Maternal heart disease has emerged as a major threat to healthy pregnancy and women’s long-term cardiovascular health. A mild increase in maternal age does not explain an increase in cardiovascular disease (CVD) during pregnancy. However, pregnancies in older women are more often associated with a higher prevalence of cardiovascular risk factors, especially diabetes, hypertension and obesity. Additionally, advances in medical care have enabled more women with congenital heart disease to live longer and reach childbearing age, leading to a growing number who will require maternity services.1
The most recent data indicate that cardiovascular diseases constitute 26.5% of pregnancy-related deaths in the US.2 Of further concern are the disparities in cardiovascular outcomes, with higher rates of morbidity and mortality among non-white women and have lower incomes.
Contributing factors include difficulties accessing pre-pregnancy clinical assessment, missed opportunities to identify cardiovascular disease (CVD) risk factors during prenatal care, gaps in high-risk intrapartum care and delays in recognising cardiovascular disease symptoms during the puerperium.2
A multidisciplinary pregnancy heart team can play a critical role in ensuring the safety of the pregnant woman and the fetus by providing personalised risk assessment, monitoring and delivery planning. Collaboration among specialists, such as cardiologists, obstetricians, neonatologists, anaesthesiologists, critical care specialists and cardiac surgeons, reduces maternal mortality and improves pregnancy outcomes in women with CVD.
In this paper, we will review transcatheter interventions during pregnancy and will not address cardiothoracic surgical interventions or implantable devices.
Pathophysiology of Cardiovascular Disease during Pregnancy and the Timing of Interventions
Changes in the cardiovascular system during pregnancy occur to meet the increased metabolic demands of the woman and fetus. Plasma volume and cardiac output (CO) reach a maximum of 40–50% above baseline at 28 weeks’ gestation, while 75% of this increase has occurred by the end of the first trimester. The increase in CO is achieved by an increase in stroke volume in the first half of pregnancy and a gradual increase in heart rate thereafter. Atrial and ventricular diameters increase, while ventricular function is preserved. In women with heart disease, left ventricular (LV) and right ventricular (RV) adaptation to pregnancy can be suboptimal.3–6 Maternal cardiac dysfunction is related to impaired uteroplacental flow and suboptimal fetal outcome.7
Preconception counselling is essential for all women with known CVD, while an obstetric heart team plays a crucial role in managing more complex cases defined as class >II (low to moderate risk) using the modified WHO risk assessment for maternal cardiovascular risk factors (mWHO).8
Detailed risk stratification based on the initial heart disease, including cardiomyopathy, congenital and valvular heart defects, history of coronary artery disease (CAD) and aortic diseases, has been published.8
In cardiovascular disease presenting during pregnancy, it is of utmost importance to achieve an early diagnosis as early as possible to deliver the best available treatment, which may include interventions.8
It is important to state that interventions during pregnancy should be reserved for unstable patients who are at risk of severe morbidity and/or mortality and should be postponed if the pregnancy is expected to have a favourable outcome for mother and fetus using medical management alone. The pregnancy heart team plays a crucial role in this decision-making process as it facilitates a multidisciplinary approach when assessing maternal and fetal conditions. This collaboration ensures that the risks and benefits of any intervention are carefully weighed up, ultimately leading to more informed and appropriate care strategies tailored to the challenges posed by each case.
While the timing of any intervention may vary based on the clinical scenario, it would ideally be scheduled after the fourth month of pregnancy during the second trimester. By this stage, organogenesis is complete, the fetal thyroid remains inactive and the uterine volume is comparatively small, creating more space between the fetus and the chest compared to later stages of pregnancy.
Transcatheter and percutaneous interventions may be necessary during pregnancy for both structural heart disease (including congenital heart disease) and acute coronary syndrome (ACS; Figure 1). Other interventions may also be required during pregnancy, including the use of devices, such as a pacemaker and/or defibrillator or mechanical circulatory support in cases of overt heart failure, especially for patients who develop peripartum cardiomyopathy.
Considerations on Heart Disease Interventions During Pregnancy
Structural interventions for valvular heart disease (VHD) in women of childbearing age are most commonly congenital and rheumatic, but may include acquired and native degenerative causes.
Left-sided obstructive lesions are poorly tolerated during pregnancy. Although many patients can be successfully medically managed, some may benefit from an intervention before they give birth. An asymptomatic patient may decompensate because of the normal haemodynamic changes in pregnancy.
According to European Society of Cardiology (ESC) guidelines for the management of pregnancy, severe mitral stenosis and severe symptomatic aortic stenosis are classified as mWHO IV (extremely high risk) and pregnancy should be discouraged for this patient group, or they should be considered for pre-pregnancy interventions.8
In American College of Cardiology (ACC)/American Heart Association guidelines for the management of VHD, it is recommended that any patient with severe VHD should undergo careful evaluation before pregnancy including being given an exercise test. If any symptoms occur during exercise testing, pre-pregnancy transcatheter or surgical intervention is recommended. If surgical intervention is chosen, the type of valve should be decided individually.9
If no symptoms occur and the valve is amenable, interventions such as mitral balloon valvuloplasty (MBV), aortic valve intervention (transcatheter or surgical) or mitral valve repair (in case of mitral regurgitation) are recommended (class IIA) before pregnancy.
To date, an urgent or emergency structural intervention during pregnancy could be required in the following clinical scenarios:
- Emergency structural intervention should be considered if heart failure or haemodynamic instability occurs during pregnancy, despite having pre-pregnancy counselling and choosing to pursue a pregnancy.
- Women with very high-risk valvular heart disease (mWHO class IV) that is undiagnosed at the time of conception may develop heart failure symptoms during pregnancy, especially when termination of pregnancy is not an option.
- Women with lower-risk structural heart disease and haemodynamic instability, which is thought to be caused by VHD, and with refractory symptoms despite optimal medical therapy.
- Women with acute onset of severe VHD during pregnancy, such as acute severe mitral regurgitation due to chordal rupture.
- Women with ACS during pregnancy.
Distinguishing changes that arise from a normal pregnancy from symptoms and signs of heart failure requires careful clinical assessment and investigation. If heart failure is not amenable to oral medication or any intervention, the woman may need inotropes or mechanical circulatory support and prompt delivery may be required to stabilise their condition. Urgent delivery, even if the fetus is not viable, is a significant treatment option for patients with unstable heart disease during pregnancy.10 A shared decision between the pregnancy heart team and parents should be made in such cases.
Specific Valvular Interventions
Mitral Balloon Valvuloplasty
Women with mitral stenosis are at risk of complications during pregnancy due to the haemodynamic changes and increased demands on the heart that occur during gestation. It is important to closely monitor and manage these women to prevent potential complications and ensure the best outcomes for both mother and baby.11
According to a Canadian cohort study that involved 80 pregnancies in 74 patients, the severity of mitral stenosis is a crucial factor in predicting cardiac events during pregnancy. Among patients with mild, moderate and severe mitral stenosis, the rates of adverse cardiac events, such as pulmonary oedema and arrhythmias, were 26%, 38% and 66%, respectively. Notably, there were no occurrences of death, stroke, cardiac arrest or the need for invasive interventions. Independent predictors of cardiac complications included moderate or severe stenosis (OR 3.4; 95% CI [1.2–10]) and a Cardiac Disease in Pregnancy Risk Index score of 1 or higher (OR 6.8; 95% CI [1.8–25.9]).12
Percutaneous MBV is the recommended treatment for isolated severe mitral stenosis and should ideally be undertaken before conception if pregnancy is planned, regardless of symptoms. If it is performed during pregnancy, it is preferable to plan it during the second trimester to prevent radiation exposure in the initial trimester. However, the radiation exposure associated with MBV is approximately 0.2 rads, significantly below the accepted safe dose of 5 rads. Decreasing the duration of radiation is recommended to minimise the exposure.13 Abdomino-pelvic shielding is commonly used but recent recommendations do not support this practice (see section on radiation exposure considerations below). Positive outcomes from MBV can have lasting benefits for future pregnancies (Figure 2). In a 17-year follow-up study, children exposed to radiation from this procedure as a fetus exhibited normal growth and development according to their age.14
Anatomical factors that make a patient unsuitable for MBV include severe mitral regurgitation. Unfavourable anatomy consists of valvular or subvalvular thickening, calcification, restricted leaflet mobility, and a Wilkins score of 8 or higher.15–18
Patients with a combination of severe mitral stenosis and mitral regurgitation face increased risk during pregnancy as interventions are often complex and typically restricted to high-risk surgery. In the Registry Of Pregnancy And Cardiac disease (ROPAC) registry, there were only two patients with severe mitral stenosis and both died 2 weeks post-delivery and both also had severe mitral regurgitation.11
Transcatheter Aortic Balloon Valvuloplasty
Severe aortic stenosis can be challenging to manage during pregnancy as the haemodynamic changes can exacerbate the condition, increasing the risk of heart failure, arrhythmias, syncope and other complications. The risk of cardiovascular complications during pregnancy is primarily associated with the severity of aortic stenosis and the patient’s symptoms. Symptomatic patients with severe aortic stenosis should be carefully evaluated for interventions before considering pregnancy as early intervention may help improve outcomes and reduce the risks associated with the condition during gestation.
Meanwhile, close monitoring and appropriate management are crucial for these individuals to optimise outcomes and reduce the likelihood of serious complications.
For women with severe symptoms that do not respond well to medical therapy, percutaneous balloon aortic valvuloplasty (BAV) can be considered if performed by an experienced operator. It is advisable to wait until the second trimester to minimise radiation exposure during fetal organogenesis. The success rate of BAV in treating bicuspid aortic valve stenosis in younger patients has been reported as being about 85%.19 While about 10% of patients experienced re-stenosis necessitating surgical intervention, the majority of patients did well during the follow-up period.8,9,19
Transcatheter Aortic Valve Replacement
Transcatheter aortic valve replacement (TAVR) is an established and commonly used treatment for severe symptomatic aortic stenosis in low-, moderate- and high-risk surgical candidates.20–23 However, managing severe symptomatic aortic stenosis during pregnancy poses a complex clinical dilemma due to the considerations and risks associated with the condition combined with the pregnancy. TAVR is now being considered for intermediate- and even low-risk elderly patients. The ACC guideline sets the cut-off age for the procedure as 65 years while the ESC guidelines place it at 75 years.9,24
Due to the increased risk of fetal loss, cardiac surgery should generally be avoided during pregnancy.9 The experience of TAVR in pregnant women is extremely limited, with only a few case reports available.25,26 Cases of valve-in-valve transcatheter aortic valve implantation (TAVI) in pregnancy in degenerated bioprosthetic aortic valve resulting in severe valvular stenosis have also been reported.27,28 Due to the scarcity of data and potential risks involved, careful evaluation and consideration are necessary when contemplating such procedures during pregnancy. Despite age limitations and the limited data available, TAVR is considered a potential alternative for patients who have had a failed BAV or were found to be unsuitable for BAV because of the presence of significant aortic regurgitation, the presence of high surgical risk or for those who are unsuitable for conventional surgery. The long-term durability of TAVR in younger patients with bicuspid aortic valve disease is currently uncertain. Further, the potential risk of requiring permanent pacing following the procedure should be thoroughly evaluated and considered when determining the most appropriate intervention. The decision to proceed with TAVR should be made carefully by considering the individual’s circumstances and in collaboration with a multidisciplinary team of healthcare providers. Cardiac CT is essential for the pre-TAVR assessment process. Balancing the diagnostic benefits of the scan with the radiation exposure risk is crucial in such evaluations.
Transcatheter Edge-to-Edge Mitral Valve Repair
To our knowledge, there is no current experience with transcatheter edge-to-edge mitral valve repair in pregnancy. Theoretically, it could be reserved for patients with acute severe structural mitral regurgitation refractory to medical treatment with 3D transoesophageal guidance and minimal possible radiation.
Pulmonary Balloon Valvuloplasty
Mild-to-moderate pulmonary stenosis (PS) seems to be well tolerated during pregnancy, although there is limited data available on this topic. Patients with severe PS may experience a worsening of symptoms during pregnancy. While severe symptomatic PS carries a lower risk of significant adverse outcomes for both the mother and the fetus during pregnancy compared to more complex cardiac conditions, the need for pulmonary balloon valvuloplasty (PBV) during pregnancy is rare.29 In an older study on pregnancy in women with PS, an excessive number of serious non-cardiac complications and mortality were observed in their children.30
Nonetheless, close monitoring and appropriate management are crucial to ensure the well-being of both mother and the baby throughout pregnancy, and there are several reported cases where PBV was performed during pregnancy with favourable outcomes.31,32
Congenital Heart Disease
Congenital heart disease (CHD) is one of the most common pre-existing cardiac conditions in pregnant women, as advances in paediatric cardiology and surgery have allowed more CHD patients to survive into adulthood. Pregnancy poses unique risks to this patient group and they require careful monitoring and, in some cases, interventions to ensure the safety of mother and baby. Pregnant women with CHD need specialised, multidisciplinary care, but most CHD patients can have a safe pregnancy with careful monitoring.
All possible valvular interventions in CHD, including aortic and pulmonary stenosis have been addressed above, with the exception of aortic coarctation. Cardiac interventions during pregnancy are reserved for severe cases, with percutaneous procedures preferred over surgery. Other CHD interventions, such as defect closure, peripheral pulmonary artery stenosis angioplasty/stenting, and conduit stenting in various diagnoses are very uncommon during pregnancy and are not further analysed in this paper.
Aortic Coarctation
Pregnancy should be avoided in women with unrepaired severe aortic coarctation (CoA) or recoarctation (re-CoA), which is classified as mWHO IV – extremely high risk. The main complication during pregnancy is uncontrolled hypertension, while dissection can also occur. Transcatheter therapy for coarctation during pregnancy has been reported.33,34 Transcatheter intervention for CoA or re-CoA (using a covered stent) is possible during pregnancy but should only be performed for refractory hypertension or maternal or fetal compromise. (Table 1)
Coronary Interventions
As maternal age increases, the prevalence of CAD increases among patients with a pregnancy or a contemplated pregnancy. It is reported that for every year increase in maternal age over 35, there is a 20% increase in acute MI (AMI) risk.35
Women with chronic CAD who become pregnant are at high risk of adverse maternal and fetal outcomes and are best managed by a multidisciplinary obstetric heart team.35
Ideally, preconception evaluation should include assessment of functional status, ventricular function and residual ischaemia, according to guidelines. There is no clear evidence of when a pregnancy should be attempted after ACS. Any residual ischaemia should ideally be addressed before pregnancy.8,35,36
Development of pregnancy-related ACS/AMI is most common during the third trimester or postpartum. Its clinical presentation is the same as in the non-pregnant population, but the aetiology differs. The majority of CAD has non-atherosclerotic mechanisms – MI with normal coronary arteries and ischaemia with normal coronary arteries, including pregnancy-related spontaneous coronary artery dissection (P-SCAD). Other mechanisms of pregnancy-related ACS/AMI include coronary thrombosis secondary to hypercoagulability of pregnancy, angiographically normal coronaries with vasospasm and microvascular dysfunction.8,37–40
ECG interpretation can be challenging, as inverted T waves and ST-segment depression may exist in the absence of coronary ischaemia. A rise in serum troponin should suggest myocardial ischaemia, even in the presence of pre-eclampsia.
Despite the increased risk of AMI in pregnancy, only 45% of cases are reported to undergo cardiac catheterisation.36 In cases of low-risk ACS with haemodynamic stability, no arrhythmias or heart failure, a conservative treatment may be chosen.8
In cases of ST-elevation MI with standard indications for immediate revascularisation, percutaneous coronary intervention is the treatment of choice and should not be postponed. Given the high mortality associated with ST-elevation MI in pregnancy, percutaneous coronary intervention is the preferred reperfusion therapy and should not be delayed for delivery.36 Delivery should be postponed (if possible) for at least 2 weeks after an acute MI to facilitate maternal management.8
P-SCAD is one of the most common causes of ACS during pregnancy. Potential pregnancy-related precipitating factors include fluctuating oestrogen/progesterone levels resulting in structural changes in coronary vasculature, in a background of fibromuscular dysplasia or connective tissue disease and increased coronary shear stresses associated with labour. A conservative approach following coronary angiography is preferred due to the vulnerability of arteries during pregnancy and due to the danger of an increased dissected area.38–40
Additionally, SCAD has high rates of recurrence (~10% at 3-year follow-up) and major adverse cardiovascular effects. Therefore, women of childbearing age with a history of SCAD should be carefully counselled regarding the risk of recurrent events.
Pharmacological therapy post-percutaneous coronary intervention should balance maternal benefit and fetal risk. Aspirin is safe and clopidogrel may be used for the shortest possible period. Other P2Y12 antiplatelets, such as ticagrelor and prasugrel, should be avoided. The duration of dual antiplatelet therapy with second/third-generation drug-eluting stents can be shortened, particularly in the absence of great thrombotic burden.8
Radiation Exposure Considerations
Most of the data on the effect of radiation on the fetus derives from observations made of victims of high-level radiation exposure. The potential risks to the fetus of exposure to ionising radiation depend on the stage of pregnancy and the absorbed dose. Observed radiation-induced abnormalities (typically at doses of 100–200 mGy) include growth restriction, intellectual disability, malignancies, congenital malformations and neurological effects.40,41
Catheter-based diagnostic and interventional studies should not be avoided for fear of radiation exposure, especially when these studies can dramatically change maternal and fetal management and improve outcomes. However, keeping radiation exposure as low as can reasonably be achieved is the goal when a diagnostic or therapeutic procedure needs to be performed during pregnancy.
The actual risk of radiation exposure to the fetus in a cardiac catheterisation lab is currently unclear and not well defined. The timing of transcatheter intervention in terms of fetal risk is a crucial factor to consider when managing women in pregnancy. Fetal risk associated with radiation exposure varies and the level of radiation exposure and the risks involved are directly linked to the gestational age of the fetus. Essentially, the larger the fetus, the more radiation it can absorb. However, the fetus is most susceptible to radiation effects during its first trimester, especially within the initial 8 weeks when organ development primarily takes place. By the second trimester of pregnancy, organogenesis is complete and the fetal thyroid is still inactive.41–43
Consequently, early in the second trimester is typically considered the most suitable time to expose a fetus to radiation. This timing helps strike a balance by minimising radiation doses compared to later stages of pregnancy, while avoiding exposure during the critical early stages of pregnancy.
Also in the second trimester, the uterine volume is still small, so there is a greater distance between the fetus and the chest than in later months; therefore, there is no reason to postpone a necessary intervention until later.
According to the Centers for Disease Control and Prevention, a fetal radiation dose <50 mGy is considered safe.44 Based on the limited data available, fetal radiation exposure during most cardiac catheterisation procedures generally remains below the threshold dose for adverse fetal events.
The primary source of radiation exposure to the fetus is scattered from the mother, assuming that the uterus is not in the direct line of sight.40,42,43 As a result, using lead shielding on a pregnant woman’s abdomen or pelvis is not advised. While this practice may prevent direct fluoroscopy of the fetus, it could potentially elevate the overall fetal radiation dose by trapping radiation scatter.41,43,45,46
Current evidence suggests that a single cardiovascular imaging study with radiation during pregnancy is safe and should be undertaken at all times when clinically justified. In fact, this exposure often falls below the more conservative dose limits recommended by the National Council on Radiation Protection and Measurements.41,47,48
Conclusion
Transcatheter interventions may be necessary during pregnancy under various circumstances. The pregnancy heart team meeting is essential when considering cardiac interventions during pregnancy, as it ensures a comprehensive and coordinated approach to managing the unique challenges faced by these patients. As there is a lack of sufficient data regarding the safety and efficacy of transcatheter interventions during pregnancy, each case should be carefully evaluated by the heart pregnancy team. Given the delicate balance between maternal health and fetal development, the team collaborates to evaluate the risks and benefits of any intervention. It is crucial that transcatheter interventions are not delayed if they are essential for the health of the mother and the fetus. When performed for appropriate indications, these interventions have demonstrated favourable outcomes during pregnancy.