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Location matters: left heart obstruction in pregnancy
European Journal of Obstetrics & Gynecology and Reproductive Biology 196 (2016) 38–43
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European Journal of Obstetrics & Gynecology and Reproductive Biology journal homepage: www.elsevier.com/locate/ejogrb
Location matters: left heart obstruction in pregnancy Margaret Fuchs a, Ali N. Zaidi b, Justin Rose a, Tracey Sisk a, Curt J. Daniels a, Elisa A. Bradley a,* a The Ohio State University Department of Internal Medicine, Division of Cardiovascular Medicine, and Nationwide Children’s Hospital Heart Center, Columbus, OH, United States b Albert Einstein College of Medicine/Montefiore Medical Center, New York, NY, United States
A R T I C L E I N F O
A B S T R A C T
Article history: Received 1 July 2015 Received in revised form 21 October 2015 Accepted 28 October 2015
Objectives: Left heart obstruction in pregnancy is associated with higher rates of morbidity/mortality. The primary aim of this study was to evaluate maternal cardiovascular, obstetric, and fetal/infant events in pregnant women with left heart obstruction. Study design: Pregnant women with current or repaired left heart obstruction were retrospectively analyzed (2000–2014): mitral stenosis, left ventricular outflow tract obstruction (subvalvar, valvar, supravalvar), and coarctation of the aorta. Maternal cardiovascular events were defined as: heart failure, arrhythmia, urgent/emergent cardiac surgery or percutaneous transcathter intervention, transient ischemic attack/cerebrovascular accident, and death up to 6 months postpartum. Results: There were 90 pregnancies in 67 women (29 7 years old) who had 15 maternal cardiovascular events. Isolated mitral stenosis (n = 6) or >1 serial left heart obstructive lesion (n = 6) were the source of the event in the majority pregnancies. Women with isolated mitral stenosis had increased cardiovascular events compared to other single left heart obstructive lesions (OR 18.6, 95% CI: 3.8–91.1). If >1 serial obstructive lesion was present, there was also an increased risk of maternal cardiovascular events (OR 6.8, 95% CI: 1.6– 29.1), however isolated mitral stenosis carried similar risk to serial left heart obstructive lesions (OR 2.7, 95% CI: 0.7–11.2). Baseline characteristics associated with events included: New York Heart Association functional class >2 (27% vs. 0, p < 0.001), any current left heart obstruction (73% vs. 36%, p = 0.01), severe left heart obstruction (40% vs. 29%, p < 0.001), and higher Cardiac Disease in Pregnancy (‘‘CARPREG’’) score (1.2 0.7 vs. 0.5 0.7, p = 0.01). There was no difference in rate of obstetric/fetal/infant complications in women with cardiovascular events; however, term birth weight was lower (2.7 0.5 vs. 3.1 0.6 kg, p = 0.01). There was no maternal mortality. Conclusions: Isolated mitral stenosis and serial (>1) left heart obstructive lesions carry the highest risk of maternal cardiovascular events. We are the first to show higher event rates in women with serial left heart obstructive lesions. The data supports the need for specialized and experienced high-risk obstetriccardiac teams to care for women with left heart obstruction, and demonstrates excellent outcomes in a complex cohort of pregnant women with all types of left heart obstruction. ß 2015 Elsevier Ireland Ltd. All rights reserved.
Keywords: Left ventricular outflow tract obstruction Pregnancy Left heart obstruction
Introduction Increased cardiovascular demand in the setting of pregnancy is accomplished in part by augmenting cardiac output with higher heart rate and increased stroke volume. For women
* Corresponding author at: Davis Heart Lung Research Institute, Division Cardiovascular Medicine, 473 West 12th Avenue, Columbus, OH 43210, United States. Tel.: +1 614 722 5622; fax: +1 614 722 5638. E-mail address: [email protected] (E.A. Bradley). http://dx.doi.org/10.1016/j.ejogrb.2015.10.026 0301-2115/ß 2015 Elsevier Ireland Ltd. All rights reserved.
with pre-existing left heart obstruction, meeting the demand for increased stroke volume can be difficult. Individual types of left heart obstruction, such as aortic stenosis, have been evaluated in pregnancy. No group, however, has evaluated maternal cardiovascular, obstetric, and fetal/infant events in a comprehensive group of women with all types of left heart obstruction (current or history of obstruction) who undergo pregnancy, labor, and delivery. The goal of the present study was to evaluate maternal cardiovascular, obstetric, and fetal events in pregnant women with current or prior left heart obstruction.
M. Fuchs et al. / European Journal of Obstetrics & Gynecology and Reproductive Biology 196 (2016) 38–43
Methods Pregnant women with left heart obstruction were retrospectively analyzed (2000–2014). Cardiovascular lesions causing left heart obstruction included: mitral stenosis (MS), left ventricular outflow tract obstruction (LVOTO: subvalvar, valvar, supravalvar), Coarctation of the Aorta (CoA), and combination disease with more than one level of left heart obstruction. Patients with current or surgically corrected left heart lesions were included. All women were seen by a multi-disciplinary team which included: high risk maternal fetal medicine obstetricians, cardiologists with expertise in the management of adult congenital heart disease and pregnancy, and cardiac anesthesiologists, as well as nurses and social workers from each of these disciplines. Basic demographic data was collected and included: age, number of pregnancies, height, weight, tobacco use history, presence of hypertension prior to pregnancy, history of prior cardiac event [1] (heart failure, transient ischemic attack, cerebrovascular accident, or arrhythmia), left ventricular ejection fraction, prior heart surgery, and medication history. Additionally, we collected and analyzed pre-pregnancy (up to 12 weeks gestation) and post-pregnancy echocardiograms as well as advanced cardiac imaging (cardiac computed tomography or magnetic resonance imaging) to evaluate mean and peak gradients, valve area when applicable, and heart function. Current left heart obstruction was defined as: mitral valve area <2 cm2 with mean gradient >5 mmHg pulmonary artery pressure >30 mmHg, aortic valve area <1.5 cm2 with LVOT mean/peak gradient 20/36 mmHg, or in the case of CoA a peak isthmus gradient 20 mHg. Severe left heart obstruction was defined by previously published criteria including aortic valve (subvalvar, valvar, supravalvar) mean/peak gradient 40/60 mmHg or valve area 1.0 cm2, mitral valve mean gradient 10 mHg or valve area 1.0 cm2, or CoA peak gradient 30 mmHg [2,3]. Each pregnancy was evaluated independently to determine if there were any maternal cardiovascular events (CV event) up to 6 months post-partum. Cardiovascular events were defined as: heart failure (New York Heart Association/NYHA functional class >2, pulmonary edema, new or increasing diuretic dose), arrhythmia, urgent/emergent cardiac surgery or percutaneous trans-catheter intervention, transient ischemic attack or stroke, and death. Obstetric events evaluated included: antepartum hemorrhage (>24 weeks gestation), pregnancy induced hypertension (>140/ 90 mmHg after 20 weeks gestation), pre-eclampsia (>300 g/L/ 24 hours proteinuria or ++ dipstick), eclampsia (preeclampsia plus seizures), gestational diabetes, preterm premature rupture of membranes (<37 weeks gestation), pre-term labor (<37 weeks gestation), postpartum hemorrhage (>500 mL vaginal or 1000 mL cesarean section delivery), and venous thromboembolism. Descriptive characteristics of the type of labor and assistance in the second stage of labor were also collected. Fetal and infancy complications evaluated were: preterm birth (24–37 weeks gestation), small for gestational age (<5th percentile), birth weight, respiratory distress syndrome, intraventricular hemorrhage, fetal demise (death >20 weeks gestation), perinatal mortality (still birth >24 weeks to death 1 week post-birth), and neonatal mortality (death up to 1 month of age). Respiratory distress syndrome and intraventricular hemorrhage were assessed from the clinical chart and recorded if listed in the diagnosis. The local institutional review board approved this retrospective study. Descriptive data for maternal, obstetric, and fetal events were generated. Comparisons were made between pregnancies with or without cardiovascular event. Continuous variables were evaluated with independent T-tests, and categorical and ordinal variables were evaluated with Fisher’s exact tests. Risk of specific type of obstructive lesion was evaluated with an
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odds ratio. Pre-pregnancy echocardiographic data and postpartum echo data were compared in all patients when available and assessed with paired T-tests. All significance tests were evaluated with a type I error rate of 5% (a = 0.05). Data are presented as means with standard deviation and/or frequency (%). The data were analyzed using SPSS (IBM Corp. IBM SPSS Statistics for Windows, Version 21.0. Armonk, NY).
Results There were 90 pregnancies in 67 women with left heart obstruction (29 7 years, Gravida 2.3 1.3). All women had a current or prior (repaired) diagnosis of at least one lesion causing left heart obstruction (Bicuspid aortic valve/BAV = 34, Unicuspid aortic valve/UAV = 2, CoA = 28, MS = 13, Other = 13). Diagnoses in women with ‘‘other’’ types of obstruction included: subaortic membrane, Shone’s complex [4], combination MS and AS, AS post AVR, and transitional AV canal defect with AS. Within this cohort, there were 25 pregnancies in women with at least two left heart obstructive lesions (second lesion: BAV = 16, CoA = 2, Other = 7). There were 3 patients with Shone’s complex. Of the 90 pregnancies that occurred, 15 were complicated by maternal cardiovascular events. Table 1 outlines baseline characteristics of the entire cohort and of those with and without maternal cardiovascular events. Mitral stenosis was the single most common isolated diagnosis (n = 6) present in the 15 (17%) pregnancies complicated by a maternal cardiovascular event. However, an equal number of women (n = 6) had serial left heart obstructive lesions associated with a maternal cardiovascular event. The absolute risk of a maternal CV event with each diagnosis was: single non-mitral left heart obstructive lesion: 4/100 pregnancies, >1 serial left heart obstructive lesions 24/100 pregnancies, and isolated mitral stenosis 46/100 pregnancies. Women with isolated MS had increased CV events compared to women with other single left heart obstructive lesions (OR 18.6, 95% CI: 3.8–91.1). In pregnancies complicated by >1 serial obstructive lesion, there was also an increased risk of maternal CV events (OR 6.8, 95% CI: 1.6–29.1), however isolated MS carried similar risk to serial left heart obstructive lesions (OR 2.7, 95% CI: 0.7–11.2). Specific details regarding maternal cardiovascular events in pregnancy are detailed in Table 2. Women were more likely to have a CV event during pregnancy if they had elevated baseline NYHA functional class (27%(4) vs. 0(0), p < 0.001), any current left heart obstruction (73%(11) vs. 36%(28), p = 0.01), current severe left heart obstruction (60%(9) vs. 10%(5), p < 0.001), and higher baseline CARPREG score (1.2 0.7 vs. 0.5 0.7, p = 0.01) (Table 1, Fig. 1). There was no difference in adverse CV events in women with prosthetic mechanical valves (7% vs. 3%, p = 0.42). Specific cardiac diagnoses associated with a CV event, as compared to rates of these diagnoses in women without CV events are listed in Fig. 2. There was no significant difference in obstetric complications in those with or without a maternal cardiovascular event. Rates of vaginal delivery and Cesarean section were similar in women with and without cardiovascular events. Fetal/infant complications were not different between these two groups. However, term birth weight was lower in women with a cardiovascular event (2.7 0.5 vs. 3.1 0.6 kg, p = 0.01). One patient (BAV without current left heart obstruction) had intrauterine fetal death at 29 weeks gestation due to trisomy 18 in the fetus (accounting for the 1 case of fetal demise and perinatal mortality). Neonate death occurred at 3 weeks of age in the offspring of a patient with a normal functioning BAV. This infant had severe congenital aortic stenosis with successful percutaneous intervention, but died after the procedure due to severe sepsis (Table 3).
M. Fuchs et al. / European Journal of Obstetrics & Gynecology and Reproductive Biology 196 (2016) 38–43
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Table 1 Baseline descriptive characteristics. Variable
Age (years) Gravida (# pregnancies) Baseline BMI (kg/m2) History tobacco use Hypertension Prior cardiac event* NYHA functional class >2 Left heart obstructiona EF < 40% CARPREG score Severe left heart obstructionb Previous cardiac surgery >1 prior cardiac surgery Mechanical valve On anticoagulation Bioprosthetic valve Taking a beta blocker Taking diuretics
All pregnancies
Cardiovascular event
NO cardiovascular event
Mean SD or frequency (%) (n = 90)
Mean SD or frequency (n = 15)
Mean SD or frequency (n = 75)
29 7 2.3 1.3 28 6 18 (20) 18 (20) 10 (11) 4 (1) 39 (42) 0 (0) 0.6 0.6 14 (15) 57 (62) 29 (32) 3 (1) 6 (1) 3 (1) 29 (32) 0 (0)
33 6 3.1 1.5 27 8 3 (20) 3 (20) 2 (13) 4 (27) 11 (73) 0 (0) 1.2 0.7 9 (60) 8 (53) 5 (33) 1 (7) 2 (13) 0 (0) 5 (33) 0 (0)
28 6 2.2 1.3 28 5 15 (20) 15 (20) 8 (10) 0 (0) 28 (36) 0 (0) 0.5 0.7 5 (10) 49 (63) 24 (31) 2 (3) 1 (1) 6 (1) 24 (31) 0 (0)
p value
0.11 0.17 0.54 1.00 1.00 0.66 <0.001 0.01 1.00 0.01 <0.001 0.56 1.00 0.42 0.06 0.58 1.00 1.00
BMI, body mass index; CARPREG, cardiac disease in pregnancy score; EF, ejection fraction; NYHA, New York Heart Association; SD, standard deviation. * Prior cardiac event defined as: heart failure, transient ischemic attack, cerebrovascular accident, or arrhythmia. a Left heart obstruction = mitral valve area <2 cm, aortic valve area <1.5 cm, peak CoA gradient 20 mmHg. b Severe left heart obstruction = aortic valve gradient mean 40 mmHg, peak 60 mmHg, valve area 1.0 cm2, mitral valve gradient mean 10 mmHg, valve area 1.0 cm2, CoA peak gradient 30 mmHg.
In 48 pregnancies pre-conception/first trimester and postpartum echocardiograms were available and were analyzed (BAV = 22, UAV = 2, CoA = 6, MS = 5, Combination BAV + CoA = 5, Other = 8). Pre- and post-partum comparison echocardiograms were not available or obtained in all cases due lack of follow up or care being obtained elsewhere. Pregnancies comprising the
‘‘other’’ category included: transitional AV canal defect with AS (2), subaortic membrane (2), Shone’s complex (2), combination MS/AS (1), and AS post AVR (1). On average the time between the initial echocardiogram and post-partum echocardiogram was 1.0 0.8 years. In these pregnancies, those with left ventricular outflow tract obstruction had a baseline mean gradient of
Table 2 Description of maternal cardiovascular events. Diagnosis
Event
1.1
Rheumatic MS
4.1
CoA, BAV
Atrial fibrillation 3 months post-partum. MS mean gradient 5 mmHg (pre and post-pregnancy); had 2 prior balloon valvuloplasties most recently 6 years prior to pregnancy CoA gradient 120 mmHg, covered stent placed 32 weeks. CoA was diagnosed in pregnancy due to uncontrolled blood pressure. Fetal heart tones depressed after stent, delivered by Cesarean section at 32 weeks CHF requiring diuresis 4 days post-partum. Had moderate AS during pregnancy (mean 30/peak 52 mmHg), gradients stable throughout pregnancy/delivery. Membrane and CoA previously repaired (age 4) CHF requiring diuresis post-delivery. Mod-severe LVOTO at baseline (mean 44/peak 70 mmHg), higher post-partum (mean 61/ peak 108 mmHg) Severe AS of mechanical AVR (mean 55/peak 80 mmHg), replaced with bioprosthetic valve at 16 weeks gestation CHF third trimester requiring diuresis. Mean mitral gradient 14 mmHg in early pregnancy, no AS. Required invasive monitoring during labor and delivered via cesarean section CHF with severe pulmonary edema requiring intubation post-delivery. Mean MS gradient 3rd trimester 29 mmHg–first time patient presented. Mean gradient 14 mmHg post-partum Mitral balloon valvuloplasty at 24 weeks gestation. Diagnosed with MS during pregnancy when mean gradient 17 mmHg with symptoms. Post intervention gradient 8 mmHg Mitral balloon valvuloplasty at 30 weeks gestation. Diagnosed with MS during pregnancy, mean gradient 38 mmHg with symptoms. Post intervention gradient 9 mmHg. Inpatient until delivery at 37 weeks Post-delivery covered stent peak gradient 30 mmHg. Prior subclavian flap and subaortic membrane resection 2
Patient ID
17.1
49.1
CoA, BAV, sub-aortic membrane BAV, supravalvar AS BAV Rheumatic AS and MS Rheumatic MS
60.1
Rheumatic MS
73.1
Rheumatic MS
74.1
80.1
CoA, subaortic membrane Subaortic membrane BAV
84.2 84.3
Rheumatic MS Rheumatic MS
85.1
BAV, subaortic membrane
20.1 21.1 29.1
76.2
CHF in third trimester until delivery requiring diuresis. Previous subaortic membrane resection 3 years prior. Pregnancy gradients stable with moderate LVOTO (mean 38, peak 64 mmHg) Severe AS 16 weeks (mean 66/peak 108 mmHg) underwent mechanical AVR. Atrial flutter requiring cardioversion 21 weeks gestation CHF third trimester requiring diuresis. Mean mitral gradient prior to pregnancy 8 mmHg. Patient did not follow-up CHF third trimester requiring diuresis. This was first presentation and patient delivered in the ICU with invasive monitoring on this admission. Mean mitral gradient prior to pregnancy 6 mmHg, at presentation 14 mmHg. Patient did not follow up Balloon valvotomy 24 weeks gestation (mean 65/peak 100 mmHg at 13 weeks). Subaortic membrane repaired age 16. Invasive monitoring with vaginal delivery in ICU
AS, aortic stenosis; BAV, bicuspid aortic valve; CHF, congestive heart failure; CoA, coarctation; ICU, intensive care unit; ID, identification; LVOTO, left ventricular outflow tract obstruction; MS, mitral stenosis.
M. Fuchs et al. / European Journal of Obstetrics & Gynecology and Reproductive Biology 196 (2016) 38–43
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Fig. 1. Likelihood of cardiovascular event based on type of left heart lesion. Patients with serial left heart obstruction had similar odds of cardiovascular event when compared to mitral stenosis (OR, 95% CI). Greater than one left heart obstruction was associated with greater risk of cardiovascular event when compared to one left heart obstructive lesion. Mitral stenosis conferred greater risk of cardiovascular event compared to one left heart obstructive lesion. MS, mitral stenosis; LHO, left heart obstruction
Table 3 Obstetric, fetal, infant complications. Variable
All pregnancies
CV event
NO CV event
Mean SD or frequency (%) (n = 90)
Mean SD or frequency (%) (n = 15)
Mean SD or frequency (%) (n = 75)
7
20
Obstetric 27 complications Antepartum 3 (3) hemorrhage 0 Pregnancy induced HTN 7 (8) Preeclampsia Eclampsia 0 Gestation diabetes 7 (8) PPROM 2 (2) Pre-term labor 4 (4) Postpartum 4 (4) hemorrhage 0 VTE Type of delivery Vaginal delivery 34 (38) Assisted vaginal 18 (20) delivery 50 (56) C-section delivery Elective C-section 33 (37) Emergent C-section 14 (16) Fetal/infant complications Preterm birth 20 (22) Small for 2 (2) gestational age 2.9 0.6 Birth weight (kg) 3 (3) RDS IVH 0 Fetal demise 1 (1) Perinatal mortality 1 (1) Neonatal mortality 1 (1)
p value
2 (13)
1 (1)
0.06
0
0
1.00
0 0 2 1 1 1
7 0 5 1 3 3
(13) (7) (7) (7)
0
(9) (7) (1) (4) (4)
0
0.59 1.00 0.32 0.30 0.52 0.52 1.00
6 (40) 4 (27)
28 (37) 14 (19)
0.78 0.48
8 (53) 6 (40) 2 (13)
42 (56) 27 (36) 12 (16)
1.00 0.77 1.00
5 (33) 0
15 (20) 2 (3)
0.30 1.00
2.7 0.5
3.1 0.6
0.01
0 0 0 0 0
3 0 1 1 1
1.00 1.00 1.00 1.00 1.00
(4) (1) (1) (1)
C-section, cesarean section; HTN, hypertension; IVH, intraventricular hemorrhage; PPROM, premature passive rupture of membranes; RDS, respiratory distress syndrome; SD, standard deviation; TIA, transient ischemic attack; VTE, venous thromboembolism.
Fig. 2. Type of cardiovascular diagnoses in pregnancies without/without CV events. Percentage of cardiac diagnoses that occurred in pregnancy in those with cardiovascular (CV) events (black bars) and those without CV events (white bars). NYHA > 2: New York Heart Association functional class during pregnancy greater than 2.
25 16 mmHg and peak gradient of 34 26 mmHg. In patients with MS, the baseline mean gradient was 10 7 mmHg. Overall heart function as evaluated by echo did not significantly change (ejection fraction 60 5% vs. 59 5%, p = 0.33) over the course of pregnancy. No difference in mean and peak gradients between pre-conception and post-pregnancy echocardiograms was found (Fig. 3). Discussion Expected hemodynamic changes occur in pregnancy and include: 50% increase in cardiac output met by increased stroke volume and heart rate [5], increased total blood volume [6], and decline in systemic vascular resistance [7]. These changes are well tolerated in women with structurally normal hearts. However when left heart obstruction is present, from valve disease or other etiology, these hemodynamic changes are less well tolerated and can lead to a poor outcome [8]. When considering all types of left heart obstruction, our study showed that overall these women do reasonably well, even if intervention was required during pregnancy. Previous studies have shown that maternal cardiovascular events in patients with mitral stenosis are substantial, and that this diagnosis in particular carries the greatest maternal cardiovascular morbidity risk when compared to other types of left heart obstruction [9,10]. In a cohort without any mortality, our results indicate that MS carries the greatest risk of a maternal cardiovascular complication when considering isolated forms of left heart obstruction. The results of one prior large study evaluating all types of congenital heart disease in pregnancy suggested a higher rate of maternal cardiovascular events when MS was combined with another form
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M. Fuchs et al. / European Journal of Obstetrics & Gynecology and Reproductive Biology 196 (2016) 38–43
Fig. 3. Left heart obstructive gradients pre/post-pregnancy. Mean (A) and peak (B) gradients in women with pre and post-pregnancy echocardiograms. No significant difference in mean gradient was seen irrespective of the type of left heart obstruction. BAV, bicuspid aortic valve; UAV, unicuspid aortic valve; COA, coarctation of aorta; MS, mitral stenosis; BAV + COA, bicuspid aortic valve and coarctation of aorta.
of left heart obstruction [11]. However, this study did not report on specific types of left heart obstruction or directly compare single left heart obstructive lesions with multiple left heart obstructive lesions. There have been other studies evaluating isolated forms of left heart obstruction, including aortic stenosis, coarctation, and even in those with prosthetic valves [12–16]. We are the first to directly compare all types of LHO and to show that an equal number of maternal cardiovascular events occurred in women with serial (>1) left heart obstruction, independent of mitral valve involvement. This indicates that women with more than one left heart obstructive lesion have a similar risk of sustaining a maternal cardiovascular event, when compared to women with isolated MS. The CARPREG score [1] was evaluated in this cohort, and although generally predicted event rates, there were two women with cardiovascular events that had a score of zero. This may suggest an independent maternal cardiovascular risk in those with serial left heart obstructive lesions. It is not surprising that women with worse functional class and higher degrees of left heart obstruction had more maternal cardiovascular events. In this cohort, we have showed that with careful management by a high risk obstetric and cardiac team, women with current left heart obstruction can do reasonably well during pregnancy, labor, and delivery, even if intervention is required. Women that required intervention had minimal fetal or obstetric complications. Of the 6 patients that had a cardiac event and required intervention, 3 had uneventful term deliveries (all by C-section). The other 3 patients had preterm deliveries (2 of them at 36 weeks), and all babies survived without further sequelae.
Although there appeared to be a higher rate of antepartum hemorrhage in women with a cardiovascular event, the result was not statistically significant. The overall number of patients affected was small and is a limitation of this study. No other obstetric complications were significantly different between women with and without cardiovascular events. This included rates of elective and emergent C-section, a vital consideration when counseling women with left heart obstruction. It is equally important to mention that women with left heart obstruction had no difference in rates of vaginal delivery vs. Cesarean section, and that the number of prior pregnancies had no effect on rates of maternal, obstetric, or fetal/infant outcomes. Birth weight was significantly lower in women with a cardiovascular event, even when accounting for gestational age at delivery. This has been found in prior studies [10] although the reason is not completely clear. We postulate that there may be a lack of appropriate cardiac output to the placenta/fetus relative to the hemodynamic changes of pregnancy in women with left heart obstructive lesions. Overall rates of preterm birth in our study, while not varying between study groups, were higher than the general U.S. population (20% vs. 11%) [17]. Our patient population also had higher rates of pre-pregnancy hypertension (20%) and preeclampsia (8%) than the general US population (11% and 3.4% respectively) [18]. These cardiovascular conditions often accompany structural heart disease. While these comorbidities did not appear to influence maternal or fetal outcomes, it may be that these cardiovascular conditions lead practitioners to manage patients more conservatively, and in some cases prompt earlier delivery. There are several limitations to this study. The data is retrospective, and therefore can identify associations between conditions and outcomes, but is limited in ability to predict prospective events. This ‘‘real world’’ cohort likely represents women with more significant left heart obstruction than the general population, as the data was collected at a tertiary referral center with a high-risk obstetric-cardiac program. It is difficult to determine whether or not the same conclusions could be made in a cohort with milder disease. Cardiovascular, obstetric, and fetal/ infant outcomes may be different in a center without a high-risk maternal obstetric-cardiac team and/or capabilities to provide intervention in complex anatomy. It is possible that the availability of elective C-section may result in higher overall rates of C-section in a tertiary-care center population. Data regarding infant outcomes, including presence or absence of congenital heart disease, was limited or not available in the majority of this cohort, and is a limitation of this study. Finally, the sample size, while larger than most prior studies, is still small, thus impeding the ability to draw absolute conclusions from the data observed. In conclusion, women with left heart obstruction do reasonably well in pregnancy, even when antenatal intervention is required. Isolated mitral stenosis and serial (>1) left heart obstructive lesions carry the highest risk of maternal cardiovascular events, and patients as well as physicians should be counseled as such. Obstetric, delivery, and fetal/infant complications are similar in women with and without maternal cardiovascular events who have left heart obstruction; birth weight at term, however, was lower in women with an event. Despite a number of high-risk patients and cardiovascular events, there was no maternal mortality. This data supports the need for specialized and experienced high-risk obstetric-cardiac teams to care for women with left heart obstruction, and demonstrates good outcomes in a cohort with all types of left heart obstruction. Financial disclosures None.
M. Fuchs et al. / European Journal of Obstetrics & Gynecology and Reproductive Biology 196 (2016) 38–43
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Contents lists available at ScienceDirect
European Journal of Obstetrics & Gynecology and Reproductive Biology journal homepage: www.elsevier.com/locate/ejogrb
Location matters: left heart obstruction in pregnancy Margaret Fuchs a, Ali N. Zaidi b, Justin Rose a, Tracey Sisk a, Curt J. Daniels a, Elisa A. Bradley a,* a The Ohio State University Department of Internal Medicine, Division of Cardiovascular Medicine, and Nationwide Children’s Hospital Heart Center, Columbus, OH, United States b Albert Einstein College of Medicine/Montefiore Medical Center, New York, NY, United States
A R T I C L E I N F O
A B S T R A C T
Article history: Received 1 July 2015 Received in revised form 21 October 2015 Accepted 28 October 2015
Objectives: Left heart obstruction in pregnancy is associated with higher rates of morbidity/mortality. The primary aim of this study was to evaluate maternal cardiovascular, obstetric, and fetal/infant events in pregnant women with left heart obstruction. Study design: Pregnant women with current or repaired left heart obstruction were retrospectively analyzed (2000–2014): mitral stenosis, left ventricular outflow tract obstruction (subvalvar, valvar, supravalvar), and coarctation of the aorta. Maternal cardiovascular events were defined as: heart failure, arrhythmia, urgent/emergent cardiac surgery or percutaneous transcathter intervention, transient ischemic attack/cerebrovascular accident, and death up to 6 months postpartum. Results: There were 90 pregnancies in 67 women (29 7 years old) who had 15 maternal cardiovascular events. Isolated mitral stenosis (n = 6) or >1 serial left heart obstructive lesion (n = 6) were the source of the event in the majority pregnancies. Women with isolated mitral stenosis had increased cardiovascular events compared to other single left heart obstructive lesions (OR 18.6, 95% CI: 3.8–91.1). If >1 serial obstructive lesion was present, there was also an increased risk of maternal cardiovascular events (OR 6.8, 95% CI: 1.6– 29.1), however isolated mitral stenosis carried similar risk to serial left heart obstructive lesions (OR 2.7, 95% CI: 0.7–11.2). Baseline characteristics associated with events included: New York Heart Association functional class >2 (27% vs. 0, p < 0.001), any current left heart obstruction (73% vs. 36%, p = 0.01), severe left heart obstruction (40% vs. 29%, p < 0.001), and higher Cardiac Disease in Pregnancy (‘‘CARPREG’’) score (1.2 0.7 vs. 0.5 0.7, p = 0.01). There was no difference in rate of obstetric/fetal/infant complications in women with cardiovascular events; however, term birth weight was lower (2.7 0.5 vs. 3.1 0.6 kg, p = 0.01). There was no maternal mortality. Conclusions: Isolated mitral stenosis and serial (>1) left heart obstructive lesions carry the highest risk of maternal cardiovascular events. We are the first to show higher event rates in women with serial left heart obstructive lesions. The data supports the need for specialized and experienced high-risk obstetriccardiac teams to care for women with left heart obstruction, and demonstrates excellent outcomes in a complex cohort of pregnant women with all types of left heart obstruction. ß 2015 Elsevier Ireland Ltd. All rights reserved.
Keywords: Left ventricular outflow tract obstruction Pregnancy Left heart obstruction
Introduction Increased cardiovascular demand in the setting of pregnancy is accomplished in part by augmenting cardiac output with higher heart rate and increased stroke volume. For women
* Corresponding author at: Davis Heart Lung Research Institute, Division Cardiovascular Medicine, 473 West 12th Avenue, Columbus, OH 43210, United States. Tel.: +1 614 722 5622; fax: +1 614 722 5638. E-mail address: [email protected] (E.A. Bradley). http://dx.doi.org/10.1016/j.ejogrb.2015.10.026 0301-2115/ß 2015 Elsevier Ireland Ltd. All rights reserved.
with pre-existing left heart obstruction, meeting the demand for increased stroke volume can be difficult. Individual types of left heart obstruction, such as aortic stenosis, have been evaluated in pregnancy. No group, however, has evaluated maternal cardiovascular, obstetric, and fetal/infant events in a comprehensive group of women with all types of left heart obstruction (current or history of obstruction) who undergo pregnancy, labor, and delivery. The goal of the present study was to evaluate maternal cardiovascular, obstetric, and fetal events in pregnant women with current or prior left heart obstruction.
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Methods Pregnant women with left heart obstruction were retrospectively analyzed (2000–2014). Cardiovascular lesions causing left heart obstruction included: mitral stenosis (MS), left ventricular outflow tract obstruction (LVOTO: subvalvar, valvar, supravalvar), Coarctation of the Aorta (CoA), and combination disease with more than one level of left heart obstruction. Patients with current or surgically corrected left heart lesions were included. All women were seen by a multi-disciplinary team which included: high risk maternal fetal medicine obstetricians, cardiologists with expertise in the management of adult congenital heart disease and pregnancy, and cardiac anesthesiologists, as well as nurses and social workers from each of these disciplines. Basic demographic data was collected and included: age, number of pregnancies, height, weight, tobacco use history, presence of hypertension prior to pregnancy, history of prior cardiac event [1] (heart failure, transient ischemic attack, cerebrovascular accident, or arrhythmia), left ventricular ejection fraction, prior heart surgery, and medication history. Additionally, we collected and analyzed pre-pregnancy (up to 12 weeks gestation) and post-pregnancy echocardiograms as well as advanced cardiac imaging (cardiac computed tomography or magnetic resonance imaging) to evaluate mean and peak gradients, valve area when applicable, and heart function. Current left heart obstruction was defined as: mitral valve area <2 cm2 with mean gradient >5 mmHg pulmonary artery pressure >30 mmHg, aortic valve area <1.5 cm2 with LVOT mean/peak gradient 20/36 mmHg, or in the case of CoA a peak isthmus gradient 20 mHg. Severe left heart obstruction was defined by previously published criteria including aortic valve (subvalvar, valvar, supravalvar) mean/peak gradient 40/60 mmHg or valve area 1.0 cm2, mitral valve mean gradient 10 mHg or valve area 1.0 cm2, or CoA peak gradient 30 mmHg [2,3]. Each pregnancy was evaluated independently to determine if there were any maternal cardiovascular events (CV event) up to 6 months post-partum. Cardiovascular events were defined as: heart failure (New York Heart Association/NYHA functional class >2, pulmonary edema, new or increasing diuretic dose), arrhythmia, urgent/emergent cardiac surgery or percutaneous trans-catheter intervention, transient ischemic attack or stroke, and death. Obstetric events evaluated included: antepartum hemorrhage (>24 weeks gestation), pregnancy induced hypertension (>140/ 90 mmHg after 20 weeks gestation), pre-eclampsia (>300 g/L/ 24 hours proteinuria or ++ dipstick), eclampsia (preeclampsia plus seizures), gestational diabetes, preterm premature rupture of membranes (<37 weeks gestation), pre-term labor (<37 weeks gestation), postpartum hemorrhage (>500 mL vaginal or 1000 mL cesarean section delivery), and venous thromboembolism. Descriptive characteristics of the type of labor and assistance in the second stage of labor were also collected. Fetal and infancy complications evaluated were: preterm birth (24–37 weeks gestation), small for gestational age (<5th percentile), birth weight, respiratory distress syndrome, intraventricular hemorrhage, fetal demise (death >20 weeks gestation), perinatal mortality (still birth >24 weeks to death 1 week post-birth), and neonatal mortality (death up to 1 month of age). Respiratory distress syndrome and intraventricular hemorrhage were assessed from the clinical chart and recorded if listed in the diagnosis. The local institutional review board approved this retrospective study. Descriptive data for maternal, obstetric, and fetal events were generated. Comparisons were made between pregnancies with or without cardiovascular event. Continuous variables were evaluated with independent T-tests, and categorical and ordinal variables were evaluated with Fisher’s exact tests. Risk of specific type of obstructive lesion was evaluated with an
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odds ratio. Pre-pregnancy echocardiographic data and postpartum echo data were compared in all patients when available and assessed with paired T-tests. All significance tests were evaluated with a type I error rate of 5% (a = 0.05). Data are presented as means with standard deviation and/or frequency (%). The data were analyzed using SPSS (IBM Corp. IBM SPSS Statistics for Windows, Version 21.0. Armonk, NY).
Results There were 90 pregnancies in 67 women with left heart obstruction (29 7 years, Gravida 2.3 1.3). All women had a current or prior (repaired) diagnosis of at least one lesion causing left heart obstruction (Bicuspid aortic valve/BAV = 34, Unicuspid aortic valve/UAV = 2, CoA = 28, MS = 13, Other = 13). Diagnoses in women with ‘‘other’’ types of obstruction included: subaortic membrane, Shone’s complex [4], combination MS and AS, AS post AVR, and transitional AV canal defect with AS. Within this cohort, there were 25 pregnancies in women with at least two left heart obstructive lesions (second lesion: BAV = 16, CoA = 2, Other = 7). There were 3 patients with Shone’s complex. Of the 90 pregnancies that occurred, 15 were complicated by maternal cardiovascular events. Table 1 outlines baseline characteristics of the entire cohort and of those with and without maternal cardiovascular events. Mitral stenosis was the single most common isolated diagnosis (n = 6) present in the 15 (17%) pregnancies complicated by a maternal cardiovascular event. However, an equal number of women (n = 6) had serial left heart obstructive lesions associated with a maternal cardiovascular event. The absolute risk of a maternal CV event with each diagnosis was: single non-mitral left heart obstructive lesion: 4/100 pregnancies, >1 serial left heart obstructive lesions 24/100 pregnancies, and isolated mitral stenosis 46/100 pregnancies. Women with isolated MS had increased CV events compared to women with other single left heart obstructive lesions (OR 18.6, 95% CI: 3.8–91.1). In pregnancies complicated by >1 serial obstructive lesion, there was also an increased risk of maternal CV events (OR 6.8, 95% CI: 1.6–29.1), however isolated MS carried similar risk to serial left heart obstructive lesions (OR 2.7, 95% CI: 0.7–11.2). Specific details regarding maternal cardiovascular events in pregnancy are detailed in Table 2. Women were more likely to have a CV event during pregnancy if they had elevated baseline NYHA functional class (27%(4) vs. 0(0), p < 0.001), any current left heart obstruction (73%(11) vs. 36%(28), p = 0.01), current severe left heart obstruction (60%(9) vs. 10%(5), p < 0.001), and higher baseline CARPREG score (1.2 0.7 vs. 0.5 0.7, p = 0.01) (Table 1, Fig. 1). There was no difference in adverse CV events in women with prosthetic mechanical valves (7% vs. 3%, p = 0.42). Specific cardiac diagnoses associated with a CV event, as compared to rates of these diagnoses in women without CV events are listed in Fig. 2. There was no significant difference in obstetric complications in those with or without a maternal cardiovascular event. Rates of vaginal delivery and Cesarean section were similar in women with and without cardiovascular events. Fetal/infant complications were not different between these two groups. However, term birth weight was lower in women with a cardiovascular event (2.7 0.5 vs. 3.1 0.6 kg, p = 0.01). One patient (BAV without current left heart obstruction) had intrauterine fetal death at 29 weeks gestation due to trisomy 18 in the fetus (accounting for the 1 case of fetal demise and perinatal mortality). Neonate death occurred at 3 weeks of age in the offspring of a patient with a normal functioning BAV. This infant had severe congenital aortic stenosis with successful percutaneous intervention, but died after the procedure due to severe sepsis (Table 3).
M. Fuchs et al. / European Journal of Obstetrics & Gynecology and Reproductive Biology 196 (2016) 38–43
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Table 1 Baseline descriptive characteristics. Variable
Age (years) Gravida (# pregnancies) Baseline BMI (kg/m2) History tobacco use Hypertension Prior cardiac event* NYHA functional class >2 Left heart obstructiona EF < 40% CARPREG score Severe left heart obstructionb Previous cardiac surgery >1 prior cardiac surgery Mechanical valve On anticoagulation Bioprosthetic valve Taking a beta blocker Taking diuretics
All pregnancies
Cardiovascular event
NO cardiovascular event
Mean SD or frequency (%) (n = 90)
Mean SD or frequency (n = 15)
Mean SD or frequency (n = 75)
29 7 2.3 1.3 28 6 18 (20) 18 (20) 10 (11) 4 (1) 39 (42) 0 (0) 0.6 0.6 14 (15) 57 (62) 29 (32) 3 (1) 6 (1) 3 (1) 29 (32) 0 (0)
33 6 3.1 1.5 27 8 3 (20) 3 (20) 2 (13) 4 (27) 11 (73) 0 (0) 1.2 0.7 9 (60) 8 (53) 5 (33) 1 (7) 2 (13) 0 (0) 5 (33) 0 (0)
28 6 2.2 1.3 28 5 15 (20) 15 (20) 8 (10) 0 (0) 28 (36) 0 (0) 0.5 0.7 5 (10) 49 (63) 24 (31) 2 (3) 1 (1) 6 (1) 24 (31) 0 (0)
p value
0.11 0.17 0.54 1.00 1.00 0.66 <0.001 0.01 1.00 0.01 <0.001 0.56 1.00 0.42 0.06 0.58 1.00 1.00
BMI, body mass index; CARPREG, cardiac disease in pregnancy score; EF, ejection fraction; NYHA, New York Heart Association; SD, standard deviation. * Prior cardiac event defined as: heart failure, transient ischemic attack, cerebrovascular accident, or arrhythmia. a Left heart obstruction = mitral valve area <2 cm, aortic valve area <1.5 cm, peak CoA gradient 20 mmHg. b Severe left heart obstruction = aortic valve gradient mean 40 mmHg, peak 60 mmHg, valve area 1.0 cm2, mitral valve gradient mean 10 mmHg, valve area 1.0 cm2, CoA peak gradient 30 mmHg.
In 48 pregnancies pre-conception/first trimester and postpartum echocardiograms were available and were analyzed (BAV = 22, UAV = 2, CoA = 6, MS = 5, Combination BAV + CoA = 5, Other = 8). Pre- and post-partum comparison echocardiograms were not available or obtained in all cases due lack of follow up or care being obtained elsewhere. Pregnancies comprising the
‘‘other’’ category included: transitional AV canal defect with AS (2), subaortic membrane (2), Shone’s complex (2), combination MS/AS (1), and AS post AVR (1). On average the time between the initial echocardiogram and post-partum echocardiogram was 1.0 0.8 years. In these pregnancies, those with left ventricular outflow tract obstruction had a baseline mean gradient of
Table 2 Description of maternal cardiovascular events. Diagnosis
Event
1.1
Rheumatic MS
4.1
CoA, BAV
Atrial fibrillation 3 months post-partum. MS mean gradient 5 mmHg (pre and post-pregnancy); had 2 prior balloon valvuloplasties most recently 6 years prior to pregnancy CoA gradient 120 mmHg, covered stent placed 32 weeks. CoA was diagnosed in pregnancy due to uncontrolled blood pressure. Fetal heart tones depressed after stent, delivered by Cesarean section at 32 weeks CHF requiring diuresis 4 days post-partum. Had moderate AS during pregnancy (mean 30/peak 52 mmHg), gradients stable throughout pregnancy/delivery. Membrane and CoA previously repaired (age 4) CHF requiring diuresis post-delivery. Mod-severe LVOTO at baseline (mean 44/peak 70 mmHg), higher post-partum (mean 61/ peak 108 mmHg) Severe AS of mechanical AVR (mean 55/peak 80 mmHg), replaced with bioprosthetic valve at 16 weeks gestation CHF third trimester requiring diuresis. Mean mitral gradient 14 mmHg in early pregnancy, no AS. Required invasive monitoring during labor and delivered via cesarean section CHF with severe pulmonary edema requiring intubation post-delivery. Mean MS gradient 3rd trimester 29 mmHg–first time patient presented. Mean gradient 14 mmHg post-partum Mitral balloon valvuloplasty at 24 weeks gestation. Diagnosed with MS during pregnancy when mean gradient 17 mmHg with symptoms. Post intervention gradient 8 mmHg Mitral balloon valvuloplasty at 30 weeks gestation. Diagnosed with MS during pregnancy, mean gradient 38 mmHg with symptoms. Post intervention gradient 9 mmHg. Inpatient until delivery at 37 weeks Post-delivery covered stent peak gradient 30 mmHg. Prior subclavian flap and subaortic membrane resection 2
Patient ID
17.1
49.1
CoA, BAV, sub-aortic membrane BAV, supravalvar AS BAV Rheumatic AS and MS Rheumatic MS
60.1
Rheumatic MS
73.1
Rheumatic MS
74.1
80.1
CoA, subaortic membrane Subaortic membrane BAV
84.2 84.3
Rheumatic MS Rheumatic MS
85.1
BAV, subaortic membrane
20.1 21.1 29.1
76.2
CHF in third trimester until delivery requiring diuresis. Previous subaortic membrane resection 3 years prior. Pregnancy gradients stable with moderate LVOTO (mean 38, peak 64 mmHg) Severe AS 16 weeks (mean 66/peak 108 mmHg) underwent mechanical AVR. Atrial flutter requiring cardioversion 21 weeks gestation CHF third trimester requiring diuresis. Mean mitral gradient prior to pregnancy 8 mmHg. Patient did not follow-up CHF third trimester requiring diuresis. This was first presentation and patient delivered in the ICU with invasive monitoring on this admission. Mean mitral gradient prior to pregnancy 6 mmHg, at presentation 14 mmHg. Patient did not follow up Balloon valvotomy 24 weeks gestation (mean 65/peak 100 mmHg at 13 weeks). Subaortic membrane repaired age 16. Invasive monitoring with vaginal delivery in ICU
AS, aortic stenosis; BAV, bicuspid aortic valve; CHF, congestive heart failure; CoA, coarctation; ICU, intensive care unit; ID, identification; LVOTO, left ventricular outflow tract obstruction; MS, mitral stenosis.
M. Fuchs et al. / European Journal of Obstetrics & Gynecology and Reproductive Biology 196 (2016) 38–43
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Fig. 1. Likelihood of cardiovascular event based on type of left heart lesion. Patients with serial left heart obstruction had similar odds of cardiovascular event when compared to mitral stenosis (OR, 95% CI). Greater than one left heart obstruction was associated with greater risk of cardiovascular event when compared to one left heart obstructive lesion. Mitral stenosis conferred greater risk of cardiovascular event compared to one left heart obstructive lesion. MS, mitral stenosis; LHO, left heart obstruction
Table 3 Obstetric, fetal, infant complications. Variable
All pregnancies
CV event
NO CV event
Mean SD or frequency (%) (n = 90)
Mean SD or frequency (%) (n = 15)
Mean SD or frequency (%) (n = 75)
7
20
Obstetric 27 complications Antepartum 3 (3) hemorrhage 0 Pregnancy induced HTN 7 (8) Preeclampsia Eclampsia 0 Gestation diabetes 7 (8) PPROM 2 (2) Pre-term labor 4 (4) Postpartum 4 (4) hemorrhage 0 VTE Type of delivery Vaginal delivery 34 (38) Assisted vaginal 18 (20) delivery 50 (56) C-section delivery Elective C-section 33 (37) Emergent C-section 14 (16) Fetal/infant complications Preterm birth 20 (22) Small for 2 (2) gestational age 2.9 0.6 Birth weight (kg) 3 (3) RDS IVH 0 Fetal demise 1 (1) Perinatal mortality 1 (1) Neonatal mortality 1 (1)
p value
2 (13)
1 (1)
0.06
0
0
1.00
0 0 2 1 1 1
7 0 5 1 3 3
(13) (7) (7) (7)
0
(9) (7) (1) (4) (4)
0
0.59 1.00 0.32 0.30 0.52 0.52 1.00
6 (40) 4 (27)
28 (37) 14 (19)
0.78 0.48
8 (53) 6 (40) 2 (13)
42 (56) 27 (36) 12 (16)
1.00 0.77 1.00
5 (33) 0
15 (20) 2 (3)
0.30 1.00
2.7 0.5
3.1 0.6
0.01
0 0 0 0 0
3 0 1 1 1
1.00 1.00 1.00 1.00 1.00
(4) (1) (1) (1)
C-section, cesarean section; HTN, hypertension; IVH, intraventricular hemorrhage; PPROM, premature passive rupture of membranes; RDS, respiratory distress syndrome; SD, standard deviation; TIA, transient ischemic attack; VTE, venous thromboembolism.
Fig. 2. Type of cardiovascular diagnoses in pregnancies without/without CV events. Percentage of cardiac diagnoses that occurred in pregnancy in those with cardiovascular (CV) events (black bars) and those without CV events (white bars). NYHA > 2: New York Heart Association functional class during pregnancy greater than 2.
25 16 mmHg and peak gradient of 34 26 mmHg. In patients with MS, the baseline mean gradient was 10 7 mmHg. Overall heart function as evaluated by echo did not significantly change (ejection fraction 60 5% vs. 59 5%, p = 0.33) over the course of pregnancy. No difference in mean and peak gradients between pre-conception and post-pregnancy echocardiograms was found (Fig. 3). Discussion Expected hemodynamic changes occur in pregnancy and include: 50% increase in cardiac output met by increased stroke volume and heart rate [5], increased total blood volume [6], and decline in systemic vascular resistance [7]. These changes are well tolerated in women with structurally normal hearts. However when left heart obstruction is present, from valve disease or other etiology, these hemodynamic changes are less well tolerated and can lead to a poor outcome [8]. When considering all types of left heart obstruction, our study showed that overall these women do reasonably well, even if intervention was required during pregnancy. Previous studies have shown that maternal cardiovascular events in patients with mitral stenosis are substantial, and that this diagnosis in particular carries the greatest maternal cardiovascular morbidity risk when compared to other types of left heart obstruction [9,10]. In a cohort without any mortality, our results indicate that MS carries the greatest risk of a maternal cardiovascular complication when considering isolated forms of left heart obstruction. The results of one prior large study evaluating all types of congenital heart disease in pregnancy suggested a higher rate of maternal cardiovascular events when MS was combined with another form
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M. Fuchs et al. / European Journal of Obstetrics & Gynecology and Reproductive Biology 196 (2016) 38–43
Fig. 3. Left heart obstructive gradients pre/post-pregnancy. Mean (A) and peak (B) gradients in women with pre and post-pregnancy echocardiograms. No significant difference in mean gradient was seen irrespective of the type of left heart obstruction. BAV, bicuspid aortic valve; UAV, unicuspid aortic valve; COA, coarctation of aorta; MS, mitral stenosis; BAV + COA, bicuspid aortic valve and coarctation of aorta.
of left heart obstruction [11]. However, this study did not report on specific types of left heart obstruction or directly compare single left heart obstructive lesions with multiple left heart obstructive lesions. There have been other studies evaluating isolated forms of left heart obstruction, including aortic stenosis, coarctation, and even in those with prosthetic valves [12–16]. We are the first to directly compare all types of LHO and to show that an equal number of maternal cardiovascular events occurred in women with serial (>1) left heart obstruction, independent of mitral valve involvement. This indicates that women with more than one left heart obstructive lesion have a similar risk of sustaining a maternal cardiovascular event, when compared to women with isolated MS. The CARPREG score [1] was evaluated in this cohort, and although generally predicted event rates, there were two women with cardiovascular events that had a score of zero. This may suggest an independent maternal cardiovascular risk in those with serial left heart obstructive lesions. It is not surprising that women with worse functional class and higher degrees of left heart obstruction had more maternal cardiovascular events. In this cohort, we have showed that with careful management by a high risk obstetric and cardiac team, women with current left heart obstruction can do reasonably well during pregnancy, labor, and delivery, even if intervention is required. Women that required intervention had minimal fetal or obstetric complications. Of the 6 patients that had a cardiac event and required intervention, 3 had uneventful term deliveries (all by C-section). The other 3 patients had preterm deliveries (2 of them at 36 weeks), and all babies survived without further sequelae.
Although there appeared to be a higher rate of antepartum hemorrhage in women with a cardiovascular event, the result was not statistically significant. The overall number of patients affected was small and is a limitation of this study. No other obstetric complications were significantly different between women with and without cardiovascular events. This included rates of elective and emergent C-section, a vital consideration when counseling women with left heart obstruction. It is equally important to mention that women with left heart obstruction had no difference in rates of vaginal delivery vs. Cesarean section, and that the number of prior pregnancies had no effect on rates of maternal, obstetric, or fetal/infant outcomes. Birth weight was significantly lower in women with a cardiovascular event, even when accounting for gestational age at delivery. This has been found in prior studies [10] although the reason is not completely clear. We postulate that there may be a lack of appropriate cardiac output to the placenta/fetus relative to the hemodynamic changes of pregnancy in women with left heart obstructive lesions. Overall rates of preterm birth in our study, while not varying between study groups, were higher than the general U.S. population (20% vs. 11%) [17]. Our patient population also had higher rates of pre-pregnancy hypertension (20%) and preeclampsia (8%) than the general US population (11% and 3.4% respectively) [18]. These cardiovascular conditions often accompany structural heart disease. While these comorbidities did not appear to influence maternal or fetal outcomes, it may be that these cardiovascular conditions lead practitioners to manage patients more conservatively, and in some cases prompt earlier delivery. There are several limitations to this study. The data is retrospective, and therefore can identify associations between conditions and outcomes, but is limited in ability to predict prospective events. This ‘‘real world’’ cohort likely represents women with more significant left heart obstruction than the general population, as the data was collected at a tertiary referral center with a high-risk obstetric-cardiac program. It is difficult to determine whether or not the same conclusions could be made in a cohort with milder disease. Cardiovascular, obstetric, and fetal/ infant outcomes may be different in a center without a high-risk maternal obstetric-cardiac team and/or capabilities to provide intervention in complex anatomy. It is possible that the availability of elective C-section may result in higher overall rates of C-section in a tertiary-care center population. Data regarding infant outcomes, including presence or absence of congenital heart disease, was limited or not available in the majority of this cohort, and is a limitation of this study. Finally, the sample size, while larger than most prior studies, is still small, thus impeding the ability to draw absolute conclusions from the data observed. In conclusion, women with left heart obstruction do reasonably well in pregnancy, even when antenatal intervention is required. Isolated mitral stenosis and serial (>1) left heart obstructive lesions carry the highest risk of maternal cardiovascular events, and patients as well as physicians should be counseled as such. Obstetric, delivery, and fetal/infant complications are similar in women with and without maternal cardiovascular events who have left heart obstruction; birth weight at term, however, was lower in women with an event. Despite a number of high-risk patients and cardiovascular events, there was no maternal mortality. This data supports the need for specialized and experienced high-risk obstetric-cardiac teams to care for women with left heart obstruction, and demonstrates good outcomes in a cohort with all types of left heart obstruction. Financial disclosures None.
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