Surgery for Marfan Syndrome: Large Series Argues for Earlier Intervention Than Guidelines Suggest

A majority of patients with Marfan syndrome who underwent emergency aortic root replacement in a large contemporary cohort had an aortic root diameter smaller than guideline cutoffs for prophylactic surgery. So finds a research letter published by Cleveland Clinic investigators in the Journal of the American College of Cardiology (2019;73:733-734).

The observational study also found that prophylactic root replacement surgery was associated with significantly improved survival and freedom from aortic dissection compared with emergency surgery among the cohort of Marfan syndrome patients.

“Taken together, these findings suggest that Marfan syndrome patients with ascending aortopathy may benefit from prophylactic aortic root replacement surgery earlier than is indicated by current guidelines based on aortic root dilation,” says senior author Lars Svensson, MD, PhD, Chairman of Cleveland Clinic’s Miller Family Heart & Vascular Institute.

What degree of dilation predisposes to dissection?

Current joint guidelines from a number of cardiovascular societies recommend prophylactic aortic root replacement when the aortic diameter reaches ≥ 5 cm — or ≥ 4 to 4.5 cm when the patient has certain risk factors.

“Despite this recommendation, aortic dissection can and does occur with lesser degrees of dilation,” notes the study’s lead author, Milind Desai, MD, Professor of Medicine at Cleveland Clinic Lerner College of Medicine. “So we decided to evaluate outcomes of recent Marfan syndrome patients who underwent aortic root replacement at Cleveland Clinic. We were particularly interested in determining the proportion of patients who presented with acute type A dissection whose aortic diameter was below the recommended threshold for elective surgery.”

Looking for answers in a 500-patient sample

The researchers reviewed the records of more than 1,000 patients with suspected Marfan syndrome who presented for aortic surgery at Cleveland Clinic from 1990 through 2016. After exclusion of those younger than 18, those with prior aortic root replacement surgery or surgery elsewhere on the aorta, and those not meeting the stricter revised Ghent criteria, 491 patients were eligible for the analysis.

Patients’ aortic root diameter was determined based on their baseline echocardiogram (available for all patients) and chest contrast-enhanced CT angiogram or MR angiogram (performed at Cleveland Clinic in 93 percent of patients).

Patients were classified as having either emergency aortic root replacement (n = 192), defined as taking place within 24 hours of admission, or prophylactic aortic root replacement (n = 299). Their operations were classified into the following subtypes:

• Valve-sparing root replacement (VSRR) — done using the Cleveland Clinic modification of the valve-sparing reimplantation operation — which was performed in 53 percent of the prophylactic group and 20 percent of the emergency group
• Composite valve aortic graft replacement (CVG), performed in 25 percent of the prophylactic group and 66 percent of the emergency group
• Combined operation (root replacement + aortic arch replacement ± descending aortic surgery), performed in 22 percent of the prophylactic group and 15 percent of the emergency group

Results: Modest dilation in most emergency cases

Results showed that a majority of emergency surgery patients had an aortic root diameter smaller than the guideline-recommended thresholds for prophylactic surgery, specifically:

• 62 percent had an aortic height index < 2.43 cm/m (the prespecified threshold for dilation)
• 56 percent had an aortic root diameter < 4.5 cm
• 67 percent had an aortic root diameter < 5 cm

Of the seven in-hospital deaths that occurred across the cohort, six occurred in the emergency group and one in the prophylactic group.

Over median follow-up of 8.0 years (interquartile range, 4.8 to 11.2 years), mortality was significantly higher in the emergency group than in the prophylactic group (27 percent vs. 11 percent; P < .001). In both groups, mortality was significantly higher following CVG compared with VSRR.

On Cox survival analysis, prophylactic surgery was associated with a lower rate of long-term composite events (death, aortic dissection type A or B, need for redo aortic surgery) compared with emergency surgery (hazard ratio = 0.31; 95% CI, 0.21-0.46).

Encouraging findings on dissection prevention

“While we have made great strides in the surgical management of Marfan patients, the guidelines might need to readdress size thresholds beyond which we should refer patients for prophylactic root replacement surgery,” observes Dr. Desai.

“This study was gratifying in showing that prophylactic surgery prevented most patients from developing later aortic dissection,” adds Dr. Svensson. “Indeed, in our follow-up of patients who had reimplantation of the aortic valve — that is, the valve-sparing operation — only 1.4 percent later developed a new dissection, mostly in the descending aorta.”