter

Yes

Structured PICO

What are the long-term clinical outcomes, event-free survival, and sex differences in adults with subvalvular aortic stenosis?

Population

312 adults with subvalvular aortic stenosis (SAS), median age 26.0 years, 44.2% female, prospectively registered in the Dutch Congenital Cor Vitia registry between 2001-2019.

Comparator

Age- and sex-matched general population (for survival); internal comparisons by sex and baseline operative state.

Outcome

Survival and event-free survival (composite endpoint of mortality, heart failure, arrhythmic events, pacemaker implantation, thrombo-embolic events, SAS-, AVS- and SVAS-related (re)intervention, treated aortic aneurysm, acute aortic dissection, endocarditis, and other cardiac surgery/intervention).composite

Adults with subvalvular aortic stenosis have survival comparable to the general population, though event rates remain considerable, particularly arrhythmic events in women and previously operated patients.

Abstract

Abstract Background/Purpose To investigate the clinical course and outcomes of adult patients with subvalvular aortic stenosis (SAS), with a focus on male-female differences. Methods All adults with SAS, prospectively registered in the Dutch Congenital Cor Vitia registry between 2001-2019, were included. Survival and event-free survival (composite endpoint of mortality, heart failure, arrhythmic events, pacemaker implantation, thrombo-embolic events, SAS-, AVS- and SVAS-related (re)intervention, treated aortic aneurysm, acute aortic dissection, endocarditis, and other cardiac surgery/intervention) were assessed. Survival was compared to the age- and sex-matched general population. Recurrent events were analysed with Poisson regression. Longitudinal changes in echocardiographic peak velocity were analysed using linear mixed models. Differences in operative state at baseline and sex were evaluated for baseline characteristics, treatment strategy, survival, recurrent events and SAS progression. Results In total, 312 patients were included (age:26.0(IQR:20.0,35.3)years, 44.2% female, 68.3% with previous SAS correction, 24.7% with ≥moderate aortic regurgitation (AR)), encompassing 4,423 follow-up years (median:16(IQR:10,20)). Unadjusted 15-year survival was 92.9%(95%CI:89.6%-96.3%) and event-free survival was 53.2%(95%CI:44.8%-63.3%). Survival was significantly lower in those already operated at baseline compared to the unoperated cohort(p=0.009), but did not differ between sexes(p=0.083). There were no significant differences in event-free-survival between operative state(p=0.49) or sex(p=0.84). 507 cardiovascular events occurred in 146 patients. Risk factors of arrhythmic events were: prior myectomy (incidence rate ratio (IRR):1.7(95%CI:1.1-2.9),p=0.032), female sex (IRR:1.8(95%CI:1.1-2.9),p=0.024) and peak velocity at inclusion ((IRR:1.3(95%CI:1.0-1.8), per 1 m/s increment,p=0.031). Prior SAS correction (IRR:4.5(95%CI:1.0-9.5),p=0.045) and moderate AR (IRR:5.2(95%CI:2.1-12.8),p0.001) were associated with heart failure. The cumulative incidence of aortic valve surgery due to AR at 15-years was 7.6% (95%CI:4.7%-11.0%). SAS intervention during follow-up occurred more often in the unoperated cohort(p=0.001). Peak velocity progression at first spline was 0.1m/s (p=0.357) and second spline 0.3m/s (p=0.032). No patient showed fast progression (0.3m/s per year). Conclusions Survival in adults with SAS was comparable to that of the matched general population. However, survival was lower in operated patients compared to unoperated patients, likely reflecting the more severe phenotype in this group, while no significant differences were observed between sexes. Despite this, event rates were considerable, particularly arrhythmic events in women and operated patients, as well as events related to AR surgery. No rapid progression of SAS was observed in adulthood, suggesting that less frequent echocardiographic follow-up may be sufficient in selected cohorts.Figure 1 Figure 2

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