O2050: Mitral Annular Disjunction is Associated with Clinical Outcomes in Pediatric Patients with Loeys-Dietz Syndrome

Background: Mitral annular disjunction (MAD) is an abnormal separation between the posterior mitral valve (MV) leaflet hinge point and the left ventricular (LV) wall. It has been associated with MV prolapse (MVP), MV regurgitation, increased risk of arrhythmia, and sudden cardiac death in adults. There is also an increased prevalence of MAD in adult patients with connective tissue disorders. However, the burden of MAD and its association with clinical outcomes in pediatric patients with Loeys-Dietz syndrome (LDS) has not been described. We aim to assess MAD prevalence in pediatric LDS and its associations with echocardiographic findings and outcomes.

Methods: We included patients with LDS, defined by a pathogenic change in TGFBR1, TGFBR2, SMAD2, SMAD3, TGFB2 or TGFB3, age ≤18 years who were evaluated at a large, tertiary care children’s hospital between 2012-2024 and included in the Collaborative for Longitudinal Aortic Research in the Young (CLARITY) registry. MAD was defined as MV-LV separation ≥2mm as determined by review of parasternal long axis images on initial echocardiogram (Figure 1). First, associations between MAD and initial echocardiogram findings (aortic root dilation: z score ≥2, LV dilation: LV end-diastolic volume z score ≥2, LV dysfunction: ejection fraction < 55%) were evaluated using logistic regression for categorical variables and Mann-Whitney U for continuous outcome variables. Subsequently, associations between MAD and the outcomes of arrhythmia and aortic events (dissection or surgical replacement of the thoracic aorta) were evaluated using logistic regression.

Results: Of 72 patients meeting inclusion criteria, 56.9% were male. MAD was detected in 38.9% patients, with age range at initial echocardiogram noted to have MAD from 1 day to 18.8 years and was commonly associated with MVP (in 28.6% of those with MAD versus 4.5% without, p=0.011). MAD was also associated with LV dilation (25.0% in MAD versus 2.3% without, p=0.047) and aortic root dilation (85.7% in MAD versus 56.8% without, p=0.014)(Figure 1), but not LV dysfunction. MAD was detected in a similar proportion in all age quartiles. Patients with SMAD3 (OR 8.00) and TGFBR2 (OR 3.76) mutations were more likely to have MAD when compared to TGFBR1, though only met significance criteria for SMAD3 (Table 1). MAD was more common in both those with arrhythmias (in 55.6% with arrhythmias versus 6.3% without) and aortic events (in 58.8% with event versus 12.7% without) but did not meet significance criteria for either (Table 1).

Conclusion: In conclusion, MAD exhibits a high prevalence in pediatric LDS patients, similarly in all age groups, and diagnosed as young as 1 day old. MAD was commonly seen with MVP, aortic root dilation, and LV dilation. Further studies are needed to evaluate how MAD predicts clinical outcomes in LDS.