Dr. Brickner is co-director of the Adult Congenital Heart Disease Program at UT Southwestern Medical Center, Dallas, Texas.
Management challenges in pregnancies complicated by maternal heart disease are complex, requiring ongoing involvement of a team of specialists.
Cardiovascular disease (CVD) is one of the leading causes of morbidity and mortality during pregnancy.1 This review will give an overview of the types of CVD seen in pregnancy, present a risk stratification scheme to assess cardiovascular risk during pregnancy, and address the importance of coordinated care.
Physiologic changes in pregnancy
Pregnancy places an increased workload on the heart, including increases in circulating blood volume, plasma volume, heart rate, and cardiac output.2 This is usually well tolerated by healthy mothers but may not be by women with preexisting CVD who have inadequate cardiovascular reserve. During labor and delivery, additional hemodynamic changes including increased heart rate, arterial pressure, central venous pressure, and cardiac output place additional stress on the maternal heart. Pregnancy may also lower the threshold for rhythm disturbances.3 Pregnancy is also a prothrombotic state with hypercoagulable changes occurring early in pregnancy and persisting well into the postpartum period, thus increasing the risk of intracardiac thrombus and cardioembolic events.4 For these reasons, preconceptual counseling is necessary for women with preexisting CVD to clearly define both maternal and fetal risks of pregnancy.5
Congenital heart disease
In developed countries, congenital heart disease (CHD) has become the most common type of maternal CVD complicating pregnancy.6-8 CHD is the most common form of birth defect and, due to advances in congenital heart surgery and interventional catheterization procedures, most patients with CHD now survive well into adulthood. Many patients with CHD (as well as many physicians) mistakenly assume that if one or more surgeries were performed during childhood, CHD is repaired or “cured.” However, for many of these patients, there are significant residual anatomic abnormalities or sequelae from the original surgery that may affect cardiovascular function. Some surgical procedures are considered palliative whereas others restore more normal or nearly normal intracardiac anatomy. Many patients are unaware or have only limited knowledge of their specific CHD diagnosis or their specific surgical repair. Likewise, many women with CHD are not aware of their specific risks for pregnancy due to their heart disease. Thus, a patient’s stated history of CHD “repair” is often inaccurate and her knowledge of her specific pregnancy risk is often inadequate. Therefore, preconceptual counseling and risk stratification are very important for the CHD population.
Approximately 50% of all patients with CHD have a simple defect such as a secundum atrial septal defect (ASD), ventricular septal defect (VSD), patent ductus arteriosus (PDA), isolated mild aortic or pulmonary valve disease, or a repaired simple ASD, VSD, or PDA. For women with these simple defects, pregnancy is usually well-tolerated with no significant increase in morbidity or mortality.
The remaining nearly 50% of all patients with CHD are those with either moderate or complex defects, including individuals with a single ventricle, a systemic right ventricle, pulmonary hypertension, persistent cyanosis, valvular disease, and other complicated issues. Pregnancy in women with moderate or complex defects may or may not be well-tolerated and the risk of fetal and maternal complications (including both morbidity and mortality) is significantly increased. The most common maternal complications are arrhythmias and heart failure, but stroke, cardioembolic events and infection may also occur.5-7 Fetal complications include spontaneous abortion, intrauterine fetal demise, preterm birth, small for gestational age, and neonatal and perinatal death.6-8
For mothers with moderate or complex CHD, maternal cardiovascular complications are more frequent, and involvement of a cardiologist specializing in adult congenital heart disease is critical for the optimal management of these patients. Several specific types of CHD are associated with particular risks.5-9
Moderate forms of CHD include coarctation of the aorta and tetralogy of Fallot. Coarctation of the aorta is often diagnosed and treated in childhood, but the diagnosis may also be missed. Mothers with unrepaired coarctation of the aorta are at increased risk of aortic rupture and dissection during pregnancy, pregnancy-induced hypertension, preeclampsia and eclampsia, as well as intrauterine growth retardation and prematurity.10 Even with repair, mothers are at increased risk for hypertension, pregnancy-induced hypertension, preeclampsia, eclampsia, heart failure, and arrhythmias as well as a small risk of aortic dissection.11
Tetralogy of Fallot is the most common form of cyanotic CHD and is usually diagnosed and repaired in childhood. Mothers with repaired tetralogy of Fallot may be left with residual pulmonary regurgitation or right ventricular (RV) outflow tract obstruction, leaving either a volume or pressure overload on the RV. Either of these situations can result in maternal complications such as arrhythmias or right heart failure symptoms.12,13 Mothers with severe pulmonary regurgitation may develop worsening RV enlargement during pregnancy that does not resolve after delivery, thus increasing the risk of arrhythmias and/or heart failure.
Some forms of CHD result in the RV serving as the “systemic ventricle,” supplying the systemic circulation. This is most commonly seen in mothers with a history of D-transposition of the great arteries with a prior “atrial switch repair” (Mustard or Senning operation) or in mothers with L-transposition of the great arteries (also known as congenitally corrected transposition). The RV is not anatomically designed for this role and, thus, may not tolerate the additional workload of pregnancy. These patients are at increased risk for arrhythmias, heart failure and a decline in RV function during pregnancy.14 Mothers with D-transposition of the great arteries who have undergone an arterial switch procedure, where the aorta is realigned to arise from the left ventricle, have significantly fewer pregnancy complications.15
Patients with CHD may have cyanosis due to unrepaired CHD or to complications associated with their surgical repairs. Some patients with cyanotic CHD may have had a “palliative” surgical procedure to improve pulmonary blood flow or improve cyanosis, but which leaves behind significant anatomic abnormalities. Maternal cyanosis results in an increased risk of both thrombosis and bleeding and places mothers at risk for stroke, bleeding complications, and paradoxical (right to left) embolism resulting in stroke or brain abscess. Maternal cyanosis significantly increases fetal risk with a poor likelihood of fetal survival when maternal oxygen saturation < 85%.16
Even patients with very complex forms of CHD with only a single ventricle can now routinely survive to adulthood and reach childbearing age. The Fontan operation refers to a surgical procedure to resolve cyanosis by directing systemic venous return to the pulmonary arteries without an intervening pump, with the single ventricle supplying the power for both systemic and pulmonary blood flow. This procedure is applied to a variety of underlying defects; thus, the specific type of congenital heart defect varies from patient to patient. The Fontan operation is a palliative procedure which does not “correct” the underlying congenital heart defect, but does allow for improved quality of life and often prolonged survival into adulthood. Mothers who have undergone the Fontan operation are at a significantly increased risk for prematurity, miscarriage, low fetal birth weight as well as maternal risks of arrhythmias, heart failure, and stroke.17,18
Valvular heart disease/native valve disease
Valvular heart disease is another common cause of maternal cardiovascular disease complicating pregnancy and is the leading form of CVD seen in underdeveloped countries. Left-sided valvular lesions (aortic and mitral valve disease) are the most common. Both aortic and mitral regurgitation are usually well-tolerated in pregnancy, unless ventricular dysfunction is present. Mothers with moderate to severe obstructive valve lesions have more difficulty tolerating the volume load and increased workload during pregnancy, and these patients may develop symptoms of heart failure, chest pain, or arrhythmias (and rarely, syncope) during pregnancy.5,6 Both aortic and mitral stenosis can result in an inability to adequately increase cardiac output; thus, exertional symptoms are common. The severity of exertional symptoms is usually a good marker of how well the patient will be able to tolerate labor and delivery. Pulmonary hypertension may be seen in patients with advanced left-sided valvular disease (particularly with mitral stenosis) and these patients are at particular risk for hemodynamic compromise during labor and delivery and require careful management.19
Prosthetic valve disease
Patients who have undergone prior valve replacement are a particular challenge in pregnancy. Bioprosthetic valves may be placed in a young woman who is interested in pregnancy since pregnancy is usually well-tolerated with a normally functioning bioprosthesis. For a mother with a mechanical prosthesis, anticoagulation management is complex. Warfarin provides the greatest protection against valve thrombosis and is the only agent approved for use with mechanical valves, but full anticoagulation with the drug carries a significant risk of warfarin embryopathy, as well as increased risk of miscarriage and stillbirth.4,20,21 Switching to an alternate form of anticoagulation such as unfractionated heparin or low molecular weight heparin (LMWH) carries risk as well. While LWMH is safe in pregnancy, multiple complications have been reported when used in pregnancy with mechanical valves, including valve thrombosis, hemorrhage, and both maternal and fetal mortality. The prothrombotic state of pregnancy increases the risk of mechanical valve thrombosis and the pharmacodynamic changes in pregnancy (increased renal clearance drugs and increased volume of distribution) increase the difficulty of maintaining stable anticoagulation. While there are published guidelines for management of mechanical valves in pregnancy, the underlying data are sparse. A recent prospective registry report from the ROPAC registry indicated that women with a mechanical heart valve have only a 58% chance of having an uncomplicated pregnancy.22
The term cardiomyopathy refers to a heterogeneous group of heart muscle diseases with a variety of etiologies, including genetic defects, toxic agents, infection, or most frequently, an unknown cause (idiopathic). Regardless of etiology, the presence of left ventricular (LV) dysfunction is a risk factor for maternal complications, and both ejection fraction and symptom status (often defined by New York Heart Association symptom class III or IV) are markers for increased risk.6,7 Teratogenic medications such as angiotensin-converting enzyme inhibitors (ACE inhibitors) and angiotensin-receptor blockers (ARBs) are commonly used to treat cardiomyopathy and heart failure symptoms and withdrawal of these medications prior to pregnancy may worsen cardiac function or symptoms. Treatment of heart failure during pregnancy usually involves use of hydralazine and long-acting nitrates (as a substitute for ACE inhibitors, or ARBs), diuretics, and beta-blockers. Inotropic agents may be required in low-output states with hypoperfusion, renal impairment or impaired mentation.
Peripartum cardiomyopathy is now defined as an idiopathic dilated cardiomyopathy that presents with LV dysfunction and symptoms of heart failure towards the end of pregnancy (typically in the last month) or up to 6 months following delivery. The etiology is unknown and other known causes must be ruled out, including preexisting forms of dilated cardiomyopathy, valvular disease, hypertension, coronary disease, or CHD.23,24 Maternal morbidity and mortality are high, but both partial and complete recovery of LV function may be seen in some patients. The clinical course is highly variable,24 and there is a significant risk of relapse with subsequent pregnancies. Careful counseling should be given to these patients before attempting another pregnancy.25
Coronary artery disease
While coronary artery disease (CAD) does not often present in young women, it can be seen in older mothers and those with more CAD risk factors (diabetes, hyperlipidemia, hypertension, tobacco use). Spontaneous coronary artery dissection and spontaneous coronary thrombus can also complicate pregnancy, but are usually not associated with preexisting atherosclerotic CAD. Myocardial infarction (MI) in pregnancy usually presents as an ST elevation MI (STEMI), and revascularization with percutaneous coronary intervention (PCI) is usually recommended. For non-ST elevation MI, a more conservative, noninvasive approach is often advised.26,27
Aortopathy and aortic dissection
Aortic dissection is rare in pregnancy and can occur in patients without an underlying aortopathy. There are a number of conditions, including Marfan syndrome, Loeys-Dietz syndrome, other familial aortopathies, bicuspid aortic valves (which may be associated with an aortopathy), and Turner syndrome which carry a significantly higher risk of aortic dissection during pregnancy. Specific aortic diameters at which risk is considered prohibitive or prophylactic surgery is recommended vary between the various diseases.28 Whenever possible, preconceptual counseling and assessment of aortic size should be done to determine the risk of pregnancy, and prophylactic aortic surgery may be recommended prior to pregnancy to decrease the risk of dissection during pregnancy. Close follow-up of aortic size during pregnancy and carefully planned delivery are necessary to minimize risk for women with aortic disease. Cesarean delivery is usually recommended for patients at high risk of dissection.5,6
Pulmonary hypertension may be seen as a primary disease (pulmonary arterial hypertension) or secondary to cardiac disease such as CHD and valvular disease, lung disease, thromboembolic disease or other disorders. Defined as a mean arterial pressure of 25 mmHg or greater as assessed at catheterization, the degree of pulmonary hypertension ranges from mild to severe. Eisenmenger syndrome is a particularly severe form of pulmonary hypertension due to an unrepaired shunt, and it is associated with a very high rate of maternal morbidity and mortality. The hemodynamic changes of pregnancy are not well-tolerated in women with pulmonary hypertension and an increase in pulmonary pressure, decline in RV function, clinical heart failure, and syncope may occur, resulting in death rates as high as 50%.29 For this reason, pregnancy is usually contraindicated in mothers with pulmonary hypertension and termination of pregnancy - preferably in a pulmonary hypertension facility - is often recommended.5,6,7,29 Newer therapies for treatment of pulmonary hypertension are available and can improve symptom status and mortality, but many of these drugs have significant fetal toxicity (Table 1). For women who choose to continue pregnancy, careful multidisciplinary care (including a pulmonary hypertension specialist, cardiologist, and maternal-fetal medicine specialist) in a pulmonary hypertension center is required with very frequent monitoring, consideration of early planned delivery, and prolonged postpartum care.28
Planning for pregnancy
Preconceptual counseling is necessary for women with preexisting CVD to clearly understand the risk to both mother and fetus. Education about CVD and pregnancy risk should begin at a young age, ideally involving a discussion of both maternal and fetal risk and appropriate contraceptive options. For women with CHD and women with some types of cardiomyopathy and familial aortopathies (such as Marfan syndrome), genetic counseling may be appropriate. Obstetricians should not rely solely on a patient’s self-reported history about her diagnosis or her symptom status.
Women with preexisting CVD should be referred to a maternal-fetal medicine specialist and a cardiologist who can work in collaboration to fully address maternal and fetal risks. For women with CHD in particular, consultation with an adult congenital heart disease subspecialist should be obtained to assess the specific nature of the original defect, the specific type of surgical procedure(s) or device interventions performed, presence of absence of any residual lesions, shunts, valvular dysfunction, ventricular dysfunction, arrhythmias, prior heart failure or stroke, pulmonary hypertension, residual cyanosis, or other comorbidities that may impact pregnancy risk.5-8 Cardiac imaging is imperative. Most commonly, echocardiography is performed, but cardiac magnetic resonance imaging, computed tomography angiography, and invasive cardiac catheterization may be required. Assessment of functional capacity with formal stress testing may be a valuable tool. Preconceptual counseling also should include assessment of all medications for their benefits and risks, including assessment for potentially teratogenic drugs. In some cases, alternate therapy may be able to be substituted prior to conception.
Prediction of risk
Several different risk scores have been developed to predict pregnancy risk in mothers with CVD, with the modified World Health Organization (WHO) classification felt to be the most reliable.30 (See “World Health Organization classification of maternal cardiovascular risk factors” at Contemporaryobgyn.net/cv-morbidity.) WHO Pregnancy category I indicates no significant maternal morbidity or mortality. Category II indicates a low risk of maternal mortality and a moderate risk of morbidity. Category III indicates a high risk of complications with a significantly increased risk of maternal mortality or morbidity and requires careful coordinated care with ongoing monitoring throughout the pregnancy. Some patients are classified as Category II-III with an intermediate risk of maternal mortality and morbidity, depending on their specific anatomy and clinical status. Category IV indicates that pregnancy is contraindicated due to a very high risk of maternal mortality or morbidity, and termination of pregnancy is often recommended. In a validation study comparing risk models for pregnancy complications in CHD, the risk of cardiovascular complications was 0% in WHO Class I, 6.8% in Class II, 24.5% in Class III, and 100% in Class IV.9
Coordination of care
For patients at increased risk of cardiovascular morbidity or mortality (WHO pregnancy class II or greater), pregnancy care should be coordinated between the maternal-fetal medicine obstetrician and the cardiologist. For patients with CHD, a CHD-trained physician should be involved in the care of the patient and high-risk patients should be managed at a specialized adult CHD center. For patients with the highest mortality risks, pregnancy and delivery should be in a specialized care center as well. The frequency of follow-up depends on the perceived risk to the patient and her clinical status, with follow- up every trimester for low-risk patients (Class II) and every 1 to 2 months or more frequently for patients at highest risk (Class III or IV). In some cases where maternal risk is felt to be excessive, termination of pregnancy should be recommended. A specific plan for labor, delivery, and postpartum care should be created, involving the cardiologist, ob/gyn, and anesthesiologist. For the highest-risk patients, involvement of a cardiac anesthesiologist may be indicated, as well as cardiac interventionalists, pulmonary hypertension specialists, cardiac surgeons and other specialists. Common complications to be anticipated and planned for should include arrhythmias and heart failure. Specific plans for management of complications should include the availability of telemetry monitoring, intensive care unit-level care, availability of transcatheter interventions and cardiac surgery if needed, and the ability to perform cardiopulmonary resuscitation. Prolonged maternal monitoring after delivery is important, as cardiac complications may arise in the postpartum period after successful delivery. Careful planning and integration of care between providers are vital to optimize maternal and neonatal outcomes.
Disclosure The author reports no potential conflicts of interest with regard to this article.
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