Heritable thoracic aortic diseases: Pregnancy and postpartum care

INTRODUCTION — Pregnancy in individuals at risk for thoracic aortic aneurysm or dissection is associated with elevated maternal and offspring risk.

Causes of thoracic aortic aneurysm include hereditable thoracic aortic diseases (HTADs), congenital conditions (including bicuspid aortic valve, Turner syndrome, coarctation of the aorta, and tetralogy of Fallot), hypertension, atherosclerosis, degenerative aortic disease, aortitis (inflammatory or infectious), and traumatic aortic injury. (See "Epidemiology, risk factors, pathogenesis, and natural history of thoracic aortic aneurysm and dissection".)

HTADs include [1]:

●Syndromic disorders – These include Marfan syndrome [MFS], Loeys-Dietz syndrome [LDS], vascular Ehlers-Danlos syndrome, smooth muscle dysfunction syndrome, and other syndromes attributable to pathogenic variants in FLNA, BGN, or LOX.

and

●Nonsyndromic HTADs (nsHTADs) – These include pathogenic variants in ACTA2, MYH11, PRKG1, MYLK, and familial thoracic aortic aneurysm without identified pathogenic variants in a known gene for HTAD.

The management during pregnancy and postpartum care for individuals with MFS, LDS, and nsHTAD are reviewed here.

Related issues are discussed separately:

●Preconception risk assessment and preconception management in individuals with MFS, LDS, and nsHTAD are reviewed separately. For pregnant individuals with these conditions who have not received preconception care, risk assessment and counseling is provided as soon as the patient presents for care. (See "Heritable thoracic aortic diseases: Preconception risk assessment and management".)

●Management of pregnancy in individuals with vascular Ehlers-Danlos syndrome is discussed separately. (See "Overview of the management of Ehlers-Danlos syndromes", section on 'Reproductive options and pregnancy'.)

●Management of pregnancy in individuals with bicuspid aortic valve-associated ascending aortic aneurysm is discussed separately. (See "Bicuspid aortic valve: Management during pregnancy".)

●Management of pregnancy in patients with coarctation of the aorta is discussed separately. (See "Management of coarctation of the aorta", section on 'Pregnancy'.)

●Management of Turner syndrome in adults is discussed separately. (See "Management of Turner syndrome in adults".)

●The genetics, pathogenesis, clinical manifestations, diagnosis, and management of MFS and related disorders are discussed separately. (See "Genetics, clinical features, and diagnosis of Marfan syndrome and related disorders" and "Management of Marfan syndrome and related disorders".)

ROLE OF PREGNANCY HEART TEAM — Since individuals with HTAD are at moderate or high risk of complications during or following pregnancy, they should receive specialized evaluation, counseling, and management by a multidisciplinary pregnancy heart team prior to conception and during and following pregnancy, including delivery and the postpartum period [2]. The pregnancy heart team should include, at a minimum, a cardiologist, maternal-fetal medicine specialist/obstetrician, cardiovascular surgeon, and provider with expertise in genetics (genetic counselor or geneticist) [1-3].

MONITORING DURING PREGNANCY — Monitoring in pregnant patients with HTAD includes serial imaging of the aorta, generally by transthoracic echocardiography (TTE) if prepregnancy TTE imaging provided reliable imaging of the affected/vulnerable aortic segment. Magnetic resonance imaging (MRI) without gadolinium contrast is the preferred modality for imaging of the entire aorta during pregnancy for those who have not undergone preconception evaluation or who have inadequate ascending aorta imaging by TTE.

Aortic measurement methods are discussed separately. (See "Management of Marfan syndrome and related disorders", section on 'How to measure'.)

Echocardiography — Serial clinical assessment should include TTE monitoring in all pregnant patients with HTAD, even among patients with baseline aortic root diameter ≤40 mm, assuming the ascending aorta can be adequately visualized using echocardiography [4-6]. We suggest clinical and echocardiographic follow-up every 8 to 12 weeks if the aortic root diameter remains ≤40 mm, and we suggest follow-up every four to eight weeks if the aortic root diameter is >40 mm. The frequency of clinical and imaging follow-up should be individualized depending on patient characteristics.

Our approach is similar to the approaches recommended in major society guidelines. The 2018 European Society of Cardiology guidelines suggest repeat echocardiographic imaging every 4 to 12 weeks during pregnancy and six months postpartum in patients with ascending aorta dilation [7]. Similarly, the 2022 American College of Cardiology/American Heart Association aortic disease guidelines recommend echocardiographic measurement of the aortic root and ascending aortic dimensions at least once each trimester and again several weeks postpartum for patients with an aortopathic condition such as HTAD [1].

CMR if needed — When TTE is not sufficient to image the ascending aorta, cardiovascular magnetic resonance (CMR) imaging without gadolinium is recommended over computed tomography (CT) for elective imaging in pregnant patients with aortic dilation to avoid exposing the mother and fetus to ionizing radiation [1,7]. Also, in patients with HTAD with aortic arch or descending aorta dilation or with aneurysm or chronic dissection of head or neck vessels or abdominal visceral arteries, we suggest serial CMR imaging without gadolinium during pregnancy [1].

CMR imaging without gadolinium contrast is preferred and is generally sufficient for monitoring aortic size [2]. Gadolinium should generally be avoided in the pregnant patient, unless there is a specific indication for gadolinium contrast and the potential benefit is deemed to outweigh the potential risk to the fetus (see "Diagnostic imaging in pregnant and lactating patients", section on 'Magnetic resonance imaging'). Transesophageal echocardiography (TEE) is an alternative for imaging the thoracic aorta, but the distal ascending aorta and proximal aortic arch are generally not well visualized by this modality and serial comparison is challenging.

In a patient with suspected aortic dissection, CT is the preferred imaging modality.

PHARMACOLOGIC MANAGEMENT

Beta blocker — For pregnant patients with HTAD, we suggest beta blocker therapy [1]. Labetalol or extended-release metoprolol are the preferred beta blockers in pregnant patients since atenolol may impair fetal growth. The dose of beta blocker is adjusted to maintain the heart rate after submaximal exercise (eg, running up and down two flights of stairs) <100 beats per minute (bpm).

The use of beta blocker therapy in pregnant patients with HTAD is an extension of the indication for beta blocker therapy in patients with MFS with aortic dilation. Since pregnancy is associated with increased risk of aortic complications, we suggest beta blocker therapy during pregnancy in patients with or without aortic dilation in an attempt to minimize progressive aortic dilation and risk of aortic dissection by decreasing aortic wall stress. This approach is based largely on indirect evidence in nonpregnant patients with MFS. Limited evidence is available on the effects of beta blocker therapy in pregnant patients with MFS and other HTADs. Observational studies suggest that beta blocker therapy does not abolish the risk of progressive aortic dilation and aortic dissection during pregnancy [8]. (See "Management of Marfan syndrome and related disorders", section on 'Beta blocker'.)

A study from the Registry of Pregnancy and Cardiac Disease (ROPAC) found that beta blocker therapy during pregnancy was not associated with significant difference in fetal birth weight [9].

Discontinue ARB prior to conception — Patients with HTAD are commonly treated with an angiotensin II receptor blocker (ARB) with or without a beta blocker to reduce the risk of aortic complications. Patients with HTAD who are taking an ARB should be gradually transitioned to beta blocker therapy prior to conception, given the risk of congenital malformation and fetal loss with gestational use of an ARB. Down-titration of the ARB to off and up-titration of the beta blocker as appropriate (to maintain the heart rate after submaximal exercise <100 bpm) should occur over a period of weeks prior to conception. (See "Treatment of hypertension in pregnant and postpartum patients" and "Adverse effects of angiotensin converting enzyme inhibitors and receptor blockers in pregnancy".)

Blood pressure control — Strict guideline-directed blood pressure control is recommended for all pregnant patients with HTAD [1,7]. Dose adjustment of therapy for aortic preservation is suggested when the systolic blood pressure exceeds 130 mmHg. Angiotensin converting enzyme inhibitors and ARBs are teratogens and thus contraindicated during pregnancy. (See "Treatment of hypertension in pregnant and postpartum patients" and "Adverse effects of angiotensin converting enzyme inhibitors and receptor blockers in pregnancy".)

Anticoagulant management — For pregnant patients with HTAD who require anticoagulation (eg, for atrial fibrillation or prosthetic valve), management of anticoagulants during pregnancy is discussed separately. (See "Use of anticoagulants during pregnancy and postpartum" and "Management of antithrombotic therapy for a prosthetic heart valve during pregnancy".)

VALVE DISEASE — Patients with MFS or other HTADs may have valve disease, primarily aortic regurgitation (generally associated with aortic dilation) or mitral valve prolapse, often accompanied by mitral regurgitation. Management of these valve lesions prior to and during pregnancy including indications for valve intervention are discussed separately. (See "Pregnancy and valve disease".)

MANAGEMENT OF AORTIC DISSECTION — The diagnosis and management of acute aortic emergency or aortic dissection that occurs during pregnancy or the postpartum period are similar to that for aortic dissection in general. (See "Overview of acute aortic dissection and other acute aortic syndromes" and "Clinical features and diagnosis of acute aortic dissection" and "Management of acute type A aortic dissection" and "Management of acute type B aortic dissection" and "Surgical and endovascular management of acute type B aortic dissection".)

Given the lethal nature of aortic dissection, prompt diagnosis and intervention are critical. A review including papers describing 36 females with MFS with aortic dissection antepartum or postpartum reported a 21 percent maternal mortality rate and 12 percent fetal mortality rate [8].

When aortic dissection is suspected, confirming the diagnosis is the first priority. For pregnant patients presenting with a high clinical suspicion for acute aortic dissection, CT is the test of choice given its widespread availability, reliability, and imaging speed. Other imaging modalities, such as TEE or CMR are generally reserved for nonacute settings (eg, follow-up of chronic aortic dissection) [10,11]. When CMR is performed, no gadolinium contrast is generally required, although gadolinium may be appropriate if it enhances the clarity of the diagnosis. Limited data suggest that the risk to the fetus of gadolinium may be minimal [12]. (See "Diagnostic imaging in pregnant and lactating patients" and "Clinical features and diagnosis of acute aortic dissection".)

Optimal treatment of aortic dissection during pregnancy requires individualized management by a multidisciplinary pregnancy and aortic heart team. The choice of medical, percutaneous, or surgical aortic treatment is based upon the patient's diagnosis, stability, the location of aortic dissection, and the gestational age of the fetus.

The following recommendations are in broad agreement with recommendations in the 2022 American College of Cardiology/American Heart Association aortic guidelines [1]:

●For type A dissection (dissection involving the ascending aorta) – Patients with acute type A dissection require urgent surgical repair, as discussed separately. (See "Management of acute type A aortic dissection".)

•For type A dissection during the first or second trimester, urgent surgical repair is performed with the fetus in situ with fetal monitoring as appropriate. Fetal loss is common during hypothermia and prolonged cardiopulmonary bypass, and there is an increased rate of teratogenesis [13]. (See "Management of acute type A aortic dissection" and "Anesthesia for nonobstetric surgery during pregnancy".)

The high maternal and fetal risk associated with cardiovascular surgery during the second trimester was illustrated by a meta-analysis of 179 observational studies with a total of 386 patients, of whom 120 underwent cesarean delivery prior to cardiovascular surgery [14]. The most common indication for cardiovascular surgery was aortic aneurysm or dissection (31.3 percent).

During the second trimester:

-Fetal mortality for cesarean delivery prior to cardiovascular surgery was 37.5 percent and for cardiovascular surgery with fetus in situ was 33.9 percent.

-Maternal mortality for cesarean delivery prior to cardiovascular surgery was 37.5 percent and 4.6 percent for surgery with the fetus in situ.

•For type A dissection during the third trimester, we recommend urgent cesarean delivery immediately preceding aortic repair.

In the above cited meta-analysis, cesarean delivery prior to cardiovascular surgery was associated with lower fetal mortality than cardiovascular surgery with the fetus in situ during the third trimester (4.5 versus 29.4 percent) [14]. In a multivariable model, cesarean delivery prior to surgery was associated with a reduced risk of fetal mortality (odds ratio 0.19, 95% CI 0.06-0.56). Maternal mortality during the third trimester was similar for those undergoing cesarean delivery prior to surgery to that for those undergoing surgery with a fetus in situ (6.3 versus 8.8 percent).

●For type B dissection (aortic dissection not involving the ascending aorta, including aortic arch dissection not involving the ascending aorta) – Type B dissection is generally treated medically unless intervention (percutaneous stent or surgery) is required to treat acute complications such as malperfusion, aortic rupture, or subacute aortic leak. When type B aortic dissection requires intervention during pregnancy, nonsurgical methods are generally preferred as they may be the safest approach for mother and fetus [15], but the approach should be individualized. (See "Management of acute type B aortic dissection".)

In patients with aortic dissection, pharmacologic interventions to reduce shear stress and blood pressure are needed (eg, treatment with esmolol) (table 1) but the administration of nitroprusside during pregnancy should be avoided when feasible to avoid possible fetal thiocyanate toxicity. (See "Management of acute type B aortic dissection", section on 'Medical management'.)

DELIVERY

Location — Given the risk of aortic dissection and other cardiovascular complications, all pregnant patients with HTAD, especially those with aortic root aneurysm (aortic root ≥40 mm) should be delivered at an aortic care referral center where emergency aortic surgical repair is available on site and performed regularly [1,7].

Consider risk of dural ectasia — Prior to attempting epidural anesthesia, the likely presence of dural ectasia should be considered in patients with MFS and LDS [16]. Dural sac dilation can be present in up to 90 percent of patients with MFS and LDS and may be asymptomatic or associated with low back pain, headache, or proximal leg pain, weakness, or numbness. Dural ectasia can be visualized by lumbosacral MRI or CT studies (image 1), generally performed prior to conception as part of comprehensive aortic imaging.

Although dural ectasia is not an absolute contraindication for epidural anesthesia, the increased risk of dural puncture or inadequate anesthesia should be discussed with the patient. It has been recommended that the epidural technique be performed in the lateral decubitus position to decrease the possibility of extension of the ectatic dural sac into the epidural space [17]. It is important to recognize that an increased amount of cerebrospinal fluid volume is generally present with dural ectasia, which may lead to spinal anesthesia failure [18]. Consultation with an experienced obstetrical anesthesiologist is recommended prior to delivery to determine the type of anesthetic and management strategy. (See "Genetics, clinical features, and diagnosis of Marfan syndrome and related disorders", section on 'Dural ectasia'.)

Mode of delivery — There is no strong consensus regarding the preferred mode of delivery for patients with HTAD since scant evidence is available. The method of delivery should be carefully considered and individualized. We do not believe that there is sufficient information to endorse any general recommendations. General obstetric principles should be applied to select the least hemodynamically stressful mode of delivery in the context of the particular pregnancy at hand unless there is an overriding specific obstetric indication for cesarean delivery. This approach is in keeping with the position of the Professional Advisory Board of the Marfan Foundation [19].

Beta blocker therapy is continued during labor to minimize surges in blood pressure and cardiac output.

Presence of one or more of the following features is associated with increased risk of aortic complications: a dilated ascending aortic diameter (≥40 mm, particularly if >45 mm) [1,7], prior aortic dissection [7], and documented progressive aortic dilation during pregnancy (≥3 mm/year).

●For ascending aorta <40 mm – With an ascending aorta diameter of <40 mm, assisted vaginal delivery is preferable for most patients.

Cesarean delivery is advised only for obstetric indications or if there are aortic risk factors such as a rapidly enlarging aorta (≥3 mm/year) or severe cardiovascular disease such as aortic dissection.

During vaginal delivery, epidural anesthesia should be provided to minimize pain and associated cardiovascular changes that would put further stress on the vasculature. (See "Anesthesia for labor and delivery in high-risk heart disease: General considerations".)

●For ascending aorta ≥40 mm and <45 mm – For patients with ascending aorta diameter ≥40 mm and <45 mm and no other aortic risk factors, either vaginal delivery or cesarean delivery is reasonable. This approach applies to patients with HTAD, including those with LDS. Some obstetric providers prefer scheduled cesarean delivery for patients with LDS types 1 to 3, as there was one study [20] that reported uterine rupture; however, this has not been reported in subsequent studies.

●For ascending aorta diameter ≥45 mm or other high-risk features – In patients with an ascending aorta diameter ≥45 mm, progressive aortic dilation during pregnancy (≥3 mm/year), or prior or chronic aortic dissection, cesarean delivery is generally preferred. (See "Anesthesia for labor and delivery in high-risk heart disease: General considerations".)

As noted above, acute type A aortic dissection is an indication for urgent cesarean delivery if the fetus is viable, followed by or with simultaneous aortic repair. (See 'Management of aortic dissection' above.)

Antibiotic prophylaxis — The role of antibiotic prophylaxis prior to delivery in patients with valve disease is discussed separately. (See "Pregnancy and valve disease" and "Prevention of endocarditis: Antibiotic prophylaxis and other measures".)

POSTPARTUM CARE — Due to the increased risk of aortic dissection postpartum, patients with HTAD should be monitored for complications during the first four to six weeks postpartum. Postpartum follow-up should be individualized and may range from one postpartum visit for low-risk patients to weekly follow-up with imaging during the first few weeks for high-risk patients. Patients should be alerted about the increased risk of aortic dissection postpartum and encouraged to present promptly for evaluation and imaging should symptoms of persistent chest or back discomfort occur.

In patients with HTAD with aortic root/ascending aortic ≥40 mm, we continue beta blocker therapy for six weeks or more postpartum [1]. For patients with HTAD with normal aortic dimension, the decision regarding duration of postpartum beta blocker therapy should be made using shared decision making with the pregnancy heart team.

For patients with HTAD and aortic root/ascending aortic diameter >40 mm, long-term recommendations for beta blocker therapy or angiotensin II receptor blocker apply during and after the postpartum period, with modifications made in consultation with the infant's pediatric clinician if the patient is breastfeeding.

Labetalol, metoprolol, or propranolol therapy is commonly considered compatible with breastfeeding, but a decision regarding use is made based upon an individualized assessment of potential benefits and risks in consultation with the pediatrician. ARB therapy is generally not administered during breastfeeding as evidence is lacking on its use in this setting. (See "Management of Marfan syndrome and related disorders", section on 'Drug therapy' and "Treatment of hypertension in pregnant and postpartum patients", section on 'Drug options during breastfeeding'.)

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Aortic dissection and other acute aortic syndromes" and "Society guideline links: Marfan syndrome" and "Society guideline links: Management of cardiovascular diseases during pregnancy".)

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Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)

●Basics topic (see "Patient education: Marfan syndrome (The Basics)")

SUMMARY AND RECOMMENDATIONS

●Multidisciplinary care – Multidisciplinary preconception, pregnancy, and postpartum care for patients with hereditable thoracic aortic disease (HTAD) should be provided by a pregnancy heart team at a center with experience in management of HTAD, and access to maternal fetal medicine, specialized imaging, and cardiac/aortic surgical intervention is recommended for all patients with HTAD. The pregnancy heart team should include, at a minimum, a cardiologist, maternal-fetal medicine specialist/obstetrician, anesthesiologist, cardiovascular surgeon, and provider with expertise in genetics (genetic counselor or geneticist). (See 'Role of pregnancy heart team' above.)

●General management during pregnancy – All pregnant patients with HTAD require regular cardiovascular follow-up during pregnancy with individualized frequency of follow-up and imaging. (See 'Monitoring during pregnancy' above.)

•Monitoring – For monitoring during pregnancy, we suggest clinical and echocardiographic follow-up every 8 to 12 weeks if the aortic root diameter remains ≤40 mm for Marfan syndrome (MFS) and Loeys-Dietz syndrome (LDS), and we suggest follow-up every four to eight weeks if the aortic root diameter is >40 mm. (See 'Monitoring during pregnancy' above.)

•Beta blocker therapy – For patients with HTAD, we suggest beta blocker therapy during pregnancy and for at least six weeks postpartum (Grade 2C). The duration of therapy should be individualized based on patient diagnosis, aortic dimension, and shared decision making between the patient and pregnancy heart team. We prefer labetalol or metoprolol during pregnancy. The goal of beta blocker therapy is to minimize progressive aortic dilation and the risk of aortic dissection, although limited supporting data are available in this setting. (See 'Pharmacologic management' above.)

•Treatment of hypertension – Strict blood pressure control is recommended for all pregnant patients with MFS. (See 'Pharmacologic management' above and "Treatment of hypertension in pregnant and postpartum patients".)

●Aortic dissection during pregnancy (See 'Management of aortic dissection' above.)

•Type A (ascending aorta) dissection – Patients with acute type A dissection require urgent surgical aortic repair. (See "Management of acute type A aortic dissection".)

-During the first or second trimester – For type A aortic dissection during the first or second trimester, urgent surgical repair is performed with the fetus in situ with fetal monitoring as appropriate. (See "Management of acute type A aortic dissection" and "Anesthesia for nonobstetric surgery during pregnancy".)

-During the third trimester – For most patients with type A dissection during the third trimester, we recommend urgent cesarean delivery prior to urgent aortic repair (Grade 1B).

•Type B (not involving the ascending aorta) dissection – Type B dissection is generally treated medically unless intervention (percutaneous stent or surgery) is required to treat acute complications.

●Delivery – All pregnant patients with HTAD should deliver at a medical center where emergency aortic repair is frequently performed. The mode of delivery should be carefully considered and individualized for patients with HTAD by a multidisciplinary pregnancy heart team. Beta blocker therapy is continued during labor to minimize surges in blood pressure and cardiac output. (See 'Delivery' above.)

•For ascending aorta <40 mm – With an ascending aorta diameter of <40 mm, vaginal delivery is preferable for most patients.

Cesarean delivery is advised only for obstetric indications or if there are aortic risk factors such as a rapidly enlarging aorta (≥3 mm/year), or severe cardiovascular disease such as aortic dissection. (See "Anesthesia for labor and delivery in high-risk heart disease: General considerations".)

•For ascending aorta ≥40 mm and <45 mm – For patients with ascending aorta diameter ≥40 mm and <45 mm and no other aortic risk factors, either vaginal delivery or cesarean delivery is reasonable. This approach applies to patients with HTAD, including those with LDS. Some obstetric providers prefer scheduled cesarean delivery for patients with LDS types 1, 2, or 3.

•For ascending aorta diameter ≥45 mm or other high-risk features – In patients with an ascending aorta diameter ≥45 mm, progressive aortic dilation during pregnancy (≥3 mm/year), or prior or chronic aortic dissection, cesarean delivery is generally preferred. (See "Anesthesia for labor and delivery in high-risk heart disease: General considerations".)

●Postpartum care – Due to the increased risk of aortic dissection postpartum, patients with HTAD should be monitored for complications during the first four to six weeks postpartum. For patients with HTAD and aortic root/ascending aortic diameter >40 mm, long-term recommendations for beta blocker therapy or angiotensin II receptor blocker (ARB) apply during and after the postpartum period, with modifications made in consultation with the infant's pediatric clinician if the patient is breastfeeding. (See 'Postpartum care' above.)

ACKNOWLEDGMENT — The UpToDate editorial staff acknowledges Michael J Wright, MBChB, MSc, who contributed to earlier versions of this topic review.