By Ahizechukwu C. Eke, MD, PhD, MPH
Associate Professor in Maternal Fetal Medicine, Division of Maternal Fetal Medicine, Department of Gynecology & Obstetrics, Johns Hopkins University School of Medicine, Baltimore
Pregnant patients with severe cardiac disease experience a higher risk of adverse cardiac outcomes compared to those with mild to moderate disease.
Steiner JM, et al. Cardiac and pregnancy outcomes of pregnant patients with congenital heart disease according to risk classification system. Am J Cardiol 2021;161:95-101.
Cardiovascular disease (CVD) is the leading cause of maternal mortality in pregnant women, accounting for 4.23 deaths per 100,000 live births, and constitutes approximately 27% of pregnancy-related deaths in the United States.1,2 The incidence of CVD during pregnancy continues to rise. Sadly, care for pregnant women with cardiac disease often is suboptimal because of delays in detection and missed opportunities related to management during pregnancy.
The likelihood of maternal cardiovascular complications in women with cardiac disease during pregnancy can be predicted using risk-scoring and stratification systems. The three universally used methods include the ZAHARA, Cardiac Disease in Pregnancy (CARPREG), and the modified World Health Organization (mWHO) risk-stratification systems.3-5 These systems were developed by incorporating maternal clinical and echocardiographic data from pregnant patients with cardiac disease. In 2018, the American College of Cardiology (ACC) developed the Adults with Congenital Heart Diseases (ACHD) classification system that took into consideration cardiac anatomic defects and physiologic changes associated with underlying cardiac defects.6 In this paper, Steiner and colleagues aimed to determine whether maternal cardiac and pregnancy outcomes varied by disease severity according to three cardiac risk-scoring systems: the ACC classification by ACHD anatomic severity, the ACC ACHD physiologic class, and the mWHO class.6
This was a retrospective cohort study of pregnant adults 18 years of age and older at a single academic teaching hospital in Seattle between September 2009 and April 2019. Inclusion criteria were all pregnancies with ACHD that resulted in live births during the study period. Women were excluded if they had intrauterine fetal demise or miscarriages, or if they had incomplete outcome data.6 Cardiac defects by ACHD anatomic lesion severity, ACHD physiologic class, and mWHO class were the three primary exposures assessed in pregnant women.
Cardiac and pregnancy variables were evaluated as individual and composite outcomes. Pregnancy outcomes included intrauterine growth restriction, small for gestational age, neonatal intensive care unit (ICU) admission, preterm birth (< 37 weeks gestation), postpartum hemorrhage, preeclampsia, and cesarean delivery.6 Composite pregnancy outcomes evaluated included intrauterine growth restriction, preterm birth, postpartum hemorrhage, preeclampsia, maternal death, fetal death, and infant death. Cardiac outcomes included cardiac hospitalization or ICU stay during pregnancy, arrhythmia, heart failure, thromboembolism, stroke, and aortic dissection.6 A composite cardiac outcome including arrhythmia, heart failure, stroke, and thromboembolism also was determined. The primary outcomes were a composite of cardiac and pregnancy outcome measures.6
During the study period, 245 pregnancies from 198 pregnant patients met inclusion criteria. One hundred fifty-six patients (79%) contributed one pregnancy, 37 (19%) had two pregnancies, and five (2%) had three or more pregnancies. The mean maternal age was 28.8 ± 5.7 years. Ten percent of patients had ACHD anatomic class, 41% were ACHD physiologic class, and 19% were mWHO class. The most common maternal cardiac comorbidity was a history of arrhythmia (20%). The number of adverse cardiac and maternal outcomes during pregnancy were proportionally higher among women with more complex anatomic lesions, a higher physiologic class, and a higher mWHO class, except preterm birth rate, which was similar between groups. In the primary analysis assessing the association between the composite cardiac outcome and ACHD anatomy, there was a 2.9-fold increased risk for the composite adverse cardiac outcome among those with complex ACHD (adjusted incidence rate ratio [aIRR], 2.90; 95% confidence interval [CI], 1.08-7.81). Assessing cardiac outcome-specific risks, there were increased risks for arrhythmia associated with increasing severity as defined by ACHD anatomy (aIRR, 2.85; 95% CI, 0.93-8.75), physiologic class (aIRR, 7.88; 95% CI, 1.05-58.99), and mWHO class (aIRR, 3.08; 95% CI, 1.12-8.52). In analyses assessing pregnancy outcomes, there was no significant association between the composite pregnancy outcome and ACHD anatomy, physiologic class, or mWHO class. In the sensitivity analyses, in which the role of parity, gravidity, and severity of cardiac defects in the associations between ACHD severity and outcomes were evaluated, the results for all exposures and the composite cardiac and pregnancy outcomes were similar between groups.
COMMENTARY
In this study, there was an increased risk of adverse cardiac outcomes with more severe ACHD irrespective of the risk classification system, with the most common adverse cardiac outcome being arrhythmia. Physiologic changes during pregnancy aggravate cardiac disease.7 For example, maternal heart rate increases by approximately 10 to 15 bpm, and cardiac output increases by about 30% to 50% (because of increased blood volume and heart rate) during pregnancy.7 Maternal blood pressure falls by 10 mmHg to 15 mmHg as a result of a reduction in peripheral vascular resistance caused by progesterone-induced vasodilation and a low-resistance circuit during normal pregnancy. While systolic ejection murmurs (grades 1 or 2) are the most common types of murmurs that occur during pregnancy, diastolic murmurs are rarely caused by physiologic changes associated with pregnancy.7 Other factors that can influence maternal cardiac hemodynamic status during pregnancy include postural changes (supine vs. left lateral recumbent position), blood loss, and spinal anesthesia.
The cardiac lesions (irrespective of risk classification system) that limit the ability to increase cardiac output during pregnancy and carry increased risk of mortality include valvular stenosis (aortic and mitral with valve area < 1.5 cm2), poor ventricular systolic function, cyanotic heart disease, ischemic heart disease, aortic root dilation (> 4 cm), and pulmonary arterial hypertension (PAH).8 Arrhythmias are the most common cardiac complication in women with cardiac disease during pregnancy and carry an even greater risk of maternal morbidity and mortality and adverse fetal outcomes. These arrhythmias could be atrial (fibrillation or flutter) or ventricular (fibrillation or flutter) and may precipitate heart failure and/or thrombotic complications in pregnant women.9 PAH (with pulmonary arterial pressures > 30 mmHg) and Eisenmenger’s syndrome carry the highest risk of maternal mortality. Optimal management of women with CVD during pregnancy is, therefore, critically important.10 An important first step is to stratify cardiac risk using the ZAHARA, CARPREG, mWHO, or ACC classification system, and co-manage severe cardiac disease with a cardiologist. Avoiding tachycardia by reducing strenuous physical activity and using beta-blockers to slow the heart rate is encouraged during pregnancy and labor. Optimization of volume status, avoidance of hypotension, maintenance of left uterine displacement, and aggressive treatment of blood loss are key management principles during delivery.
Careful fluid management is critical during labor, since an abrupt increase in preload at delivery may lead to an increase in right atrial pressure and pulmonary edema. Avoiding ergonovine maleate is recommended, since it causes rapid autotransfusion and can precipitate pulmonary edema in cardiac patients during the postpartum period. Women with inherited arrhythmias (inherited channelopathies, long QT syndrome) should be offered a consultation with a clinical geneticist to discuss follow-up and testing of the baby at an appropriate age.11 Electrical DC cardioversion should be reserved for women with atrial fibrillation or flutter with hemodynamic compromise. Anticoagulation should be used in accordance with standard practice for the management of atrial arrhythmias in nonpregnant women. Finally, preconception counseling and consideration of pre-pregnancy intervention is recommended for women with moderate to severe cardiac disease.12 A safe and highly effective postpartum contraceptive method should be used to promote pregnancy planning and birth spacing. The Centers for Disease Control and Prevention medical eligibility criteria (MEC) has guidance on which contraception is safe with postpartum women with cardiac disease.
In summary, encouraging pre-pregnancy CVD assessment, identifying and tackling missed opportunities for CVD risk factors during prenatal care, providing appropriate intrapartum and postpartum management of CVD, and preventing delays in recognition of CVD symptoms during the puerperium will reduce morbidity and mortality from CVD in pregnant women.
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- Creanga AA, et al. Pregnancy-related mortality in the United States, 2006-2010. Obstet Gynecol 2015;125:5-12.
- Creanga AA, et al. Pregnancy-related mortality in the United States, 2011-2013. Obstet Gynecol 2017;130:366-373.
- Drenthen W, et al. Predictors of pregnancy complications in women with congenital heart disease. Eur Heart J 2010;31:2124-2132.
- Silversides CK, et al. Pregnancy outcomes in women with heart disease: The CARPREG II Study. J Am Coll Cardiol 2018;71:2419-2430.
- European Society of Gynecology (ESG); Association for European Paediatric Cardiology (AEPC); German Society for Gender Medicine (DGesGM); Regitz-Zagrosek V, et al. ESC guidelines on the management of cardiovascular diseases during pregnancy: The Task Force on the Management of Cardiovascular Diseases during Pregnancy of the European Society of Cardiology (ESC). Eur Heart J 2011;32:3147-3197.
- Steiner JM, et al. Cardiac and pregnancy outcomes of pregnant patients with congenital heart disease according to risk classification system. Am J Cardiol 2021;161:95-101.
- Eke AC. An update on the physiologic changes during pregnancy and their impact on drug pharmacokinetics and pharmacogenomics. J Basic Clin Physiol Pharmacol 2021; Dec 8. doi: 10.1015/jbcpp-2021-0312. [Online ahead of print].
- Writing Committee Members; Otto CM, et al. 2020 ACC/AHA guideline for the management of patients with valvular heart disease: Executive summary: A report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines. J Am Coll Cardiol 2021;77:450-500.
- Bright RA, et al. Maternal heart failure. J Am Heart Assoc 2021;10:e021019.
- American College of Obstetricians and Gynecologists’ Presidential Task Force on Pregnancy and Heart Disease and Committee on Practice Bulletins–Obstetrics. ACOG Practice Bulletin No. 212: Pregnancy and Heart Disease. Obstet Gynecol 2019;133:e320-e356.
- Seth R, et al. Long QT syndrome and pregnancy. J Am Coll Cardiol 2007;49:1092-1098.
- Simpson LL. Preconception considerations. Semin Perinatol 2014;38:236-239.
