Mitral annular disjunction distance is associated with adverse outcomes in children and young adults with connective tissue disorders.

Abstract

Introduction: Mitral annular disjunction (MAD) is a pathologic fibrous separation of the mitral valve hinge point from the ventricular myocardium. The aims of this study were to describe the range of MAD distance by cardiac magnetic resonance (CMR) in children and young adults with connective tissue disorders (CTDs) versus a healthy control sample, and to assess the MAD distance as a predictor of adverse cardiovascular outcomes.

Methods: This was a retrospective, single-center study of healthy subjects and patients with Marfan syndrome, Loeys-Dietz syndrome, Ehlers-Danlos syndrome, or nonspecific CTD who underwent CMR between 01/01/2000 and 01/01/2020. The MAD distance was measured from the 2-chamber, 4-chamber, and left ventricular outflow tract views in systole and diastole and analyzed as absolute values as well as indexed to BSA and height. The primary outcome was a composite defined as the presence of significant ventricular arrhythmias, cardiac arrest, and/or death. Age-adjusted odds ratios with 95% confidence intervals and c-statistic are reported. Classification and Regression Tree analysis was performed to identify the most discriminating binary threshold to predict occurrence of the composite outcome.

Results: 30 healthy control subjects and 254 patients with CTD met inclusion criteria. The mean ± SD age at initial CMR was 17±6 years for patients with CTD and 14±3 years for controls. The mean MAD distance was larger in patients with CTD compared to the control sample, and the maximum MAD distance in the control sample was 3.6mm. Median follow-up in the CTD group was 5 years (IQR 3-11 years). Thirty-four (15%) patients met the composite outcome. Systolic MAD distance was positively associated with the composite outcome. The optimal binary threshold for height-indexed maximum systolic MAD distance was 0.033mm/cm with an event rate of 18.6% at/above threshold versus 2.6% below threshold (AUC 0.74). The association was independent of other important clinical predictors.

Conclusions: A small MAD distance can be measured in healthy children and young adults. Children and young adults with CTD have a longer MAD distance than healthy control subjects, and a longer MAD distance is associated with adverse outcomes.