Marfan syndrome (MFS) is a genetic condition that causes connective tissue problems, including an increased risk of aortic aneurysm and dissection. Nupoor Narula, MD, MSc, a cardiologist at New York-Presbyterian/Weill Cornell Medicine and her mentor, Mary J. Roman, MD, also a cardiologist at NewYork-Presbyterian/Weill Cornell Medicine, led a team that recently published a pivotal paper assessing risk factors for type B dissections in people with MFS. Drawing from the institution's extensive aortic aneurysm registry, the clinicians and researchers showed that patients with type B dissection represent a cohort of patients with a more severe overall phenotype. The study was published in the Journal of the American College of Cardiology in November 2023.
Reducing the Risk of Aortic Dissection
Aortic dissections can have catastrophic outcomes. Type A dissections occur in the ascending aorta, while type B dissections affect the descending aorta. The incidence of type A dissections in people with MFS has been reduced by improvement in detection, initiation of evidence-based medical therapy, and timely referral for surgical intervention, including elective aortic root replacement (ARR). However, the rate of type B dissections has been on the rise.
Individuals with Marfan Syndrome are at an increased risk of an aortic dissection.
People with MFS undergo periodic aortic monitoring. While cardiac imaging may show enlarged aortic size in people at risk of a type A dissection, pre-dissection imaging of the descending aorta in people who experience type B dissections is typically normal or shows minimal dilation. Dr. Narula and her team therefore undertook this study to identify risk factors for type B dissection.
Risk Factors for Type B Dissection
The aortic aneurysm registry at NewYork-Presbyterian/Weill Cornell Medicine is one of the largest single-center aortic disease registries in the world and includes more than four decades of systematic clinical and imaging data. Of the more than 730 patients in the longitudinal registry, up to 350 of them have MFS. In the study, Dr. Narula and her colleagues analyzed registry data to compare demographic and anthropometric features, cardiovascular disease, and surgical history between 336 MFS patients with and without type B dissection.
They found that 14% of the patients experienced a type B dissection and 49% had undergone elective ARR. Patients with type B dissection were more likely to have had elective ARR (79% versus 46%). Among those with pre-dissection imaging, the descending aorta was normal or minimally dilated (less than 4 cm) in 88%. Multivariable analysis showed that patients with type B dissection were more likely to have undergone ARR and independent mitral valve surgery, to have had a type II dissection, and to have lived longer.
Among the patients with type B dissection who had ARR, 26 of them experienced a type B dissection after the procedure while 11 had it before ARR. "This is an active area of study to determine why individuals who have this elective grafting go on to develop type B dissection," explains Dr. Narula. During ARR, a stiff conduit is inserted in the ascending aorta. "One potential contributory theory is that the grafts may result in downstream hemodynamic effects and adverse distal aortic remodeling as has been shown by echocardiography and cardiac MRI-based data from Dr. Jonathan Weinsaft’s imaging laboratory."
The take-home message is, we can insert a graft to prevent type A dissections, but we can't forget about the rest of the aorta.
— Dr. Nupoor Narula
Next Steps
Dr. Narula, Dr. Roman, and their fellow NewYork-Presbyterian/Weill Cornell Medicine investigators — including Richard Devereux, MD, Director of the Adult Echocardiography Laboratory, and Jonathan Weinsaft, MD, Chief of the Greenberg Division of Cardiology — want to further their research by exploring the role of genotype in adverse aortic events. They will also analyze the hemodynamic implications of elective ARR. In addition, they found that 10 patients had a distal anastomosis dissection, defined as a dissection distal to the aortic graft, and they would like to study the mechanism behind this phenomenon.
"Despite all of our efforts to monitor patients with Marfan syndrome, they can still experience distal aortic events. We need to determine which patients are most likely to experience type B dissections," Dr. Narula asserts. "It's a very important topic that requires further investigation. The take-home message is, we can insert a graft to prevent type A dissections, but we can't forget about the rest of the aorta."
A Designated Marfan Clinic
The MFS Clinic at NewYork-Presbyterian/Weill Cornell Medicine is one of the strongest in the country. It is designated by the Marfan Foundation as a Marfan Syndrome and Related Conditions Clinic. Drs. Roman and Devereux have developed the nomograms for indexing aortic root size limits for age, sex, and body size, which is critical in this patient population and in patients with inherited aortic diseases overall. The clinic has data going back to 1982 that is meticulously curated and verified.
There is exceptional imaging expertise and coordination with NewYork-Presbyterian/Weill Cornell Medicine's Department of Cardiothoracic Surgery, led by world-renowned aortic surgeon and department chair Leonard Girardi, MD. Patients who are referred to the clinic from the Department of Cardiothoracic Surgery or those referred to surgery from the clinic benefit from exceptional interdisciplinary cardiovascular care.
"Several papers have been published reporting absolutely phenomenal surgical outcomes for people with connective tissue diseases at Cornell," Dr. Narula says. NewYork-Presbyterian/Weill Cornell Medicine clinicians also recently published pivotal research regarding pregnancy in people with MFS, data which were used to inform clinical guidelines for the care of these patients. Additionally, in a new NYP Advances video, she discusses how she evaluated longitudinal data of pregnancy cohorts to determine risk of vascular complication for pregnant women with MFS. "We truly are one of the premier centers internationally for the management of inherited aortic diseases," Dr. Narula concludes.
