In patients with Marfan syndrome (MFS), mitral annular disjunction (MAD) is associated with arrhythmias and an increased need for mitral valve intervention, and more intensive MAD is associated with an increased incidence of aortic events.
Clinicians would be wise, therefore, to assess MAD in these patients via cardiac imaging, as it may be a marker for adverse outcomes, according to study results published in JAMA Cardiology.
“Owing to the difficulties in predicting outcomes among patients with MFS, there is an unmet need for additional prognostic indicators,” wrote Anthony Demolder, MD, of Ghent University Hospital, Ghent, Belgium, and colleagues. “Recently, mitral annular disjunction (MAD), defined as a separation between the mitral valve hinge point and the left ventricular (LV) myocardium, in patients with or without MVP has received particular interest as a potential marker or substrate for ventricular arrhythmia and SCD. A recent report on aortic outcomes in a surgical population of patients with MFS suggests that aortic events occur at a younger age among patients with MAD. However, data on the prevalence of MAD and its association with cardiovascular outcomes and arrhythmia among a nonsurgical population of patients with MFS are lacking.”
They conducted this retrospective, single-center study to define the prevalence of MAD in patients with MFS and assess any associations with arrhythmias and cardiovascular outcomes. To do so, they followed 142 patients (median age at first exam: 25 years; 51% female) with MFS from Jan. 1, 2004, through Dec. 31, 2019.
During this time, Demolder and fellow researchers assessed outcome measures that included aortic events (including aortic dissection and prophylactic aortic surgery), mitral valve surgery, arrhythmic events (including sustained ventricular tachycardia [VT] and sudden cardiac death [SCD]), and all-cause mortality. All patients underwent semiannual transthoracic echocardiographic imaging, 24-hour Holter monitoring as indicated or annually, 12-lead electrocardiography, and genetic variant classification for variants in the FBN1 gene, which most patients with MFS carry.
In all, 48 patients (34%) had MAD, and these patients were more likely to be younger at diagnosis compared with those without (median age: 16 vs 28 years, respectively), have more frequent mitral valve prolapse (71% vs 15%; P˂0.001), more mitral regurgitation (79% vs 45%), larger mitral annual diameter (mean end-systolic diameter: 38 vs 32 mm; mean end-diastolic diameter: 34 vs 31 mm), increased median indexed left ventricular diameters, lower median left ventricular ejection fraction (66% vs 69%), and higher aortic root z scores (4.1 vs 3.0; P˂0.001). There were no differences between the groups in PR interval, or QRS or QTc durations.
In addition, MAD patients had a higher incidence of ventricular ectopy (42% vs 21%; P=0.03) and nonsustained ventricular tachycardia (39% vs 17%; P=0.01).
Although the incidence of aortic events was similar in patients with and without MAD (35% vs 25%, respectively; P=0.24), MAD patients in the upper MAD tertile (>10 mm) had a higher incidence of aortic events compared with those with MAD of ≤10 mm (60% vs 21%; P=0.01).
“Although patients in the upper MAD tertile (>10 mm) showed a higher prevalence of prophylactic aortic surgery, the low number of patients in this group precludes definite conclusions. Whether the severity of MAD may be associated with the need for prophylactic aortic surgery requires further investigation,” wrote Demolder and colleagues.
Finally, five patients with arrhythmic events and seven who required mitral valve surgery all had MAD.
“Our results suggest that patients with MFS and significant MAD may require close clinical follow-up and Holter monitoring. A recent case report of a young patient with MFS presenting with extensive MAD, ventricular arrhythmia, and the need for mitral valve surgery is indicative of our findings. The presence of MAD should be reported in the routine cardiac evaluation, potentially requiring further assessment with CMR imaging. However, therapeutic implications remain unclear, and more evidence from outcome studies and risk stratification is mandatory,” concluded Demolder et al.
Study limitations included its retrospective design, the low incidence of certain observation, the inability to characterize the morphologic characteristics and origin of PVCs, the failure to report cardiac magnetic resonance imaging data because images were not available for all patients. Finally, researchers noted that they did not assess myocardial fibrosis because late gadolinium enhancement by cardiac magnetic resonance imaging was not performed.
In patients with Marfan syndrome, mitral annular disjunction was associated with a higher need for mitral valve intervention and a higher incidence of arrhythmic events.
Assessing the presence and extent of MAD should be considered in the routine cardiac evaluation of patients with MFS, as they may be potential markers for adverse outcomes.
Liz Meszaros, Deputy Managing Editor, BreakingMED™
Demolder reported receiving grants from Ghent University and is supported by a Methusalem grant of the Flemish government and the Ghent University.
Cat ID: 914
Topic ID: 74,914,438,496,497,730,914,138,192,925,240,481,96