Less than 5% (0.2%-4%) of pregnancies in the western world are complicated by cardiovascular diseases;¹ however, the incidence of cardiovascular disease in pregnancy is increasing. This increase is due in part to the increasing prevalence of cardiovascular risk factors such as obesity, hypertension, and diabetes, as well as increasing age at first pregnancy and improved survival of patients with congenital heart disease, with many of these patients now reaching childbearing age. Because of this, cardiovascular disease is now one of the major causes of nonobstetric maternal mortality in the western world.

Several physiologic changes occur during a normal pregnancy to accommodate increasing metabolic demands of the mother and fetus. Hemodynamic changes include blood volume expansion, increase in cardiac output, and decrease in systemic vascular resistance. There are also changes in cardiac anatomy and blood vessels. These changes can put additional strain on patients with underlying heart disease or cardiovascular risk factors (Table 10-1).

HEMODYNAMIC CHANGES

Pregnancy

Cardiac output increases by 30% to 50% in normal pregnancy. This increase in cardiac output starts around the 5th gestational week and plateaus around 20 weeks. Early in pregnancy, cardiac output increases primarily due to an increase in stroke volume (Figure 10-1). However, in the third trimester, increases in heart rate contribute more to cardiac output as stroke volume plateaus. Heart rate increases throughout pregnancy by about 15 beats per minute, starting at around 20 weeks’ gestation and increasing to up to 32 weeks’ gestation. The heart rate stays high until 2 to 5 days postpartum and then gradually decreases. Late in pregnancy, cardiac output can be affected by posture, likely due to mechanical compression of the inferior vena cava by the gravid uterus, resulting in decreased venous return and, in turn, decreased stroke volume. Moving from the left lateral decubitus to supine position can decrease cardiac output by as much as 25% to 30%. This is felt to be the mechanism of supine hypotensive syndrome, a syndrome of hypotension, bradycardia, and occasionally syncope in pregnant women when supine.

Blood pressure and total peripheral resistance decrease during pregnancy. Mean blood pressure starts decreasing early in gestation, with a nadir in the second trimester. However, in the third trimester, blood pressure starts rising and may reach prepregnancy levels. Several mechanisms have been suggested for this fall in vascular resistance including: (1) uteroplacental circulation providing a low resistance circuit, (2) increased nitric oxide production leading to vasodilation, (3) increased endothelial prostaglandin production, and (4) decreased aortic stiffness.

Plasma volume increases by about 45% above nonpregnant values. The exact mechanism is not known but it is thought that it may be in part due to renin-angiotensin-aldosterone system being stimulated by nitric oxide vasodilation. This increase is possibly adaptive in reducing hemodynamic instability after blood loss. Red cell mass also increases during pregnancy. However, plasma volume increases more than red cell mass, leading to the physiologic anemia of pregnancy. This physiologic anemia is likely adaptive as it causes a decrease in blood viscosity, which may counteract the increased thrombotic risk in pregnancy and may also improve intervillous perfusion.

There are also structural cardiac changes that occur during pregnancy. Echocardiographic studies have shown a mild increase in the dimensions of all cardiac chambers. End diastolic volume of the left ventricle increases, but the end systolic volume remains stable, which results in an increase in stroke volume. With dilatation of ventricular cavities comes dilation of valve annuli, and there may be some amount of mitral, tricuspid, and pulmonic regurgitation. There also appears to be an increase in left ventricular mass and wall thickness in normal pregnancy, primarily during the first trimester.

Labor and Delivery

Several factors of labor and delivery have significant effects on the cardiovascular system including pain, anxiety, bleeding, physical exertion, uterine contraction, and anesthesia. Cardiac output increases during labor due to increases in both stroke volume as well as heart rate. Stroke volume increases during labor because blood from uterine sinusoids is pushed into the systemic circulation with each contraction. During active labor, cardiac output further increases due to the physical exertion of delivery. Immediately after delivery, autotransfusion from uterine involution can result in an increase in cardiac output by up to 80%. Increases in heart rate due to pain, anxiety, and blood loss can further increase cardiac output during labor (Figure 10-2).

Both systolic and diastolic blood pressure also increase during labor and delivery and are related to the magnitude of contractions, position of the patient, amount of pain, and anxiety. Analgesia, specifically spinal epidural anesthesia, may cause a marked decrease in systemic vascular resistance with a compensatory increase in stroke volume and heart rate.

Postpartum

The early postpartum period is associated with a high risk of cardiac decompensation because of further intravascular volume loading in a relatively short period of time. There is a significant increase in preload within 10 minutes after delivery, which can result in significant volume overload. As mentioned earlier, there is autotransfusion of blood from the involuting uterus back into the systemic circulation. Additionally, the gravid uterus is no longer compressing the inferior vena cava allowing for a rapid increase in venous return. In the absence of cardiovascular disease, this increase in preloads results in an increase in stroke volume and cardiac output. In the presence of cardiomyopathy and/or fixed heart obstruction, this increase in preload can lead to volume overload or pulmonary edema and decreased cardiac output. Within a week of delivery, postpartum autodiuresis of 2 to 5 L occurs. During the next several weeks, hemoglobin begins to increase, heart rate and stroke volume gradually decrease resulting in a decrease in cardiac output, and vascular resistance increases. These changes result in hemodynamics gradually returning to a prepregnancy state by 8 to 12 weeks postpartum, although some studies suggest this may take up to 6 months postpartum.

Hormone-induced changes occur in the vascular system as early as the fifth gestational week. Histologic changes in the aortic media that have been reported include smooth muscle hypertrophy and hyperplasia, loss of normal corrugation of elastic fibers, and fragmentation of reticular fibers. These changes lead to increased compliance of the vascular system, which is further accentuated by the vasodilatory effects of endogenous progesterone and prostaglandins produced during pregnancy. This is of particular importance in patients with aortopathies as they are at higher risk of aneurysm formation and dissection during pregnancy as well as labor and delivery. These changes may also contribute to the increased risk of spontaneous coronary artery dissection in pregnancy and the immediate postpartum period.

CHANGES IN COAGULATION FACTORS

Pregnancy is a hypercoagulable state due to changes in the concentration and effects of particular coagulation factors. Protein S decreases and resistance to protein C develops in the second and third trimesters. Other coagulation factors including factors I, II, V, VII, VIII, X, and XII increase in concentration. These changes lead to an approximately 20% reduction in prothrombin and partial thromboplastin times. The hypercoagulable state of pregnancy is adaptive in that it leads to less bleeding during delivery and in the immediate postpartum period. However, this also puts patients at risk for serious thromboembolic events.

The physiologic changes previously discussed are usually well tolerated in healthy women. However, these changes may be less well tolerated in patients with preexisting heart disease and may lead to adverse maternal and fetal outcomes. As such, assessment of cardiovascular risk in women with preexisting heart disease is paramount. Risk stratification should ideally occur prior to conception, although many women present for evaluation when they are already pregnant. It is important to note that a woman’s risk may change over time during pregnancy, labor, delivery, and the postpartum period depending on her underlying heart condition.

There are no standardized, evidence-based guidelines to aid in maternal risk stratification. However, several factors have been shown to increase maternal risk in women with preexisting heart disease. These factors have been evaluated in a few studies and have been used to come up with various risk-scoring models in an attempt to accurately predict the risk of maternal adverse cardiovascular events. The 2 largest studies include CARPREG and ZAHARA.

The CARPREG study was a prospective multicenter study of 562 women with congenital and acquired heart disease in Canada who underwent 599 term pregnancies between 1994 and 1999. There was a 98% live birth rate. Only 27% of patients underwent a cesarean section with the vast majority of C-sections (96%) being for obstetric reasons. Primary cardiac events, defined as cardiac death, cardiac arrest, stroke, symptomatic arrhythmia requiring treatment, or pulmonary edema, occurred in 13% of the study population. Only 55% of primary cardiac events occurred prior to delivery, confirming that labor, delivery, and the postpartum periods are also associated with significant cardiovascular risk. Three deaths occurred in this study.¹

In this study, there were 4 main predictors of maternal cardiovascular risk. These were prior cardiac event (arrhythmia, cerebrovascular event, heart failure), cyanosis or functional status (NYHA class > II), left heart obstruction, and myocardial dysfunction (ejection fraction <40%, hypertrophic or restrictive cardiomyopathy). One point was assigned to each of these predictors, and a risk index was developed to predict the level of risk. A score of 0 correlated with an estimated risk of a maternal cardiovascular event of <5%, a score of 1 with 27%, and a score of >1 with an approximately 75% risk of a maternal cardiac event.¹

The CARPREG study also suggested predictors of adverse neonatal events, including NYHA class > II or cyanosis, maternal left heart obstruction, smoking, multiple pregnancies, and use of anticoagulants during pregnancy.¹

More recently, the ZAHARA study retrospectively looked at pregnancy outcomes in women with congenital heart disease. The study population included 1802 women with congenital heart disease who had completed pregnancies between 1980 and 2007. In this population, the incidence of maternal cardiovascular and neonatal events was 7.6% and 25%, respectively. Several predictors of adverse outcomes in this study were noted to be similar to the findings of CARPREG. New associations included the presence of moderate to severe AV valve regurgitation, the presence of a mechanical valve prosthesis, and cyanotic heart disease. Based on ZAHARA data, a more complex scoring system was developed to predict maternal and neonatal risk, which included 13 variables (Table 10-2).²

While the above scoring systems help categorize patients into low-, intermediate, or high-risk groups, it is still very important to consider the risk associated with specific cardiac conditions as well as functional status and make management recommendations on a case-by-case basis.

PREGNANCY

Management of pregnant patients with underlying cardiovascular disease depends on their underlying condition. It is imperative that these patients be managed collaboratively, involving high-risk obstetricians, cardiologists specializing in pregnancy or adult congenital heart disease, and anesthesiologists in order to coordinate patient care and improve outcomes. Depending on the underlying disease process, patients may require medical therapy not traditionally required during pregnancy. They may also require more invasive procedures such as cardiac catheterizations, cardioversions, or, rarely, surgical intervention.

Patients with congenital heart disease should be offered genetic counseling as well as a fetal echocardiogram between 24 and 28 weeks’ gestation to evaluate for any significant structural abnormalities prenatally. Fetal echocardiograms should be performed by pediatric cardiologists with expertise in fetal imaging. This affords a consultation with the pediatric cardiologist if an anomaly is identified and allows for coordination of care in the postpartum period.

LABOR AND DELIVERY

As outlined earlier, significant hemodynamic changes occur during labor and delivery that can have a significant impact on the cardiovascular system. These cardiovascular changes occur frequently and more rapidly as labor progresses. As with pregnancy, management of the cardiovascular system during labor is dependent on the underlying cardiac issues.

One of the most important questions often asked of cardiologists is regarding the safest mode of delivery from a cardiovascular standpoint. While a C-section may reduce the large hemodynamic changes associated with a vaginal delivery as well as the anxiety and pain associated with a prolonged labor, there are significant cardiovascular risks as well. The amount of anesthesia required for a C-section is much higher than that given during a vaginal delivery. This can result in significant changes in systemic and pulmonary vascular resistance and affect cardiac output. Blood loss is typically higher with a C-section as compared to a vaginal delivery (1000 mL with C-section versus 500 mL with vaginal delivery), which may affect stroke volume and, in turn, cardiac output. In addition, acute blood loss can lead to tachycardia that can further impact cardiac output. Certain cardiac lesions such as right ventricular myocardial dysfunction, hypertrophic cardiomyopathy, and left ventricular outflow tract (LVOT) obstruction are dependent on preload to maintain cardiac output, and significant blood loss will result in a decrease in preload, in turn decreasing cardiac output. Compensatory tachycardia due to blood loss further decreases ventricular-filling time in certain lesions, which can further decrease cardiac output.

POSTPARTUM

Significant hemodynamic changes begin to occur immediately after delivery. There is autotransfusion of uterine blood, which occurs with involution of the uterus. This can result in significant volume overload in patients with ventricular dysfunction or fixed obstructive lesions that are unable to tolerate large fluid shifts. Large fluid shifts can also result in electrolyte disturbances that may lead to arrhythmias in patients with underlying heart disease. In addition, there is a relatively rapid increase in both the pulmonary and systemic vascular resistance within the first 72 hours postpartum. This can lead to life-threatening pulmonary hypertension in patients with underlying pulmonary vascular disease or worsening ventricular function in patients with underlying ventricular dysfunction or significant structural heart disease. Depending on the underlying heart disease, patients may require invasive cardiac monitoring and or telemetry monitoring for a period of time postpartum until hemodynamics stabilize.

Hypertension is the most common medical problem in pregnancy. It occurs in up to 15% of pregnancies and accounts for significant morbidity and mortality, increasing the risk of CVA, abruptio placentae, and DIC in the mother. In the fetus, it increases the risk of prematurity, IUGR, and intrauterine death. Hypertension in pregnancy is defined as SBP ≥140 mm Hg or DBP ≥90 mm Hg. It is classified as mild (140-159/90-109) or severe (≥160/110). Elevated blood pressure in pregnancy may be due to several different etiologies, including:

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  Preexisting Hypertension: Blood pressure ≥140/90 mm Hg that presents prior to pregnancy or prior to 20 weeks of gestation. It may be masked in early pregnancy due to the physiologic drop in blood pressure that occurs in the first trimester.

  
  
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  Gestational Hypertension: Pregnancy-induced hypertension (blood pressure ≥140/90) that develops after the 20th gestational week and usually resolves within 42 days postpartum.

  
  
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  Preeclampsia/eclampsia: Elevated blood pressure ≥140/90 mm Hg associated with proteinuria (>0.3 g/24 h). Risk factors for preeclampsia include nulliparity, multiple fetuses, diabetes, or hydatidiform mole. Signs and symptoms of eclampsia include right upper quadrant (RUQ) and epigastric pain due to hepatic congestion, headache and visual changes due to cerebral edema, occipital lobe blindness, hyperreflexia, and clonus. Preeclampsia may also present as the HELLP syndrome consisting of hemolysis, elevated liver enzymes, and low platelet count in addition to hypertension and proteinuria. Eclampsia is defined as seizures occurring in the presence of preeclampsia when the seizures cannot be explained by any other condition.

MANAGEMENT

Most women with hypertension in pregnancy have mild hypertension. Nonpharmacologic therapy should be considered in these patients, including limitation of activities and bed rest in the left lateral decubitus position. Salt restriction is not recommended as it may lead to intravascular volume depletion. Also, weight loss during pregnancy is not recommended as it may lead to reduced neonatal weight and slower growth in infants of these patients. However, there are established guidelines for healthy weight gain during pregnancy and these should be emphasized.

Pharmacologic treatment of mild or moderate hypertension in pregnancy is controversial as too aggressive of treatment may result in uteroplacental insufficiency and affect fetal growth and development. However, untreated hypertension may lead to stroke and placental abruption as well as coronary ischemia, heart failure, and volume overload. So need for treatment should be determined based on the risk-benefit ratio of pharmacologic therapy and may require discussion between both high-risk obstetrics and cardiology.

CASE 1

A 31-year-old G7P4 woman with insulin-dependent (Type I) diabetes mellitus, 3-vessel coronary artery disease, ischemic cardiomyopathy with LVEF 35%, hypertension, and hyperlipidemia presents with non-ST elevation myocardial infarction. Precatheterization pregnancy test was positive and patient was found to be 7 weeks pregnant. Catheterization was postponed and patient was treated medically with heparin, aspirin, β-blockers, hydralazine, and nitrates. Patient was reportedly on an angiotensin-converting enzyme (ACE)-inhibitor, which was discontinued upon results of pregnancy test. Her echocardiogram on admission showed a left ventricular ejection fraction of 30%. Her previous cardiac catheterization images are shown in Figures 10-3 and 10-4.

Patient was counseled on the risks of continuing pregnancy and her medical therapy was optimized for coronary artery disease and ventricular dysfunction in the setting of pregnancy. She suffered a spontaneous abortion at 13 weeks’ gestation.

Coronary artery disease remains a rare condition in women of childbearing age; however, given the growing epidemic of obesity, glucose intolerance/diabetes, hypertension, and hyperlipidemia in addition to more women postponing pregnancy until older ages, there are patients of childbearing age with significant underlying coronary atherosclerosis that can contribute to both maternal and fetal morbidity and mortality. Because of the increase in cardiac output and heart rate associated with pregnancy, these patients are at risk for myocardial ischemia due to myocardial oxygen supply-demand mismatch. This is especially concerning during labor and delivery, when cardiac output can increase by 80% in a relatively short period of time. In addition, several of the medications used for treatment of coronary artery disease and plaque stabilization are teratogenic and must be discontinued prior to conception. Ideally, patients with coronary artery disease or significant coronary artery risk factors should have prepregnancy evaluation, including a thorough history, physical, and a stress test to assess for any significant ischemia. Based on the patient’s functional status and symptoms, assessment of ventricular function may also be warranted. Optimization of medical therapy with discontinuation of teratogenic drugs is also important as a majority of the teratogenic effects occur in the first trimester during organogenesis. For patients with coronary disease who present after conception, a thorough evaluation of symptoms and optimization of medical therapy would be an appropriate starting point. Based on symptomatology, further functional evaluation with submaximal stress testing may be indicated. Cardiac catheterization can be performed safely during pregnancy with appropriate fetal shielding and should be considered in patients presenting with an acute coronary syndrome or in patients with large areas of ischemia on functional testing.

Coronary artery dissection is a rare event; however, there is a relatively high incidence of spontaneous dissection associated with pregnancy, especially in the postpartum state. The etiology of this is unknown, although suggested hypotheses include alterations in the arterial walls related to endogenous hormonal changes of pregnancy, inflammation, or underlying connective tissue disorders.³ These patients will present with an acute coronary syndrome and should be treated as such, although thrombolytics should be avoided due to risk of life-threatening hemorrhage.

Cardiomyopathy occurring in pregnancy is rare and of diverse etiology. Careful history taking and physical examination together with echocardiographic evaluation can help distinguish normal physiologic changes of pregnancy from pathologic ventricular dysfunction. Biomarkers may be helpful in making a diagnosis, but do not confirm it. N-terminal prohormone of brain natriuretic peptide (NT-proBNP) is reportedly higher in pregnant patients versus nonpregnant controls, but should still fall within the normal range. Levels may be elevated with CHF and preeclampsia. Initial management of ventricular dysfunction during pregnancy is similar to management in nonpregnant patients, starting with medications including β-blockers, nitrates, diuretics, and digoxin. Of note, ACE inhibitors and angiotensin receptor blockers (ARBs) are teratogenic and should not be used during pregnancy. In patients who are on ACE inhibitors or ARBs prior to becoming pregnant, these medications should be stopped immediately upon even the possibility of pregnancy. In severe cases of ventricular dysfunction, advanced heart failure therapies including mechanical assist devices and heart transplant may be necessary.

CASE 2

A 44-year-old G2P1 woman with a past medical history of peripartum cardiomyopathy presents at 8 weeks’ gestation for further cardiac evaluation. During her first pregnancy, she presented 1 week postpartum with dyspnea and lower extremity edema. An echocardiogram at that time showed a left ventricular ejection fraction of 25%. She was treated with diuretics, ACE-inhibitors, and β-blockers with improvement in her ventricular function upto 50%. She was counseled on the risk of recurrence and avoidance of future pregnancies. However, she presents 6 years later with an unexpected pregnancy and NYHA class II heart failure symptoms. A baseline echo showed a left ventricular ejection fraction of 55%. During second trimester, she developed orthopnea and lower-extremity edema and an echo showed a decrease in ventricular function to 45%. She was treated with β-blockers and diuretics which improved her symptoms and stabilized her ventricular function.