53.1a General considerations

Given the increased morbidity and mortality in pregnant women with cardiovascular disease, it is important for clinicians to understand how to manage cardiovascular disease during pregnancy. This chapter discusses epidemiology, haemodynamic, haemostatic, and metabolic alterations during pregnancy, genetic testing and counselling, cardiovascular diagnosis in pregnancy, and infective endocarditis.

Maternal mortality remains an important international concern, although rates have reduced by 44% in the past 25 years.¹ An important cause of maternal mortality is cardiovascular disease (CVD), which is the leading cause of maternal mortality in Western countries, most often due to myocardial infarction, cardiomyopathy, and congenital heart disease. The mortality rate of pregnant women with CVD is 1%, much higher compared to 0.007% in the normal population, and higher in developing countries (3.9%) versus developed countries (0.6%).² Case fatality rates remain high in aortic dissection, acute myocardial infarction, and peripartum cardiomyopathy. Hypertensive disorders are the most frequent CVD conditions during pregnancy and are associated with long-term CVD morbidity.³ It is thus important for clinicians to understand how to manage CVD during pregnancy.

Physiological changes occur during pregnancy to meet the metabolic demands of the fetus and to prepare the mother for delivery. Cardiac output increases early in the first trimester and can rise to 80–85% above baseline by the third trimester.⁴ This increase in cardiac output is due to increases in stroke volume, heart rate, and preload blood volume, as well as a decrease in systemic vascular resistance. Physiological dilatation of all four chambers occurs during pregnancy, with increases in left ventricular volume (20–30%), right ventricular volume (18%), and left ventricular mass (45–50%) in the third trimester.⁴ These morphological adaptations lead to eccentric hypertrophy during pregnancy and reverse by approximately 6 months postpartum.⁵ Systolic blood pressure remains unchanged whereas diastolic blood pressure may decrease during the first and second trimesters and then increase back to baseline during the third trimester. Thus, blood pressures in the range of prehypertension and hypertension are not normal during pregnancy and predict postpartum maternal adverse outcomes.^6,7

During labour, cardiac output augmentation occurs due to uterine contractions, pain, and anxiety. Both systolic and diastolic blood pressures are increased during uterine contractions and peak in the second stage of labour. Cardiac output increases by 80% immediately after delivery due to autotransfusion and then rapidly decreases within 10 min and returns to prelabour values within 24 h.³

Haemostatic changes in pregnancy include increased levels of coagulation factors and reduced levels of inhibitors, which lead to a hypercoagulable state of pregnancy.⁸ Standard coagulation tests do not significantly change, but recent studies have shown that in pregnant women receiving low-molecular-weight heparin for venous thromboembolism prophylaxis, plasma anti-factor Xa levels are lower than expected, indicating a tendency for subtherapeutic dosing.⁹

Maternal metabolism is anabolic during early gestation and becomes catabolic in late gestation to support a rapidly growing fetus.¹⁰ Maternal insulin resistance develops to limit glucose consumption by the mother and to shunt glucose to the placenta for fetal growth. This insulin resistance leads to lipolysis and increased concentrations of fatty acids and glycerol, particularly during late pregnancy. Insulin levels rise during the second and third trimesters, as well as levels of triglycerides, total cholesterol, and low-density lipoprotein (LDL) cholesterol.¹⁰

Patients with cardiovascular conditions should undergo consultation about the risk of inheritance depending on the type of disease. Genetic counselling is recommended to help determine prognosis, presence of genetic reproductive risks, involvement of other organs, and education of other family members who may benefit from preventive or treatment interventions.¹¹ The recurrence risk for a congenital heart defect is approximately 4% and is higher in the offspring of affected mothers than in those of affected fathers.³ Certain defects such as atrioventricular septal defect appear to be single-gene defects whereas tetralogy of Fallot appears to be a polygenic disorder. Since autosomal dominant-inherited conditions (such as Marfan, hypertrophic cardiomyopathy, and long QT syndrome) have a 50% inheritance risk, genetic counselling is highly recommended for parents with these conditions.³

The European Society of Cardiology (ESC) Guidelines support the use of prenatal chromosomal diagnosis via chorionic villus sampling, as well as fetal nuchal fold thickness measurement for women aged over 35 years to screen for major fetal cardiac defects.³ Preimplantation genetic diagnosis for genetic defects is also now possible for patients receiving assisted reproductive services.

In evaluating women with suspected heart disease, the history and physical examination can provide relevant information to prompt further diagnostic studies. Descriptions of syncope or palpitations can help identify disorders such as long QT syndrome, while detailed family histories can help elicit suspicion for hypertrophic cardiomyopathy or Marfan syndrome. A family history of sudden death should also be asked about to help identify any genetic propensity to life-threatening arrhythmias. Exercise intolerance and shortness of breath should be assessed for all patients at risk for heart failure. Women with ischaemic heart disease should be asked about their angina frequency and stability. All women should be questioned about any prior history of prior preterm labour, gestational hypertension, pre-eclampsia/eclampsia, and gestational diabetes.

A cardiovascular exam includes auscultation for new and pathological murmurs, changes in murmurs, and assessment for heart failure. Physiological changes in pregnancy may produce murmurs and signs suggestive of heart failure, so further testing such as echocardiography or B-type natriuretic peptide may be needed to help distinguish normal physiology from pathology. In a healthy pregnancy, B-type natriuretic peptide remains in a normal range throughout the three trimesters and postpartum period, similar to non-pregnant women,¹² and may be useful for prognostication during pregnancy.¹³ Blood pressure, proteinuria, and oxygen saturation should also be assessed as per the ESC Guidelines.³

Normal pregnancy can lead to various electrocardiogram (ECG) changes, although most pregnant women have normal ECGs. ECG changes may include left axis deviation, presence of prominent Q waves in inferior leads, and flat or inverted T waves in leads III and V1–V3.¹⁴ Most pregnant women with palpitations have benign arrhythmias.¹⁵ However, for patients complaining of palpitations with a history of structural heart disease or who have a prior history of arrhythmia, Holter monitoring should be performed for assessment of arrhythmia frequency, duration, and correlation with symptoms.

Transthoracic echocardiography remains the preferred tool to assess cardiac structure and function in pregnancy. Transthoracic echocardiography should be performed in pregnant women with worsening dyspnoea with signs of heart failure, with a diastolic murmur or a new systolic murmur that worsens with the Valsalva manoeuvre, or with elevated B-type natriuretic peptide. In particular, women with preeclampsia and worsening dyspnoea or oedema should undergo transthoracic echocardiography to screen for peripartum cardiomyopathy.¹⁶ Transoesophageal echocardiography is rarely required but may be indicated to assess prosthetic heart valves for thrombus or endocarditis, or detect other structural abnormalities not well seen with transthoracic echocardiography. In addition, transoesophageal echocardiography is used to guide structural interventions such as percutaneous valve replacement.

Exercise treadmill testing or exercise stress echocardiography should be performed prior to pregnancy in women with known heart disease for risk assessment, as it can provide insight into the woman’s functional capacity and haemodynamic response to stress. Exercise-induced changes in valve haemodynamics, ventricular function, pulmonary artery pressure, exercise capacity, chronotropic response, and symptoms can help determine how well a woman will tolerate the haemodynamic changes of pregnancy and thus aid in risk stratification and clinical decision-making. Exercise stress testing is considered safe in pregnancy and does not increase the risk of spontaneous abortions.³ The ESC Guidelines recommend achieving submaximal heart rates (80% of predicted maximal heart rate) in asymptomatic pregnant women with suspected CVD.³ Dobutamine stress should be avoided.

Magnetic resonance imaging may be considered in selected pregnant patients if transthoracic or transoesophageal echocardiography is not able to provide an adequate diagnosis and if it will affect the care of the patient or fetus during the pregnancy. Gadolinium-based contrast agents should not be administered to pregnant patients, as the risk to the fetus remains unknown and may be harmful.¹⁷

Radiation risk to the fetus varies depending on the radiation dose and the time of exposure. The risk of malignancy, miscarriage, or major malformations is negligible in fetuses exposed to 50 mGy or less.³ The teratogenicity of radiation is dose dependent, with the risk of fetal malformation increasing significantly at fetal doses above 150–200 mGy. Procedures should be delayed until at least the 15th gestational week, when the fetus’s central nervous system is less sensitive to radiation effects. Since the carcinogenic risk of ionizing radiation follows a linear no-threshold risk model, radiation exposure in utero should remain an important concern. Studies suggest an association between in utero irradiation and an increased risk of childhood cancer; this risk is highest after a first-trimester radiation exposure compared with a second- or third-trimester exposure.¹⁸

Most medical procedures involve doses to the fetus well below 50 mGy (Table 53.1a.1), including chest radiography, computed tomography of the chest, and coronary catheterization procedures. The risks and benefits of performing procedures with radiation should be discussed with the patient, and all radiation doses must be kept ‘as low as reasonably achievable’ (ALARA), including shielding the uterus from direct radiation and following protocols to minimize radiation exposure.

Infective endocarditis is a rare but serious condition in pregnancy, with an incidence of 0.006%, maternal mortality rate of 11–22%, and fetal mortality rate of 14%.¹⁹ Incidence is higher in patients with prosthetic valves, congenital heart disease, and rheumatic heart disease, and intravenous drug users.¹⁹

Diagnosis and treatment of infective endocarditis are generally the same in pregnant patients as non-pregnant patients, with careful consideration of fetotoxic effects of antibiotics.³ All patients with infective endocarditis should be evaluated by an infectious disease specialist, cardiologist, and cardiac surgeon, for discussion about the timing of surgical intervention. Early surgery should be considered in patients with valve dysfunction leading to heart failure and left-sided infective endocarditis caused by highly resistant organisms. The Early Surgery Versus Conventional Treatment for Infective Endocarditis (EASE) trial demonstrated that early surgery in patients with large vegetations significantly reduced all-cause mortality, systemic embolism, and recurrence of infective endocarditis.²⁰ As there is a higher risk for fetal death associated with cardiac surgery during early pregnancy, cardiac operations should be deferred until after the 28th gestational week, and a viable fetus should be delivered prior to surgery when possible.³

Antibiotic prophylaxis for endocarditis is reasonable prior to selected dental procedures for high-risk patients; however, antibiotic prophylaxis is not recommended during vaginal or caesarean delivery, or other genitourinary, gastrointestinal, or respiratory procedures.³