Pregnancy and Marfan: New insight into risks

SNOWMASS, COLO–Pregnancy increases the long-term risk of aortic complications in women with Marfan syndrome, according to a recent prospective study causing a stir among adult congenital heart disease specialists.

"This is the first study that says, ‘Even if the aortic root size is okay before pregnancy, the aorta is going to get bigger during pregnancy and it’s not going to go back to baseline. And if your aorta is bigger at the outset, there is a risk for long-term adverse outcomes,’ " Dr. Carole A. Warnes explained at the annual cardiovascular conference at Snowmass sponsored by the American College of Cardiology (ACC).

This study on pregnancy’s impact on aortic growth rate and complications in patients with Marfan syndrome sheds much needed light on an area where there has been a paucity of data. The deficiency of data is reflected in discordant recommendations in the current U.S., European, and Canadian guidelines, said Dr. Warnes, professor of medicine at the Mayo Clinic, Rochester, Minn.

The U.S. guidelines put forth jointly by the ACC, American Heart Association, American Association for Thoracic Surgery, and other groups advocate that Marfan syndrome patients avoid pregnancy if their aortic root diameter exceeds 40 mm and recommend prophylactic aortic replacement in those interested in pregnancy (J. Am. Coll. Cardiol. 2010;55:e27-129).

In contrast, the European guidelines (Eur. Heart J. 2010;31:2915-57) consider an aortic root diameter of 45 mm or less to be generally safe, while strongly discouraging pregnancy in Marfan syndrome patients with a measurement above that threshold because of the associated increased dissection risk. The Canadian guidelines take a similar stance, albeit with a safety threshold of 44 mm rather than 45 mm (Can. J. Cardiol. 2010;26:e80-e97).

The Europeans qualify their position by noting that patients with a prepregnancy aortic root diameter of 40-45 mm who have a rapid aortic root growth rate or a family history of dissection ought to be considered high risk for pregnancy. The European and Canadian guidelines characterize dissection as a rare problem in patients with an aortic root diameter of less than 40 mm.

The recent Utah study included 98 women with Marfan syndrome, 69 of whom collectively had 199 pregnancies, with 170 live births, 26 spontaneous abortions, and 2 ectopic pregnancies.

Serial echocardiograms demonstrated that the aortic growth rate was significantly greater during pregnancy than beforehand, and after pregnancy it didn’t return to baseline. Obstetric complications occurred in 10% of pregnancies. Adverse fetal outcomes occurred in 13%.

Reassuringly, there were no catastrophic peripartum complications. No one required cardiac surgery or experienced aortic dissection during pregnancy. However, women with a prior pregnancy had a greater prevalence of both aortic dissection and elective aortic surgery during long-term follow-up, compared with matched childless women with Marfan syndrome. Thus, it’s important during prepregnancy counseling of women with Marfan syndrome to let them know they’ll need to have elective aortic root surgery at a younger age than if they remain childless, Dr. Warnes noted.

A larger initial root diameter and a faster increase in diameter were independent predictors of long-term adverse cardiovascular events in the Utah study.

Besides the recent Utah study, only two other prospective studies of pregnancy’s impact on aortic growth and complications have been done. Both were much smaller. In an editorial accompanying the Utah study, Dutch physicians combined the three studies to get a fuller picture. No type A dissections occurred during 145 pregnancies in 78 nonoperated women with Marfan syndrome. Of 25 women with an aortic root diameter of 40-51 mm during 29 pregnancies, one experienced a type B dissection, two had carotid artery dissections, and one developed accelerated aortic regurgitation, which went from mild to severe during pregnancy.

Five women underwent aortic root replacement (three electively), prior to six pregnancies. Two of them developed a type B dissection during pregnancy. Both women who underwent a valve-sparing elective aortic root replacement prior to pregnancy had pregnancies complicated by a worsening of aortic regurgitation, which went from trivial to moderate. These findings raise a red flag for Dr. Warnes.

"Even if they’ve had a successful root replacement, it doesn’t mean they’re out of the woods in terms of pregnancy. I think we have to question the role of prophylactic root replacement [as recommended in the U.S. guidelines] because these women will still have type B dissections, and trying to look for a type B dissection during pregnancy is a real difficult issue," the cardiologist observed.

The authors of the editorial concluded that Marfan syndrome patients without previous cardiac complications and who have a baseline aortic root diameter not in excess of 45 mm seem to tolerate pregnancy well as long as they receive good clinical care before, during, and after pregnancy. In contrast, pregnancy should be discouraged in patients with a history of aortic dissection because they are at elevated risk for aortic complications (J. Am. Coll. Cardiol. 2012;60:230-1).

Marfan syndrome is a genetic connective tissue disorder with an incidence of roughly 1 in 5,000 and autosomal dominant inheritance, so the fetus of an affected mom has a 50% chance of having the disorder. Dr. Warnes said that because the diagnostic criteria were overhauled in 2010, patients believed to have Marfan syndrome really ought to be referred to a specialized center in order to confirm or refute the diagnosis according to the contemporary Ghent criteria.

Dr. Warnes reported having no relevant financial interests.

[email protected]

SNOWMASS, COLO–Pregnancy increases the long-term risk of aortic complications in women with Marfan syndrome, according to a recent prospective study causing a stir among adult congenital heart disease specialists.

"This is the first study that says, ‘Even if the aortic root size is okay before pregnancy, the aorta is going to get bigger during pregnancy and it’s not going to go back to baseline. And if your aorta is bigger at the outset, there is a risk for long-term adverse outcomes,’ " Dr. Carole A. Warnes explained at the annual cardiovascular conference at Snowmass sponsored by the American College of Cardiology (ACC).

This study on pregnancy’s impact on aortic growth rate and complications in patients with Marfan syndrome sheds much needed light on an area where there has been a paucity of data. The deficiency of data is reflected in discordant recommendations in the current U.S., European, and Canadian guidelines, said Dr. Warnes, professor of medicine at the Mayo Clinic, Rochester, Minn.

The U.S. guidelines put forth jointly by the ACC, American Heart Association, American Association for Thoracic Surgery, and other groups advocate that Marfan syndrome patients avoid pregnancy if their aortic root diameter exceeds 40 mm and recommend prophylactic aortic replacement in those interested in pregnancy (J. Am. Coll. Cardiol. 2010;55:e27-129).

In contrast, the European guidelines (Eur. Heart J. 2010;31:2915-57) consider an aortic root diameter of 45 mm or less to be generally safe, while strongly discouraging pregnancy in Marfan syndrome patients with a measurement above that threshold because of the associated increased dissection risk. The Canadian guidelines take a similar stance, albeit with a safety threshold of 44 mm rather than 45 mm (Can. J. Cardiol. 2010;26:e80-e97).

The Europeans qualify their position by noting that patients with a prepregnancy aortic root diameter of 40-45 mm who have a rapid aortic root growth rate or a family history of dissection ought to be considered high risk for pregnancy. The European and Canadian guidelines characterize dissection as a rare problem in patients with an aortic root diameter of less than 40 mm.

The recent Utah study included 98 women with Marfan syndrome, 69 of whom collectively had 199 pregnancies, with 170 live births, 26 spontaneous abortions, and 2 ectopic pregnancies.

Serial echocardiograms demonstrated that the aortic growth rate was significantly greater during pregnancy than beforehand, and after pregnancy it didn’t return to baseline. Obstetric complications occurred in 10% of pregnancies. Adverse fetal outcomes occurred in 13%.

Reassuringly, there were no catastrophic peripartum complications. No one required cardiac surgery or experienced aortic dissection during pregnancy. However, women with a prior pregnancy had a greater prevalence of both aortic dissection and elective aortic surgery during long-term follow-up, compared with matched childless women with Marfan syndrome. Thus, it’s important during prepregnancy counseling of women with Marfan syndrome to let them know they’ll need to have elective aortic root surgery at a younger age than if they remain childless, Dr. Warnes noted.

A larger initial root diameter and a faster increase in diameter were independent predictors of long-term adverse cardiovascular events in the Utah study.

Besides the recent Utah study, only two other prospective studies of pregnancy’s impact on aortic growth and complications have been done. Both were much smaller. In an editorial accompanying the Utah study, Dutch physicians combined the three studies to get a fuller picture. No type A dissections occurred during 145 pregnancies in 78 nonoperated women with Marfan syndrome. Of 25 women with an aortic root diameter of 40-51 mm during 29 pregnancies, one experienced a type B dissection, two had carotid artery dissections, and one developed accelerated aortic regurgitation, which went from mild to severe during pregnancy.

Five women underwent aortic root replacement (three electively), prior to six pregnancies. Two of them developed a type B dissection during pregnancy. Both women who underwent a valve-sparing elective aortic root replacement prior to pregnancy had pregnancies complicated by a worsening of aortic regurgitation, which went from trivial to moderate. These findings raise a red flag for Dr. Warnes.

"Even if they’ve had a successful root replacement, it doesn’t mean they’re out of the woods in terms of pregnancy. I think we have to question the role of prophylactic root replacement [as recommended in the U.S. guidelines] because these women will still have type B dissections, and trying to look for a type B dissection during pregnancy is a real difficult issue," the cardiologist observed.

The authors of the editorial concluded that Marfan syndrome patients without previous cardiac complications and who have a baseline aortic root diameter not in excess of 45 mm seem to tolerate pregnancy well as long as they receive good clinical care before, during, and after pregnancy. In contrast, pregnancy should be discouraged in patients with a history of aortic dissection because they are at elevated risk for aortic complications (J. Am. Coll. Cardiol. 2012;60:230-1).

Marfan syndrome is a genetic connective tissue disorder with an incidence of roughly 1 in 5,000 and autosomal dominant inheritance, so the fetus of an affected mom has a 50% chance of having the disorder. Dr. Warnes said that because the diagnostic criteria were overhauled in 2010, patients believed to have Marfan syndrome really ought to be referred to a specialized center in order to confirm or refute the diagnosis according to the contemporary Ghent criteria.

Dr. Warnes reported having no relevant financial interests.

[email protected]

SNOWMASS, COLO–Pregnancy increases the long-term risk of aortic complications in women with Marfan syndrome, according to a recent prospective study causing a stir among adult congenital heart disease specialists.

"This is the first study that says, ‘Even if the aortic root size is okay before pregnancy, the aorta is going to get bigger during pregnancy and it’s not going to go back to baseline. And if your aorta is bigger at the outset, there is a risk for long-term adverse outcomes,’ " Dr. Carole A. Warnes explained at the annual cardiovascular conference at Snowmass sponsored by the American College of Cardiology (ACC).

This study on pregnancy’s impact on aortic growth rate and complications in patients with Marfan syndrome sheds much needed light on an area where there has been a paucity of data. The deficiency of data is reflected in discordant recommendations in the current U.S., European, and Canadian guidelines, said Dr. Warnes, professor of medicine at the Mayo Clinic, Rochester, Minn.

The U.S. guidelines put forth jointly by the ACC, American Heart Association, American Association for Thoracic Surgery, and other groups advocate that Marfan syndrome patients avoid pregnancy if their aortic root diameter exceeds 40 mm and recommend prophylactic aortic replacement in those interested in pregnancy (J. Am. Coll. Cardiol. 2010;55:e27-129).

In contrast, the European guidelines (Eur. Heart J. 2010;31:2915-57) consider an aortic root diameter of 45 mm or less to be generally safe, while strongly discouraging pregnancy in Marfan syndrome patients with a measurement above that threshold because of the associated increased dissection risk. The Canadian guidelines take a similar stance, albeit with a safety threshold of 44 mm rather than 45 mm (Can. J. Cardiol. 2010;26:e80-e97).

The Europeans qualify their position by noting that patients with a prepregnancy aortic root diameter of 40-45 mm who have a rapid aortic root growth rate or a family history of dissection ought to be considered high risk for pregnancy. The European and Canadian guidelines characterize dissection as a rare problem in patients with an aortic root diameter of less than 40 mm.

The recent Utah study included 98 women with Marfan syndrome, 69 of whom collectively had 199 pregnancies, with 170 live births, 26 spontaneous abortions, and 2 ectopic pregnancies.

Serial echocardiograms demonstrated that the aortic growth rate was significantly greater during pregnancy than beforehand, and after pregnancy it didn’t return to baseline. Obstetric complications occurred in 10% of pregnancies. Adverse fetal outcomes occurred in 13%.

Reassuringly, there were no catastrophic peripartum complications. No one required cardiac surgery or experienced aortic dissection during pregnancy. However, women with a prior pregnancy had a greater prevalence of both aortic dissection and elective aortic surgery during long-term follow-up, compared with matched childless women with Marfan syndrome. Thus, it’s important during prepregnancy counseling of women with Marfan syndrome to let them know they’ll need to have elective aortic root surgery at a younger age than if they remain childless, Dr. Warnes noted.

A larger initial root diameter and a faster increase in diameter were independent predictors of long-term adverse cardiovascular events in the Utah study.

Besides the recent Utah study, only two other prospective studies of pregnancy’s impact on aortic growth and complications have been done. Both were much smaller. In an editorial accompanying the Utah study, Dutch physicians combined the three studies to get a fuller picture. No type A dissections occurred during 145 pregnancies in 78 nonoperated women with Marfan syndrome. Of 25 women with an aortic root diameter of 40-51 mm during 29 pregnancies, one experienced a type B dissection, two had carotid artery dissections, and one developed accelerated aortic regurgitation, which went from mild to severe during pregnancy.

Five women underwent aortic root replacement (three electively), prior to six pregnancies. Two of them developed a type B dissection during pregnancy. Both women who underwent a valve-sparing elective aortic root replacement prior to pregnancy had pregnancies complicated by a worsening of aortic regurgitation, which went from trivial to moderate. These findings raise a red flag for Dr. Warnes.

"Even if they’ve had a successful root replacement, it doesn’t mean they’re out of the woods in terms of pregnancy. I think we have to question the role of prophylactic root replacement [as recommended in the U.S. guidelines] because these women will still have type B dissections, and trying to look for a type B dissection during pregnancy is a real difficult issue," the cardiologist observed.

The authors of the editorial concluded that Marfan syndrome patients without previous cardiac complications and who have a baseline aortic root diameter not in excess of 45 mm seem to tolerate pregnancy well as long as they receive good clinical care before, during, and after pregnancy. In contrast, pregnancy should be discouraged in patients with a history of aortic dissection because they are at elevated risk for aortic complications (J. Am. Coll. Cardiol. 2012;60:230-1).

Marfan syndrome is a genetic connective tissue disorder with an incidence of roughly 1 in 5,000 and autosomal dominant inheritance, so the fetus of an affected mom has a 50% chance of having the disorder. Dr. Warnes said that because the diagnostic criteria were overhauled in 2010, patients believed to have Marfan syndrome really ought to be referred to a specialized center in order to confirm or refute the diagnosis according to the contemporary Ghent criteria.

Dr. Warnes reported having no relevant financial interests.

[email protected]