Association of Mitral Annular Disjunction With Cardiovascular Outcomes Among Patients With Marfan Syndrome

Abstract

IMPORTANCE Mitral annular disjunction (MAD) has received particular interest in patients with mitral valve prolapse, ventricular tachycardia, and sudden cardiac death. The clinical significance of MAD for patients with Marfan syndrome (MFS) remains largely unexplored. OBJECTIVE To define the prevalence of MAD and examine its association with cardiovascular outcomes and arrhythmia among patients with MFS. DESIGN, SETTING, AND PARTICIPANTS This retrospective, single-center cohort study included 142 patients with a diagnosis of MFS based on the revised Ghent criteria and a confirmed (likely) pathogenic variant in the FBN1 gene who underwent regular follow-up between January 1, 2004, and December 31, 2019. MAIN OUTCOMES AND MEASURES The presence of MAD was assessed by echocardiography, and the extent of MAD was categorized in tertiles. Patients also underwent resting electrocardiography and 24-hour Holter monitoring. Outcomes included aortic events (aortic dissection or prophylactic aortic surgery), arrhythmic events (defined as sustained ventricular tachycardia or sudden cardiac death), and mitral valve surgery. RESULTS A total of 142 patients (72 female patients [51%]; median age at first examination, 25 years [range, 2-64 years]) were evaluated. Forty-eight patients (34%) had MAD. Patients with MAD had larger aortic root z scores than patients without MAD (4.1 [interquartile range, 2.8-5.7] vs 3.0 [interquartile range, 1.8-4.0]; P < .001) and more often had mitral valve prolapse (34 of 48 [71%] vs 14 of 94 [15%]; P < .001), ventricular ectopy (14 of 33 [42%] vs 15 of 70 [21%]; P = .03), and nonsustained ventricular tachycardia (13 of 33 [39%] vs 12 of 70 [17%]; P = .01). During follow-up, aortic events occurred at similar rates among patients with vs without MAD (15 of 43 [35%] vs 21 of 84 [25%]; P = .24), but patients in the upper MAD tertile (>10 mm) showed a higher occurrence of aortic events compared with patients with MAD of 10 mm or smaller (9 of 15 [60%] vs 6 of 28 [21%]; P = .01). Patients with arrhythmic events (n = 5) and patients requiring mitral valve surgery (n = 7) were observed exclusively in the group displaying MAD.CONCLUSIONS AND RELEVANCE This study suggests that MAD among patients with MFS is associated with the occurrence of arrhythmic events, a higher need for mitral valve intervention, and, among patients with extensive MAD, more aortic events. Cardiac imaging for patients with MFS should consider the assessment of MAD as a potential marker for adverse outcomes.

Imaging Considerations and Clinical Implications of Mitral Annular Disjunction

“…56 Another recent article reported that 34% of 142 patients with Marfan syndrome had MAD as diagnosed by TTE. 57 Patients with MAD had larger aortic root z scores and more MVP, ventricular ectopy, and NSVT. This association between MAD and genetic connective tissue disorders raises the question of related causative mechanisms and warrants further investigation.…”

EHRA expert consensus statement on arrhythmic mitral valve prolapse and mitral annular disjunction complex in collaboration with the ESC Council on valvular heart disease and the European Association of Cardiovascular Imaging endorsed cby the Heart Rhythm Society, by the Asia Pacific Heart Rhythm Society, and by the Latin American Heart Rhythm Society

“…disease including more arrhythmic events, a higher need for mitral valve intervention, and among patients with extensive MAD, more arrhythmic events. 66,67 The first large prospective cohort of isolated MVP with systematic MAD assessment reported a prevalence of 30% of MAD, generally in younger patients. 15 Advanced myxomatous-degeneration, denoted by marked leaflet-redundancy and bileaflet-MVP, was the strongest MAD-associated MVP feature.…”

Association of Pectus Excavatum With Ventricular Remodelling and Mitral Valve Abnormalities in Marfan Syndrome

“…In an animal model with MFS, the increased TGF-β activity and signalling has been shown to correlate temporally and spatially with mitral valve pathology. 5 Demolder et al 33 described a 34% prevalence of MAD in MFS patients which was associated with the occurrence of arrhythmic events, a higher need for mitral valve intervention and increased aortic events in the form of dissection and prophylactic aortic surgery for dilatation. Chivulescu et al 34 reported a 41% prevalence of MAD in a combined cohort of MFS and Loeys-Dietz syndrome patients, associated with a more severe disease phenotype characterized by aortic surgery at younger age and frequent need for mitral surgery.…”