Cardiac Conditions That May Affect Pregnancy

Hypertension

Hypertension is the most common medical problem encountered in pregnancy, occurring in 2% to 3% of pregnancies. It can be divided into four types:

• 1.

  Chronic hypertension

• 2.

  Preeclampsia

• 3.

  Preeclampsia superimposed on chronic hypertension

• 4.

  Gestational hypertension

Traditionally, chronic hypertension in pregnancy has been defined as blood pressure over 140 mm Hg systolic or 90 mm Hg diastolic before pregnancy or before 20 weeks of gestation. The new recommendations from the American College of Cardiology (ACC) and the American Heart Association now classify normal blood pressure as less than 120 mm Hg systolic and 80 mm Hg diastolic and stage 1 hypertension as a systolic pressure of 130 to 139 mm Hg or a diastolic pressure of 80 to 89 mm Hg. The American College of Obstetrics and Gynecology’s (ACOG’s) latest guidelines state that for a woman classified as having stage 1 hypertension before pregnancy, it is reasonable to treat her as having chronic hypertension. For a pregnant woman without a prior diagnosis of hypertension who presents with a blood pressure in the stage I range, it is unclear what the best option is, and further investigation is warranted. Low-dose aspirin to prevent preeclampsia has not proven beneficial in this group.

The new onset of hypertension after the first 20 weeks of gestation should arouse suspicion of preeclampsia. Preeclampsia is usually defined as pregnancy-induced hypertension combined with proteinuria over 300 mg/24 hours. However, proteinuria is not universally present in preeclampsia. The 2013 ACOG guidelines state that in the absence of proteinuria, preeclampsia is diagnosed as hypertension in association with thrombocytopenia (platelet count <100,000/μL), impaired liver function (elevated blood levels of liver transaminases to twice normal), the new development of renal insufficiency (elevated serum creatinine >1.1 mg/dL or a doubling of serum creatinine in the absence of other renal disease), pulmonary edema, or new-onset cerebral or visual disturbances. Chronic hypertension is a risk factor for preeclampsia, increasing the risk four- to fivefold. Gestational hypertension is characterized by the onset of hypertension after 20 weeks of pregnancy in the absence of proteinuria or other signs of preeclampsia.

Endothelial dysfunction represents one suggested mechanism whereby hypertensive disorders of pregnancy lead to multiple organ failure, including cardiomyopathy, acute kidney disease, pulmonary edema, respiratory collapse, seizures, and death. Serum concentrations of vasodilators such as nitric oxide, prostacyclin, and hyperpolarization factor are shown to decrease among women with hypertensive disorders of pregnancy, and serum concentrations of vasoconstrictors such as endothelin-1 and thromboxane A2 increase. Upstream regulatory changes contributing to the shift in concentration of these vasoactive molecules include a diminishment in proangiogenic factors such as vascular endothelial growth factor and placental-like growth factor and an increase in antiangiogenic factors such as soluble FMS-like tyrosine kinase inhibitor-1, endoglin, and angiotensin II. The effects of these changes include increased capillary permeability and enhanced vascular smooth muscle contractility clinically witnessed as edema, labile elevations in blood pressure, increased systemic vascular resistance, and vasospasm to numerous organs, including the brain, retina, kidneys, liver, and uteroplacental interface. In addition, recent evidence supports an association between the imbalance in these angiogenic factors and the subsequent development of peripartum cardiomyopathy.

Because of these vascular changes, the intravascular volume among women with hypertensive disorders of pregnancy may be altered. Women with preeclampsia often demonstrate a diminished intravascular volume manifested by hemoconcentration, elevated hematocrit, and elevated serum osmolality. Additionally, their intravascular oncotic pressure drops secondary to increased albumin secretion into the urine and interstitial compartment. Decreased intravascular volume may potentiate the already enhanced vascular smooth muscle contractility in an overexaggerated homeostatic attempt to restore perfusion to maternal organs. However, 70% of the intravascular volume lies in venules, which contain little vascular smooth muscle and contractility. As more volume is forced out of the intravascular compartment through dysfunctional endothelial walls by increased hydrostatic pressure and diminished oncotic pressure, the volume within the venules and venous system decreases. These physiologic changes to the maternal vasculature can be assessed by astute clinical examination, laboratory evaluation, and sonography.

Hypertension (blood pressure over 140/90 mm Hg) developing after 20 weeks’ gestation mandates an evaluation to exclude preeclampsia. Preeclampsia occurs in an estimated 5% of pregnancies and is twice as common during a woman’s first pregnancy.

In mild cases of hypertension (blood pressure <160/100 mm Hg) during pregnancy, treatment has not been found to reduce the incidence of preeclampsia. In many women with preexisting hypertension, it is possible to reduce or eliminate their antihypertensive drugs during pregnancy because the normal decline in blood pressure that occurs with pregnancy also occurs in women with hypertension.

Several options are available for the emergency treatment of patients with severe acute-onset hypertension. These include intravenous (IV) labetalol and IV hydralazine. Oral nifedipine is also an option. Labetalol should be avoided in women with asthma. IV nitroprusside should be used only for the shortest possible time because of concerns of cyanide and thiocyanate toxicity.

For chronic oral therapy during pregnancy, methyldopa, labetalol, and nifedipine are considered acceptable. Methyldopa is often considered the drug of choice because of its historic safety record. It does not alter maternal cardiac output or blood flow to the uterus and kidneys. Labetalol has been shown to be as effective as methyldopa in pregnant women, and it does not alter uterine or renal blood flow. However, its safety record is not as well established as that of methyldopa. Oral hydralazine appears generally safe for fetuses, but a few cases of thrombocytopenia have been reported. It may be combined with methyldopa or labetalol. Hydrochlorothiazide may be considered as a second- or third-line agent.

Vasodilator antihypertensives such as hydralazine, nifedipine, and nitroprusside should be avoided in patients with left heart obstruction (e.g., aortic stenosis or coarctation).

Atenolol should be avoided as it has been associated with growth retardation in the fetus.

Angiotensin-converting enzyme (ACE) inhibitors have been associated with a number of fetal adverse events, including growth retardation, renal failure, persistent patent ductus arteriosus, respiratory distress, hypotension, and prepartum death. They are contraindicated during pregnancy.

Diuretics may be used to treat patients with hypertension, but they reduce maternal plasma volume and may cause electrolyte disturbance. They may be used to treat those with preeclampsia.

Women with chronic hypertension should be considered at risk for preeclampsia, and consideration should be given to initiation of low-dose aspirin (81 mg/day), which should be initiated between weeks 12 and 16.

Recent studies have shown that the development of preeclampsia or gestational hypertension are risk factors for the development of hypertension and adverse cardiac events later in life.

Postpartum Hypertension

Postpartum hypertension may be caused by persistence of gestational hypertension or preeclampsia or arise de novo after delivery. The incidence is unknown, in part because many women do not have their blood pressure checked between the immediate postpartum period and their follow-up at 6 weeks. Of women who are hypertensive during pregnancy, roughly half will continue to have hypertension postpartum.

Etiologies for new-onset postpartum hypertension include delayed mobilization of the increased plasma volume that occurs during normal pregnancy and fluid retention related to the use of nonsteroidal antiinflammatory drugs. The use of ergot alkaloids (to treat uterine atony) also may initiate or exacerbate hypertension.

Patients with chronic hypertension can be expected to have hypertension postpartum.

Preeclampsia may persist or even present postpartum. The majority of postpartum preeclampsia develops within 48 hours after delivery, but it can first manifest as late as 6 weeks postpartum. Preeclampsia is the most common cause for persistent hypertension after delivery.

Studies of women with preeclampsia superimposed on chronic hypertension show that their blood pressures often increase at 3 to 6 days postpartum.

Reversible cerebral vasoconstriction syndrome is a poorly understood angiopathy that develops between days 3 and 14 postpartum. The presenting symptoms are thunderclap headaches and other neurologic manifestations such as seizures and visual disturbance. Hypertension is present in 60% of patients.

Evaluation of a woman with new onset postpartum hypertension should include evaluation for proteinuria to exclude late-onset preeclampsia. Treatment of hypertension is similar to that in pregnant women. Furosemide given to patients who experience antenatal preeclampsia reduces the need for other antihypertensive agents.

A major concern in treating postpartum women with hypertension is to avoids antihypertensive drugs that could be excreted into breast milk and affect a breastfeeding baby.

Congenital Heart Disease

Most data regarding cardiac and obstetric risk to women with congenital heart disease (CHD) during pregnancy derive from retrospective case series. Many women with CHD considering pregnancy may have received inconsistent guidance regarding pregnancy risks. Because of these concerns, the ACC has developed guidelines for physicians caring for women with CHD who are considering pregnancy or who are already pregnant. Although many women with CHD tolerate the hemodynamic changes of pregnancy, others may face significant immediate or late risks of pregnancy, including volume overload, arrhythmias, progressive cardiac dysfunction, and death. Cardiac medications may need to be adjusted during pregnancy and counseling provided to discuss the options for and potential impact of these changes. Substitutes must be found for medications they are taking that may be teratogenic (e.g., ACE inhibitors, angiotensin-receptor blockers).

Some specific complications may be more common in women with certain types of CHD, such as hypertension, which is more common in women with coarctation. The offspring of patients with adult congenital heart disease (ACHD) have an increased risk of CHD and other events such as prematurity. All women with CHD should receive appropriate counseling regarding contraception choices. To achieve optimal outcomes, we recommend a multidisciplinary team that includes ACHD specialists and maternal-fetal medicine obstetricians with expertise in caring for women with heart disease.

The ACC guidelines are outlined next along with the anatomic pathologic (AP) classification scheme used by the organization.

• 1.

  Women with congenital heart disease should receive prepregnancy counseling with input from an adult congenital cardiologist to determine maternal cardiac, obstetric, and fetal risks, as well as potential long-term risks to the mother.

• 2.

  An individualized plan of care that addresses expectations and contingencies should be developed for and with women with CHD who are pregnant or who may become pregnant and shared with the woman and all caregivers.

• 3.

  Women with ACHD receiving chronic anticoagulation should be counseled, ideally before conception, on the risks and benefits of specific anticoagulants during pregnancy.

• 4.

  Women with ACHD AP classification IB-D, IIA-D, and IIIA-D should be managed collaboratively during pregnancy by ACHD cardiologists, obstetricians, and anesthesiologists experienced in ACHD

• 5.

  In collaboration with an adult congenital heart cardiologist to ensure accurate assessment of pregnancy risk, patients at high risk of maternal morbidity or mortality, including women with pulmonary arterial hypertension, Eisenmenger syndrome, severe systemic ventricular dysfunction, severe left-sided obstructive lesions, or ACHD AP classification ID, IID, and IIID, should be counseled against becoming pregnant or be given the option of terminating pregnancy.

• 6.

  Men and women of childbearing age with CHD should be counseled on the risk of CHD recurrence in offspring.

• 7.

  Exercise testing can be useful for risk assessment in women with ACHD classification IC-D, IIA-D, and IIID who are considering pregnancy.

The ACHD AP Classification scheme referred to uses anatomy and physiological stage to classify patients with ACHD. The scheme, outlined later, uses three classifications for complexity of anatomy (I, II, III) and four for physiologic stage (A, B, C, D) ( Table 5.1 ).

Pulmonary Hypertension

Pulmonary hypertension is defined as a mean pulmonary arterial pressure greater than 25 mm Hg as assessed by right heart catheterization. Pulmonary hypertension may be caused by cardiac disease with right-to-left shunting of blood (Eisenmenger syndrome), associated with connective tissue disease or idiopathic (primary). It probably would be best to consider patients with pulmonary hypertension as belonging to one of these three distinct groups. Unfortunately, all these conditions are rare, and the number of pregnant patients with them is small, so almost all series mix the three groups. During pregnancy, pulmonary resistance falls in normal women. In patients with pulmonary hypertension, this fall is limited, leading to a rise in pulmonary pressures, which often leads to right heart failure. Shifting of the intraventricular septum caused by the increased right heart pressures also may impair left heart filling, leading to diastolic left-sided impairment, which compromises cardiac output. Women with Eisenmenger syndrome may have increasing right-to-left shunting, which leads to hypoxemia and may lead to increased pulmonary vasoconstriction and worsening right heart failure. Pulmonary hypertension during pregnancy is a high-risk situation for both the mother and the fetus, so pregnancy in women with pulmonary hypertension should be discouraged. The maternal mortality rate has been reported as high as 56% in patients with severe pulmonary hypertension, although more recent studies indicate mortality rates of 17% in patients with idiopathic pulmonary hypertension and 28% in those with CHD. One series from France has reported a mortality rate as low as 5% in a group of women with pulmonary hypertension associated with CHD. One reason for the much lower rate may be the apparent lower mortality rate in women who respond to calcium channel blockers or other therapy. Most cases of death in women with pulmonary hypertension occur in the early postpartum period. Heart failure is the most common cause, but others include sudden death and thromboembolism.

If a woman with pulmonary hypertension does become pregnant, she must be monitored carefully, and if signs of decompensation are detected, early therapeutic abortion should be considered.

Neonatal survival rates are about 90%. The main risks to the fetus are related to maternal hypoxemia and include preterm delivery, growth retardation, and stillbirth.

Many of the drugs used to treat patients with pulmonary hypertension are contraindicated during pregnancy. Endothelin receptor antagonists are category X. Calcium channel blockers are category C. Sildenafil has been used in individual cases and appears to be safe, but experience with the drug is limited. Continuous infusion of prostacyclin (epoprostenol) has been used in select patients with good outcomes reported.

For women with pulmonary hypertension, it is unclear whether vaginal delivery or cesarean section is preferable, but guidelines from the Pulmonary Vascular Research Institute recommend cesarean section. The adverse effects of vaginal delivery include Valsalva maneuver, which increases intrathoracic pressure, labor-induced vagal responses, sympathetic nervous system activation cause by pain, and autotransfusion during uterine contraction. If vaginal delivery is chosen, low-dose epidural analgesia is strongly recommended; if dosed slowly, it has little deleterious effect on hemodynamics. If cesarean section is performed, slowly titrated epidural anesthesia is ideal because it minimizes adverse hemodynamic effects. At least 20 to 30 minutes is required to achieve an adequate block while maintaining stable hemodynamics. General anesthesia and spinal anesthesia can be administered safely but cause more significant hemodynamic disturbance. They require close monitoring (including invasive hemodynamic monitors) and strict attention to fluid status, oxygenation, and ventilation. If general anesthesia is required, intubation, laryngoscopy, and positive-pressure ventilation will likely increase pulmonary pressure. Extracorporeal membrane oxygenation should be available. Delivery in the operating room should be considered.

If necessary, the physician may consider inducing labor; there are cases in which prostaglandin E and oxytocin have been used with good outcome. Prostaglandin E generally reduces pulmonary artery pressure. Oxytocin is a vasodilator and must be used cautiously to avoid hypotension.

It is probably best to avoid direct pulmonary artery pressure monitoring with a Swan-Ganz catheter because there is an increased risk of pulmonary artery rupture and thrombosis in patients with pulmonary hypertension.

The patient’s hemodynamics may not return to baseline for 6 months, so monitoring must be continued after delivery. Several weeks of in-hospital monitoring postpartum is usually recommended.

Symptomatic postpartum therapy may include inhaled nitric oxide, inhaled iloprost, or IV epoprostenol.

Thromboembolic risk is high, and generally thromboprophylaxis should be initiated. In women with a history of thromboembolic disease, higher levels of anticoagulation may be needed.

Fluid management is difficult because both hyper- and hypovolemia are detrimental.

Because pregnancy is to be discouraged in patients with pulmonary hypertension, contraception is often prescribed. Estrogen-containing contraceptives are not recommended because of the increased risk of venous thromboembolism and the deleterious effects of estrogen on the pulmonary vasculature. Progesterone-only preparations, such as medroxyprogesterone acetate and etonogestrel, may be used. Intrauterine devices (IUDs) and progestin-only implants are acceptable contraceptive methods for women with pulmonary hypertension. However, on insertion, IUDs and implants may cause vasovagal responses, and such responses may be poorly tolerated in women with pulmonary hypertension.

Increased Risk for Thrombosis

Pregnant women may require anticoagulation for many reasons, including high risk of deep vein thrombosis (DVT), prosthetic heart valves, and atrial fibrillation. In some patients, such as those with pulmonary hypertension or cardiomyopathy, anticoagulation should be considered. Low-molecular-weight heparin (LMWH) and unfractionated heparin are the agents of choice. LMWHs do not reliably prolong the partial thromboplastin time, which may make monitoring difficult.

Pregnancy induces a hypercoagulable state through multiple mechanisms. It increases levels of factors VII, VIII, IX, X, and fibrinogen; reduces levels of proteins S and C; and reduces fibrinolysis. The risk of a thromboembolic event is three to five times higher during pregnancy than in the nonpregnant state. Pregnancy also promotes venous stasis because of progesterone-mediated venous dilation and compression of the vena cava by the uterus. Patients with preeclampsia may develop nephrotic syndrome, which can lead to acquired antithrombin deficiency, further enhancing a hypercoagulable state.

Several groups have proposed scoring systems for assessment of thromboembolic risk in pregnant women. Dargaud et al. proposed the system presented in Table 5.2 .

They also proposed a prophylactic management strategy based on this protocol. Using this strategy, outlined in Table 5.3 , in 286 patients resulted in only three DVTs. One occurred during pregnancy and two in the postpartum period after withdrawal of LMWH. One patient had a serious postpartum hemorrhage.

Investigators from Sweden (Lindgvist et al.) have suggested this point scoring system to address risk of thrombosis in pregnancy. The schema is outlined in Table 5.4 .

After adding together all risk factors, a total of 1 point or less indicates that no preventive action is needed. A total of 2 points indicates that short-term prophylaxis (e.g., with LMWH) should be used. Prophylactic treatment should be started 2 hours after delivery and given 7 days postpartum. A total of 3 points increases the necessary duration of postpartum prophylaxis to 6 weeks. A previous distal DVT indicates a minimum of 12 weeks (3 months) of therapeutic anticoagulation therapy. A previous proximal DVT or pulmonary embolism requires a minimum of 26 weeks (6.5 months) of therapy. If the therapy duration reaches delivery time, the remaining duration may be given after delivery, possibly extending the minimum of 6 weeks of postpartum therapy. In a very high-risk pregnancy, high-dose antepartum prophylaxis should be continued at least 12 weeks after delivery.

Women with antiphospholipid syndrome should have an additional low-dose prophylactic treatment of aspirin.

Coumadin cause teratogenesis. However, warfarin can be used after 12 weeks for patients with prosthetic valves.

When LWMH is used, we recommend checking anti–factor Xa levels after treatment is started and every 1 to 3 months thereafter, keeping levels (checked 4 hours after the dose) at 0.5 to 1.2 U/mL. Patients should be monitored for heparin-induced thrombocytopenia, although it appears rare in pregnancy.

Left Ventricular Dysfunction

Left ventricular (LV) dysfunction is usually divided into two types, systolic and diastolic. Systolic dysfunction is pump failure, which leads to pulmonary congestion and, if severe enough, to fluid retention, right ventricular (RV) overload, and edema. Diastolic dysfunction is failure of ventricular relaxation, which leads to increased end diastolic pressure, which is reflected in increased left atrial pressure. Increased left atrial pressure inhibits pulmonary venous return and may lead to pulmonary congestion and dyspnea.

Right Ventricular Dysfunction

Right ventricular dysfunction usually leads to edema. There is no good treatment for patients with RV dysfunction per se. It is unclear that beta blockers, ACE inhibitors, hydralazine nitrate combinations, or digitalis can improve RV function. If the RV dysfunction is caused by pulmonary hypertension, that condition can be treated as outlined in the section on pulmonary hypertension. Diuretics can relieve edema.

Cyanotic Congenital Heart Disease

Cyanotic CHD comprises a mixed group of patients, including some who have right-to-left shunts, some who have had partial surgical repairs, and some who did not undergo intervention. The more common etiologies are tetralogy of Fallot, Ebstein’s anomaly with an atrial septal defect, pulmonary atresia, and tricuspid atresia. If pulmonary hypertension develops such that right-sided pressures approximate left-sided pressures, a persistent right-to-left or bidirectional shunt will occur, a condition known as Eisenmenger syndrome.

All women with cyanotic CHD have an increased maternal and fetal risk during pregnancy. Women with Eisenmenger syndrome have a particularly high risk.

Women with cyanosis tend to have erythrocytosis, which predisposes them to thrombotic events. Anticoagulants must be used judiciously, as these patients are also predisposed to bleeding complications. Compression stockings are often recommended to prevent DVT. Diuresis can aggravate the thrombotic tendency, so diuretics must be used cautiously. These women also appear to be at risk for congestive heart failure and endocarditis. Fetal risk is also increased. The worse the cyanosis, the higher the risk of spontaneous abortion. Fetuses that do survive are at increased risk of premature birth and low birth weight.

The prognosis for pregnant women with Eisenmenger syndrome is very bleak. In one study, over half of the women died as a consequence of their pregnancy. Women with Eisenmenger syndrome should be counseled against pregnancy. If they do become pregnant, termination of the pregnancy should be considered. If pregnancy is continued, patients should be treated as are others with pulmonary hypertension.

Valvular Lesions