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Mouse models of congenital aortic valve malformations are useful for studying disease pathobiology, but most models have incomplete penetrance [e.g., ∼2 to 77% prevalence of bicuspid aortic valves (BAVs) across multiple models]. For longitudinal studies of pathologies associated with BAVs and other congenital valve malformations, which manifest over months in mice, it is operationally inefficient, economically burdensome, and ethically challenging to enroll large numbers of mice in studies without first identifying those with valvular abnormalities. To address this need, we established and validated a novel in vivo high-frequency (30 MHz) ultrasound imaging protocol capable of detecting aortic valvular malformations in juvenile mice. Fifty natriuretic peptide receptor 2 heterozygous mice on a low-density lipoprotein receptor-deficient background (Npr2+/−;Ldlr−/−; 32 males and 18 females) were imaged at 4 and 8 wk of age. Fourteen percent of the Npr2+/−;Ldlr−/− mice exhibited features associated with aortic valve malformations, including 1) abnormal transaortic flow patterns on color Doppler (recirculation and regurgitation), 2) peak systolic flow velocities distal to the aortic valves reaching or surpassing ∼1,250 mm/s by pulsed-wave Doppler, and 3) putative fusion of cusps along commissures and abnormal movement elucidated by two-dimensional (2-D) imaging with ultrahigh temporal resolution. Valves with these features were confirmed by ex vivo gross anatomy and histological visualization to have thickened cusps, partial fusions, or Sievers type-0 bicuspid valves. This ultrasound imaging protocol will enable efficient, cost effective, and humane implementation of studies of congenital aortic valvular abnormalities and associated pathologies in a wide range of mouse models. NEW & NOTEWORTHY: We developed a high-frequency ultrasound imaging protocol for diagnosing congenital aortic valve structural abnormalities in 4-wk-old mice. Our protocol defines specific criteria to distinguish mice with abnormal aortic valves from those with normal tricuspid valves using color Doppler, pulsed-wave Doppler, and two-dimensional (2-D) imaging with ultrahigh temporal resolution. This approach enables early identification of valvular abnormalities for efficient and ethical experimental design of longitudinal studies of congenital valve diseases and associated pathologies in mice. [ABSTRACT FROM AUTHOR]

OBJECTIVES Left ventricular outflow tract obstruction (LVOTO) is a major cause of morbidity and mortality in infants with interrupted aortic arch (IAA). Left Ventricular Outflow Tract (LVOT) development may be flow-mediated, thus IAA morphology may influence LVOT diameter and subsequent reintervention. We investigated the association of IAA morphology [type and presence of aortic arch aberrancy (AAb)] with LVOT diameter and reintervention. METHODS All surgical patients with IAA (2001–2022) were reviewed at a single institution. We compared IAA-A versus IAA-B; IAA with aortic AAb versus none; IAA-B with aberrant subclavian (AAbS) artery versus others. Primary outcomes included LVOT diameter (mm), LVOTO at discharge (≥50 mmHg), and LVOT reintervention. RESULTS Seventy-seven infants (mean age 10 ± 19 days) were followed for 7.6 (5.5–9.7) years. Perioperative mortality was 3.9% (3/77) and long-term mortality was 5.2% (4/77). Out of 51 IAA-B (66%) and 22 IAA-A (31%) patients, 30% (n  = 22) had AAb. Smaller LVOT diameter was associated with IAA-B [IAA-A: 5.40 (4.68–5.80), IAA-B: 4.60 (3.92–5.50), P  = 0.007], AAb [AAb: 4.00 (3.70–5.04) versus none: 5.15 (4.30–5.68), P  = 0.006], and combined IAA-B + AAbS [IAA-B + AAbS: 4.00 (3.70–5.02) versus other: 5.00 (4.30–5.68), P  = 0.002]. The likelihood of LVOTO was higher among AAb [ N  = 6 (25%) vs N  = 1 (2%), P  = 0.004] and IAA-B + AAbS [ N  = 1 (2%) vs N  = 6 (30%), P  = 0.002]. Time-to-event analysis showed a signal towards increased LVOT reintervention in IAA-B + AAbS (P  = 0.11). CONCLUSIONS IAA-B and AAb are associated with small LVOT diameter and early LVOTO, especially in combination. This may reflect lower flow in the proximal arch during development. Most reinterventions occur in IAA-B + AAbS, hence these patients should be carefully considered for LVOT intervention at the time of initial repair. [ABSTRACT FROM AUTHOR]