Anne Marie Valente Boston Children’s Hospital; Brigham and Women’s Hospital; Harvard Medical School, Boston, MA, USA Profound hemodynamic changes occur during pregnancy. They are usually well tolerated by women with structurally normal hearts, however these changes may not be tolerated as well in women with underlying cardiac conditions. It is important to understand the effects such hemodynamic changes may have on women with congenital heart disease (CHD). Echocardiography has an important role in the evaluation and management of women with heart disease during pregnancy [1]. Chamber enlargement, valve annular dilation, and increased amounts of mild valvular regurgitation are time‐related events during normal pregnancy, resulting from reversible cardiac remodeling induced by physiologic volume overload. These aspects should be considered for correct interpretation of Doppler echocardiographic findings in pregnant women [2]. Several guideline documents include the use of echocardiography in the management of pregnant women. The 2014 American Heart Association/American College of Cardiology guideline for the management of patients with valvular heart disease recommends that all patients with suspected valve stenosis or regurgitation should undergo an echocardiogram before pregnancy [3]. The 2018 European Society of Cardiology guidelines for the management of cardiovascular diseases during pregnancy recommend echocardiography for any pregnant patient with unexplained or new cardiovascular signs or symptoms [4]. Many women experience symptoms of exercise intolerance, fatigue, and pedal edema during the later stages of pregnancy or develop a flow‐related systolic murmur. However, occasionally previously undiagnosed cardiac disease may be unmasked during pregnancy. Echocardiography should be considered in any pregnant women with a history of cardiac disease, concerning symptoms, arterial desaturation, or any new holo‐systolic or diastolic murmur [5]. This chapter reviews the hemodynamic changes that occur with pregnancy and the echocardiographic changes that accompany this process with an emphasis on these changes in women with heart disease. During pregnancy, dramatic changes in hemodynamics occur (Figure 43.1). On average, there is a 40–50% increase in the circulating blood volume that occurs during pregnancy [6]. There is up to a 50% increase in cardiac output in pregnancy, which peaks at the end of the second trimester. This rise in cardiac output is due primarily to augmentation in stroke volume with some contribution from a rise in heart rate [7]. The heart rate generally increases 10% from prepregnancy values. At the same time, there is a dramatic decrease in systemic vascular resistance, due largely to the effects of uterine circulation and endogenous hormones. There is a widening of the pulse pressure, with a disproportionate decrease in the diastolic blood pressure. Throughout pregnancy, the increase in venous tone increases preload, and decreases in aortic stiffness reduce afterload [8]. Body position can also influence the hemodynamics in pregnant women. In the supine position, women may experience decreased preload, stroke volume, and cardiac output due to the compression of the inferior vena cava from the gravid uterus [9]. Therefore, women may be more comfortable in the left lateral decubitus position. During labor and delivery, there is a further abrupt increase in cardiac output related in part to the associated pain and anxiety. Uterine contractions can lead to marked increases in both systolic and diastolic blood pressure and surges in cardiac output [10]. After delivery, there is an initial surge in preload related to the autotransfusion of uterine blood into the systemic circulation and to inferior vena cava decompression. Stroke volume and cardiac output increase as much as 10% and persist for at least 24 hours following delivery. Hemodynamics usually normalize by 12 weeks postpartum, but there is some evidence that hemodynamics in women with underlying heart disease do not return to the prepregnancy baseline [11]. Pregnancy is also associated with a hypercoagulable state due to relative increases in fibrinogen, plasminogen activator inhibitors, clotting factors VII, VIII, X, von Willebrand factor, and platelet adhesion molecules, as well as relative decreases in protein S activity and acquired resistance to activated protein C [12,13]. Figure 43.1 Hemodynamic changes expected with pregnancy. (a–c) Heart rate, stroke volume, and cardiac output. Values on the x axis are from pulsed‐wave Doppler. (d, e) Arterial pressure and peripheral resistance. Values on the y axis are represented as mean ± standard deviation. (f) Plasma volume. Source: (a–c) Adapted from Mabie WC, et al. A longitudinal study of cardiac output in normal human pregnancy. Am J Obstet Gynecol 1994;170:849–56. (d, e)Adapted from Stout K. Role of echocardiography in the diagnosis and management of heart disease in pregnancy. In: Otto C (ed.) The Practice of Clinical Echocardiography, 4th edn, 2012, Chapter 35, Figure 35‐5, which was adapted from Easterling TR, et al. Maternal hemodynamics in normal and preeclamptic pregnancies: a longitudinal study. Obstet Gynecol 1990;76:1061–9, Figures 1, 2, 3. (f) Adapted from Silversides C. Physiological changes in pregnancy. In: Oakley C, Warnes CA (eds) Heart Disease in Pregnancy, 2nd edn, BMJ Books, 2007, Chapter 2, Figure 2.1. ISBN: 978‐1‐4051‐3488‐0. Echocardiography is an important imaging tool as it allows assessment of cardiac structure and function in women in various stages of pregnancy. There are inconsistent data delineating the normal echocardiographic parameters during pregnancy, as the majority of uncomplicated pregnancies do not require echocardiography and data obtained in a standardized fashion are limited. Differences in the position of the patient (supine versus left lateral decubitus), timing of gestation, and technical variables contribute to the discrepancies found in the literature. For example, during late pregnancy, significant increases in left ventricular (LV) ejection fraction (EF) (11%), end‐diastolic volume (21%), stroke volume (35%), and cardiac output (24%) were observed in the left lateral decubitus compared to the supine position [14]. There is a spectrum of cardiac responses to normal pregnancy, which adds to the difficulties in providing normal values for echocardiographic changes during pregnancy. A summary of the echocardiographic changes expected during pregnancy is listed in Table 43.1. Table 43.1 Normal echocardiographic changes during pregnancy Throughout pregnancy, ventricular size and mass increase. On average, the LV end‐diastolic dimension increases several millimeters [15]. LV mass increases by 5–10% and is proportional to the increased workload of pregnancy. This results in eccentric hypertrophy, as the ratio of wall thickness to the ventricular radius does not change [16]. Left ventricular systolic function does not appear to change significantly during pregnancy. There have been reports of a transient increase in LVEF during the early stages of pregnancy which then falls in the third trimester. However, one confounder is that the Teichholz formula, which assumes an ellipsoid LV shape, is utilized for calculation of EF and may not be appropriate for pregnant patients due to the geometric changes of the ventricle. Bamfo and colleagues evaluated LV long‐axis function and used tissue Doppler imaging in order to avoid geometric assumptions and reported that long‐axis shortening decreased significantly at the septal but not the lateral margin of the mitral valve annulus. This may reflect that the changes in ventricular geometry affect the septum more than the lateral wall of the LV [17]. The data on the effects of pregnancy on myocardial contractility are conflicting. Geva et al. used a load‐adjusted measure of contractility and reported a transient decrease in myocardial contractility due to a decrease in the end‐systolic stress not matched by an increased rate in corrected velocity circumferential shortening [18]. Bamfo et al. reported a progressive increase in the Tei index throughout pregnancy and the postpartum period, and postulated an intrinsic abnormality in contractility associated with pregnancy [17]. In contrast, others have reported no significant changes or an increase in myocardial contractility during pregnancy [19, 20]. Left ventricular diastolic function appears preserved despite increases in preload and LV hypertrophy. Transmitral velocities are flow dependent and reflect the increased preload in pregnancy with peak mitral inflow velocity increases in early diastole (E) and atrial systole (A). As pregnancy progresses, there is an increased amount of atrial contraction contributing to LV filling resulting in higher A‐wave velocities. The proportional change in A is greater than the change in E, resulting in a diminished E/A ratio throughout pregnancy. Using tissue Doppler as a load‐independent assessment, investigators have shown that LV relaxation is preserved during pregnancy. The ratio of e′ to E remains within normal limits throughout pregnancy and reflects normal LV filling pressures [8]. The ratio of e′/a′ decreases throughout pregnancy, reflecting the enhanced atrial contraction. Savu and colleagues performed tissue Doppler strain and strain rate and 3D speckle tracking on 51 pregnant women and reported a significant, reversible decrease in global and segmental longitudinal deformation in both the LV and right ventricle (RV) late in pregnancy. The decrease in longitudinal deformation was seen at all three levels in the LV (basal, mid, and apical) and most notably at the inferior, inferoseptal, and anteroseptal walls. In the RV, the decrease in longitudinal deformation was most notable at the apical level. These investigators also documented an increase in the cardiac globularity as defined by a decreased sphericity index [21]. The left atrium increases up to 10% in size during pregnancy [22]. Using 3D echocardiography, Yosefy et al. documented significant increases in the LA systolic and diastolic volume, and LA stroke volumes (all indexed to body surface area). These investigators confirmed the reduction in E/A ratio as pregnancy progresses with a decrease in the diastolic E wave, forcing the left atrium to increase the atrial kick (A wave) [23]. Pulmonary artery pressure remains normal during pregnancy due to vascular recruitment in the highly capacitant pulmonary circulation resulting in decreased pulmonary vascular resistance [24]. There is a slight increase in valvar annular diameters during pregnancy and an increase in regurgitant flow velocities from the tricuspid, mitral, and pulmonary valves. Right‐sided heart valve velocities increase during pregnancy, but rarely exceed 2 m/s. Physiologic valvar regurgitation is common in pregnancy, mainly involving right‐sided valves in late gestational periods, occasionally persisting in the early puerperium [2]. Despite the increase in valvar regurgitation, women rarely are symptomatic from these changes [25]. Aortic root and LV outflow tract dimensions increase by 1–2 mm during pregnancy and do not always return to pre‐pregnancy baseline values [26]. During pregnancy, 25% of women have small pericardial effusions. There is some evidence that women with greater weight gain during pregnancy have a higher incidence of effusions [27]. In 1948, Lund reported the hemodynamic changes during pregnancy, labor, and the postpartum period in 25 women with CHD who delivered at the University of Minnesota [28]. Many of the observations made at that time still hold true today. The normal physiologic changes of pregnancy may exacerbate the underlying hemodynamics of women with heart disease, resulting in clinical symptoms and sometimes decompensation during pregnancy. In contrast to the echocardiographic changes observed during pregnancy in women with structurally normal hearts, the hemodynamic adaptations to pregnancy in women with structural heart disease are less well studied. In a study of 29 women with structural heart disease that utilized echocardiography before conception, during pregnancy, and postpartum, Cornette et al. confirmed increases in stroke volume and cardiac output. The magnitude of the increase, however, was lower than that described in normal populations and more comparable to patterns observed in pregnancies complicated by growth restriction. There was a significant increase in the E/e′ ratio and decrease in the EF after pregnancy compared to pre‐pregnancy values, suggesting a negative influence of pregnancy on systolic function in women with cardiac disease [29]. These data are in contrast to those of Uebing et al. who did not find any deleterious effect of pregnancy on 53 women with heart disease who had undergone pregnancy. However, they described a persistent increase in RV size in patients with repaired tetralogy of Fallot (TOF) who had undergone pregnancy [30]. The potential for accelerated RV remodeling was confirmed in a study with cardiac magnetic resonance imaging (MRI) in pregnant women with repaired TOF [31]. Valvar velocities are known to increase in pregnant women with valvular heart disease. In a study of 66 pregnant women with semilunar valve stenosis, the peak and mean gradients increased on average 21 ± 3% and 24 ± 3%, respectively, in women with aortic stenosis, and 31 ± 3% (both peak and mean) across the pulmonary valve in women with pulmonary stenosis compared to preconception values [32]. This highlights the importance of placing the diagnostic testing results in context with the physiologic changes of pregnancy based on timing of acquisition of the echocardiographic images. Despite the fact that most women do not have cardiac complications during pregnancy, cardiovascular disease is a leading cause of pregnancy‐related mortality. An analysis from the Centers for Disease Control’s National Pregnancy Mortality Surveillance System from 2011 to 2015 revealed that cardiovascular conditions were responsible for at least one‐third of all pregnancy‐related deaths [33]. In 2001, The Cardiac Disease in Pregnancy (CARPREG) investigators published data from 13 Canadian centers addressing risk stratification [34]. They examined the outcomes of 599 pregnancies in women with heart disease, 74% with some form of CHD. There was a 13% incidence of maternal cardiac complications, primarily symptomatic heart failure or arrhythmias; however, 1% of pregnancies were complicated by maternal embolic stroke or cardiac death. Four predictors of adverse maternal cardiac outcomes were identified, including: prior cardiac event or arrhythmia; advanced New York Heart Association class or cyanosis defined as a resting oxygen saturation <90%; left heart obstruction, defined as a peak LV outflow tract gradient of ≥30 mmHg; and systemic ventricular dysfunction, defined as an EF <40% [34]. These data provided the framework for multiple subsequent publications evaluating risk factors for women with heart disease during pregnancy [35,36]. In 2013, the European Society of Cardiology reported the results of pregnancies in 1321 women with heart disease (66% of whom had CHD) from 28 countries over a 4‐year period. Of those, 15% were hospitalized during pregnancy, most commonly for management of heart failure symptoms. The investigators concluded that the majority of women with heart disease could deliver safely if they had undergone an adequate pre‐pregnancy evaluation and received high‐quality specialized care during pregnancy and the postpartum period [37]. Balint and colleagues have reported that women with CHD who suffer a cardiac event during pregnancy have a greater risk of long‐term cardiac events [38]. In 2018, Silversides et al published CARPREG 2, which included 1938 pregnancies in women with cardiac disease (63% CHD) and included a weighted‐risk score for adverse outcomes. The highest‐weighted risk factors (weight of 3 points) include a prior history of cardiac events or arrhythmias, decreased functional status (New York Heart Association class ≥III), and presence of a mechanical heart valve. Risk factors that account for 2 points include: ventricular dysfunction, high‐risk left‐sided valve disease/LV outflow tract obstruction, pulmonary hypertension, coronary artery disease, and high‐risk aortopathy. One point was assigned for late pregnancy assessment or no prior cardiac intervention. In this cohort, 16% of women experienced an adverse cardiac outcome, primarily heart failure and arrhythmias. The predicted risks for cardiac events stratified according to point score were ≤1 point (5%), 2 points (10%), 3 points (15%), 4 points (22%), and >4 points (41%) [39]. Serious cardiac events, such as cardiac arrest or death, urgent cardiac interventions, heart failure or arrhythmias requiring admission to the intensive care unit occur rarely in pregnant women with heart disease. In the CARPREG registry of 1315 pregnancies in women with heart disease, a serious cardiac event occurred in 3.6% of pregnancies, of which approximately one‐half were determined to be preventable [40]. This highlights the importance of awareness of patient‐specific risk. The European Society of Cardiology published an extensive set of guidelines for management of cardiovascular diseases during pregnancy in 2018. This includes the modified World Health Organization (WHO) Classification to determine disease‐specific risk (Table 43.2) [4]. Maternal cardiac complications, however, are not the only adverse outcomes to consider when counseling women with heart disease regarding pregnancy risks [41]. Neonatal and obstetric adverse outcomes must also be considered. Neonatal complications included premature birth, small for gestational age (SGA), respiratory distress, fetal or neonatal death, as well as fetal CHD [42]. CHD was identified in 8% of the offspring of the 183 live births of mothers with CHD but not with a recognized genetic syndrome [42]. Table 43.2 The modified World Health Organization (mWHO) classification for maternal cardiac risk Source: Modified 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;39:3165–241. ASI, aortic size index; EF, ejection fraction; HTAD, heritable thoracic aortic disease; NYHA, New York Heart Association; WHO, World Health Organization. Obstetric complications appear to be higher in women with heart disease. In one report of 113 pregnancies in 65 women with CHD, adverse obstetric outcomes occurred in 32%. These events included preterm delivery, postpartum hemorrhage, and preterm premature rupture of membranes. Importantly, women who avoided the Valsalva maneuver during delivery had increased rates of postpartum hemorrhage and third‐ or fourth‐degree vaginal lacerations [43]. Due to the tremendous advances in the evaluation and management of CHD over the past several decades, the etiology of the majority of maternal heart disease in Western societies is congenital in origin. In general, women with small left‐to right shunts, normal exercise tolerance and oxygen saturation, and no history of arrhythmias tolerate pregnancy well. Women with unrepaired atrial septal defects (ASDs) may experience increased volume loading of the right heart and are predisposed to volume retention and palpitations in pregnancy [44]. Meticulous attention to intravenous line care is essential, as these women are at risk for paradoxical embolism and stroke. Women with small ventricular septal defects (VSDs) tolerate pregnancy well. Echocardiography, however, should be performed to confirm the high transseptal gradient across the defect, as any evidence of Eisenmenger syndrome would dramatically change the risk to the mother. Similarly, women with small patent ductus arteriosus remain asymptomatic in pregnancy, unless the flow is large enough to produce LV dilation. There is some evidence that women with both repaired and unrepaired septal defects are at risk for adverse obstetric outcomes, including pre‐eclampsia and SGA neonates. The most common type of right ventricular outflow obstruction in women of childbearing age is pulmonary valve stenosis (PS). The majority of women with mild forms of PS tolerate pregnancy well, as mild forms of PS usually do not progress in adulthood [45]. Women may present with greater degrees of right ventricular outflow tract obstruction and have right ventricular hypertrophy (Figure 43.2, Video 43.1). In a retrospective, single‐center study of 114 pregnant women with prior right ventricular outflow tract interventions, the risk of cardiac complications was low and not related to the degree of outflow tract obstruction [46]. Women with severe right ventricular outflow tract obstruction who become pregnant must be monitored closely for signs of right ventricular dysfunction. The incidence of maternal hypertensive disorders, particularly pre‐eclampsia, may be increased in women with PS [47]. Figure 43.2 (a) Apical four‐chamber view of severe right ventricular hypertrophy in a woman with Alagille syndrome and hypoplastic branch pulmonary arteries who presented with an unplanned pregnancy at 24 weeks’ gestation. (b) Contrast injection in the proximal left pulmonary artery (arrow) confirming branch pulmonary artery stenosis. The patient underwent balloon angioplasty of this stenosis with immediate improvement in her pulmonary pressures. LA, left atrium; LV, left ventricle; RA, right atrium; RV, right ventricle. Source: Daniels CJ, Zaidi AN (eds) Color Atlas and Synopsis of Adult Congenital Heart Disease, McGraw‐Hill, 2015, Chapter 11, Figure 11‐7. Reproduced with permission of McGraw‐Hill Education. Echocardiographic changes in pregnant women with Ebstein anomaly have not been extensively studied. Pregnant women with Ebstein anomaly are at risk for arrhythmias and heart failure, which appear to occur in women with greater degrees of tricuspid regurgitation and worse right ventricular function [48]. Women with Ebstein anomaly and interatrial shunts are at risk for stroke from a paradoxical embolus. Obstetric complications in these women include prematurity, preterm delivery, and postpartum hemorrhage [49, 50]. Physiologically corrected transposition of the great arteries (congenitally corrected TGA, L‐loop TGA) is a congenital abnormality that may not be diagnosed until later in life. These patients have atrioventricular (AV) and ventriculoarterial discordance resulting in a systemic RV, which may become dysfunctional over time. Other associated cardiac anomalies include a VSD, PS, Ebstein anomaly, or dysplastic tricuspid valves. Maternal risk is often determined by the functional status, systemic RV function, presence of associated lesions, and arrhythmias. The Royal Brompton Hospital reported over four decades of experience with women with physiologically corrected TGA, which included 45 pregnancies and 27 live births. Cardiovascular complications occurred in 26% of these women, including heart failure, worsening cyanosis, and cerebral vascular accident [51]. The Mayo Clinic experience over 17 years included 60 pregnancies with 83% live births, and a lower prevalence of maternal cardiac complications; one woman with significant tricuspid valve regurgitation developed heart failure symptoms, and multiple pregnancy‐related complications (including toxemia, congestive heart failure, endocarditis, and myocardial infarction) were experienced by one woman who had a total of 12 pregnancies [52]. In a study of 20 pregnancies in 13 women with physiologically corrected TGA, the most common cardiovascular complication during pregnancy was supraventricular arrhythmias and there was no deterioration of systemic right ventricular function observed by echocardiography [53]. Any degree of cyanosis places both the mother and the fetus at significant risk. Maternal cyanosis is exacerbated during pregnancy as the fall in systemic vascular resistance increases right‐to‐left shunting. Additionally, hypoxemia induces erythrocytosis, which will further increase the potential for thrombosis, and, in the setting of an intracardiac shunt, risk for paradoxical embolism and stroke. In a study of 44 cyanotic women who underwent 96 pregnancies, only 12% of pregnancies resulted in live births when the maternal oxygen saturation was <85%. Maternal cardiac complications occurred in 32% and included heart failure, endocarditis, and thrombotic complications [54].
CHAPTER 43
Pregnancy and Heart Disease
Introduction
Physiologic hemodynamic changes in pregnancy and delivery
Normal echocardiographic changes with pregnancy
Echocardiographic parameter
Changes during pregnancy
Left atrium
↑ 3–4 mm
Left ventricular end‐diastolic dimension
↑ 2–3 mm
Left ventricular mass
↑ 5–10%
Left ventricular ejection fraction
Unchanged or slightly ↑
E/A ratio
↓
E/e′ ratio
Unchanged
e′/a′ ratio
↓
Valve annulus diameter
↑ 1–2 cm
Valvar regurgitation
Physiologic tricuspid, pulmonary, mitral valve regurgitation (not aortic)
Small pericardial effusion
Present in ~25%
Echocardiographic changes in women with heart disease during pregnancy
Risk stratification for pregnant women with heart disease
mWHO I
mWHO II
mWHO II–III
mWHO III
mWHO IV
Diagnosis (if otherwise well and uncomplicated)
Small or mild
Successfully repaired simple lesions (atrial or ventricular septal defect, patent ductus arteriosus, anomalous pulmonary venous drainage)
Atrial or ventricular ectopic beats, isolated
Unoperated atrial or ventricular septal defect
Repaired tetralogy of Fallot
Most arrhythmias (supraventricular arrhythmias)
Turner syndrome without aortic dilatation
Mild left ventricular impairment (EF >45%)
Hypertrophic cardiomyopathy
Native or tissue valve 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 bicuspid aortic valve pathology
Repaired coarctation
Atrioventricular septal defect
Moderate left ventricular impairment (EF 30–45%)
Previous peripartum cardiomyopathy without any residual left ventricular impairment
Mechanical valve
Systemic right ventricle with good or mildly decreased ventricular function
Fontan circulation
If otherwise the patient is well and the cardiac condition uncomplicated
Unrepaired cyanotic heart disease
Other complex heart disease
Moderate mitral stenosis
Severe asymptomatic aortic stenosis
Moderate aortic dilatation (40–45 mm in Marfan syndrome or other HTAD; 45–50 mm in bicuspid aortic valve, Turner syndrome ASI 20–25 mm/m2, tetralogy of Fallot <50 mm)
Ventricular tachycardia
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/m2, tetralogy of Fallot >50 mm)
Vascular Ehlers–Danlos
Severe (re)coarctation
Fontan with any complication
Risk
No detectable increased risk of maternal mortality and no/mild increased risk in morbidity
Small increased risk of maternal mortality or moderate increase in morbidity
Intermediate increased risk of maternal mortality or moderate to severe increase in morbidity
Significantly increased risk of maternal mortality or severe morbidity
Extremely high risk of maternal mortality or severe morbidity
Specific congenital heart lesions
Left‐to‐right shunts
Right ventricular outflow tract obstruction
Ebstein anomaly
Physiologically corrected transposition of the great arteries
Cyanotic lesions
Pulmonary vascular disease and Eisenmenger syndrome
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