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Canadian Journal of Cardiology

Canadian Cardiovascular Society: Clinical Practice Update on Cardiovascular Management of the Pregnant Patient

      Abstract

      The number of women of childbearing age with cardiovascular disease (CVD) is growing because of increased survival of children with congenital heart disease. More women are also becoming pregnant at an older age, which is associated with increased rates of comorbidities including hypertension, diabetes, and acquired CVD. Over the past decade the field of cardio-obstetrics has significantly advanced with the development of multidisciplinary cardio-obstetric programs (COPs) to address the increasing burden of CVD in pregnancy. With the introduction of formal COPs, pregnancy outcomes in women with heart disease have improved. COPs provide preconception counselling, antenatal and postpartum cardiac surveillance, and labor and delivery planning. Prepregnancy counselling in a COP should be offered to women with suspected CVD who are of childbearing age. In women who present while pregnant, counselling should be performed in a COP as early as possible in pregnancy. The purpose of counselling is to reduce the risk of pregnancy to the mother and fetus whenever possible. This is done through accurate maternal and fetal risk stratification, optimizing cardiac lesions, reviewing safety of medications in pregnancy, and making a detailed plan for the pregnancy, labor, and delivery. This Clinical Practice Update highlights the COP approach to prepregnancy counselling, risk stratification, and management of commonly encountered cardiac conditions through pregnancy. We highlight “red flags” that should trigger a more timely assessment in a COP. We also describe the approach to some of the cardiac emergencies that the care provider might encounter in a pregnant woman.

      Résumé

      Le nombre de femmes en âge de procréer atteintes d’une maladie cardiovasculaire (MCV) augmente en raison du meilleur taux de survie des enfants atteints d’une cardiopathie congénitale. De plus, davantage de femmes sont enceintes à un âge plus avancé, ce qui est associé à des taux accrus de comorbidités comme l’hypertension, le diabète et la MCV acquise. Au cours de la dernière décennie, le domaine de la cardiologie obstétrique a fait des progrès considérables avec l’apparition de programmes de cardio-obstétrique (PCO) multidisciplinaires visant à répondre au fardeau croissant des MCV chez les femmes enceintes. Avec l’arrivée des PCO officiels, les issues de grossesse des femmes atteintes d’une maladie cardiaque se sont améliorées. Les PCO offrent des consultations préconception, une surveillance cardiaque prénatale et post-partum, ainsi qu’une planification de l’accouchement. Les consultations prégrossesse dans un PCO devraient être offertes aux femmes chez qui l’on soupçonne une MCV et qui sont en âge de procréer. Pour les femmes qui consultent alors qu’elles sont déjà enceintes, les consultations devraient se tenir dans un PCO le plus tôt possible dans la grossesse. L’objectif des consultations est de réduire les risques liés à la grossesse à la fois pour la mère et le fœtus lorsque possible. Cela se fait par une stratification du risque maternel et fœtal précise, l’optimisation des lésions cardiaques, l’examen de l’innocuité des médicaments pris durant la grossesse, et l’élaboration d’un plan détaillé pour la grossesse, le travail et l’accouchement. Cette mise à jour de la pratique clinique souligne l’approche des PCO à l’égard des consultations prégrossesse, de la stratification du risque et de la prise en charge des maladies cardiaques fréquemment observées durant la grossesse. Nous mettons en évidence les signaux d’alarme qui nécessitent une évaluation plus rapide dans un PCO. Nous décrivons aussi l’approche à privilégier à l’égard de certaines urgences cardiaques que les prestataires de soins pourraient voir chez les femmes enceintes.
      The number of women of childbearing age with cardiovascular disease (CVD) is growing because of increased survival of children with congenital heart disease (CHD) and other childhood cardiac conditions. As well, women are becoming pregnant at an older age and thus carry increased rates of comorbidities including hypertension, diabetes, and acquired CVD.
      • Lima F.V.
      • Yang J.
      • Xu J.
      • Stergiopoulos K.
      National trends and in-hospital outcomes in pregnant women with heart disease in the United States.
      Although many women with CVD will consider pregnancy, it is important that they have preconception counselling to clarify the level of risk imposed by pregnancy for them and their offspring.
      • Siu S.C.
      • Sermer M.
      • Colman J.M.
      • et al.
      Prospective multicenter study of pregnancy outcomes in women with heart disease.
      • Silversides C.K.
      • Grewal J.
      • Mason J.
      • et al.
      Pregnancy outcomes in women with heart disease: the CARPREG II study.
      • Siu S.C.
      • Colman J.M.
      • Sorensen S.
      • et al.
      Adverse neonatal and cardiac outcomes are more common in pregnant women with cardiac disease.
      In a large contemporary cohort managed at 2 Canadian multidisciplinary cardio-obstetric programs (COPs), 3.5% of pregnancies were complicated by serious cardiovascular events with the most frequent being cardiac death/arrest, heart failure (HF), arrhythmias, and urgent cardiac interventions.
      • Pfaller B.
      • Sathananthan G.
      • Grewal J.
      • et al.
      Preventing complications in pregnant women with cardiac disease.
      Maternal cardiac mortality remains a concern and there is still much work to do because it is often preventable.
      • Pfaller B.
      • Sathananthan G.
      • Grewal J.
      • et al.
      Preventing complications in pregnant women with cardiac disease.
      ,
      • Graves C.R.
      • Davis S.F.
      Cardiovascular complications in pregnancy: it is time for action.
      Over the past decade the field of cardio-obstetrics has significantly advanced with the development of multidisciplinary COPs to address the increasing burden of CVD in pregnancy (Fig. 1).
      • Davis M.B.
      • Walsh M.N.
      Cardio-obstetrics.
      • Sharma G.
      • Lindley K.
      • Grodzinsky A.
      Cardio-obstetrics: developing a niche in maternal cardiovascular health.
      • Wolfe D.S.
      • Hameed A.B.
      • Taub C.C.
      • Zaidi A.N.
      • Bortnick A.E.
      Addressing maternal mortality: the pregnant cardiac patient.
      With the introduction of formal COPs, pregnancy outcomes in women with heart disease have improved.
      • Silversides C.K.
      • Grewal J.
      • Mason J.
      • et al.
      Pregnancy outcomes in women with heart disease: the CARPREG II study.
      COPs provide preconception counselling, antenatal and postpartum cardiac surveillance, labor and delivery planning, and are informed by our enhanced understanding of pregnancy risks, disease pathogenesis, and treatment options. The development of risk prediction tools coupled with a better understanding of the effect of pregnancy on specific cardiac conditions has led to better risk stratification.
      • Siu S.C.
      • Sermer M.
      • Colman J.M.
      • et al.
      Prospective multicenter study of pregnancy outcomes in women with heart disease.
      ,
      • Silversides C.K.
      • Grewal J.
      • Mason J.
      • et al.
      Pregnancy outcomes in women with heart disease: the CARPREG II study.
      Fresh insights have been gained into the pathobiology of conditions such as peripartum cardiomyopathy (PPCM) and pregnancy-associated myocardial infarction. There have been multiple advances in medical (eg, vasodilators for pulmonary hypertension [PHT] and interventional (eg, ablation without use of fluoroscopy, percutaneous valve intervention) care for pregnant women.
      Figure thumbnail gr1
      Figure 1Multidisciplinary cardio-obstetrics team.
      Canadian COPs exist in almost every province and act as regional referral centres (Supplemental Table S1). Although Canada has a publicly funded health care system created to provide universal health services, geographic, socioeconomic, racial, and ethnic disparities continue to affect health outcomes. In a geographically large and diverse country such as Canada, novel methods of care delivery, including virtual visits and satellite clinics need to be used.
      In addition to this Clinical Practice Update, guidelines and position statements on the care of pregnant women with CVD have been issued from the European Society of Cardiology,
      • Regitz-Zagrosek V.
      • Roos-Hesselink J.W.
      • Bauersachs J.
      • et al.
      2018 ESC guidelines for the management of cardiovascular diseases during pregnancy.
      the American Heart Association,
      • Mehta L.S.
      • Warnes C.A.
      • Bradley E.
      • et al.
      Cardiovascular considerations in caring for pregnant patients: a scientific statement from the American Heart Association.
      ,
      • Canobbio M.M.
      • Warnes C.A.
      • Aboulhosn J.
      • et al.
      Management of pregnancy in patients with complex congenital heart disease: a scientific statement for healthcare professionals from the American Heart Association.
      and the American Society of Obstetrics and Gynecology.
      • Moussa H.N.
      • Rajapreyar I.
      ACOG Practice Bulletin No. 212: pregnancy and heart disease.
      Care providers should consider referring any woman with suspected CVD who is considering pregnancy or is pregnant to a COP. This Clinical Practice Update highlights, as reference for care providers, the COP approach to prepregnancy counselling, risk stratification, and management through pregnancy. Special attention is also drawn to the lesions most commonly encountered by care providers in the community. We highlight “red flags” that should trigger a more timely assessment in a COP. We also describe the approach to some of the cardiac emergencies that the care provider might encounter in a pregnant woman.

      Approach to the Pregnant Woman With CVD

      Physiologic changes of pregnancy

      Pregnancy is associated with progressive increases in red cell and plasma volume and heart rate, resulting in an approximate 40% increase in cardiac output, which peaks in the third trimester. The decrease in vascular resistance and systemic blood pressure is maximal during the second trimester. During labor, cardiac output increases further, and is only partially blunted by regional anesthesia. After delivery, with cessation of caval compression by the uterus, an increase in venous return from lower extremities transiently increases cardiac output. Cardiac output does not fully return to baseline until the sixth postpartum month. Alterations in protein binding, and hepatic and renal function modify pharmacokinetics during the ante- and postpartum period. Increased clotting factor production and reduced fibrinolytic activity result in a prothrombotic state.

      Pregnancy complications in women with cardiac disease

      Pregnancy-associated changes can lead to decompensation in women with previous CVD. A prospective Canadian study reported cardiovascular complications in 16% of pregnancies; HF and arrhythmias were the most common complications; maternal mortality was < 1%.
      • Silversides C.K.
      • Grewal J.
      • Mason J.
      • et al.
      Pregnancy outcomes in women with heart disease: the CARPREG II study.
      HF is most likely to occur in the second or third trimester or in the postpartum period.
      • Grewal J.
      • Silversides C.K.
      • Colman J.M.
      Pregnancy in women with heart disease: risk assessment and management of heart failure.
      In addition to cardiac complications, pregnant women with CVD are at increased risk for obstetric (gestational hypertension and postpartum hemorrhage), and fetal and neonatal complications (preterm birth, intrauterine growth restriction). The probability of transmission of CHD to the fetus can range from 3% to 50% depending on the type of parental CHD.
      • van der Linde D.
      • Konings E.E.
      • Slager M.A.
      • et al.
      Birth prevalence of congenital heart disease worldwide: a systematic review and meta-analysis.
      ,
      • Gill H.K.
      • Splitt M.
      • Sharland G.K.
      • Simpson J.M.
      Patterns of recurrence of congenital heart disease: an analysis of 6,640 consecutive pregnancies evaluated by detailed fetal echocardiography.
      This is higher than the 1% risk in offspring born to parents without CHD.

      Counselling before and during pregnancy

      Prepregnancy counselling in a COP should be offered to women with suspected CVD including structural, electrical, and coronary heart disease. In women who present while pregnant, counselling should be performed in a COP as early as possible in pregnancy.
      • Pfaller B.
      • Sathananthan G.
      • Grewal J.
      • et al.
      Preventing complications in pregnant women with cardiac disease.
      The purpose of counselling is to reduce the risk of pregnancy to the mother and fetus whenever possible. This is done through accurate maternal and fetal risk stratification, optimizing cardiac lesions, discussing possible prepregnancy interventions, reviewing safety of medications in pregnancy, and making a detailed plan for the pregnancy, labor, and delivery.
      • Silversides C.K.
      • Grewal J.
      • Mason J.
      • et al.
      Pregnancy outcomes in women with heart disease: the CARPREG II study.
      ,
      • Pfaller B.
      • Sathananthan G.
      • Grewal J.
      • et al.
      Preventing complications in pregnant women with cardiac disease.
      ,
      • Haberer K.
      • Silversides C.K.
      Congenital heart disease and women’s health across the life span: focus on reproductive issues.
      Care providers should consider referring any woman with suspected CVD who would benefit from prepregnancy counselling or who is pregnant to a COP.

      Management planning

      Risk stratification in a woman with CVD requires a nuanced approach and is best undertaken in a COP. It is helpful for referring care providers to be aware of the following points.
      There are many predictors of maternal cardiovascular complications in pregnant women with CVD. A number of risk stratification tools have been developed from large populations with a spectrum of CVD such as Zwangerschap bij Aangeboren Hartafijkingen (Pregnancy With Congenital Heart Disease) (ZAHARA), Registry Of Pregnancy And Cardiac Disease (ROPAC), and Cardiac Disease in Pregnancy (CARPREG).
      • Siu S.C.
      • Sermer M.
      • Colman J.M.
      • et al.
      Prospective multicenter study of pregnancy outcomes in women with heart disease.
      ,
      • Silversides C.K.
      • Grewal J.
      • Mason J.
      • et al.
      Pregnancy outcomes in women with heart disease: the CARPREG II study.
      ,
      • Drenthen W.
      • Pieper P.G.
      • Roos-Hesselink J.W.
      • et al.
      Outcome of pregnancy in women with congenital heart disease: a literature review.
      • Drenthen W.
      • Boersma E.
      • Balci A.
      • et al.
      Predictors of pregnancy complications in women with congenital heart disease.
      • Ruys T.P.
      • Roos-Hesselink J.W.
      • Hall R.
      • et al.
      Heart failure in pregnant women with cardiac disease: data from the ROPAC.
      The CARPREG risk scores were derived and validated within the Canadian population (Fig. 2).
      • Siu S.C.
      • Sermer M.
      • Colman J.M.
      • et al.
      Prospective multicenter study of pregnancy outcomes in women with heart disease.
      ,
      • Silversides C.K.
      • Grewal J.
      • Mason J.
      • et al.
      Pregnancy outcomes in women with heart disease: the CARPREG II study.
      The original CARPREG risk score incorporated 4 functional predictors to classify pregnancies as being at low, intermediate, or high risk for maternal cardiovascular complications. The CARPREG II risk score is used to calculate the risk of maternal cardiovascular complications according to functional, lesion-specific, and process of care predictors (Fig. 2).
      • Silversides C.K.
      • Grewal J.
      • Mason J.
      • et al.
      Pregnancy outcomes in women with heart disease: the CARPREG II study.
      ,
      • D’Souza R.D.
      • Silversides C.K.
      • Tomlinson G.A.
      • Siu S.C.
      Assessing cardiac risk in pregnant women with heart disease: how risk scores are created and their role in clinical practice.
      The modified World Health Organization (mWHO) risk classification system, was developed using expert consensus to classify maternal cardiac lesions into 5 risk classes corresponding to increasing maternal cardiovascular risk (Supplemental Table S2).
      European Society of Gynecology (ESG), Association for European Paediatric Cardiology (AEPC), German Society for Gender Medicine (DGesGM), 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).
      The CARPREG II risk score has superior predictive accuracy compared with the mWHO risk classification system and the original CARPREG risk score (Fig. 2).
      • D’Souza R.D.
      • Silversides C.K.
      • Tomlinson G.A.
      • Siu S.C.
      Assessing cardiac risk in pregnant women with heart disease: how risk scores are created and their role in clinical practice.
      Figure thumbnail gr2
      Figure 2Maternal cardiovascular risk calculation using the Cardiac Disease in Pregnancy (CARPREG) risk scores. NYHA, New York Heart Association functional class. ∗ Excluding events preceding previous cardiac surgery. Right ventricular systolic pressure ≥ 50 mm Hg in the absence of right ventricular outflow tract obstruction. Angiographically proven coronary artery obstruction or past myocardial infarction. § Marfan syndrome, bicuspid aortopathy with aortic dimension > 45 mm, Loeys-Dietz syndrome, vascular Ehlers-Danlos syndrome, or previous aortic dissection or pseudoaneurysm. No previous repair of congenital lesion, valve repair/replacement, or percutaneous/surgical treatment of arrhythmia. First antenatal assessment > 20 weeks gestation.
      Risk stratification tools should always be supplemented by lesion-specific data and clinical judgement. One approach is to identify pregnancies in women with cardiac lesions associated with high risk of serious maternal cardiovascular complications with high mortality rates (Fig. 3).
      • D’Souza R.D.
      • Silversides C.K.
      • Tomlinson G.A.
      • Siu S.C.
      Assessing cardiac risk in pregnant women with heart disease: how risk scores are created and their role in clinical practice.
      In women without high-risk lesions, the CARPREG II risk score can be used to integrate individual patient and lesion characteristics. For those who prefer the mWHO risk classification system, we recommend that general predictors of cardiovascular complications (such as history of previous cardiac events and arrhythmias) be incorporated, which further stratify risk within each mWHO category.
      Figure thumbnail gr3
      Figure 3Proposed approach for assessing risk of cardiac complications in pregnant women with heart disease. CARPREG, Cardiac Disease in Pregnancy; LV, left ventricular. ∗ Exercise testing, cardiac imaging data, compliance, comorbid conditions, and socioeconomic status and medications including anticoagulants.
      Assisted reproduction technologies can pose additional risks in women with CVD because of ovarian hyperstimulation, thromboembolism, and likelihood of multifetal pregnancy.
      • Haberer K.
      • Silversides C.K.
      Congenital heart disease and women’s health across the life span: focus on reproductive issues.
      Recurrence of CHD and frequency of preterm delivery are further increased.
      Although the assessment of obstetric and fetal/neonatal risk is beyond the scope of this article, it is a very important part of the comprehensive risk assessment that should be provided in a COP.
      • Haberer K.
      • Silversides C.K.
      Congenital heart disease and women’s health across the life span: focus on reproductive issues.
      ,
      • D’Souza R.D.
      • Silversides C.K.
      • Tomlinson G.A.
      • Siu S.C.
      Assessing cardiac risk in pregnant women with heart disease: how risk scores are created and their role in clinical practice.
      When counselling takes place before conception, there are opportunities to better define and mitigate risk by: (1) cardiac testing to define cardiac lesion and functional capacity; (2) stopping medications contraindicated in pregnancy and ascertaining clinical stability without these medications; (3) interventions to reduce risk (ie, smoking cessation, intervention for severe aortic stenosis [AS] or mitral stenosis [MS]); and (4) offering genetic counselling if appropriate.
      • Haberer K.
      • Silversides C.K.
      Congenital heart disease and women’s health across the life span: focus on reproductive issues.
      ,
      • Halpern D.G.
      • Weinberg C.R.
      • Pinnelas R.
      • et al.
      Use of medication for cardiovascular disease during pregnancy: JACC State-of-the-Art Review.
      Regardless of when the counselling occurs, the following areas need to be discussed and recommendations provided:
      • (A)
        Cardiovascular medications: Figure 4 shows cardiac medications that can be used during pregnancy and those that are contraindicated during pregnancy and/or lactation.
        • Halpern D.G.
        • Weinberg C.R.
        • Pinnelas R.
        • et al.
        Use of medication for cardiovascular disease during pregnancy: JACC State-of-the-Art Review.
        ,
        • Cauldwell M.
        • Dos Santos F.
        • Steer P.J.
        • et al.
        Pregnancy in women with congenital heart disease.
        Figure thumbnail gr4
        Figure 4Cardiac medications safety in pregnancy and breastfeeding.
        • Halpern D.G.
        • Weinberg C.R.
        • Pinnelas R.
        • et al.
        Use of medication for cardiovascular disease during pregnancy: JACC State-of-the-Art Review.
        ,
        • Cauldwell M.
        • Dos Santos F.
        • Steer P.J.
        • et al.
        Pregnancy in women with congenital heart disease.
        ACE, angiotensin-converting enzyme; ARB, angiotensin receptor blocker; ARNi, angiotensin receptor neprilysin inhibitor; ERA, endothelin receptor antagonist; SGLT-2, sodium-glucose cotransporter-2.
      • (B)
        Site and type of pregnancy care: The optimal plan for follow-up, investigations, and delivery is determined in the COP, which takes into account cardiac/noncardiac risk and the woman’s home community with the following options: (1) exclusive care in a COP (recommended for moderate- to high-risk pregnancies); (2) shared care between a COP and local obstetric care, after initial evaluation in a COP (possible for moderate-risk pregnancies provided there is sufficient local cardiac and obstetric expertise); and (3) initial review in a COP, no regular cardiology care during pregnancy, and local obstetric care (recommended for low-risk pregnancies). Local care can also include community cardiology and midwifery in addition to obstetrics.
      • (C)
        Fetal echocardiogram when there is increased risk of CHD in the fetus determined by the presence of CHD in either the mother or father. A fetal echocardiogram is performed at 20 weeks’ gestation and is in addition to the routine anatomic ultrasound examination.
      • (D)
        Management during labor and delivery: Vaginal delivery is recommended in most instances, with cesarean delivery reserved for specific cardiac conditions and circumstances including: (1) a woman who presents in labor while receiving vitamin K antagonists or having been receiving one in the preceding 2 weeks; (2) severe PHT; (3) severely decompensated woman in whom delivery needs to be achieved quickly; and (4) aggressive aortic pathology. Induction at term is considered for high-risk pregnancies, for women receiving heparin or who have to relocate to their site of delivery. Invasive hemodynamic monitoring is seldom indicated but may be used in select situations in which the hemodynamic data are required to guide management. In women with intracardiac shunts, air and particulate filters in intravenous lines might help prevent embolism. For patients who are at moderate to high risk, a multidisciplinary meeting should be convened in the antepartum period to develop and document a labor and delivery plan.

      Valvular Heart Disease

      Native and acquired valvular disease remain important causes of maternal morbidity and mortality. Women with a mechanical valve are at especially high risk for complications in pregnancy.
      • van Hagen I.M.
      • Roos-Hesselink J.W.
      • Ruys T.P.
      • et al.
      Pregnancy in women with a mechanical heart valve: data of the European Society of Cardiology Registry of Pregnancy and Cardiac Disease (ROPAC).
      Care providers should be aware of red flags indicative of women at particularly high risk of complications (Fig. 5).
      • van Hagen I.M.
      • Roos-Hesselink J.W.
      • Ruys T.P.
      • et al.
      Pregnancy in women with a mechanical heart valve: data of the European Society of Cardiology Registry of Pregnancy and Cardiac Disease (ROPAC).
      Figure thumbnail gr5
      Figure 5Preconception and pregnancy red flags: valvular heart disease. BNP, brain natriuretic peptide; NYHA, New York Heart Association.

      Native valve disease

      Stenotic lesions

      Women with stenotic valve lesions are at risk for cardiac complications during pregnancy because of the inability of the heart to accommodate the increase in cardiac output across the fixed valve orifice. Common cardiovascular complications include arrhythmias and HF, and in general, can be treated medically.
      Percutaneous balloon valvuloplasty (PBV) as a bridge to surgery or as a therapeutic option for stenotic valvular disease should be considered during a patient’s pregnancy when pharmacologic therapy is ineffective for those with severe congenital aortic stenosis (AS) or rheumatic MS with less than moderate concurrent regurgitation. PBV using fluoroscopic guidance should ideally be performed after 15 weeks’ gestation and the completion of organogenesis. PBV may be performed using transesophageal echocardiography guidance to reduce or obviate the need for ionizing radiation.
      • Kultursay H.
      • Turkoglu C.
      • Akin M.
      • et al.
      Mitral balloon valvuloplasty with transesophageal echocardiography without using fluoroscopy.

      Mitral stenosis

      The severity of MS determined prepregnancy using standard criteria determines the risk of decompensation. Pregnant women with severe MS have a 3% mortality risk, 37% risk of developing pulmonary edema, and a 16% risk of developing new or recurrent arrhythmias.
      • Ducas R.A.
      • Javier D.A.
      • D’Souza R.
      • Silversides C.K.
      • Tsang W.
      Pregnancy outcomes in women with significant valve disease: a systematic review and meta-analysis.
      In contrast, pregnant women with moderate MS might experience the same complications in 1%, 18%, and 5%, respectively. Women with severe MS should be counselled about the potential significant complications to mother and fetus and should be evaluated for a valvular intervention before pregnancy.
      • Hameed A.
      • Karaalp I.S.
      • Tummala P.P.
      • et al.
      The effect of valvular heart disease on maternal and fetal outcome of pregnancy.
      ,
      • Silversides C.K.
      • Colman J.M.
      • Sermer M.
      • Siu S.C.
      Cardiac risk in pregnant women with rheumatic mitral stenosis.
      If already pregnant, women with severe MS can be offered the option of early pregnancy termination.
      Pregnant women with MS are at risk for atrial arrhythmias and this can be associated with thromboembolic complications.
      • Siu S.C.
      • Sermer M.
      • Colman J.M.
      • et al.
      Prospective multicenter study of pregnancy outcomes in women with heart disease.
      ,
      • Ducas R.A.
      • Javier D.A.
      • D’Souza R.
      • Silversides C.K.
      • Tsang W.
      Pregnancy outcomes in women with significant valve disease: a systematic review and meta-analysis.
      ,
      • Silversides C.K.
      • Colman J.M.
      • Sermer M.
      • Siu S.C.
      Cardiac risk in pregnant women with rheumatic mitral stenosis.
      Women with MS and atrial fibrillation or a previous thromboembolic episode should be anticoagulated. Anticoagulation can also be considered in women with no documented atrial fibrillation but who have moderate or greater MS with spontaneous echo contrast in the left atrium, a large left atrium (≥ 60 cc/m2), or HF. In women with HF, rate-slowing medications (ie, β-blockers) will slow the heart rate, extend diastolic filling time, reduce the transmitral gradients, and decrease the left atrial pressure and pulmonary venous congestion. Diuretics can also be used to treat HF refractory to adequate rate control.

      Aortic valve stenosis

      Pregnancy is usually well tolerated in women with asymptomatic mild to moderate AS. An exercise test might help to risk-stratify women by eliciting symptoms, arrhythmias with exertion, and assessment of exercise tolerance and blood pressure response to exercise. Women with moderate to severe asymptomatic AS should be monitored carefully for the development of symptoms (angina, arrhythmias, syncope, HF) during pregnancy. As a result of appropriate medical attention and management, maternal mortality is no longer common.
      • Hameed A.
      • Karaalp I.S.
      • Tummala P.P.
      • et al.
      The effect of valvular heart disease on maternal and fetal outcome of pregnancy.
      ,
      • Silversides C.K.
      • Colman J.M.
      • Sermer M.
      • Farine D.
      • Siu S.C.
      Early and intermediate-term outcomes of pregnancy with congenital aortic stenosis.
      ,
      • Orwat S.
      • Diller G.P.
      • van Hagen I.M.
      • et al.
      Risk of pregnancy in moderate and severe aortic stenosis: from the multinational ROPAC registry.
      In a recent meta-analysis, the risks of death, pulmonary edema, and new or recurrent arrhythmias were 2%, 9%, and 4%, respectively, in pregnant women with severe AS and 0%, 8%, and 2%, respectively, in pregnant women with moderate AS.
      • Ducas R.A.
      • Javier D.A.
      • D’Souza R.
      • Silversides C.K.
      • Tsang W.
      Pregnancy outcomes in women with significant valve disease: a systematic review and meta-analysis.
      Women with severe AS who develop HF should be treated with diuresis. If women remain symptomatic or have HF despite medical therapy, consideration should be given to relief of the AS either with a PBV or surgical aortic valve replacement. In select cases, transcatheter aortic valve implantation might be an option.

      Regurgitant lesions

      Aortic and pulmonary regurgitant lesions are usually well tolerated during pregnancy.
      • Pfaller B.
      • Javier A.
      • Grewal J.
      • et al.
      Risks associated with valvular regurgitation during pregnancy.
      However, moderate to severe atrioventricular regurgitant lesions are associated with a 15% rate of adverse outcomes including HF and arrhythmias, particularly in the setting of ventricular dysfunction and PHT.
      • Pfaller B.
      • Javier A.
      • Grewal J.
      • et al.
      Risks associated with valvular regurgitation during pregnancy.
      In those with moderate to severe rheumatic mitral regurgitation, HF can occur in 20%-25% of patients.
      • vanHagen I.
      • Thorne S.
      • Taha N.
      • et al.
      Pregnancy outcomes in women with rheumatic mitral valve disease: results from the Registry of Pregnancy and Cardiac Disease.
      This can be managed medically in most cases with diuretics and afterload reduction.

      Prosthetic valves and anticoagulation

      The advantages and disadvantages of the various prosthetic valves (bioprosthetic, mechanical, homografts) should be discussed in detail before choosing a valve for a woman of childbearing age.
      • Bhagra C.J.
      • D’Souza R.
      • Silversides C.K.
      Valvular heart disease and pregnancy part II: management of prosthetic valves.
      The choice of valve dictates the care required through a pregnancy, most importantly the requirement for anticoagulation. Pregnancy in women with a mechanical valve is high risk and they should be counselled about the potential significant complications to mother and fetus. During pregnancy, these women require regular clinical and echocardiographic follow-up.
      Anticoagulation for women with a mechanical valve may be achieved with warfarin, low molecular weight heparin, or full-dose unfractionated heparin. There are multiple anticoagulation regimens, which require meticulous attention to detail, which should be managed within a COP in conjunction with hematology expertise.
      • Elkayam U.
      Anticoagulation therapy for pregnant women with mechanical prosthetic heart valves: how to improve safety?.
      There is no ideal anticoagulant for pregnant women with mechanical valves because there are varying maternal and fetal risks associated with the different types of anticoagulation strategies (Fig. 6).
      • Elkayam U.
      Anticoagulation therapy for pregnant women with mechanical prosthetic heart valves: how to improve safety?.
      Warfarin is associated with the lowest risk of valve thrombosis but crosses the placenta and poses the highest risk of miscarriage, fetal embryopathy, fetopathy, and fetal death. These risks are highest if warfarin is taken in the first trimester and/or warfarin dose exceeds 5 mg daily, although some fetal risk remains with use in the second to third trimesters. Heparin does not cross the placenta and is therefore not associated with fetal risk, however, the rates of maternal valve thrombosis and maternal mortality are higher than with warfarin particularly when heparin is not appropriately dosed and monitored. With all of this in mind, there are 3 potential strategies: (1) warfarin throughout pregnancy, particularly if the required dose is < 5 mg daily; (2) heparin throughout pregnancy; and (3) sequential therapy, with heparin during the first trimester and warfarin during the second and third trimesters.
      Figure thumbnail gr6
      Figure 6Pros and cons of anticoagulation strategies in pregnancy. INR, international normalized ratio; LMWH, low molecular weight heparin; PTT, partial thromboplastin time; UFH, unfractionated heparin; VKA, vitamin K antagonist.
      The risk of mechanical valve thrombosis was 4.7% in the ROPAC and this was associated with a 20% mortality.
      • van Hagen I.M.
      • Roos-Hesselink J.W.
      • Ruys T.P.
      • et al.
      Pregnancy in women with a mechanical heart valve: data of the European Society of Cardiology Registry of Pregnancy and Cardiac Disease (ROPAC).
      In a recent meta-analysis, the risk of a thromboembolic complication with a mechanical valve was 3%-9%, dependent on the anticoagulation regimen.
      • D’Souza R.
      • Ostro J.
      • Shah P.S.
      • et al.
      Anticoagulation for pregnant women with mechanical heart valves: a systematic review and meta-analysis.
      Valve thrombosis can be a serious complication resulting in maternal morbidity and mortality as well as fetal loss. If valve thrombosis is suspected, emergent transfer to a COP cardiac surgical center should be undertaken.

      Cardiomyopathy

      Cardiomyopathy and other myocardial diseases are common cardiac causes of maternal morbidity and mortality. In women with a known cardiomyopathy, a major component of preconception counselling involves reviewing regular medications because many standard HF therapies are contraindicated in pregnancy (angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, angiotensin receptor neprilysin inhibitors, mineralocorticoid receptor antagonists, ivabradine, and sodium-glucose cotransporter-2 (SGLT2) inhibitors (Fig. 4). Assessing left ventricular (LV) function without such medications improves risk stratification before pregnancy. Diuretics and β-blockers should be continued and hydralazine and nitrates are alternatives to the contraindicated medications. If pregnancy occurs with use of usual HF medication, contraindicated medications should be discontinued as soon as possible. Tracking echocardiographic parameters and brain natriuretic peptide serially during pregnancy helps direct proactive care. Similarly, all women post heart transplantation require close review before pregnancy, including review of immunosuppressant medications, and follow-up through pregnancy at a COP.

      Acute HF

      Effort intolerance, fatigue, and ankle edema are common findings during normal pregnancy and therefore similar signs and symptoms of HF can be missed. Suspicion should be high with new onset of “asthma,” persisting sinus tachycardia, orthopnea, and paroxysmal nocturnal dyspnea. HF presentation during pregnancy occurs generally in the second or third trimester or in the postpartum period.
      • Ruys T.P.
      • Roos-Hesselink J.W.
      • Hall R.
      • et al.
      Heart failure in pregnant women with cardiac disease: data from the ROPAC.
      The assessment and treatment of acute HF follow the same principles as for the nonpregnant patient (Fig. 7). Care providers should be aware of red flags indicative of women particularly at higher risk of complications (Fig. 8).
      Figure thumbnail gr7
      Figure 7Management of acute heart failure during pregnancy. ACEI, angiotensin-converting enzyme inhibitor; ARB, angiotensin receptor blocker; HF, heart failure; I.V., intravenous; MRA, mineralocorticoid receptor antagonist.
      Figure thumbnail gr8
      Figure 8Preconception and pregnancy red flags: cardiomyopathy. BNP, brain natriuretic peptide; NYHA, New York Heart Association.

      Peripartum cardiomyopathy

      PPCM is an idiopathic condition with LV systolic dysfunction (ejection fraction [EF] < 45%) occurring toward the end of pregnancy or within 5 months after delivery, when no other cause is found. When assessing the patient, it is important to take a comprehensive family history because genetic forms of dilated cardiomyopathy might be unmasked and present similarly. The risk factors for developing PPCM include African ethnicity, maternal age, smoking, diabetes, preeclampsia, and multiparity. There has been research interest in the use of bromocriptine, a prolactin inhibitor, to treat PPCM but this remains an unproven therapy.
      • Davis M.B.
      • Arany Z.
      • McNamara D.M.
      • Goland S.
      • Elkayam U.
      Peripartum cardiomyopathy: JACC State-of-the-Art Review.
      Despite the possible association between prolactin and PPCM, there is no strong evidence at present to recommend avoiding breastfeeding.

      Women with known preexisting cardiomyopathy

      Dilated cardiomyopathy

      Dilated cardiomyopathy of any etiology might present before or during pregnancy. Predictors of cardiovascular complications including mortality are an EF < 40% and/or New York Heart Association functional classification of III-IV.
      • Grewal J.
      • Siu S.C.
      • Ross H.J.
      • et al.
      Pregnancy outcomes in women with dilated cardiomyopathy.
      Pregnancy in women with severe LV systolic dysfunction (EF < 30%) is very high risk and counselling about the potential significant complications to mother and fetus should occur.
      • Grewal J.
      • Siu S.C.
      • Ross H.J.
      • et al.
      Pregnancy outcomes in women with dilated cardiomyopathy.
      If already pregnant, early termination should be offered. In patients with familial or genetic forms of cardiomyopathy, a full genetic assessment should be performed before pregnancy.

      Previous PPCM

      Patients with previous PPCM and normalization of LV function with good contractile reserve on stress echocardiography can consider future pregnancy after thorough risk stratification and understanding that there is a risk of recurrent PPCM.
      • Davis M.B.
      • Arany Z.
      • McNamara D.M.
      • Goland S.
      • Elkayam U.
      Peripartum cardiomyopathy: JACC State-of-the-Art Review.
      However, persisting LV dysfunction predisposes women to recurrent HF, ventricular dysfunction, and even death in up to 25% and pregnancy should be discouraged.
      • Davis M.B.
      • Arany Z.
      • McNamara D.M.
      • Goland S.
      • Elkayam U.
      Peripartum cardiomyopathy: JACC State-of-the-Art Review.
      After an episode of PPCM, expert counselling should be routinely offered regarding recurrence risk in a future pregnancy.

      Hypertrophic cardiomyopathy

      Most patients with familial hypertrophic cardiomyopathy do well during pregnancy. Exceptions are women with prepregnancy symptoms despite optimal medical treatment, moderate or greater LV dysfunction, diastolic dysfunction, PHT, and/or severe LV outflow tract obstruction.
      • Ommen S.R.
      • Mital S.
      • Burke M.A.
      • et al.
      2020 AHA/ACC guideline for the diagnosis and treatment of patients with hypertrophic cardiomyopathy: a report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines.
      β-Blockers and diuretics might be of benefit particularly in women with symptoms related to systolic or diastolic dysfunction.

      Ischemic Heart Disease

      Pregnancy is associated with a three- to fourfold increase in acute coronary syndrome (ACS) risk compared with age-matched nonpregnant women. It is most commonly related to coronary atherosclerotic plaque rupture, dissection, or myocardial infarction in the absence of coronary artery disease (thrombosis, vasospasm, microvascular dysfunction).
      • Roth A.
      • Elkayam U.
      Acute myocardial infarction associated with pregnancy.
      ,
      • Elkayam U.
      • Jalnapurkar S.
      • Barakkat M.N.
      • et al.
      Pregnancy-associated acute myocardial infarction: a review of contemporary experience in 150 cases between 2006 and 2011.
      Incidence of ACS ranges between 3 and 8 cases per 100,000 deliveries with mortality upward of 7%.
      • James A.H.
      • Jamison M.G.
      • Biswas M.S.
      • et al.
      Acute myocardial infarction in pregnancy: a United States population-based study.
      ,
      • Smilowitz N.R.
      • Gupta N.
      • Guo Y.
      • et al.
      Acute myocardial infarction during pregnancy and the puerperium in the United States.
      Presentation is typically in the third trimester and postpartum periods, and management is dependent on the clinical presentation and underlying cause, which is best determined using coronary angiography (Fig. 9).
      • Roth A.
      • Elkayam U.
      Acute myocardial infarction associated with pregnancy.
      ,
      • Elkayam U.
      • Jalnapurkar S.
      • Barakkat M.N.
      • et al.
      Pregnancy-associated acute myocardial infarction: a review of contemporary experience in 150 cases between 2006 and 2011.
      Figure thumbnail gr9
      Figure 9Management of ACS during pregnancy. ACS, acute coronary syndrome; ASA, acetylsalicylic acid; CT, computed tomography; MINOCA, myocardial infarction in the absence of coronary artery disease; PCI, percutaneous coronary intervention.

      Atherosclerosis/thrombosis

      Acute ST-segment elevation myocardial infarction (STEMI) or high-risk non-STEMI due to plaque rupture or thrombosis requires a timely invasive strategy (Fig. 9). In the case that percutaneous coronary intervention (PCI) is not readily available, women should be safely transferred to a site with PCI capabilities. Thrombolysis can be considered in women with STEMI because it does not cross the placenta, but it is not a preferred option because coronary dissection is a leading cause of myocardial infarction in pregnant women, and should not be treated with thrombolysis.
      • Sousa Gomes M.
      • Guimaraes M.
      • Montenegro N.
      Thrombolysis in pregnancy: a literature review.
      Low-risk ACS should be managed conservatively. Women with preexisting coronary atherosclerosis have a 10% risk of experiencing an ischemic event in pregnancy, are considered high risk, and should continue low-dose aspirin and β-blocker therapy through pregnancy.
      • Lameijer H.
      • Burchill L.J.
      • Baris L.
      • et al.
      Pregnancy in women with pre-existent ischaemic heart disease: a systematic review with individualised patient data.
      Care providers should be aware of red flags indicative of women particularly at higher risk of complications (Fig. 10).
      Figure thumbnail gr10
      Figure 10Preconception and pregnancy red flags: ischemic heart disease.

      Pregnancy-associated spontaneous coronary artery dissection

      ACS presentation due to pregnancy-associated spontaneous coronary artery dissection (p-SCAD) is commonly associated with left main, left anterior descending, or multivessel involvement and thus is associated with ventricular dysfunction and life-threatening maternal complications.
      • Hayes S.N.
      • Kim E.S.H.
      • Saw J.
      • et al.
      Spontaneous coronary artery dissection: current state of the science: a scientific statement from the American Heart Association.
      There must be a high clinical suspicion of p-SCAD because localized dissections can be missed. Conservative management with monitoring in-hospital is preferred, with lesion healing expected to occur over months.
      • Hayes S.N.
      • Kim E.S.H.
      • Saw J.
      • et al.
      Spontaneous coronary artery dissection: current state of the science: a scientific statement from the American Heart Association.
      Pharmacologic management consists of β-blockers and antiplatelet therapy. PCI can propagate the dissection and should only be considered if high-risk features are present.
      • Hayes S.N.
      • Kim E.S.H.
      • Saw J.
      • et al.
      Spontaneous coronary artery dissection: current state of the science: a scientific statement from the American Heart Association.
      Because there is a risk of recurrence of p-SCAD, repeat pregnancy is high risk and women should be counselled about the potential significant complications to mother and fetus.

      Arrhythmias in Pregnancy

      Many different arrhythmias can present in pregnancy and care providers should be aware of red flags indicative of women at higher risk of complications (Fig. 11). Consultation with an electrophysiologist within a COP can be considered.
      Figure thumbnail gr11
      Figure 11Preconception and pregnancy red flags: arrhythmias. ER, emergency room; LV, left ventricular.

      Supraventricular arrhythmia

      Up to 0.5% of pregnancies will be complicated by supraventricular tachycardia (SVT).
      • Lameijer H.
      • Burchill L.J.
      • Baris L.
      • et al.
      Pregnancy in women with pre-existent ischaemic heart disease: a systematic review with individualised patient data.
      The first presentation of SVT during pregnancy is not uncommon.
      • Li J.M.
      • Nguyen C.
      • Joglar J.A.
      • Hamdan M.H.
      • Page R.L.
      Frequency and outcome of arrhythmias complicating admission during pregnancy: experience from a high-volume and ethnically-diverse obstetric service.
      The most common SVTs in pregnancy are atrioventricular nodal reentry and atrioventricular reentrant tachycardia; Figures 12 and 13 show an outline of management strategies. Wolff-Parkinson-White syndrome with an accessory pathway can be associated with a worsening arrhythmia burden in pregnancy. Supraventricular arrhythmias occur in up to 15% of patients with structural heart disease during pregnancy, and in many cases the hemodynamic changes exacerbate arrhythmia in a previously stable patient. Risk factors include preexisting arrhythmia, mitral valve disease, β-blocker use before pregnancy, and left-sided structural lesions.
      • Silversides C.K.
      • Harris L.
      • Haberer K.
      • et al.
      Recurrence rates of arrhythmias during pregnancy in women with previous tachyarrhythmia and impact on fetal and neonatal outcomes.
      Figure thumbnail gr12
      Figure 12Management of narrow complex tachycardia with no known structural heart disease during pregnancy. AV, atrioventricular; I.V., intravenous.
      Figure thumbnail gr13
      Figure 13Management of narrow complex tachycardia with known structural heart disease during pregnancy. AV, atrioventricular; I.V., intravenous.
      Atrial fibrillation or flutter is most commonly seen in women with structural heart disease and there are various therapeutic options to consider including cardioversion (Fig. 14). There is little consensus regarding thromboprophylaxis for atrial fibrillation or flutter in pregnancy in the absence of structural heart disease.
      • Cumyn A.
      • Sauve N.
      • Rey E.
      Atrial fibrillation with a structurally normal heart in pregnancy: an international survey on current practice.
      Anticoagulation should be initiated if atrial flutter or fibrillation or intra-atrial reentrant tachycardia is documented in any pregnant woman with structural heart disease. Although established risk scoring systems have not been validated for use in pregnancy, anticoagulation should be initiated with a Congestive Heart Failure, Hypertension, Age ≥ 75, Diabetes, and Prior Stroke/Transient Ischemic Attack (doubled) (CHADS2) risk factor score ≥ 1 in the absence of structural heart disease.
      • Regitz-Zagrosek V.
      • Roos-Hesselink J.W.
      • Bauersachs J.
      • et al.
      2018 ESC guidelines for the management of cardiovascular diseases during pregnancy.
      Figure thumbnail gr14
      Figure 14Management of atrial fibrillation/flutter during pregnancy. ∗Anticoagulation should be initiated in the presence of structural heart disease and/or CHADS2 risk score ≥ 1. COP, cardio-obstetric program; TEE, transesophageal echocardiography.

      Ventricular arrhythmias

      Ventricular arrhythmias (VAs) range from asymptomatic isolated premature ventricular beats to nonsustained ventricular tachycardia or sustained VAs resulting in syncope or sudden cardiac death. Sustained VAs are more common in women with structural heart disease.
      • Li J.M.
      • Nguyen C.
      • Joglar J.A.
      • Hamdan M.H.
      • Page R.L.
      Frequency and outcome of arrhythmias complicating admission during pregnancy: experience from a high-volume and ethnically-diverse obstetric service.
      ,
      • Silversides C.K.
      • Harris L.
      • Haberer K.
      • et al.
      Recurrence rates of arrhythmias during pregnancy in women with previous tachyarrhythmia and impact on fetal and neonatal outcomes.
      Overall, 27% of women with a history of VA will have a recurrence in pregnancy,
      • Silversides C.K.
      • Harris L.
      • Haberer K.
      • et al.
      Recurrence rates of arrhythmias during pregnancy in women with previous tachyarrhythmia and impact on fetal and neonatal outcomes.
      with increased risk of adverse neonatal outcomes.
      • Silversides C.K.
      • Harris L.
      • Haberer K.
      • et al.
      Recurrence rates of arrhythmias during pregnancy in women with previous tachyarrhythmia and impact on fetal and neonatal outcomes.
      Assessment should include screening for inherited arrhythmia disorders or cardiomyopathy. PPCM must be considered when VAs complicate the last several weeks of pregnancy or early postpartum period.
      • Regitz-Zagrosek V.
      • Roos-Hesselink J.W.
      • Bauersachs J.
      • et al.
      2018 ESC guidelines for the management of cardiovascular diseases during pregnancy.
      Established guidelines for the acute and long-term management of VAs should be followed, but consultation with an arrhythmia specialist is recommended (Fig. 15). Catheter ablation should be considered for significant VAs detected before pregnancy.
      • Priori S.G.
      • Blomstrom-Lundqvist C.
      • Mazzanti A.
      • et al.
      2015 ESC guidelines for the management of patients with ventricular arrhythmias and the prevention of sudden cardiac death: the Task Force for the Management of Patients with Ventricular Arrhythmias and the Prevention of Sudden Cardiac Death of the European Society of Cardiology (ESC). Endorsed by: Association for European Paediatric and Congenital Cardiology (AEPC).
      Alternatively, medical stabilization, followed by catheter ablation post partum can be considered. Catheter ablation can be considered during pregnancy in cases of refractory arrhythmia in a centre with experienced operators, with a nonfluoroscopic approach if available. Lead shielding can reduce the dose of radiation to the fetus but does not eliminate exposure. Although cardiac arrest is rare in pregnancy, emergent cesarean delivery for fetal rescue is indicated if there is no return of spontaneous circulation after 4 minutes of resuscitation. Emergent cesarean delivery might also be performed as a part of the maternal resuscitation.
      • Jeejeebhoy F.M.
      • Zelop C.M.
      • Lipman S.
      • et al.
      Cardiac arrest in pregnancy: a scientific statement from the American Heart Association.
      Other resuscitation considerations include, ideally obtaining intravenous access above the diaphragm, early advanced airway management including difficult airway anticipation, and manual left uterine displacement.
      Figure thumbnail gr15
      Figure 15Management of wide complex tachycardia during pregnancy. AF, atrial fibrillation; ECG, electrocardiogram; I.V., intravenous; LQTS, long QT syndrome; q5min, every 5 minutes; QRSd, QRS duration.

      Device considerations

      Detailed guidelines governing implantable cardioverter-defibrillator (ICD) implantation have been published and are not altered by pregnancy. Women with a pacemaker or an ICD should be evaluated before pregnancy and at least once during pregnancy to determine dependency on pacing as well as basic device settings and system integrity. When using monopolar electrosurgery, the current path should be directed away from the device and the duration of bursts limited to avoid pacing inhibition or inappropriate ICD therapy. A magnet should always be immediately available in the delivery room.

      Aortic Disease

      Pregnancy among women with heritable thoracic aortic disease (HTAD) is associated with increased maternal cardiovascular risk, dependent specifically on the underlying HTAD type and associated red flags (Fig. 16). There is an increased risk of progressive aortic dilation and dissection due to associated hemodynamic and hormonal changes.
      • Elkayam U.
      • Goland S.
      • Pieper P.G.
      • Silversides C.K.
      High-risk cardiac disease in pregnancy: part II.
      Although uncommon, when aortic dissection occurs, it is associated with 30% maternal mortality.
      • Elkayam U.
      • Goland S.
      • Pieper P.G.
      • Silversides C.K.
      High-risk cardiac disease in pregnancy: part II.
      Therefore, it is imperative that women with HTAD be identified before conception, have imaging of the entire aorta and branch vessels, gene panel testing when applicable, and receive accurate counselling around aortic dissection risk. Genetic counselling to discuss the results and implications of gene testing and options around preimplantation genetic diagnosis is important. Critical to this is making a definitive diagnosis of the cause of the aortopathy before pregnancy whenever possible because it affects risk assessment and delivery of care through pregnancy. The need for prophylactic aortic root surgery for the prevention of aortic dissection should be considered before pregnancy. Other coexistent cardiac issues should also be evaluated and warrant attention.
      Figure thumbnail gr16
      Figure 16Preconception and pregnancy red flags: aortopathy. ASI, aortic size indexed; BAV, bicuspid aortic valve.

      Bicuspid aortic valve

      Ascending aortic dilation can occur in the absence of valve dysfunction, and is present in up to 50% of patients. The rate of dissection is low at approximately 0.03% outside of pregnancy and likely increases to a small degree in pregnancy specifically among women with a dilated aorta.
      • Michelena H.I.
      • Khanna A.D.
      • Mahoney D.
      • et al.
      Incidence of aortic complications in patients with bicuspid aortic valves.
      However, bicuspid aortic valve accounts for only a small percentage of dissections in pregnancy and is a more benign aortopathy compared with other HTADs.
      • Januzzi J.L.
      • Isselbacher E.M.
      • Fattori R.
      • et al.
      Characterizing the young patient with aortic dissection: results from the International Registry of Aortic Dissection (IRAD).
      Prophylactic aortic surgery to facilitate safe pregnancy should be considered at an ascending aortic diameter > 50 mm.

      Marfan syndrome

      Overall risk of dissection in pregnancy is increased at approximately 3%, although the risk in women with an aortic root < 40 mm is approximately 1%.
      • Smith K.
      • Gros B.
      Pregnancy-related acute aortic dissection in Marfan syndrome: a review of the literature.
      The risk of dissection can be as high as 10% in women with aortic root diameter > 40 mm, rapid dilatation of aorta, or history of dissection.
      • Elkayam U.
      • Goland S.
      • Pieper P.G.
      • Silversides C.K.
      High-risk cardiac disease in pregnancy: part II.
      Pregnancy should be avoided in the setting of an ascending aortic diameter ≥ 45 mm and prophylactic aortic surgery should be considered, however the risk of type B dissection remains. In the setting of intermediate aortic dimensions of 40-45 mm, other factors such as family history of dissection and rate of aortic growth help to inform the risk of moving forward with a pregnancy.

      Vascular Ehlers-Danlos syndrome

      This is a severe connective tissue disorder characterized by frail vascular tissue. Vascular and/or organ rupture during pregnancy has been reported to be as high as 50% and mortality reported to be approximately 6%.
      • Rudd N.L.
      • Nimrod C.
      • Holbrook K.A.
      • Byers P.H.
      Pregnancy complications in type IV Ehlers-Danlos syndrome.
      Pregnancy is therefore very high risk and women should be counselled about the potential significant complications to mother and fetus.

      Turner syndrome

      The risk of aortic dissection in pregnancy has been reported to be approximately 1%-2%, on the basis of extrapolation from retrospective data.
      • Karnis M.F.
      • Zimon A.E.
      • Lalwani S.I.
      • et al.
      Risk of death in pregnancy achieved through oocyte donation in patients with Turner syndrome: a national survey.
      ,
      • Chevalier N.
      • Letur H.
      • Lelannou D.
      • et al.
      Materno-fetal cardiovascular complications in Turner syndrome after oocyte donation: insufficient prepregnancy screening and pregnancy follow-up are associated with poor outcome.
      More recent multicentre data would suggest that risk is lower among women without structural heart disease.
      • Grewal J.
      • Valente A.M.
      • Egbe A.C.
      • et al.
      Cardiovascular outcomes of pregnancy in Turner syndrome.
      As such, we can expect to see more pregnancies in Turner syndrome patients with a structurally normal heart and/or mosaicism.
      • Grewal J.
      • Valente A.M.
      • Egbe A.C.
      • et al.
      Cardiovascular outcomes of pregnancy in Turner syndrome.
      Pregnancy has been thought to be higher risk among those with aortic size indexed of 2.5 cm/m2 or aortic size index of 2.0 cm/m2 with at least 1 of hypertension, bicuspid aortic valve, aortic coarctation, or transverse arch elongation and requires close surveillance.

      Loeys-Dietz syndrome

      Loeys-Dietz syndrome results in widespread medium or large vessel vascular disease and its natural history is more aggressive with increased rates of vascular and uterine rupture compared with Marfan syndrome. Although recent data suggest more favourable outcomes than previously thought, pregnancy is still high risk and cannot be considered safe at any aortic dimension.
      • Frise C.J.
      • Pitcher A.
      • Mackillop L.
      Loeys-Dietz syndrome and pregnancy: the first ten years.
      Pregnancy is contraindicated in the setting of an ascending aortic diameter ≥ 45 mm and prophylactic aortic surgery should be considered, however, the risk of type B dissection remains. The literature is evolving and this particular scenario is an example of the critical role that a COP can play in counselling and guide decision-making. In this case factors such as family history of dissection and rate of aortic growth help to inform the risk of moving forward with a pregnancy.
      Follow-up through pregnancy will depend on the underlying aortopathy and associated red flags. Regular echocardiographic assessment of the aorta should occur every 4-12 weeks during pregnancy and at 3 and 6 months post partum. Women with known distal aortic dilation should undergo magnetic resonance imaging (MRI) in pregnancy to assess stability. Similarly, women with HTAD who present in pregnancy without comprehensive imaging of the entire aorta before pregnancy should undergo MRI. Noncontrast MRI is thought to be safe in pregnancy but is generally avoided in the first trimester. In general, it is advised to avoid the use of gadolinium-based contrast agents during pregnancy. Medical therapy for HTAD has been adopted from Marfan data, and β-blockers remain the treatment of choice to reduce aortic wall shear stress and growth rate.
      • Shores J.
      • Berger K.R.
      • Murphy E.A.
      • Pyeritz R.E.
      Progression of aortic dilatation and the benefit of long-term beta-adrenergic blockade in Marfan’s syndrome.
      ,
      • Krishnamoorthy P.
      • Garg J.
      • Shah N.
      • et al.
      Effect of beta-blockers on progressive aortic dilatation in patients with Marfan’s syndrome.
      Strict blood pressure control is important to reduce risk of aortic dissection. Aortic dissection occurs most commonly in the third trimester or early postpartum period, and chest pain should lead to rapid assessment for aortic dissection (Fig. 17). The preferred diagnostic modality would be computed tomography imaging of the aorta; it is rapid, does not require sedation, and can clearly define the extent of aortic dissection. Most dissections involve the ascending aorta (type A), but dissections in the descending aorta can also occur (type B). Previous aortic root replacement does not preclude a woman from having a type B dissection in pregnancy. Normal aortic dimensions in patients with HTAD also do not preclude a woman from having a dissection.
      Figure thumbnail gr17
      Figure 17Management of an aortic event in pregnancy. HTAD, heritable thoracic aortic disease; MFM, Maternal-Fetal Medicine; TEVAR, thoracic endovascular aortic repair.

      Congenital Heart Disease

      Just under 1% of the population have CHD and advances in surgery and cardiology result in most women born with moderate to severely complex disease now reaching childbearing age.
      • van der Linde D.
      • Konings E.E.
      • Slager M.A.
      • et al.
      Birth prevalence of congenital heart disease worldwide: a systematic review and meta-analysis.
      CHD accounts for most patients managed in a COP. The wide spectrum of lesions and repairs necessitates their inclusion within such a clinic with a cardiologist who has expertise in adult CHD and obstetric cardiology.
      In the past, severity of disease was classified according to anatomy but recent guidelines have acknowledged that the severity of disease and therefore pregnancy risk is determined by a combination of native anatomy, surgical repair, and current physiologic status (Fig. 18).
      • Stout K.K.
      • Daniels C.J.
      • Aboulhosn J.A.
      • et al.
      2018 AHA/ACC guideline for the Management of adults with congenital heart disease: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines.
      For example, a woman with a simple uncomplicated atrial septal defect will have a very low risk of complications whereas a woman with a similar-sized atrial septal defect with associated PHT will be at significant risk of complications. We therefore recommend that all women with CHD undergo evaluation and risk stratification by a COP-based adult CHD specialist. Follow-up through pregnancy will depend on their risk secondary to native anatomy, surgical repair, and physiologic status.
      Figure thumbnail gr18
      Figure 18Anatomic and physiologic risk classification of congenital heart disease in pregnancy. Anatomic and physiologic risk classification of congenital heart disease in pregnancy. Adapted from the classification system outlined in Stout et al.
      • Stout K.K.
      • Daniels C.J.
      • Aboulhosn J.A.
      • et al.
      2018 AHA/ACC guideline for the Management of adults with congenital heart disease: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines.
      ASD, atrial septal defect; AVSD, atrioventricular septal defect; CoAo, coarctation of the aorta; NYHA, New York Heart Association; PDA, patent ductus arteriosus; PHT, pulmonary hypertension; PR, pulmonic regurgitation; PS, pulmonic stenosis; TGA, transposition of the great arteries; ToF, tetralogy of Fallot; VSD, ventricular septal defect.

      Pulmonary Hypertension

      For a detailed outline of the causes and definitions of PHT the reader is referred to the recent Canadian Cardiovascular Society position statement.
      • Hirani N.
      • Brunner N.W.
      • Kapasi A.
      • et al.
      Canadian Cardiovascular Society/Canadian Thoracic Society position statement on pulmonary hypertension.
      Maternal cardiovascular risk in pregnancy depends on the etiology of the PHT. Advances in therapies for group 1 pulmonary arterial hypertension have helped to improve maternal cardiovascular outcomes. However, maternal cardiovascular risk remains high and women with significant pulmonary arterial hypertension should be counselled about the potential significant complications to mother and fetus.
      • Sliwa K.
      • van Hagen I.M.
      • Budts W.
      • et al.
      Pulmonary hypertension and pregnancy outcomes: data from the Registry Of Pregnancy and Cardiac Disease (ROPAC) of the European Society of Cardiology.
      We strongly recommend that all women with PHT need careful preconception assessment to determine pregnancy risk and identify any interventions or therapies that mitigate that risk. If pregnancy is pursued then close surveillance within a COP in collaboration with PH experts is essential.

      Conclusion

      Cardio-obstetrics is an emerging field. Cardiologists should be aware that pregnancy is a cardiovascular stress and that women of childbearing age with CVD should have preconception counselling within a COP. These programs offer comprehensive multidisciplinary pregnancy care. Canadian COPs have been established at most major Canadian centres. There is also growing recognition that cardiology and obstetric trainees should have exposure to this field of cardiology.

      Acknowledgements

      The authors acknowledge and sincerely thank Dr Jack Colman for taking the time to review this document and provide his feedback. He has been a leader in this field and his input has been invaluable. The authors also thank Dr Varinder Randhawa for taking the time to participate in our many conference calls and providing helpful feedback on this document.

      Supplementary Material

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