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Introduction:Cardiovascular disease is the leading cause of morbidity and premature mortality in Marfan Syndrome (MFS), with ≥ 50% of patients developing a secondary, dilated cardiomyopathy from chronic valvular regurgitation. Apart from significant valvular disease, patients with MFS have evidence of systolic dysfunction, suggestive of a primary cardiomyopathy. However, prior cross-sectional studies have been limited by small sample sizes and short durations of follow-up. Our aim was therefore to determine the true prevalence and long-term outcomes of a primary cardiomyopathy in MFS.Methods:We performed a retrospective chart review of all adult patients with a confirmed diagnosis of MFS followed at Stanford Health Care. Those with significant valvular dysfunction (≥moderate aortic or mitral regurgitation), coronary artery disease, or prior cardiac surgery were excluded. Myocardial dysfunction (MD) was defined as a left ventricular ejection fraction (EF) <55%, as assessed by echocardiography or on cardiac MRI. Genetic, sociodemographic, and potential cardiac risk modifiers were also recorded.Results:A total of 753 patients with confirmed MFS were identified and followed over a median of 8 years (IQR 4, 13). Of the initial cohort, 241 patients (47% male, 71% Caucasian) met inclusion criteria and defined the at-risk population. MD was present in 30 patients (12.4%), with a median age of onset at 32 years (IQR 24.5, 44.8), median EF of 50.9% (IQR 48.0, 53.8), and evidence of clinical heart failure (NYHA Class ≥2) in 10% of patients. There was no significant association with the majority of queried sociodemographic and traditional cardiovascular risk variables. MD was more commonly observed in patients with larger aortic root diameters (aortic root ≥ 4.0 cm: AOR=4.2, 95% CI=1.2-15.0, p=0.03); however, corresponding use of goal-directed medical heart failure therapies did not appear to be protective against the development of MD (p=0.5).Conclusions:Even in the absence of significant valvular pathology, MD is prevalent in MFS from a young age, indicative of a primary cardiomyopathy. While dysfunction is often subclinical and mild in nature, it can progress across the lifespan and appears to be refractory to standard medical heart failure therapies.

Introduction:Reintervention rate after percutaneous balloon valvuloplasty (BV) for critical congenital pulmonary valve stenosis (PS) is unknown.Hypothesis:Repeat BV or surgical intervention within 1 year of BV for critical PS is uncommon.Methods:The Pediatric Health Information Systems database was queried for patients admitted at ?3 days of age from 2004-2018 with a principal diagnosis of PS who received prostaglandin and underwent primary BV. Study data included demographic variables, resource utilization (e.g. length of stay, ECMO use, etc), and reintervention during either the index hospitalization or a subsequent readmission to the index hospital within 1 year. Freedom from reintervention or death was assessed with Kaplan-Meier analysis, and risk factors were examined with multivariate analysis.Results:Balloon valvuloplasty was the principal procedure for critical PS in 1014 patients (53% male) from 49 hospitals (Table). Reintervention occurred in 4.6% (47/1014) during the index hospitalization (32 BV and 15 operative). On readmission, 44 patients (4.3%) underwent reintervention at a median of 81 (IQR: 54,144) days after initial BV. Among patients with reintervention during the index hospitalization, 17% (8/47) also underwent reintervention during a readmission. In-hospital mortality was 1.3% during the study. Freedom from death or reintervention was 91% at 1-year. Male sex was the only risk factor predictive of reintervention (OR: 2.1; 95% CI: 1.2-3.5; p=0.009).Conclusions:Reintervention for critical PS was not uncommon at 1-year in this large, retrospective multicenter study. Male sex is associated with increased rate of reintervention.

Introduction:Aortic dilation and dissection are life-threatening traits in Marfan syndrome (MFS). Clinical emphasis is often on what exercises to avoid to minimize risk of aortic dissection, rather than promoting regular exercise. Furthermore, MFS patients often lead sedentary lives due to self-imposed limitations. We have shown in an MFS mouse model that mild aerobic exercise can improve aortic wall characteristics and reduce stiffness leading to slower rates of aortic dilation.Hypothesis:We hypothesized that regular mild aerobic exercise can decrease aortic stiffness in pediatric MFS patients.Methods:We enrolled MFS patients aged 8-19 years old followed in our center to participate in a 6-month exercise intervention, excluding those with ventricular dysfunction or prior history of aortic surgery. We instructed patients to take 10,000 steps a day, tracked by an activity tracker. We checked in with patients weekly via phone call or text-messaging. At baseline and 6 months, aortic dimensions, arterial stiffness, endothelial function, and physical activity indices were obtained. Time spent in sedentary or vigorous activity was measured by accelerometry.Results:Nineteen patients (14.5?3.3 years old, 11 males) have been enrolled. Table 1 summarizes baseline data and initial results. Nine patients completed the intervention and 10 are currently participating. Three out of the 9 patients took at least 10,000 steps/day during the intervention. The other 6 patients increased their daily steps by 10% from 1stto 6thmonth. In these 9 patients, we observed a decrease in mean aortic root z-score by 9% and mean aortic stiffness indices by 30%.Conclusions:Our pilot baseline data confirm the rationale for the intervention showing that pediatric MFS patients have stiff aortas and lead sedentary lives. Our preliminary results are promising and support that this lifestyle intervention has great potential to improve arterial health in this vulnerable patient population.

Introduction:The cardiac-valvular and vascular subtypes of Ehlers-Danlos Syndrome (EDS) have significant cardiovascular issues, specifically aortic or mitral valve dysfunction, and arterial dilation and dissection. The prevalence and significance of such abnormalities in patients with classical (cEDS) or hypermobile EDS (hEDS) remain unclear. In the absence of guidelines, many experts recommend screening and surveillance echocardiograms for all patients with EDS, regardless of subtype. Here we report the prevalence of structural or functional cardiac abnormalities in a large cohort of cEDS and hEDS patients.Hypothesis:Clinically meaningful cardiac abnormalities in patients with cEDS and hEDS are uncommon.Methods:Retrospective chart review identified 532 pediatric patients with potential EDS evaluated at our institution from January 2014 through April 2019. Of those with confirmed hEDS and cEDS, echocardiograms were obtained in 99 hEDS and 14 cEDS patients. We reviewed echocardiograms for aortic dilation, aortic or mitral valve abnormalities, and other structural heart disease.Results:Of the 113 patients reviewed, 102 (90.3%) had normal echocardiograms. Two patients had a dilated aortic root at the sinuses of Valsalva (Z-scores of 2.19 and 2.49), and one patient had ascending aorta dilation (Z-score 2.43). The aortic annulus Z-scores were all within normal limits. Two patients had mild mitral valve abnormalities (thickening and redundancy). Three patients had borderline or mild mitral valve prolapse without regurgitation. Three patients had congenital heart disease unlikely to be related to EDS and required intervention. In total, 8 patients (7.1%) had echocardiographic findings likely attributable to EDS, all of which were mild and did not require intervention.Conclusions:Clinically significant cardiovascular involvement in patients with cEDS or hEDS is uncommon. When present, valvular anomalies or aortic dilation were mild and did not require intervention. Echocardiographic evaluation and surveillance in patients with cEDS and hEDS is unnecessary in the absence of clinical findings or positive family history.