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Sex Differences and Survival in Adults With Bicuspid Aortic Valves: Verification in 3 Contemporary Echocardiographic Cohorts

View Article: PubMed Central - PubMed

ABSTRACT

Background: Sex‐related differences in morbidity and survival in bicuspid aortic valve (BAV) adults are fundamentally unknown. Contemporary studies portend excellent survival for BAV patients identified at early echocardiographic‐clinical stages. Whether BAV adults incur a survival disadvantage throughout subsequent echocardiographic‐clinical stages remains undetermined.

Methods and results: Analysis was done of 3 different cohorts of consecutive patients with echocardiographic diagnosis of BAV identified retrospectively: (1) a community cohort of 416 patients with first BAV diagnosis (age 35±21 years, follow‐up 16±7 years), (2) a tertiary clinical referral cohort of 2824 BAV adults (age 51±16 years, follow‐up 9±6 years), and (3) a surgical referral cohort of 2242 BAV adults referred for aortic valve replacement (AVR) (age 62±14 years, follow‐up 6±5 years). For the community cohort, 20‐year risks of aortic regurgitation (AR), AVR, and infective endocarditis were higher in men (all P≤0.04); for a total BAV‐related morbidity risk of 52±4% vs 35±6% in women (P=0.01). The cohort's 25‐year survival was identical to that in the general population (P=0.98). AR independently predicted mortality in women (P=0.001). Baseline AR was more common in men (P≤0.02) in the tertiary cohort, with 20‐year survival lower than that in the general population (P<0.0001); age‐adjusted relative death risk was 1.16 (95% confidence interval [CI] 1.05‐1.29) for men versus 1.67 (95% CI 1.38‐2.03) for women (P=0.001). AR independently predicted mortality in women (P=0.01). Baseline AR and infective endocarditis were higher in men (both ≤0.001) for the surgical referral cohort, with 15‐year survival lower than that in the general population (P<0.0001); age‐adjusted relative death risk was 1.34 (95% CI 1.22‐1.47) for men versus 1.63 (95% CI 1.40‐1.89) for women (P=0.026). AR and NYHA class independently predicted mortality in women (both P≤0.04).

Conclusions: Within evolving echocardiographic‐clinical stages, the long‐term survival of adults with BAV is not benign, as both men and women incur excess mortality. Although BAV‐related morbidity is higher in men in the community, and AR and infective endocarditis are more prevalent in men, women exhibit a significantly higher relative risk of death in tertiary and surgical referral cohorts, which is independently associated with AR.

No MeSH data available.


Surgical referral cohort overall and sex‐specific survival compared to the general population. A, Kaplan‐Meier 15‐year rate of survival after presurgical echocardiogram in the overall cohort vs general population expected rate. B, Kaplan‐Meier 15‐year rate of survival after presurgical echocardiogram, direct comparison by sex. C, Kaplan‐Meier 15‐year rate of survival after presurgical echocardiogram in men. D, Kaplan‐Meier 15‐year rate of survival after presurgical echocardiogram in women.
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jah31788-fig-0004: Surgical referral cohort overall and sex‐specific survival compared to the general population. A, Kaplan‐Meier 15‐year rate of survival after presurgical echocardiogram in the overall cohort vs general population expected rate. B, Kaplan‐Meier 15‐year rate of survival after presurgical echocardiogram, direct comparison by sex. C, Kaplan‐Meier 15‐year rate of survival after presurgical echocardiogram in men. D, Kaplan‐Meier 15‐year rate of survival after presurgical echocardiogram in women.

Mentions: There were 637 deaths (28%) after 6±5 years of follow‐up. The entire cohort's 15‐year survival was 38±2% versus that in an age‐ and sex‐matched sample of the US population (38% vs 61%, P<0.0001, Figure 4A). The 15‐year survival rates were 34±4% and 39±2% for women and men, respectively (P=0.15, Figure 4B). Congruent with the tertiary clinical referral cohort, the 15‐year survival of men was significantly lower than that in the general male population (39% vs 60%, relative death risk 1.34 [95% CI 1.22‐1.47], P<0.0001, Figure 4C) and a more pronounced 15‐year decreased survival was observed for women compared to the general female population (34% vs 64%, relative death risk 1.63; 95% CI 1.40‐1.89; P<0.0001, Figure 4D). The difference in relative risk of death between sexes was 1.22 (95% CI 1.02‐1.45, P=0.026). We performed multivariate analysis of baseline predictor variables including age ≥60 years, Charlson comorbidity index, BMI ≥30, ejection fraction ≥50%, severe AS, AR4+, NYHA class 3 to 4, aortic diameter, baseline IE, and known aortic coarctation (Table 7). Independent predictors of mortality were age ≥60 years and Charlson comorbidity index for both sexes; ejection fraction ≥50% and NYHA class 3 to 4 for men only. Aortic regurgitation 4+ was associated with better survival in men and independently associated with mortality in women (Table 7). When ESD/BSA was included in the multivariate analysis for the surgical cohort, AR4+ became statistically insignificant (P=0.71), and ESD/BSA became an independent predictor (HR 1.23; 95% CI 1.1‐1.39; P=0.0004, per unit change) for women only. Independent predictors remained unchanged for men. Standardized mortality analysis showed similar independent predictor variables for men, but for women only NYHA class 3 to 4 independently predicted death (2.17; 95% CI 1.44‐3.27; P=0.0002). A cutoff of 10 cm2/m for the ratio of aortic diameter cross‐sectional area by height was statistically insignificant in univariate and multivariable analyses as a mortality predictor.


Sex Differences and Survival in Adults With Bicuspid Aortic Valves: Verification in 3 Contemporary Echocardiographic Cohorts
Surgical referral cohort overall and sex‐specific survival compared to the general population. A, Kaplan‐Meier 15‐year rate of survival after presurgical echocardiogram in the overall cohort vs general population expected rate. B, Kaplan‐Meier 15‐year rate of survival after presurgical echocardiogram, direct comparison by sex. C, Kaplan‐Meier 15‐year rate of survival after presurgical echocardiogram in men. D, Kaplan‐Meier 15‐year rate of survival after presurgical echocardiogram in women.
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Related In: Results  -  Collection

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getmorefigures.php?uid=PMC5121517&req=5

jah31788-fig-0004: Surgical referral cohort overall and sex‐specific survival compared to the general population. A, Kaplan‐Meier 15‐year rate of survival after presurgical echocardiogram in the overall cohort vs general population expected rate. B, Kaplan‐Meier 15‐year rate of survival after presurgical echocardiogram, direct comparison by sex. C, Kaplan‐Meier 15‐year rate of survival after presurgical echocardiogram in men. D, Kaplan‐Meier 15‐year rate of survival after presurgical echocardiogram in women.
Mentions: There were 637 deaths (28%) after 6±5 years of follow‐up. The entire cohort's 15‐year survival was 38±2% versus that in an age‐ and sex‐matched sample of the US population (38% vs 61%, P<0.0001, Figure 4A). The 15‐year survival rates were 34±4% and 39±2% for women and men, respectively (P=0.15, Figure 4B). Congruent with the tertiary clinical referral cohort, the 15‐year survival of men was significantly lower than that in the general male population (39% vs 60%, relative death risk 1.34 [95% CI 1.22‐1.47], P<0.0001, Figure 4C) and a more pronounced 15‐year decreased survival was observed for women compared to the general female population (34% vs 64%, relative death risk 1.63; 95% CI 1.40‐1.89; P<0.0001, Figure 4D). The difference in relative risk of death between sexes was 1.22 (95% CI 1.02‐1.45, P=0.026). We performed multivariate analysis of baseline predictor variables including age ≥60 years, Charlson comorbidity index, BMI ≥30, ejection fraction ≥50%, severe AS, AR4+, NYHA class 3 to 4, aortic diameter, baseline IE, and known aortic coarctation (Table 7). Independent predictors of mortality were age ≥60 years and Charlson comorbidity index for both sexes; ejection fraction ≥50% and NYHA class 3 to 4 for men only. Aortic regurgitation 4+ was associated with better survival in men and independently associated with mortality in women (Table 7). When ESD/BSA was included in the multivariate analysis for the surgical cohort, AR4+ became statistically insignificant (P=0.71), and ESD/BSA became an independent predictor (HR 1.23; 95% CI 1.1‐1.39; P=0.0004, per unit change) for women only. Independent predictors remained unchanged for men. Standardized mortality analysis showed similar independent predictor variables for men, but for women only NYHA class 3 to 4 independently predicted death (2.17; 95% CI 1.44‐3.27; P=0.0002). A cutoff of 10 cm2/m for the ratio of aortic diameter cross‐sectional area by height was statistically insignificant in univariate and multivariable analyses as a mortality predictor.

View Article: PubMed Central - PubMed

ABSTRACT

Background: Sex&#8208;related differences in morbidity and survival in bicuspid aortic valve (BAV) adults are fundamentally unknown. Contemporary studies portend excellent survival for BAV patients identified at early echocardiographic&#8208;clinical stages. Whether BAV adults incur a survival disadvantage throughout subsequent echocardiographic&#8208;clinical stages remains undetermined.

Methods and results: Analysis was done of 3 different cohorts of consecutive patients with echocardiographic diagnosis of BAV identified retrospectively: (1) a community cohort of 416 patients with first BAV diagnosis (age 35&plusmn;21&nbsp;years, follow&#8208;up 16&plusmn;7&nbsp;years), (2) a tertiary clinical referral cohort of 2824 BAV adults (age 51&plusmn;16&nbsp;years, follow&#8208;up 9&plusmn;6&nbsp;years), and (3) a surgical referral cohort of 2242 BAV adults referred for aortic valve replacement (AVR) (age 62&plusmn;14&nbsp;years, follow&#8208;up 6&plusmn;5&nbsp;years). For the community cohort, 20&#8208;year risks of aortic regurgitation (AR), AVR, and infective endocarditis were higher in men (all P&le;0.04); for a total BAV&#8208;related morbidity risk of 52&plusmn;4% vs 35&plusmn;6% in women (P=0.01). The cohort's 25&#8208;year survival was identical to that in the general population (P=0.98). AR independently predicted mortality in women (P=0.001). Baseline AR was more common in men (P&le;0.02) in the tertiary cohort, with 20&#8208;year survival lower than that in the general population (P&lt;0.0001); age&#8208;adjusted relative death risk was 1.16 (95% confidence interval [CI] 1.05&#8208;1.29) for men versus 1.67 (95% CI 1.38&#8208;2.03) for women (P=0.001). AR independently predicted mortality in women (P=0.01). Baseline AR and infective endocarditis were higher in men (both &le;0.001) for the surgical referral cohort, with 15&#8208;year survival lower than that in the general population (P&lt;0.0001); age&#8208;adjusted relative death risk was 1.34 (95% CI 1.22&#8208;1.47) for men versus 1.63 (95% CI 1.40&#8208;1.89) for women (P=0.026). AR and NYHA class independently predicted mortality in women (both P&le;0.04).

Conclusions: Within evolving echocardiographic&#8208;clinical stages, the long&#8208;term survival of adults with BAV is not benign, as both men and women incur excess mortality. Although BAV&#8208;related morbidity is higher in men in the community, and AR and infective endocarditis are more prevalent in men, women exhibit a significantly higher relative risk of death in tertiary and surgical referral cohorts, which is independently associated with AR.

No MeSH data available.