Bicuspid aortic valve (BAV) is the most common adult congenital cardiac malformation, affecting 1–2% of the population. BAV predisposes to aortic valve disease, infective endocarditis, and thoracic aortic aneurysms with an increased lifetime risk for acute aortic dissections. Reference Siu and Silversides1 In the general population, adverse cardiovascular outcomes are increased in pregnancy due to physiologic changes including left ventricular dilation and increased cardiac output. Reference Regitz-Zagrosek, Roos-Hesselink and Bauersachs2 Pregnancy outcome studies involving BAV have focused on risks of peripartum aortic dissection, which is relatively low compared to other causes of heritable thoracic aortic disease. Reference McKeller, MacDonald, Michelena, Connolly and Sundit III3 Clinical guidelines recommend imaging of the aorta prior to pregnancy and at specified intervals during pregnancy depending on WHO risk stratification. Reference Canobbio, Warnes and Aboulhosn4 However, current guidelines make no significant distinctions between aortic disease subtypes in pregnancy. Reference Regitz-Zagrosek, Roos-Hesselink and Bauersachs2 We hypothesise that pregnancy may exacerbate peripartum cardiovascular risk in women with BAV and significant cardiac or vascular disease. We therefore analysed peripartum cardiovascular outcomes in a cohort of high-risk women who experienced early-onset complications of BAV.
Methods
There were 132 eligible participants with early-onset complications of BAV disease in the UTHealth BAV Research Registry. Reference Musfee, Guo and Pinard5 Early-onset complications of BAV are defined as moderate or severe aortic stenosis or regurgitation, large thoracic aortic aneurysms (Z-score > 4), or valve or aortic interventions prior to the age of 30 years. Participants with syndromic causes of BAV such as Loeys–Dietz syndrome were excluded. They were invited to complete an online REDCap survey about their medical history, family history of congenital heart lesions, and pregnancy history, including maternal and fetal cardiovascular complications, treatments, and outcomes. In a subset of participants with available data, pre- and post-pregnancy images were analysed to assess changes in aortic dimensions during pregnancy.
Results
Sixty registry participants completed the online survey, and 44 (73%) reported at least one pregnancy. These patients constituted the study cohort (Table 1). The mean age of participants was 49 years (SD 14), and the mean body mass index was 28.5 kg/m2 (SD 6). A total of 17 participants (39%) reported at least one cardiac or aortic surgery, including aortic valve replacement, aortic aneurysm repair, coarctation repair, or mitral valve surgery. More than one in four participants reported at least one relative who had been diagnosed with BAV, thoracic aortic aneurysm, or aortic dissection. In addition, five participants (11%) reported at least one other congenital lesion: mitral valve prolapse (4) or coarctation of the aorta (1).
Characteristics of the study cohort (N = 44)
This table depicts the demographics, family history, and medical history of women with early-onset complications of BAV disease who reported at least one pregnancy. Unless otherwise specified, percentages are in parentheses.
There were 101 pregnancies in total: 15 participants reported a single pregnancy and 29 reported multiple pregnancies (Table 2). The mean age at first pregnancy was 25 (SD 5) years. Thirty-nine women (89%) reported at least one pregnancy with uneventful term delivery, which was the most frequent delivery outcome, for a total of 75 pregnancies. In the antepartum period, 11 pregnancies (11%) in 10 participants (23%) were affected by cardiovascular events, including newly diagnosed aortic valve disease (1), newly diagnosed thoracic aortic aneurysm (1), newly diagnosed congestive heart failure (1), hypertension requiring treatment (2), pre-eclampsia (5), and HELLP syndrome (1). There were also non-cardiovascular complications in three participants: placenta previa (1), cholestasis of pregnancy (1), and acute kidney disease (1). In the postpartum period, three participants had a total of five children who were diagnosed with a congenital heart malformation, including bicuspid aortic valve (2), thoracic aortic aneurysm (2), and aortic regurgitation (1). Only four (9%) participants received guideline recommended imaging prior to and during their pregnancies. In this subgroup, the normalised increase in maximum aortic diameter and sinus of Valsalva diameter was 1.6 mm/year (SD 1.9) and 1.2 mm/year (SD 1.3), respectively. Pre-existing aortic regurgitation increased from mild to moderate (1) or severe (1) in two participants.
Maternal and fetal outcomes
This table depicts fetal delivery outcomes, maternal complications during pregnancy, and fetal congenital heart malformations in a cohort of women who experienced early complications of bicuspid aortic valve disease. Echocardiographic data are reported as the annualised mean change in aortic diameter.
Discussion
The primary objective of this study was to evaluate maternal and fetal outcomes of women with BAV who experienced early-onset vascular or aortic complications. We identified three key takeaways. First, relatively few women (9%) received guideline-recommended cardiac imaging surveillance during their pregnancies. Second, the prevalence of cardiovascular complications was high (23%). Hypertensive diseases of pregnancy were significantly increased in the study cohort (18%) compared to contemporary data (10%). Reference Aronow6 Hypertension and pre-eclampsia are the seventh leading cause of maternal mortality in the United States, accounting for 7% of pregnancy-related deaths. 7 The increased burden of hypertension in women with early-onset complications related to BAV is consistent with the severity of vascular disease in this cohort and corresponds to progressive aortic dilation during pregnancy. Image analysis confirmed that maximum aortic diameters increased relatively rapidly compared to longitudinal dilation rates of contemporary BAV cohorts. Reference Detaint, Michelena, Nkomo, Vahanian, Jondeau and Enriquez Sarano8 These characteristics are consistent with a "complex valvulo-aortopathy" phenotype with more aggressive aortic disease, as may be anticipated for patients with early-onset complications of BAV. Reference Michelena, Della Corte and Evangelista9 Third, we found that maternal outcomes for women with BAV are generally favourable. There were no maternal deaths, and the prevalence of pre-term delivery (5%) or spontaneous abortion (13%) was not significantly increased in comparison to the general population. Reference Griebel, Halvorsen, Goleman and Day10
Conclusions
We found that the risks of pre-term delivery (5%) and adverse fetal outcomes such as spontaneous abortion (13%) are not significantly increased in women with BAV compared to women in the general population. However, nearly one-fourth of women in this series developed new or worsening cardiovascular conditions during pregnancy. The prevalence of hypertensive diseases of pregnancy (18%) was also higher than reported rates in the United States (10%). Reference Aronow6 We conclude that the increased baseline risk for cardiac and aortic disease in women with BAV may be exacerbated by peripartum hypertension, emphasising the need for careful cardiovascular surveillance of women with BAV who are of reproductive age. For women with established vascular disease, coordinated peripartum cardiovascular care by a multispecialty team that includes a cardiologist, and a maternal–fetal medicine specialist can reduce the incidence of obstetric complications. Reference Davis and Walsh11
Limitations
Early-onset complications due to BAV are relatively rare. Additional studies in larger groups may be needed to validate our observations. Other potential limitations include selection or recall bias in the survey data. Images were only available for a subset of cases, and this limited our ability to detect aortic changes during pregnancy.
Acknowledgements
We are grateful to Joana Castillo Di Giacinto, BS and Jacqueline Jennings, BS for assistance with data abstraction and record retrieval. Heath Goodrum and Susan Guerrero provided bioinformatic support.
Financial support
This work was supported in part by R01HL153728 (SP).
Conflicts of interest
None.
Ethical standards
The authors assert that all procedures contributing to this work comply with the ethical standards of the relevant guidelines on human experimentation at the University of Texas Health Science Center at Houston and with the Helsinki Declaration of 1975, as revised in 2008, and has been approved by the institutional committees at the University of Texas Health Science Center at Houston.
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