Aortic Dissection Risk Rises in Pregnancy for Women With Marfan Syndrome

For women with Marfan syndrome (MFS), pregnancy is associated with a higher risk of aortic dissection during the peripartum period, according to new data, but the risk can be mitigated with careful follow-up and imaging.

“When a woman becomes pregnant and her circulating blood volume increases maybe by 30 to 40%, it's considered that that could perhaps put a strain on the aorta, which is already weakened because of underlying Marfan syndrome,” explained senior author Mary Roman, MD (Weill Cornell Medical College, New York, NY).

US guidelines currently recommend that among women with the connective tissue disorder, only those with aortic root diameters of 4.0 cm or less should become pregnant, while European guidelines have moved that threshold to 4.5 cm. Roman indicated that the findings of this study support moving the US guidelines toward the higher cutoff.

Changing the US cutoff from 4.0 to 4.5 cm would be “a big deal because there are so many women who have aortas in that range,” she told TCTMD. “If they go to a cardiologist who strictly goes by the US guidelines, they're going to be told, . . . ‘You may die if you become pregnant,’ and we don't think that's the case.”

Pregnancy seems to be safe in women with aortic roots up to 4.5 cm “if—and this is a big if—the woman is being cared for by a team that is attuned to all of the potential issues surrounding Marfan syndrome,” she added. Roman cited the multidisciplinary approach her team uses, which includes a clear genetic diagnosis, echocardiograms or sound wave tests each trimester, and care by cardiologists, maternal-fetal specialists, and anesthesiologists.

Retrospective Data

For the study, published in the August 31, 2021, issue of the Journal of the American College of Cardiology, Roman along with lead author Nupoor Narula, MD (Weill Cornell Medical College), and colleagues, retrospectively looked at 74 women with MFS who had 152 pregnancies between 1982 and 2020 and were treated at their center. Only 65% were aware of their MFS diagnosis prior to their first pregnancy. Pregnancies were considered “sanctioned” if their aortic root measurements were no more than 4.5 cm, based on the European guidelines, although four women in the study had measurements exceeding that threshold.

Aortic root dilatation was common both in women who had never been pregnant before and in those who had, but it was more frequent in the former group (97% vs 88%; P = 0.02). Additionally, rates of elective aortic surgery were comparable but occurred earlier in life for those who had never been pregnant before (33 vs 42 years; P = 0.003); a similar trend was seen for rates of aortic dissection (38 vs 45 years; P = 0.07).

Among the 54 women with complete or partial pregnancy imaging available, aortic root dimensions remained largely stable, with mean prepartum, intrapartum, and postpartum aortic dimensions of 3.9 cm, 4.0 cm, and 3.9 cm, respectively. Five women reported vascular complications, including two who were unaware of their MFS diagnosis and experienced type A dissections in their third trimester, two who were unaware of their MFS diagnosis and had type B dissections early postpartum, and one who had a coronary artery dissection early postpartum. These women tended to be older than those with uncomplicated pregnancies (mean 35 vs 30 years; P = 0.019).

For never-pregnant women, the age-related incidence of having elective aortic surgery was significantly higher than for ever-pregnant women (P = 0.0028), even with similar rates of elective surgery. Cumulatively, the groups were equally likely to report aortic dissection (P = 0.74), but events were higher while pregnant compared with postpartum (4.46 vs 0.88 per 100 person-years; rate ratio 5.1; 95% CI 2.0-12.9). This finding was similar when the analysis was restricted to women who had been previously pregnant (4.46 vs 0.95 per 100 person-years; rate ratio 4.7; 95% CI 1.7-12.7).

‘Relatively Safe’

In an accompanying editorial, Melissa Russo, MD (Brown University School of Medicine, Providence, RI), and Anji Yetman, MD (University of Nebraska Medical Center, Omaha), agree that the study presents “further evidence that women with Marfan syndrome can have relatively safe pregnancies with aortic root diameters up to 4.5 cm” and supports a change to the US guidelines.

They point out that while pregnancy is a high-risk time for dissection, the postpartum period also is critical. Experimental mouse studies have suggested a link between lactation and increased risk of aortic dissection, but both the study authors and the editorialists say this doesn’t seem to be the case in humans.

“Further studies are warranted to address whether breastfeeding in humans is associated with an increased risk for aortic dissection,” Russo and Yetman write. “At the present time, there is insufficient data to support a recommendation to avoid breastfeeding.”

In counseling women with MFS with aortic root diameters between 4.0 and 4.5 cm, “aortic diameter is only a single piece of the puzzle,” they say, given that there are other genetic factors at play. “If the aorta measures 4.0-4.5 cm and no additional risk factors for dissection are present, the data from Narula et al would suggest that the patient may be better served by not undergoing prophylactic aortic surgery prior to pregnancy. Once the ascending aorta is replaced, the native aorta distal to the graft is vulnerable yet not as easily visualized,” they note.

More data are needed looking at type B dissections, which are not as easily imaged on echocardiography and may require CT; this imaging can be dangerous for pregnant women with its associated radiation, the editorialists write.

“You can actually diagnose a type B dissection with a good quality echocardiogram that images more than just the heart,” Roman said, but she acknowledged the need for more data.

As for implications for women without MFS, the risk of aortic dissection is “very, very minimal but it's quantifiable,” she said. “It's pretty well established that pregnancy per se increases the dissection risk even if the woman is ‘normal.’ It's vastly increased when you have these underlying genetic aortopathies, or diseases of the aorta, that are inherited.”