P2.C041: Outcomes of Pediatric Patients with Marfan Syndrome without Aortic Root Dilation on First Echocardiogram

Background: Marfan syndrome (MFS), due to FBN1 variants, predisposes individuals to aortic root (AR) dilation and aortic dissection. Predictors of progressive dilation include larger AR dimensions and z-scores at initial evaluation. Studies, however, show ~20-30% have normal AR sizes. The decision to medically treat these individuals has been controversial. We aimed to evaluate children without AR dilation on first echocardiogram and describe their outcomes.

Methods: Patients identified with classical MFS meeting revised Ghent criteria from the Collaborative for Longitudinal Aortic Research in the Young (CLARITY) multi-institutional registry with AR z-score < 2.0 aged 0-18 years at first echocardiogram were included. Those ≥2 years old with body mass index (BMI) ≥95th percentile for sex and age at first echocardiogram were excluded given inaccuracy in utilizing z-scores in this population. Demographics, FBN1 testing, medical history, cardiac imaging data, medication use, surgical interventions, and mortality data were collected. AR dilation was defined as z-score ≥2.0. Longitudinal changes over time were analyzed with univariable mixed-effects linear regression and cardiac outcomes were reported.

Results: Of 236 subjects in CLARITY with MFS with an initial echocardiogram between 0-18 years and AR data documented, 70 (29.7%) had AR z-score < 2.0 at first echocardiogram. Of these, 10 were excluded for BMI ≥95th percentile, for a final cohort of 60. Median age at first echocardiogram was 6.9 years, while median age at diagnosis was older at 9.7 years (Table 1). Median AR z-score at first echocardiogram was +1.4 (IQR +0.9, +1.6), and 74% received medication at some point to slow AR growth. Forty-four had follow-up echocardiographic data, with median follow-up duration of 6.7 years. Mean AR dimension annual change was +0.091 ± 0.003 cm/year (compared to 0 slope p< 0.001). There was mild increase in AR z-score with mean change +0.020 ± 0.008 z-score/year (compared to 0 slope p=0.008). At most recent echocardiogram, median AR size and z-score were 3.1 cm (IQR 2.5, 3.5) and +1.5 (IQR +0.8, +2.1), respectively. The change was similar when limiting to those with AR z-score < 1.0 at first echocardiogram (n=13, slope = +0.053 ± 0.024 cm/year, p=0.029). At most recent follow-up, 31.8% had AR dilation, while 45.5% had AR dilation at some point. Two patients underwent surgical AR replacement, with maximum AR dimensions at 5.0 cm (22.9 years) and 5.7 cm (21.2 years) on magnetic resonance imaging (MRI). Both patients had asymmetric and larger AR dimensions on MRI when compared to echocardiograms.

Conclusion: In conclusion, there is mild AR progression in pediatric MFS who have no dilation at first echocardiogram, with ~46% developing dilation at some point. Importantly, 74% were treated with medications at a given time. These findings may guide clinicians in monitoring and providing medical therapy to this population.