Author + information
- aMaternal Fetal Medicine, University of California, Irvine, Irvine, California
- bUniversity of Southern California, Los Angeles, California
- cLAC+USC Medical Center, Keck School of Medicine at University of Southern California, Los Angeles, California
- ↵∗Reprint requests and correspondence:
Dr. Shahbudin H. Rahimtoola, LAC+USC Medical Center, University of Southern California, 1200 North State Street, Old General Hospital, Room 3221, Los Angeles, California 90033.
In this issue of the Journal, Orwat et al. (1) present data from ROPAC (the Registry on Pregnancy and Cardiac Disease) emphasizing that women with congenital aortic stenosis (AS), including bicuspid aortic valve, who become pregnant add an additional clinical domain that needs recognition and understanding. ROPAC is a multinational observational registry of 2,966 pregnancies with structural heart disease from 2008 to 2014 in 99 centers from 40 countries. AS comprised 96 cases among 2,966 (0.03%) total cases of structural heart defects and 23% of those with valve disease.
The study presents data on the maternal and fetal outcomes in 62 patients with moderate AS and 34 patients with severe congenital AS, highlighting the “rare” occurrence of this valve lesion in pregnancy (1). The grade of severity of AS was only on the basis of valve gradients. Observations from previous, smaller studies have subsequently led to descriptions of well-known clinical phenomena. For example, the original description of peripartum cardiomyopathy in 1971 comprised 27 patients from a single center who were diagnosed, prospectively managed, and followed for 4 or 10 years by selected physicians, who uniformly documented outcomes, including mortality (2). This was followed by a number of smaller studies. The National Heart, Lung, and Blood Institute then organized an international workshop to document the available data (3). More recently, a comprehensive paper summed up the available published reports (4).
ROPAC showed that patients with moderate AS had successful pregnancies, with no mortality and very few maternal and fetal complications in selected centers with experienced providers. The incidence of heart failure (HF) was 11.5%, and of supraventricular tachycardia, was 1.6%. About 13% of these women were hospitalized for cardiac indications. These data are helpful in counseling women with moderate AS about the low complication rates and encouraging them to complete childbearing sooner, rather than later.
Not surprisingly, the patients with severe AS had significantly higher complication rates. The leading complications were HF and arrhythmias, which confirms previous data (5). HF was encountered in 26%, the rate of hospitalization for cardiac indications was 35%, and the incidence of HF was 6.7% in patients with asymptomatic AS versus 26.3% in patients with symptomatic AS. The timing of hemodynamic deterioration correlates with the near peaking of cardiac output in mid-pregnancy that was reported previously (6). One patient had aortic balloon valvulotomy at 20 weeks of gestation. The further course of pregnancy and delivery were uneventful. However, she needed aortic valve replacement 1 month after delivery. One patient had aortic valve replacement in the first half of pregnancy and successful delivery at 38 weeks, even though cardiopulmonary bypass has traditionally been associated with a high risk of fetal mortality (7). In the current era, percutaneous transcatheter valve replacement may be an option for a select patient considered to be at very high risk of mortality. There was only 1 patient who had ventricular tachycardia/ventricular fibrillation. The odds ratio of hospitalization in severe AS versus moderate AS was 2.77. All but 2 patients were managed medically, and there were no maternal deaths.
The study protocol was complex (1). It allowed inclusion of patients who were pregnant in the year before the start of the registry or who had a prosthetic heart valve (PHV). Twenty-one of 34 (62%) had previously received PHVs; of the 17 aortic PHVs, 10 were mechanical and 7 were bioprosthetic. This makes the patients in the severe group inhomogeneous, makes data analysis more complex and may diminish its applicability, and makes management of the patient more complex.
There were no life-threatening complications in this high-risk group of patients. In patients with severe versus moderate AS, pregnancy duration was shorter and infants had lower birth weights (35% vs. 6%). The Cesarean delivery rate (75%) was exceptionally high in patients with severe AS, given the known increased risk of bleeding, thromboembolism, and volume shifts in the post-operative state, particularly in women with heart disease. Interestingly, 50% of these women had a prior successful pregnancy, which raises the question of whether pregnancy in the AS group is a prognostic factor for increased risk in future pregnancies.
Areas of Serious Concern
A major weakness of this study is that maternal mortality was only considered in the very short term (i.e., during pregnancy and 1 week post-delivery), and thus could have been significantly underestimated. The World Health Organization defines maternal mortality as the death of a woman while pregnant or within 42 days of termination of pregnancy. Previously, a 31% increase in pulmonary edema, arrhythmia, death, or cardiac intervention during follow-up had been demonstrated as intermediate and late outcomes after pregnancy in symptomatic moderate or severe AS patients (8,9). Moreover, there is also the possibility of accelerated deterioration of the diseased aortic valve due to pregnancy, which may present clinically weeks or months after delivery. For example, pregnancy after a previous episode of peripartum cardiomyopathy is known to be associated with clinical cardiac deterioration and even mortality (2,3,10).
The diagnosis of HF during pregnancy and its management may be challenging. All but 1 patient in this study had a normal left ventricular ejection fraction. Patients with severe AS presumably could have had left ventricular diastolic dysfunction, and 11.5% also had systemic hypertension, which may be of clinical concern during the normal physiological volume overload of pregnancy. The patients were treated only with diuretic agents plus restriction of physical activity. Did these patients need to be hospitalized for a period of time for HF? Information about HF after delivery may have provided better insight in determining the mechanism(s) of HF.
Only 44% of women had an echocardiogram before conception. The diagnosis of severe AS was on the basis of the gradient during the pregnant state with volume overload. Thus, the incidence of severe AS may have been overestimated and outcomes of truly severe AS may even be much worse than those documented for severe AS. The severity of AS is best defined by the aortic valve area (index) obtained from echocardiogram/Doppler studies before or within a month into pregnancy.
In summary, despite the limitations and areas of serious concern listed in the preceding text, the data from ROPAC are useful, and the investigators are to be congratulated for opening the window of another dimension in “young” women with congenital AS. The data in women with moderate AS are clinically important and valuable. One would expect that outcomes in patients with mild AS would be better, or at least similar to those in patients with moderate AS. More well-designed studies are clearly needed to further our knowledge in this area, which is essential for those with severe AS.
↵∗ Editorials published in the Journal of the American College of Cardiology reflect the views of the authors and do not necessarily represent the views of JACC or the American College of Cardiology.
Both authors have reported that they have no relationships relevant to the contents of this paper to disclose.
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