Pregnancy and Heart Disease

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Cardiovascular Changes in Pregnancy

Pregnancy is associated with hemodynamic changes that are usually well tolerated in women with normal hearts. However, the hemodynamic changes of pregnancy can lead to cardiovascular complications, especially in women with preexisting heart disease. The hemodynamic changes of pregnancy begin as early as the sixth week of gestation, with increases in plasma volume ( Table 92.1 ). Early in pregnancy, the peripheral vascular resistance decreases and there is a corresponding small drop in blood pressure (BP) by 5 to 10 mm Hg below baseline until the third trimester, when the BP increases back to baseline. The heart rate increases by approximately 10 beats/min above pre-pregnancy levels, and, in combination with increases in stoke volume, there is a resultant increase in cardiac output by 30% to 50% (see Table 92.1 ). Twin pregnancies can increase the cardiac output by a further 10% to 15%. At the time of labor and delivery and immediately postpartum, cardiac output increases a further 60% to 80%. Catecholamines, release of inferior vena cava compression, autotransfusion from uterine contractions, and blood loss all contribute to further hemodynamic changes. Mobilization of fluid during the first week after delivery can result in heart failure in women with cardiomyopathy or severe outflow tract obstruction. Many of the hemodynamic changes resolve in the first 2 weeks after delivery, although complete resolution may take as long as 6 months. In addition to the hemodynamic changes, pregnancy results in increases in renal blood flow and glomerular filtration rate, cholesterol levels, insulin resistance, and clotting (see Table 92.1 ).

Evaluation Prior to Pregnancy and During Pregnancy

Evaluation and Counseling Prior to and During Pregnancy

Pre-pregnancy counseling should be offered to females with heart disease who are of childbearing age, ideally during transition to adult cardiac care. In those women who do not present until they are pregnant, counseling should be performed as early in pregnancy as possible. Preconception counseling is universally recommended for all women with heart disease, preferably by a cardiac-obstetric or pregnancy heart team. Physicians who provide this counseling should include, as a minimum, a cardiologist with expertise in management of pregnancy in women with heart disease, as well as an obstetrician with expertise in maternal fetal medicine. ^, The purposes of pre-pregnancy or pregnancy counseling are to provide risk assessment, risk reduction, and management planning to optimize risk or mitigate effects of complications. ^{, ,} Table 92.2 summarizes the general approach to evaluation and counseling. There is preliminary evidence that establishment of a cardio-obstetric clinic was associated with a reduction in the incidence of pulmonary edema.

TABLE 92.2

Approach to Evaluation, Counseling, and Management: Before, During, and After Pregnancy

Preconception

Risk Assessment and Reduction Discuss maternal pregnancy risks (cardiac, obstetric, fetal) Discuss long-term maternal cardiac prognosis Discuss offspring risks including transmission of heart disease Referral to genetics when appropriate Modify medications as needed Smoking cessation and consideration of cardiac intervention prior to conception Management Planning Referral to cardio-obstetric center Address assisted reproductive therapy safety in women with infertility Consider alternatives to pregnancy (surrogacy or adoption) in women with prohibitive pregnancy risks Discuss contraception options for women who want to avoid pregnancy Management during antepartum and peripartum period (see below)

Pregnancy and Delivery

Referral to a cardio-obstetric center Consults with the pregnancy heart team including maternal fetal medicine and obstetric anesthesia Clinical surveillance throughout pregnancy with frequency of visits based on severity of disease Transthoracic echocardiographic surveillance during pregnancy Create and circulate a delivery plan including recommendations on the mode of delivery, induction, analgesia, safety of pushing, cardiac and postpartum monitoring Organize multidisciplinary conferences for complex or high-risk cases

Postpartum

Ensure postpartum follow-up Medication modification for breastfeeding mothers Reestablish baseline in women with structural heart disease at 6 months postpartum Arrange postpartum cardiovascular risk assessment for women with pregnancy hypertension or maternal placental syndrome For women considering another pregnancy, reevaluate pregnancy risks Discuss contraception options

Risk Stratification

Heart failure and cardiac tachyarrhythmia comprised most of the nonfatal cardiac complications reported in large studies, with maternal mortality rate of 1% or less. ^{, , ,} The rate of maternal cardiac complication is much higher in low- to middle-income countries or in populations with reduced access to health care. Predictors of maternal cardiovascular complications (summarized in Table 92.3 ) can be obtained from cardiac history, maternal New York Heart Association (NYHA) functional class, oxygen saturation, and echocardiography. Comprehensive transthoracic echocardiography should be performed and interpreted by personnel experienced in the assessment of congenital and acquired heart disease. Of the various risk stratification approaches that incorporate individual predictors into an overall risk for maternal cardiac complications in women with spectrum of cardiac lesions, two are risk scores derived and validated from the prospective Canadian Cardiac Disease in Pregnancy Study (CARPREG). The original CARPREG risk score incorporated four predictors, to classify pregnancies as being at low, intermediate, or high risk for maternal cardiovascular complications ( Fig. 92.2 , left panel ). The CARPREG II risk score calculates the risk of maternal cardiovascular complications by functional, lesion specific, and process of care predictors ( Fig. 92.2 , right panel ). The third risk stratification tool, the modified World Health Organization (mWHO) classification system, used an expert consensus approach to classify maternal cardiac lesions into five risk classes corresponding to increasing maternal cardiovascular risks ( Table 92.4 ). In a Canadian study, the CARPREG II risk score had superior predictive accuracy compared with the mWHO classification system.

TABLE 92.3

Predictors of Pregnancy Associated Complications in Women with Heart Disease

From Grewal J, Windram J, Bottega et al; Canadian Cardiovascular Society: Clinical practice update on cardiovascular management of the pregnant patient. Can J Cardiol . 2021 Jul 1:S0828-282X(21)00356-1. https://doi.org/10.1016/j.cjca.2021.06.021 ; Silversides CK, Siu SC. Heart disease in pregnancy. In: Otto CH, ed. The Practice of Clinical Echocardiography . 6th ed. Philadelphia: Elsevier; 2020.

How Predictor is Identified	Maternal Cardiac Complications	Fetal and Neonatal Complications	Gestational Hypertension	Postpartum Hemorrhage
Baseline Clinical Assessment
Cardiac events before pregnancy	Yes
Cardiovascular medications before pregnancy	Yes	Yes
NYHA functional class III or IV	Yes	Yes
Anticoagulation		Yes		Yes
Cyanosis	Yes	Yes		Yes
Smoking during pregnancy	Yes	Yes
Nulliparity			Yes
Multiple gestation		Yes
Cardiac Imaging (Primarily by Transthoracic Echocardiography) and Other Assessments
Left heart obstruction	Yes	Yes
Reduced systemic ventricular systolic dysfunction	Yes
Pulmonary atrioventricular valve regurgitation (moderate/severe)	Yes
Systemic atrioventricular valve regurgitation (moderate/severe)	Yes
Pulmonary regurgitation or depressed subpulmonary ventricular function	Yes
B-type natriuretic peptide level	Yes
Cardiopulmonary test prior to pregnancy	Yes
Maternal Cardiac Lesion
Uncorrected or corrected cyanotic heart disease	Yes	Yes
High-risk aortopathy	Yes
Coronary artery disease	Yes
Pulmonary hypertension	Yes	Yes
Aortic coarctation			Yes
Maternal systemic lupus erythematosus			Yes
Aortic valve disease			Yes
Mechanical prosthesis	Yes	Yes
Modified World Health Organization Class	Yes
Process of Care
No prior cardiac interventions	Yes
Late presentation for care	Yes
Serial Assessments During Pregnancy
Abnormal Uteroplacental Doppler		Yes
Reduction in cardiac output between 1st and 3rd trimester		Yes

NYHA , New York Heart Association.

TABLE 92.4

2018 Version of Modified World Health Organization Classification of Maternal Cardiovascular Risk

From Regitz-Zagrosek V, Roos-Hesselink JW, Bauersachs J, et al. 2018 ESC Guidelines for the management of cardiovascular diseases during pregnancy. Eur Heart J . 2018;39:3165–3241.

mWho Class	Cardiac Lesions	Maternal Cardiac Risk Assigned by 2018 Guidelines Authors ∗	Clinical Application
Class I	Small or mild pulmonary stenosis, patent ductus arteriosus, mitral valve prolapse Successfully repaired simple lesions (atrial or ventricular septal defect, patent ductus arteriosus, anomalous pulmonary venous connection) Atrial or ventricular ectopic beats, isolated	2.5%–5%	No detectable increased risk of maternal mortality and no/mild increase in morbidity
Class II	Unoperated atrial or ventricular septal defect Repaired tetralogy of Fallot Most arrhythmias (supraventricular arrhythmias) Turner syndrome without aortic dilation	5.7%–10.5%	Small increase in maternal risk mortality or moderate increase in morbidity
Class II or III	Mild left ventricular impairment (EF > 45%) Hypertrophic cardiomyopathy Native or tissue valvular heart disease not considered WHO I or IV (mild mitral stenosis, moderate aortic stenosis) Marfan or other HTAD syndrome without aortic dilatation Aorta <45 mm in association with bicuspid aortic valve pathology Repaired coarctation Atrioventricular septal defect	10%–19%	Intermediate increased risk of maternal mortality or moderate to severe increase in morbidity
Class III	Moderate left ventricular impairment (EF 30%–45%) Previous peripartum cardiomyopathy without residual left ventricular impairment Mechanical valve Systemic right ventricle with good or mildly decreased ventricular function Fontan circulation if otherwise well and the cardiac condition uncomplicated Unrepaired cyanotic heart disease Other complex congenital heart disease Moderate mitral stenosis Severe asymptomatic aortic stenosis Moderate aortic dilation (40–45 mm in Marfan syndrome or other HTAD, 45–50 mm in bicuspid aortic valve, Turner syndrome ASI 20–25 mm/m 2 , tetralogy of Fallot <50 mm) Ventricular tachycardia	19%–27%	Significantly increased risk of maternal mortality or severe morbidity.
Class IV	Pulmonary arterial hypertension Severe systemic ventricular dysfunction (EF <30% or NYHA class III–IV) Previous peripartum cardiomyopathy with any residual left ventricular impairment Severe mitral stenosis Severe symptomatic aortic stenosis Systemic right ventricle with moderate or severely decreased ventricular function Severe aortic dilatation (>45 mm in Marfan syndrome or other HTAD, >50 mm in bicuspid aortic valve, Turner syndrome ASI >25 mm/m 2 , tetralogy of Fallot >50 mm) Vascular Ehlers-Danlos Severe (re)coarctation Fontan with any complication	40%–100%	Extremely high risk of maternal mortality or severe morbidity

ASI , Aortic size index; EF , ejection fraction; HTAD , heritable thoracic aortic disease; mWHO , modified World Health Organization; NYHA , New York Heart Association functional class.

∗ Basis of risk estimates not provided.

Risk scores and risk classification approaches should always be combined with clinical judgment. One approach is to identify pregnancies in women with cardiac lesions associated with high mortality risk or with devastating implications even if there is prompt intervention ( Fig. 92.3 ). Pregnancy should be discouraged in women with high-risk cardiac lesions (as listed on Fig. 92.3 ), and termination should be considered if pregnancy occurs. Pregnant women with high-risk lesions should receive their care by a maternal heart team and deliver at a referral center.

For pregnancies in women without the aforementioned high-risk lesions, a CARPREG II risk score could be used, with subsequent modification after integrating patient (including exercise testing, compliance, comorbid conditions, socioeconomic status, anticoagulation) and lesion (i.e., type of cardiac lesions, type of operative repair, and late sequelae) specific information. For clinicians who prefer the mWHO risk-classification system, we recommend that general predictors of cardiovascular complications (e.g., prior history of heart failure and arrhythmias) be incorporated, which further stratify risk within each mWHO category ( Fig. 92.4 ). Importantly, the cardiovascular complication rate can be as high as 5% in the low-risk group. Assisted reproductive technologies (ARTs) confer additional risk to women with heart disease (see “Assisted Reproductive Technologies”).

Risk stratification should also include assessing the risk of noncardiac complications and long-term prognosis (see Table 92.3 ). Maternal cardiovascular and fetal neonatal complications are related, likely reflecting the inability of the placenta to autoregulate blood flow. The likelihood of fetoneonatal complications is increased when there are concurrent obstetric risk factors. The obstetric and fetoneonatal risks emphasize the vital role of the multidisciplinary team in comprehensive risk assessment and counseling. Pregnancy may accelerate subsequent progression to symptoms or cardiac decompensation in women with certain cardiac lesions.

Management Planning

Preconception counseling provides opportunities to optimize risk by: (1) better defining the nature of the cardiac lesion and or functional capacity by exercise or cardiopulmonary testing, imaging, or cardiac catheterization; (2) stopping medications that are contraindicated in pregnancy (e.g., afterload reducing agents in heart failure treatment) for a trial period prior to pregnancy to ascertain clinical stability; (3) interventions such as smoking cessation or intervention for severe aortic/mitral stenosis (MS); and (4) genetic consultation if the women, her first-degree relative, or her partner has congenital a heart defect. ^, Regardless of when the counseling occurs, the following areas need to be discussed and management recommendations provided:

• (A)

  Cardiovascular medications: Cardiovascular medications that are safe versus contraindicated during pregnancy (see general management section). ^,

• (B)

  Site of pregnancy care/delivery: There are three possible options: (1) Exclusive care and delivery at referral center by maternal heart team (recommended for high-risk pregnancies); (2) Joint care by local cardiology or obstetric practitioners with delivery at local center, after initial evaluation by pregnancy heart team (non–high-risk pregnancies); or (3) Initial review by pregnancy heart team and local obstetric care (for low-risk pregnancies). ^,

• (C)

  Fetal echocardiogram for same indications as for genetic counseling (see earlier).

• (D)

  Management during labor and delivery (see also section on general management):

  • (i)

    Vaginal delivery versus cardiac indications for cesarean delivery.

  • (ii)

    Spontaneous onset of labor versus induction

  • (iii)

    Indications for invasive hemodynamic monitoring

  • (iv)

    Continuous telemetry for patients with uncontrolled arrhythmias

  • (v)

    Postpartum monitoring of the mother in coronary or intensive care units for women in high cardiac risk group, including women who required hemodynamic monitoring during labor and delivery.

For patients with pregnancy who are at high risk, a multidisciplinary meeting should be convened in the antepartum period to develop and document management plan during the peripartum and early postpartum periods.

Assisted Reproductive Technologies

As with the general population, ARTs are being increasingly used for treatment of infertility and subfertility. In the cardiac population, some women, such as those with Fontan operations, cyanotic heart disease, or Turner syndrome, have higher rates of infertility. Although ARTs improve the chances of pregnancy, they are associated with complications that may be dangerous for women with heart disease.

ARTs such as in vitro fertilization or intrauterine insemination usually follow medical treatment to stimulate ovulation, and this can result in ovarian hyperstimulation syndrome. Ovarian hyperstimulation syndrome, directly related to superovulation protocols, can be particularly problematic for women with heart disease as it leads to fluid shifts into the extravascular space and thrombosis. Fluid shifts may be poorly tolerated in women with the Fontan operation and thrombosis poorly tolerated in women with mechanical valves. Therefore planning of superovulation protocols is important in women with heart disease and infertility. Women receiving in vitro fertilization are also at increased risk for pulmonary emboli, preeclampsia, and gestational hypertension. Multifetal gestations are more common in women receiving ARTs and are associated with increased hemodynamic stress when compared with singleton pregnancies. The additional hemodynamic stress may be poorly tolerated in women with severe forms of heart disease. In addition, twins and higher-order pregnancies are associated with higher rates of preeclampsia, preterm births, low birth weight babies, and neonatal mortality. One small study of fertility therapy in women with heart disease reported high rates of maternal and perinatal complications. Although fertility therapy has not been shown to be associated with long-term cardiovascular risks, failed fertility therapy is associated with higher long-term cardiovascular events.

Guidance is lacking on the optimal evaluation and treatment selection for women with heart disease. When making decisions about patient selection for ART, input from the cardiologist and the fertility specialist is crucial. Pregnancy is contraindicated in the presence of some serious cardiac conditions, and ARTs should be contraindicated in these same conditions.

General Management Principles

Care of the pregnant women with heart disease requires a multidisciplinary team often referred to as the pregnancy heart team. ^, The pregnancy heart team includes cardiologists, maternal fetal medicine specialists, obstetric anesthetists, and nursing staff with expertise in pregnancy and heart disease. Other medical specialists (i.e., hematologists), geneticists, neonatologists, and social workers are required for specific cases. The goal of the pregnancy heart team is to provide preconception counseling, coordinate pregnancy surveillance, treat complications, develop and disseminate delivery plans, and ensure appropriate postpartum follow-up (see Table 92.2 ).

The frequency of surveillance during pregnancy is based on the severity of the cardiac lesion and the maternal and fetal risk. ^, Women at low risk for cardiac complications are often seen once or twice during pregnancy with plans to deliver at a local obstetric center. Women at moderate or high risk for cardiac complications are followed more closely. In addition to clinic visits, pregnancy surveillance includes electrocardiograms, transthoracic echocardiograms, fetal ultrasounds, and, in some cases, placental ultrasounds or serial biomarkers such as BNP. Women with congenital heart disease should be offered a fetal echocardiogram at 18 to 22 weeks’ gestation to assess for congenital cardiac malformation.

When using medications during pregnancy, consideration of the maternal benefit needs to be weighed against the potential for fetal toxicity. Most cardiac drugs cross the placental barrier and expose the fetus to the drug, and therefore the lowest possible dose should be used. Benefits and side effects of drugs should be discussed with all women receiving drugs during pregnancy. Teratogenic cardiac drugs should be stopped and switched to safer alternative drugs prior to pregnancy ( Fig. 92.5 ). Drug safety during breastfeeding is based on the concentration of drug in the breast milk and may differ when compared with drug safety during pregnancy. The effectiveness of medications can be altered by the pregnancy associated changes in the volume of distribution, drug absorption, metabolism, and binding. ^, The doses of some medications, such as beta blockers, may need to be increased during pregnancy to achieve heart rate or BP control.

The safety profile of cardiovascular medications during pregnancy/lactation are summarized in Figure 92.5 . ^, Medications that are contraindicated during pregnancy because of fetal toxicity or teratogenicity are: (1) atenolol; (2) angiotensin-converting enzyme inhibitors (ACE-Is) and angiotensin II receptor blockers (ARBs); (3) aldosterone antagonists; (4) statins; (5) direct oral anticoagulants; and (6) bosentan (endothelin receptor antagonists). ACE-Is and ARBs cause second-trimester fetal nephrotoxicity, and ACE-Is are teratogenic. The recommendation to avoid atenolol, particularly in the first trimester, is based on concerns regarding higher rates of fetal growth restriction compared with other beta blockers. However, for women with heart disease, beta blockers usually do not have major effects on birth weight (mean weight reduction 191 g) when adjusted for other maternal risk factor for fetal growth restriction. Recommendations to avoid statins in pregnancy may evolve with additional safety data in the future.

For many of the newer cardiovascular medications, the fetal risk profile is not completely established and their use represent a balance between benefit versus fetal risk. Most drugs, except high-molecular-weight molecules such as heparin, cross the placenta and equilibrate in the fetal circulation over time. Importantly, some medications (ACE-Is) that are contraindicated during pregnancy can be used during lactation. The risk of some medications may be a related to gestational age. Warfarin is associated with an embryopathy when exposure occurs between 6 and 12 weeks’ gestation and needs to be discontinued prior to 6 weeks’ gestation. In the treatment of acute pericarditis during pregnancy during pregnancy, both aspirin (ASA) and nonsteroidal antiinflammatory drugs (NSAIDs) cross the placenta. Classic NSAIDs (ibuprofen, indomethacin, naproxen) or high-dose ASA can be used early in the pregnancy. After the 20th gestational week, all NSAIDs (except enteric coated ASA [ECASA] ≤100 mg daily) have the potential of causing constriction of the ductus arteriosus and impact fetal renal function and should be withdrawn by the 32nd gestational week. Lowest effective doses of prednisone may be used during pregnancy. Ibuprofen, indomethacin, naproxen, and prednisone may be considered for lactating women. Colchicine is considered to be contraindicated during pregnancy and lactation, but data are incomplete.

When possible, a spontaneous vaginal delivery is preferred. Induction is usually reserved for logistical reasons (patient lives a long distance away from the hospital) or if a delivery is complex and a specific team is required to be present during delivery. Cesarean delivery is rarely required for cardiac indications except in women who do not have warfarin discontinued at least 2 weeks prior to delivery due to the risk of neonatal intracranial hemorrhage, those with severely dilated thoracic aortas, severe refractory heart failure, or hemodynamic instability. Vaginal deliveries can be conducted in the left lateral position to avoid compression of the inferior vena cava and optimize venous return. In women at high risk for complications, delivery planning should be made in conjunction with the pregnancy heart team and should take place at a cardiac and obstetric referral center. For some women, an assisted second stage of labor (i.e., with low forceps or vacuum extraction) may be helpful to prevent a long labor. Although routine endocarditis prophylaxis is no longer recommended for all pregnant women with heart disease, infective endocarditis prophylaxis is recommended at the time of labor and delivery in those at highest risk for endocarditis, such as women with prior endocarditis, mechanical valves, or cyanotic heart disease.

Most cardiac complications during pregnancy can be treated medically. Heart failure should be treated with fluid and salt restriction and diuretics. It is important to identify and treat any precipitating factors such as tachyarrhythmias, infection, iatrogenic volume administration, and postpartum fluid shifts. Although ACE-Is and ARBs need to be stopped during pregnancy, afterload reduction with hydralazine and isosorbide dinitrate can be used. Women who develop heart failure during pregnancy require close follow-up. Delivery needs to be planned carefully in women with antepartum complications, and treatment of heart failure prior to delivery is optimal. Hemodynamic monitoring with an arterial line should be considered for selected high-risk patients (severe left ventricular systolic dysfunction, severe aortic or MS, or pulmonary hypertension). Central venous and pulmonary artery catheters are rarely indicated and should be performed by an experienced operator after careful consideration of risk versus benefits. ^, Other than for obstetric and fetal indication, planned preterm delivery (<37 weeks’ gestation) is seldom warranted for maternal cardiac reasons. Women with severe heart failure should be delivered at a center with availability of mechanical circulatory support as well as a transplant team.

Treatment of arrhythmias needs to be tailored to the individual and is based on the type of arrhythmia and the presence of underlying structural heart disease. Electrical cardioversion is safe during pregnancy, and women with tachyarrhythmias who are hemodynamically unstable require cardioversion. Bradycardias are less common during pregnancy. Pacemaker and implantable cardioverter defibrillators are safe during pregnancy and delivery. If cautery is used at the time of delivery, oversensing by the pacemaker is possible and therefore magnets should be available in the delivery room to use to eliminate oversensing.

Occasionally, women with refractory symptoms require a percutaneous or surgical intervention. Maternal abdominal lead shielding, radial approach, and procedural techniques can minimize radiation exposure to the fetus. Women with severe mitral, aortic, or pulmonary stenosis who have symptoms refractory to medical therapy may require a balloon valvuloplasty or, in very select cases, percutaneous valve insertion to relieve the outflow track obstruction. These procedures should be performed only at experienced centers because acute heart failure, arrhythmias, tamponade, and death have been reported. Obstetric back-up is required because precipitous labor can occur. Cardiac surgery during pregnancy should only be performed if no other options are available, because fetal mortality can occur in approximately 20% of cases. Urgent surgery, maternal comorbidities, and early gestational age are associated with the highest fetal risk. ^, Fetal risk can be mitigated by pulsatile perfusion, high pump flow, avoidance of hypothermic extracorporeal circulation, minimizing bypass times, and fetal monitoring. Later in gestation, delivery followed by cardiac surgery is preferred if there is adequate fetal maturity. In comparison, maternal surgical risks are similar to the nonpregnant population. A multidisciplinary pregnancy heart team with cardiology, cardiac surgery, anesthesia, obstetrics, and neonatology is necessary to optimize mother and offspring outcomes.

Cardiac arrest during pregnancy is managed similarly to the nonpregnant arrest, with the following modifications: (1) lateral uterine displacement during an arrest is required after 20 weeks’ gestation; (2) intubation may be more difficult due to changes in airway mucosa; and (3) emergency cesarean delivery should be initiated if there has been no return of spontaneous circulation within 4 minutes of the onset of arrest in a pregnant women with a fundus height at or above the umbilicus.

Specific Cardiovascular Conditions