Vascular Disease and Dissection in Pregnancy

Melinda B. Davis

Key Points

•Pregnancy increases the risk or aortic dissection by 25-fold above the baseline for the general population

•The most common risk factor for aortic aneurysm and dissection is hypertension that is most frequently encountered in the third trimester of pregnancy

•Spontaneous coronary artery dissection is the most common cause of myocardial infarction in pregnancy

Introduction

Women with vascular diseases are at increased risk for complications during pregnancy and the early postpartum period. Unfortunately, the initial presentation for women with underlying vascular disease may be with a catastrophic complication, such as aortic or coronary dissection, and may present during pregnancy. Women at risk for vascular complications include those with connective tissue disorders, such as Marfan syndrome, Ehlers-Danlos syndrome (EDS), and Loeys-Dietz syndrome; other disorders associated with aortopathy, such as bicuspid aortic valve (BAV) and Turner syndrome; and other systemic vascular disorders such as fibromuscular dysplasia. These conditions pose high risk of maternal, obstetric, and fetal complications, and appropriate management requires multiple subspecialties. In some situations, pregnancy is contraindicated. This chapter will address vascular disorders that may affect women during childbearing; major complications, including coronary and aortic dissections; and considerations for preconception counseling, antepartum, labor and delivery, and postpartum care. Genetic counseling and prenatal diagnosis of offspring should be considered.

Epidemiology

Vascular complications that occur in young women of childbearing age are most commonly related to underlying conditions. Many of these diseases may be undiagnosed in young women during pregnancy but only come to attention after an acute presentation of vascular dissection [1,2]. The true prevalence of vascular disorders and dissections in pregnancy is likely to be underestimated due to low suspicion and missed opportunities for diagnosis.

The incidence of aortic dissection in the normal population is approximately 6 per 100,000 individuals per year. Women with vascular diseases have higher risk. In the absence of pregnancy, the incidence of aortic dissection is 170 per 100,000 in Marfan syndrome [3], 36 per 100,000 in Turner syndrome [4], and 31 per 100,000 in BAV [5]. Pregnancy increases the risk 25-fold [6]. Clearly, aortic dissection can have devastating consequences. In a study of maternal mortality in the Netherlands, half of the total maternal deaths (3 per 100,000 deliveries) were attributed to aortic dissection [7]. Aortic dissections can occur in the first trimester (5%), second trimester (10%), third trimester (50%), and postpartum (20%) [8].

Spontaneous coronary artery dissection (SCAD) may account for 1%–4% of all acute coronary syndromes, but 35% of cases in women under age 50 [9]. SCAD is the most common cause of pregnancy-associated myocardial infarction, accounting for 43% of cases [10]. Pregnancy-associated SCAD portends worse outcomes with higher troponin, lower LV function, more congestive heart failure, and cardiogenic shock [11,12]. Most cases occur during late pregnancy or early postpartum, with the highest incidence being the first week postpartum; however, pregnancy-associated SCAD has been reported as little as 2 weeks after conception and >12 months postpartum, especially in women who are breastfeeding [2,13].

Vascular Disorders

Several vascular disorders cause increased risk of cardiovascular complications during pregnancy, and many have underlying genetic abnormalities. Women who present with vascular complications should undergo workup for the presence of underlying vascular diseases, and be offered genetic counseling when appropriate. Additional risk factors for aortic dissection include prior history of cardiac surgery and cardiac catheterization. Stressors that can increase the vascular wall stress and precipitate vascular dissections include hypertension, pheochromocytoma, cocaine and other stimulant drugs, weight-lifting and intense Valsalva, trauma, deceleration injury, intense emotional stress, and labor and delivery. The most common risk factor for aortic aneurysm and dissection is hypertension. Specific vascular disorders include Marfan syndrome, EDS, BAV, Turner syndrome, and fibromuscular dysplasia (Table 13.1).

Table 13.1 Vascular Diseases, Phenotypes, Genetic Mutations, and Considerations for Pregnancy
Vascular Disease	Clinical Phenotype	Vascular Features	Genetic Mutations	Consider Prophylactic Surgery before Pregnancy	Management	Follow-Up Surveillance Postpartum
Marfan syndrome	•Aortic dilatation •Ectopia lentis •Various characteristic musculoskeletal abnormalities, as well as skin, lung, and CNS	•Aortic dilatation (in 60%−80% of patients) and often starts initially at root	FBN1	≥45 mm aortic diameter (or less if other risk factors)	•Beta-blockers •Consider addition of ARB (but contraindicated in pregnancy) •? Limited data suggests avoiding CCB	•Echo and CT/MRI initially; 6 months •If stable and echo correlates with CT/MRI, CT/MRI every 3−5 years (or more often if screening descending/abdominal aorta) •If stable and <45 mm, then annual imaging •If ≥45 mm, more often (every 6 months)
Loeys-Dietz	•Craniofascial (hypertelorism, bifid uvula, cleft palate)	•Arterial tortuosity •Dissection often at aortic root, but widespread arterial involvement	TGFBR1 TGFBR2 SMAD3 TGFB2 TGFB3	≥45 mm aortic diameter (or less if other risk factors)	•Consider prophylactic surgery •Consider ARBs and/or beta-blockers	•Annual MRI (or CT) from cerebral to pelvic circulation
Vascular Ehlers-Danlos (type IV)	•Thin translucent skin •Easy bruising •Facial features (tight skin, pinched nose, thin lips) •Rupture of visceral organs	•Dilatation of aorta may not precede dissection •Entire aorta and branches at risk	COL3A1 – Type III procollagen	Pregnancy considered contraindicated. Surgery reserved for life-threatening complications or high-risk aneurysms	Celiprolol or other beta-blockers may reduce risk of aortic dissection	•Annual carotid and abdominal US •Consider thoracic aortic surveillance
Familial TAAD	•Non-syndromic •Variable associations (i.e., patent ductus arteriosus, livedo reticularis, etc.)	•Some may have dissection without preceding dilatation	ACTA2 MYH11 TGFBR2 MYLK PRKG1	≥50 mm aortic diameter; however, lack of data and attention to family history is needed	•May consider beta-blocker, but limited data	•Consider routine serial screening •Screen at risk relatives
Turner syndrome	•Short stature •Premature ovarian failure •Metabolic syndrome (obesity, glucose intolerance, hyperlipidemia) •Hypertension	•Associated with BAV in 30% and coarctation of the aorta in 12% •Dilatation often at root/ascending aorta	45XO karyotype	ASI ≥27 mm/m2	•Index the aorta diameter for BSA •Consider ARBs/ACEi and/or beta-blockers	•TTE/MRI surveillance based on aortic dimensions
Bicuspid aortic valve	•Present in 2% of the population	•Dilatation of the ascending aorta, independent of valve function	NOTCH1	≥50 mm aortic diameter (some consider if >45 mm; or if ≥5 mm increase per year)	•Consider beta-blockers during pregnancy if aorta dilated	•MRI or CT to evaluate entire aorta •Screen first-degree relatives •Follow-up imaging customized to the individual
Fibromuscular dysplasia (FMD)	•Idiopathic disease of the arterial walls leading to aneurysm, tortuosity, and dissection	•Aneurysms can occur in renal, carotid, intracranial, mesenteric, coronary arteries and aorta	May be sporadic PHACTR1	Not applicable	•Manage hypertension	•Follow-up imaging customized to the individual •Patients with SCAD need postpartum imaging from brain to pelvis to assess for FMD
Note: Additional risk factors for aortic aneurysms: family history of aortic dissection, growth rate ≥3 mm/year, hypertension. Factors that may influence the decision to proceed with prophylactic aortic repair surgery include severe mitral or aortic regurgitation and other indications for cardiac surgery such as coronary artery bypass grafting. Abbreviations: CNS, central nervous system; CCB, calcium channel blocker; TGFBR1, TGF-beta receptor 1; TGFBR2, TGF-beta receptor 2; SMAD3, SMAD family member 3; TGFB2, TGF-beta 2 ligand; TGFB3, TGF-beta 3 ligand; ACTA2, smooth muscle alpha-2-actin; MYH11, smooth muscle myosin heavy chain; TGFBR2, TGF-beta receptor 2; MYLK, myosin light-chain kinase; PRKG1, type I cGMP-dependent protein kinase regulating smooth muscle cell relaxation; BSA, body surface area; ARB, angiotensin receptor blocker; ACEi, angiotensin converting enzyme inhibitor.
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Marfan Syndrome

Marfan syndrome is an autosomal dominant disorder caused by various mutations in the gene (FBN-1 on chromosome 15) that encode for extracellular matrix protein fibrillin I [14,15]. Marfan syndrome has an estimated incidence of 1 in 5000 and involves skeletal, ocular, and cardiovascular systems. Most patients have cardiovascular involvement, and the presence of aortic dilatation confers high risk for morbidity and mortality. Valvular disease, including aortic regurgitation and prolapse of the mitral and tricuspid valves, can lead to arrhythmias and heart failure, and premature rupture of membranes can occur during pregnancy [16,17]. Clinical heterogeneity, even among individuals with the same genetic mutation, can add to the complexity of diagnosis. The original diagnostic criteria, known as the Ghent Nosology, was published in 1996, which was later revised to include many patients who do not have the fibrillin 1 mutation. The diagnosis can be challenging, and a multidisciplinary team should be involved, including clinical genetics. The diagnosis is sometimes only considered after a life-threatening complication occurs during pregnancy [17,18].

Vascular Ehlers-Danlos Syndrome

Vascular Ehlers-Danlos syndrome (EDS) (type IV) is inherited in an autosomal dominant pattern related to mutations in the COL3A1 gene. Patients with EDS are at high risk of early death due to arterial, intestinal, and uterine rupture. Arterial complications occur in an unpredictable manner, even without arterial dilatation, and surgical repair is challenging due to the friable nature of the vascular tissue. Vascular EDS poses a high risk of obstetric complications, and deaths can occur from arterial dissection or uterine rupture. In a study of 81 pregnancies, 12 women died (14.8%) [19]. A subsequent study of 565 pregnancies reported arterial dissection in 9.2%, uterine rupture in 2.6%, and maternal deaths in 6.5% [20]. Other obstetric complications in women with all types of EDS include separation of the symphysis pubis, severe postpartum hemorrhage, and preterm delivery. Pregnancy is considered contraindicated in women with vascular EDS due to the high risk of mortality, but shared decision making is essential, and women who choose to pursue pregnancy should be followed by a multidisciplinary team at a specialized center [20,21].

Bicuspid Aortic Valve

Bicuspid aortic valve (BAV) is one of the most common congenital heart defects and is present in about 1% of the population. BAV is associated with histopathologic abnormalities of the ascending aorta leading to dilation and aneurysm [22]. Among young patients <40 years with aortic dissection, BAV was present in 9% [23]. Patients with BAV should be screened for the coexistence of aortic coarctation by clinical examination and imaging, since coarctation can compound the risk of aortic aneurysms [24]. First-degree relatives of patients with BAV should also be offered screening echocardiogram to assess for valve disease and aortopathy (class IIa) [24].

Turner Syndrome

Turner syndrome is caused by the loss of part or all of the X chromosome and occurs in 1 in 2500 girls. Pregnancy in women with Turner syndrome can occur spontaneously in women with mosaic pattern (0.5%–10%), but otherwise occurs with assisted fertility treatment. Women should undergo cardiovascular evaluation prior to beginning fertility therapy [25] because Turner syndrome is associated with congenital heart disease, aortic dilatation, hypertension, diabetes, and atherosclerotic disease, as well as preeclampsia [26]. Blood pressure control and diabetes management are important. During pregnancy, the risk of death from aortic dissection may be 2%, and the risk may increase with concomitant BAV and/or aortic coarctation [27].

Fibromuscular Dysplasia

Fibromuscular dysplasia (FMD) is a vascular disease associated with arterial tortuosity, stenosis, and aneurysms in any arterial bed, but most commonly in the renal arteries, carotid arteries, and intracranial arteries [28]. Coronary dissections and aortic aneurysms can occur. Patients who present with SCAD are frequently diagnosed with FMD in another arterial circulation. Due to the high incidence of arterial aneurysms and dissections, every patient with FMD is recommended to undergo one-time head-to-pelvis cross-sectional imaging with CTA or MRA. FMD should also be suspected in young women with hypertension, severe persistent headache, TIA or stroke, aneurysms, renal infarction, or in the presence of an abdominal or carotid bruit [29].

Vascular Complications during Pregnancy

The hemodynamic stress of pregnancy (increase in blood volume, heart rate, stroke volume, and cardiac output) [30,31], partially offset by decreased peripheral vascular resistance and diastolic blood pressure, may contribute to increased risk of vascular complications during pregnancy. In addition, histologic changes in the aorta that predispose to vascular fragility that are related to the hormonal changes of pregnancy include decreased acid mucopolysaccharides, loss of normal corrugation of elastic fibers, and fragmentation of the aortic reticulin fibers [32,33]. The hemodynamic and hormonal changes increase susceptibility to vascular dissections, particularly in women with preexisting abnormal structure of the vasculature related to connective tissue diseases or fibromuscular dysplasia. Labor and delivery may cause increased aortic and coronary shear stress. Complications can occur at any time during pregnancy, but after the second trimester or postpartum are the highest risk [34]. Among women with SCAD, the highest incidence occurs in the first month postpartum, particularly in the first week, suggesting a contribution from uterine contraction and the massive increase in blood volume post-delivery [12].

Women with vascular diseases can suffer from several types of complications during pregnancy, including myocardial infarction, cardiogenic shock, hemorrhage, heart failure, arrhythmias, and venous thromboembolism. Two of the most feared complications are aortic dissection and coronary artery dissection.

Aortic Dissection

Aortic dissection occurs when an interruption in the medial layer of the aorta allows intramural hemorrhage and propagation of blood, resulting in a sudden, severe, tearing type of pain with radiation to the back. The dissection can propagate to the aortic valve causing aortic regurgitation, or blood may enter the pericardial space causing cardiac tamponade. If branch vessels are involved, ischemia of the coronary, carotid, spinal, or visceral arteries can occur.

Precise classification of thoracic aortic dissections is important. The Stanford classification scheme includes type A dissections (involving the ascending aorta) and type B dissections (involving the descending aorta, and not the ascending aorta) (Figure 13.1). The DeBakey classification scheme describes dissections in the ascending aorta, arch, and descending aorta (type I); those that are confined to the ascending aorta (type II); and those that involve the descending aorta (type III). Early and accurate diagnosis of aortic dissection is essential (Figure 13.2).