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Background: We sought to identify predictive factors for aortic valve (AoV) surgery after neonatal balloon aortic valvuloplasty (BAV) and characterize clinical outcomes of AoV surgery after neonatal BAV., Methods: Time-to-event analysis identified predictors for AoV surgery after neonatal BAV. Clinical outcomes of AoV surgery following neonatal BAV were examined., Results: This study included 96 consecutive patients who underwent neonatal BAV for congenital aortic stenosis between 1998 and 2018, in 26 of whom a fetal BAV had been performed. Fifty-six patients underwent AoV surgery at a median age of 2.0 years. Significant risk factors for AoV surgery in univariate Cox regression (result presented as hazard ratio [HR], [95% CI]; P value) were a history of fetal BAV (HR, 4.05 [95% CI, 2.19–7.40]; P<0.001), AoV annulus diameter Z score (HR, 0.56 [95% CI, 0.43–0.75]; P=0.001), the presence of endocardial fibroelastosis (HR, 2.61 [95% CI, 1.48–4.51]; P=0.001), severe left ventricular dysfunction before neonatal BAV (HR, 1.75 [95% CI, 1.03–2.97]; P=0.04), and recent era (HR, 3.08 [95% CI, 1.68–5.91]; P=0.0002) in the entire cohort. Area under the receiver operating characteristic curve and Youden J index analysis identified a cutoff value for AoV annulus diameter Z score of −2.6 in patients without fetal BAV. In 24 patients with midterm cardiac catheterization data, univariate linear regression analysis (result presented as B coefficient [95% CI]; P) showed that the presence of greater-than-moderate aortic regurgitation immediately after BAV (B coefficient, 4.8 [95% CI, 1.0–8.6]; P=0.018) and before AoV surgery (B coefficient, 6.1 [95% CI, 2.2–10.0]; P=0.004) were significant risk factors for elevated left ventricular end-diastolic pressure after AoV surgery, while concomitant endocardial fibroelastosis resection at AoV surgery had a protective effect (B coefficient, −3.8 [95% CI, −7.6 to −0.06]; P=0.05)., Conclusions: A small AoV annulus diameter Z score with a cutoff value of −2.6 and a history of fetal BAV were significantly associated with AoV surgery after neonatal BAV. Concomitant endocardial fibroelastosis resection is recommended at AoV surgery following neonatal BAV to improve left ventricular diastolic function.

Rationale: Short telomere length (TL) in leukocytes is associated with atherosclerotic cardiovascular disease (ASCVD). It is unknown whether this relationship stems from having inherently short leukocyte TL (LTL) at birth or a faster LTL attrition thereafter. LTL represents TL in the highly proliferative hematopoietic system, whereas TL in skeletal muscle represents a minimally replicative tissue., Objective: We measured LTL and muscle TL (MTL) in the same individuals with a view to obtain comparative metrics for lifelong LTL attrition and learn about the temporal association of LTL with ASCVD., Methods and Results: Our Discovery Cohort comprised 259 individuals aged 63±14 years (mean±SD), undergoing surgery with (n=131) or without (n=128) clinical manifestation of ASCVD. In all subjects, MTL adjusted for muscle biopsy site (MTL A ) was longer than LTL and the LTL-MTL A gap similarly widened with age in ASCVD patients and controls. Age- and sex-adjusted LTL ( P =0.005), but not MTL A ( P =0.90), was shorter in patients with ASCVD than controls. The TL gap between leukocytes and muscle (LTL-MTL A ) was wider ( P =0.0003), and the TL ratio between leukocytes and muscle (LTL/MTL A ) was smaller ( P =0.0001) in ASCVD than in controls. Findings were replicated in a cohort comprising 143 individuals., Conclusions: This first study to apply the blood-and-muscle TL model shows more pronounced LTL attrition in ASCVD patients than controls. The difference in LTL attrition was not associated with age during adulthood suggesting that increased attrition in early life is more likely to be a major explanation of the shorter LTL in ASCVD patients., Clinical Trial Registration: URL: http://www.clinicaltrials.gov. Unique identifier: NCT02176941., (© 2017 The Authors.)