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Ann Thorac Surg 2003;76:309-314
© 2003 The Society of Thoracic Surgeons

Review

Aortic dissection in pregnancy: analysis of risk factors and outcome

Franz F. Immer, MDa*, Anne G. Bansi, MDa, Alexsandra S. Immer-Bansi, MDb, Jane McDougall, MDc, Kenton J. Zehr, MDd, Hartzell V. Schaff, MDd, Thierry P. Carrel, MDa

a Department of Cardiovascular Surgery, Berne, Switzerland
b Institute of Anesthesiology, Berne, Switzerland
c Division of Neonatology, University Hospital, Berne, Switzerland
d Division of Cardiovascular Surgery, Mayo Clinic, Rochester, Minnesota, USA

* Address reprint requests to Dr Immer, Department of Cardiovascular Surgery, University Hospital, 3010 Berne, Switzerland
e-mail: franzimmer{at}yahoo.de


   Abstract
Top
 Abstract
Introduction
 Patients and methods
 Results
 Comment
 References
 
Aortic dissection during pregnancy is a life-threatening event. Recent studies have revealed similar histologic changes in the wall of the ascending aorta in patients with bicuspid aortic valve disease (BAVD). Based on a review of the literature, including the experience from two institutions, we looked at the patient’s characteristics in patients with thoracic aortic dissection during pregnancy. We found that aortic root enlargement (> 4cm) or an increase of aortic root size during pregnancy in patients with BAVD, and Marfan syndrome is associated with a considerable risk for the occurrence of Type A dissection.


   Introduction
Top
 Abstract
 Introduction
Patients and methods
 Results
 Comment
 References
 
Acute aortic dissection is a life-threatening event. Although rare, an association between pregnancy and aortic dissection has been reported. The first reviews were published in 1944 by Schnitker and Bayer [1] and in 1957 by Pedowitz and Perell [2]. They hypothesized that the "physiologic changes of pregnancy" accelerated the development of pathologic changes in the arterial wall. Because of increasing cardiovascular stress during pregnancy the risk of aortic dissection or rupture of an aneurysm increases with gestational age [2]. In this situation dissection and rupture of the aorta carry a high risk of maternal mortality and, if prepartum, fetal demise. The threat of such a catastrophe for the mother and her unborn child has prompted some to recommend against pregnancy in patients with Marfan syndrome [3], who are at the highest risk, if the aortic root is enlarged. Most review articles [4–9] make no distinction between patients suffering from Type A dissection (this includes the ascending aorta, De Bakey type I [ascending plus descending], and De Bakey type II [ascending only]), Type B dissection (De Bakey type III [descending only]), and aortic aneurysms. However, this difference is of great importance with regard to initial management. Patients suffering from acute Type A dissection require immediate surgery. For patients with Type B dissection, conservative medical treatment is usually recommended in the absence of rupture or malperfusion [6]. Aortic dissection associated with pregnancy is usually thoracic in location, the proximal tear occurring within the ascending aorta in 89% [10]. Konishi and his colleagues [11] reported that 70% were De Bakey type I, 19% were De Bakey type II, and only 11% were De Bakey type III.

In 1981 Pyeritz [12] reported that there was no higher rate of complications during pregnancy in a group of Marfan syndrome patients with minor cardiovascular involvement. His recommendations were that women with minor cardiovascular involvement and an aortic root diameter of less than 4 cm can be counseled of a relatively small risk of aortic dissection. These recommendations have been adopted as guidelines in obstetric textbooks [13, 14]. In 1995 Rossiter and coworkers [5] subsequently published the first prospective longitudinal evaluation of pregnancy in patients with Marfan syndrome. This study included 45 pregnancies in 21 Marfan patients over a 10-year period. Pyeritz’s recommendations were confirmed [5]. Not only was the absolute diameter of the aortic root important, but also the rapidity of aortic dilatation was important in Marfan syndrome patients, and should be taken into account [15]. Presently all recommendations focus on the occurrence of acute Type A dissection in Marfan patients. No recommendations are available concerning Type B dissection. Furthermore, Marfan syndrome is responsible for up to 50% of the reports [6, 8] published in the literature.

The aim of this study was to evaluate risk factors for the occurrence of acute Type A and Type B aortic dissection during pregnancy in a large group of patients pooled from the literature, and including patients from the Mayo Clinic (Rochester, MN, USA) and the University Hospital Berne (Berne, Switzerland) to analyze the role of bicuspid aortic valve disease (BAVD), and to review the recommendations concerning the modality of treatment in these patients.


   Patients and methods
Top
 Abstract
 Introduction
 Patients and methods
Results
 Comment
 References
 
Patients
Based on a search in MedLine and PubMed ("pregnancy," "aortic dissection," "aneurysm," "Marfan," and "bicuspid aortic valve") six reviews [4–9] and 22 case reports [16–37] between January 1983 and June 2002 were selected to be suitable for data collection. The reports of 50 patients were analyzed. Forty patients had an acute Type A aortic dissection, 35 occurred prepartum (87.5%) and 5 postpartum (12.5%). Type B dissection was described in 10 patients, 6 prepartum (60%) and 4 postpartum (40%). Four patients had an ascending aortic aneurysm, 3 patients (75%) were operated postpartum, and 1 patient prepartum (25%).

Between January 1983 and August 2002, 296 consecutive patients were operated at the Mayo Clinic for Type A aortic dissection. Twelve women (4.1%) were under the age of 45 years and 1 patient was pregnant. One intervention on the thoracoabdominal aorta was made in a patient in whom acute Type B dissection occurred during delivery.

In the same time period 275 consecutive patients were operated for acute Type A aortic dissection at the University Hospital Berne. Eight women (2.9%) were under the age of 45 years. Four of them were pregnant. In this time period 1 patient had to be operated for acute Type B dissection, occurring 1 day after delivery.

Including our experiences, a total of 45 women (78.9%) with acute Type A dissection and 12 with Type B dissection (21.1%) associated with pregnancy, were analyzed.

Methods
We focused on the following variables: diagnosis (Type A dissection, Type B dissection, aneurysm), presence of BAVD, age, presence of a systemic disease (Marfan syndrome, Ehlers-Danlos), history of hypertension, severity of aortic regurgitation, diameter of aortic root, gestational week, mode of delivery (spontaneous vaginal or cesarean section), cardiac surgical procedure (including technical details if available), maternal outcome, and neonatal outcome. The diagnosis of Marfan syndrome in our patients was based on the criteria published by De Paepe and his colleagues [38], and for the diagnosis of Ehlers-Danlos we referred to the revised nosology, Villefranche 1997, published in 1998 [39].


   Results
Top
 Abstract
 Introduction
 Patients and methods
 Results
Comment
 References
 
Patient characteristics
Patient characteristics are summarized in Table 1. There was no significant difference in age and the presence of systemic disease between patients with Type A and Type B dissections. No patient with Type B dissection had a known enlargement or aneurysm of the aortic root. The average diameter of the aortic root in patients with Type A dissection was 4.8 ± 0.9 cm at the time of dissection. The administration of beta-blocking agents is mentioned in 6 patients with Type A dissection prepartum (15%).


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  		Table 1. Summary of Patients Since 1983, in the Literature, With Aortic Dissection or Aneurysm During Pregnancy

 
Bicuspid aortic valve
Four patients (10%) had BAVD and prepartum Type A dissection. These 4 patients tended to be younger, with a median age of 27.8 ± 3.7 years, compared with 29.8 ± 4.1 years (p = ns) in patients known for Marfan syndrome, and 31.1 ± 5.1 years (p < 0.05) in the total collective of patients with prepartum Type A dissection. Dissection occurs earlier in pregnancy (p < 0.05) and fetal outcome is poor (p = ns; Table 2).


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  		Table 2. Type A Dissections (Prepartum)

 
Outcome
Maternal and fetal mortality in patients with acute Type A dissection is illustrated in Figure 1. In each time period maternal mortality is lower than fetal mortality.



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  		Fig 1. Decrease in maternal and fetal mortality in the last 20 years in patients with Type A dissection in the time period 1983 to 1989 (n = 8), 1990 to 1994 (n = 10), 1995 to 1999 (n = 12), and 2000 to 2002 (n = 10). Squares = maternal mortality; triangles = fetal mortality.

 

   Comment
Top
 Abstract
 Introduction
 Patients and methods
 Results
 Comment
References
 
Cardiovascular effects of pregnancy
During pregnancy there are increases in heart rate, stroke volume, cardiac output, and in left ventricular wall mass and end-diastolic dimensions [40]. The majority of dissections occurred in the third trimester. This is the period of maximal hemodynamic stress. The gravid uterus has been reported to cause significant compression of the aorta and iliac arteries [41], especially in the supine position. This possibly increases the outflow resistance of the lower arterial tree. The concurrent increase in cardiac ejection of blood into the upper aorta may be further predisposed to initiate an intimal tear, causing aortic dissection [42]. Based on hormonal factors a programed dilatation of the aorta, renal and placental resistance vessels, and the venous system has been observed. This improves the perfusion of the pregnant body. Specific receptors for estrogen and progesterone increase throughout pregnancy, then fall back to prepregnancy levels after parturition. Receptors have been sought in systemic arteries. These findings are variable [43–48]. However, the presence of estrogen receptors in fresh human aortic tissue has been confirmed [46]. These hormonal effects lead to a fragmentation of the reticulin fibers, diminished the amount of acid mucopolysaccharides, and favor loss of the normal corrugation of the elastic fibers [48].

As these modifications occur in every pregnancy, it may be assumed that those afflicted by aortic dissection have some additional etiologic factors, such as an inherent defect in the arterial wall. Patients with Marfan syndrome have a mutation within the fibrillin gene on chromosome 15q21 [49], the connective tissue disorder often affects cardiovascular system and may favor aortic root dilatation and aortic dissection. Abnormal biophysical properties of the aorta in patients with Marfan syndrome were found in normal-sized aortas in patients with magnetic resonance flow mapping [50]. There was decreased aortic distensibility and increased flow wave velocity in the aorta, compared with healthy control patients. This study suggests an additional wall stress in patients with Marfan syndrome, which may favor dissection during pregnancy.

Effects of bicuspid aortic valve
The incidence of documented Marfan syndrome in this review was 44% in patients with Type A dissections and 42% in patients with Type B dissections. The presence of bicuspid aortic valve, found in 2 of 5 patients in this study with acute Type A dissection and in 2 patients in the literature, may be another reason for the occurrence of aortic dissection during pregnancy. Abnormal elastic properties, similar to the findings in patients with Marfan syndrome, have been described recently by two groups [51, 52]. Similar findings have been reported by Parai and his colleagues [53], who demonstrated significantly less elastic tissue in aortas of bicuspid aortic valve patients. The results from Okamoto and associates [54] also suggest that biomechanical properties of dilated human ascending aorta are also reduced in patients with bicuspid aortic valve. A recent study found similar modifications of the aortic root and the ascending aorta in patients after repaired tetralogy of Fallot [55], which may increase the risk of dissection in this collective of patients. These changes in mechanical properties are influenced by age, which may be a reason why the average maternal age is around 31 years in dissected patients, compared with Marfan syndrome patients with bicuspid aortic valves, who tend to be younger (p = ns) and dissection occur earlier in gestation (26.8 ± 7.6 vs 31.5 ± 5.9 weeks; p < 0.05).

Differences in patient characteristics in type A and B dissection
We found no differences between patients with Type A and Type B dissection. They were similar in age (31.1 ± 5.1 vs 31.1 ± 4.2 years), gestational week at the occurrence of dissection (31.4 ± 7.5 vs 31.6 ± 7.3 weeks), and incidence of systemic disease (44% vs 42%). As described in the literature, Type B dissection is less frequent than Type A dissection [6]. This is similar to our findings of 79% acute Type A dissections and 21% acute Type B dissections. It may be speculated that this may be due to difficulty in diagnosis. Type B dissections are less symptomatic than Type A dissections and are probably underreported in the literature: they often do not require immediate surgery and are, therefore, less spectacular than Type A dissection.

Patients with enlarged aortic roots (> 4 cm, or less in patients with a low body surface area [BSA]) [56, 57] or an increasing size of the aortic root during pregnancy are at risk for the occurrence of Type A dissection. Beside the presence of a systemic disease, no risk factor can aid the clinician finding out if patients are at higher risk for Type B dissection.

Modality of treatment
Based on this review, we propose the following guidelines for treatment. If aortic root enlargement (> 4cm, or less in patients with a low BSA) is known in a Marfan syndrome patient or in a patient known to have a bicuspid aortic valve, preconceptional counseling should recommend prepregnancy surgery. Elective aortic root replacement can be performed with very low morbidity and mortality in Marfan syndrome patients [58, 59]. By choosing the surgical technique one has to remember that the composite graft introduces the need for anticoagulation, and warfarin has clear potential for teratogenecity, although valve sparing procedures and homografts have their own issues, which have to be considered.

Based on the data from Lind and Wallenburg [9] preconceptional counseling took place only in 25% of Marfan syndrome patients before pregnancy. If aortic root enlargement is found in a pregnant patient, close echocardiographic surveillance and blood pressure management is mandatory. If the aortic root is larger than 4 cm or a progression of aortic root enlargement is observed, a beta-receptor blocking drug should be administered. Beta-receptor blocking drugs may have important maternal and fetal side effects and should be used cautiously [60–62]. They can increase the uterine tone and contractility and decrease umbilical blood flow. Furthermore, although propranolol is probably not a teratogen, it is associated with adverse fetal and neonatal effects and use should be decided on an individual basis [60, 61, 63]. The primary aim of intrapartum management in patients with Marfan syndrome or a bicuspid aortic valve and aortic root enlargement is to reduce the cardiovascular stress of labor and delivery. In patients at risk, elective fetal lung maturation should be induced at 26-weeks gestation. Hospitalization of high-risk patients should be considered between 28 and 32 weeks. When possible, consultation with a neonatologist should be also arranged at this time so that the parents can be adequately informed about the treatment options and risks for a preterm infant. We recommend delivery by cesarean section in regional anesthesia to prevent blood pressure peaks, which may induce dissection. Aortic root surgery should be done a few days after delivery. Close monitoring and administration of beta-blocking drugs should continue up to 3 months postpartum. Dissection (Type A or Type B) can occur during this period. In our experience, before 30-week gestation, aortic repair with the fetus in utero is recommended. The use of intraoperative cardiotocography (CTG) for monitoring fetal heart beats during aortic surgery (or other type of surgery) may be an option to document the actuarial situation of the child. We recently reported a patient in which misinterpretation of the CTG led to an emergency caesarean section [64]. As recommended by Becker [65], high-flow, high-pressure normothermic perfusion and a perfusion index of 3.0 during cardiopulmonary bypass is probably safest for the fetus. Hypothermia decreases placental blood flow [66] and may cause fetal bradycardia, leading to intrauterine death or severe hypoxic-ischemic fetal insult [31]. However, avoiding hypothermia precludes an open distal aortic repair, which is preferable [67]. A good compromise may be the use of antegrade cerebral perfusion for brain protection and moderate hypothermia (28°C) as described by Bachet and Guilmet [68]. There are several reports of successful hypothermia or deep hypothermic circulatory arrest during pregnancy (before 28-weeks gestation). After 30-weeks of gestation, immediate cesarean section followed directly by cardiac surgery seems to be the most promising option to save the live of the mother and her unborn child. No serious complications have been reported in the literature by adapting this modality of treatment. Cardiac surgery should be performed in a hospital in which neonatal intensive care facilities are available. For safety reasons cardiopulmonary bypass can be installed simultaneously during cesarean section (femoral or axillary cannulation). In patients with Type B dissection, conservative treatment is recommended in the absence of rupture or malperfusion. A high-incidence of fetal demise has been reported. This is probably due to a partial occlusion of the internal iliac artery or the ovarian arteries decreasing placental blood flow. Complications of Type B dissections require immediate surgical intervention as per acute Type A dissections.

Conclusions
Patients with a known bicuspid aortic valve and enlarged aortic root should to be counseled like Marfan syndrome patients. Normal sized patients with an aortic root size more than 4 cm (or smaller in patients with low BSA), or an increase of aortic root size during pregnancy are at high risk for the occurrence of aortic dissection, mainly in the third trimester. If possible, surgical repair of the enlarged aortic root should be done prepartum. In patients in whom the diagnosis of an enlarged aortic root is made during pregnancy, a close echocardiographic follow-up (4 to 6 weeks) is mandatory. In an aortic root more than 4 cm or with increasing size, beta-blocking agents should be prescribed but with caution. Development of the child should be monitored. In patients at risk elective fetal lung maturation should be induced at 26-weeks gestation and hospitalization of high-risk patients should be considered between 28 and 32 weeks. During pregnancy and during delivery, hypertensive blood pressure should be prevented; we recommend a cesarean section under regional anesthesia in all patients at risk. Aortic root surgery should be performed a few days after delivery. In case of acute Type A dissection before 30 weeks of gestation immediate surgery should be performed, and after 30-weeks gestation cesarean section followed by cardiac surgery is the best modality of treatment. Close monitoring and the administration of beta-blocking agents is mandatory up to 3 months postpartum, as late dissections may occur in this time period.


   References
Top
 Abstract
 Introduction
 Patients and methods
 Results
 Comment
 References
 

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