Abstract
Pregnancy risk assessment for patients with adult congenital heart disease (ACHD) must include physiologic and anatomic impacts. We aimed to determine whether maternal cardiac and pregnancy outcomes vary by disease severity defined according to the following 3 different classifications: ACHD anatomic severity, ACHD physiologic class, and modified World Health Organization (mWHO) class. Cardiac outcomes included a composite of arrhythmia, heart failure, stroke, and thromboembolism. Pregnancy outcomes included a composite of intrauterine growth restriction, preterm birth, preeclampsia, or postpartum hemorrhage. We employed generalized estimating equations to account for multiple pregnancies. Of the 245 pregnancies, 17.1% were preterm and 45.7% were cesarean deliveries. Cardiac hospitalizations occurred in 22.0% and arrhythmias in 12.7%. Cardiac outcomes tended to be more prevalent in people with more severe heart disease. Pregnancy outcomes were U-shaped or less prevalent in people with more severe disease. There was a 2.9-fold increased risk for the composite cardiac outcome for complex anatomy (adjusted incidence rate ratio 2.90, 95% confidence interval 1.08 to 7.81, p = 0.04), a 9.4-fold increased risk for physiologic class C or D (9.37, 1.28 to 68.79, p = 0.03), and a fourfold increased risk for mWHO class III or IV (3.99, 1.53 to 10.40, p = 0.005). There was a lower risk for the composite pregnancy outcome for mWHO class II or II to III (0.54, 0.36 to 0.79, p = 0.002) but no association with anatomy or physiology. In conclusion, physiologic class may be most accurately associated with adverse outcomes and therefore efforts to optimize hemodynamics before pregnancy may help to mitigate the risk.
The physiologic adaptations of pregnancy stress the cardiovascular system,1,2 which can lead to complications for patients with structural heart disease.3,4 Pregnancy has historically been discouraged for patients with advanced adult congenital heart disease (ACHD), however, with treatment advances, pregnancy has become a possibility in all but the most complex situations.3,5 Multiple models have been created to quantify risk, most prominently the Cardiac Disease in Pregnancy II (CARPREGII) risk index and the modified World Health Organization (mWHO) classifications3,6–8 (Supplementary Figure 1). The 2018 ACHD guidelines9 proposes the “Anatomic and Physiologic (AP) classification,” which takes into consideration the hemodynamic and physiologic impact and the underlying anatomy. Although anatomy rarely changes, physiology is dynamic, and this new classification may therefore provide an additional way to stratify pregnancy risk in patients with ACHD. The aim of this study was to assess the association between ACHD severity, defined by different ACHD classification models (anatomic lesion severity, physiologic class, and mWHO class), and adverse cardiac and pregnancy outcomes in patients with ACHD. We hypothesized that the risk for adverse cardiac and pregnancy outcomes would be higher in patients with more severe cardiac disease, irrespective of the classification system used.
Methods
We included adults aged ≥18 years with ACHD who received care for at least 1 pregnancy at the University of Washington Medical Center, a large ACHD referral center, between September 2009 and April 2019. All eligible pregnancies of patients with ACHD during this study period were included. Pregnancies with incomplete outcomes data (i.e., patients primarily managed at an outside health system) were excluded. In addition, pregnancies that ended in miscarriage or abortion ≤20 weeks were excluded from the analysis. Demographic and clinical data, including co-morbidities, cardiac events during pregnancy, and pregnancy outcomes, were collected by manual review of the electronic medical records. We utilized the mWHO criteria to estimate the cardiac risk in pregnancy given its endorsement by the European Society of Cardiology and the American Heart Association,8,10 and we described ACHD lesion type and severity according to the ACHD AP classification9 (Supplementary Table 1).
Maternal demographics and pregnancy experiences were described using mean ± SD or percentages, as appropriate. Cardiac outcomes included cardiac hospitalization or intensive care unit (ICU) stay during pregnancy, arrhythmia, heart failure, thromboembolism, stroke, and aortic dissection. Hospitalizations and ICU stays are important resource utilization outcomes, reflecting illness severity and also the costs of treatment and time invested by clinicians and patients. We also examined a composite cardiac outcome including arrhythmia, heart failure, stroke, and thromboembolism. Pregnancy outcomes included intrauterine growth restriction, small for gestational age neonates, neonatal ICU admission, preterm birth (<37 weeks’ gestation), postpartum hemorrhage, preeclampsia, and cesarean delivery. We also examined a composite pregnancy outcome including intrauterine growth restriction, preterm birth, postpartum hemorrhage, or preeclampsia. Finally, we quantified maternal, fetal, and infant deaths.
To examine the relation between ACHD severity and key adverse pregnancy and cardiac outcomes, we employed generalized estimating equations specifying the log-link, Poisson family, independent correlation structure, robust standard errors, and clustering by participant to estimate relative risks and 95% confidence intervals (CIs). This approach allowed us to include multiple pregnancies for patients contributing >1 pregnancy during the study period, understanding that subsequent pregnancies are not independent events. Some of the included patients contributed up to 3 pregnancies during the study period; we included first and second pregnancies in inferential analysis but could not include the third pregnancy in the models because of the small sample size (n = 5).
We assessed the following 3 primary exposures: pregnancy risk as estimated by ACHD anatomic lesion severity, ACHD physiologic class, and mWHO class. For their respective analyses, ACHD physiologic class C and D, mWHO class II and II to III, and mWHO class III and IV were combined given the few patients in the extremes of each classification. Our 2 primary outcomes were the composite cardiac and pregnancy outcome measures. We adjusted a priori for maternal age at pregnancy presentation and included an indicator variable for any adverse pregnancy or cardiac outcomes (defined previously) experienced in previous pregnancies that were captured during the study period; adverse pregnancy or pregnancy-related cardiac outcomes for pregnancies occurring before the beginning of the study period were not available. We were not able to account for pregnancies that occurred before September 2009 or outcomes that occurred at other institutions during the study period. We conducted 3 sensitivity analyses. In the first, we restricted the analysis to nulliparous patients to investigate the impact of data limitations in terms of adverse events in pregnancies that occurred before the study period. In the second, we restricted the analysis to the first pregnancy in the dataset as an alternative approach to reducing within-person correlation because some patients had multiple pregnancies during the study period. Finally, we suspected that there may be a compound relation when an anatomic and a physiologic classification system are used together. In a stratified analysis, we assessed for a differential effect of the mWHO class on the combined cardiac and pregnancy outcomes by physiologic class. A 2-tailed p <0.05 was used to indicate statistical significance. The study was approved by the institutional review board of the University of Washington (Seattle, Washington).
Results
For 201 patients, there were 262 pregnancies during the study period. Of these, 2 were elective abortions, 3 were induced abortions related to maternal cardiac disease, and 12 were miscarriages ≤20 weeks’ gestation. Of the 17 abortions and miscarriages, 17.6% were among women with complex ACHD (n = 3 miscarriages) and the remaining were among women with moderate ACHD. Among the remaining 198 patients with 245 completed pregnancies, 156 patients (79%) contributed 1 pregnancy, 37 (19%) had 2, and 5 (3%) had 3. The mean age at pregnancy presentation was 28.8 ± 5.7 years. The most common maternal cardiac co-morbidity was history of arrhythmia (20%) (Table 1). Approximately 10% of patients had complex ACHD anatomy, 41% were ACHD physiologic class C or D, and 19% were mWHO class III or IV (Supplementary Table 1). Within each category of ACHD anatomy, patients were of varied physiologic and mWHO classes (Figure 1). For the 42 patients with multiple pregnancies, none changed to a different ACHD anatomic group, 11 changed to a different physiologic group, and 3 changed mWHO class during the study period. Changes were usually to a higher risk group. Gestational age at first prenatal visit was not different by anatomy (simple: median 9.5, interquartile range [IQR] 7 to 19; moderate: median 13, IQR 8 to 24; complex: median 11, IQR 11 to 17.5), physiologic class (A: median 11.5, IQR 7 to 27; B: median 11.5, IQR 8 to 23; C/D: median 13, IQR 9 to 21), or mWHO class (I: median 11 wk, IQR 7 to 24; II/II to III: median 12, IQR 8 to 22.5; III/IV: median 13, IQR 9 to 21). Nulliparity was not significantly different by anatomy (simple: 36.5%; moderate: 39.6%; complex: 62.5%), physiologic class (A: 38.1%; B: 44.1%; C/D: 40.4%), or mWHO class (I: 38.2%; II/II to III: 37.5%; III/IV: 56.5%). There were 2 fetal deaths, 3 neonatal deaths, and no maternal deaths.
Table 1.
Demographics and maternal co-morbidities by pregnancy
| Characteristic | N* (%); Mean±SD |
|---|---|
|
| |
| Age at Pregnancy (years) | 28.8±5.7 |
| White | 171 (69.8%) |
| Black | 18 (7.3%) |
| Hispanic | 16 (6.5%) |
| Asian | 28 (11.4%) |
| American Indian/Alaska Native | 4(1.6%) |
| Undefined Race/Ethnicity | 8 (3.3%) |
| Married | 171 (69.8%) |
| Employed | 125 (51.0%) |
| Health Insurance | |
| Public | 98 (40.0%) |
| Private | 134 (54.7%) |
| None | 4(1.6%) |
| Number of Pregnancies Overall (median, range) | 2(1–13) |
| Gestation at First Care (weeks; mean±SD) | 16.2±10.6 |
| Received Adult congenital heart disease Care during Pregnancy | 195 (79.6%) |
| Coronary Artery Disease | 3 (1.2%) |
| Arrhythmia | 49 (20.0%) |
| Heart Failure | 12 (4.9%) |
| Systemic Hypertension | 26 (10.6%) |
| Pulmonary Hypertension | 22 (9.0%) |
| Pacemaker/Defibrillator | 14 (5.7%) |
| Mechanical Heart Valve | 7 (2.9%) |
| History of Stroke | 11 (4.5%) |
| History of Thromboembolism | 5 (2.0%) |
| History of Aortic Dissection | 1 (0.4%) |
| History of Anxiety | 40 (16.3%) |
| History of Depression | 43 (17.6%) |
N = 245 pregnancies contributed by 198 women.
Figure 1.
Distribution of physiologic and mWHO class classifications among anatomic groups in pregnant patients. (A) ACHD physiologic class distribution and (B) mWHO class distribution). Please see Supplementary Data file.
Of the 245 completed pregnancies, antepartum cardiac hospitalizations occurred in 22.0% (n = 54), arrhythmias in 12.7% (n = 31), and heart failure in 3.3% (n = 8). Overall, 17.1% (n = 42) were preterm and 45.7% (n = 112) were cesarean deliveries. The number of adverse cardiac outcomes during pregnancy was proportionally higher among patients with more complex lesions, a higher physiologic class, and higher mWHO class (Table 2). Adverse pregnancy outcomes tended to be U-shaped (lowest risk in those with moderate disease) or were lower among patients with more complex lesions, higher physiologic class, and higher mWHO class. When stratified by parity, the rates of adverse cardiac outcomes by classification system were more variable; however, adverse pregnancy outcomes tended to be more frequent in nulliparous patients. The preterm birth rate was similar in the groups (Table 3).
Table 2.
Descriptive outcomes by adult Congenital Heart Disease severity
| Cardiac outcomes by adult congenital heart disease severity | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|
|
| ||||||||||
| Outcome | ACHD Anatomy |
ACHD Physiologic Class* |
mWHO Class |
Total N=245 | ||||||
| Simple (n= 52) | Moderate (n= 169) | Complex (n= 24) | A (n= 42) | B (n= 102) | C/D (n= 99) | I (n= 55) | II (II-m) (n= 144) | III/IV (n= 46) | ||
|
| ||||||||||
| Hospitalization | 8 (15.4%) | 37 (21.9%) | 9 (37.5%) | 11(26.2%) | 15(14.7%) | 28 (28.3%) | 13 (23.6%) | 18 (12.5%) | 23 (50.0%) | 54 (22.0%) |
| Intensive care unit Stay | 1 (1.9%) | 6 (3.6%) | 0 | 0 | 2 (2.0%) | 5 (5.1%) | 0 | 1 (0.7%) | 6 (13.0%) | 7 (2.9%) |
| Arrhythmia† | 5 (9.6%) | 20(11.8%) | 6 (25.0%) | 1(2.4%) | 12(11.8%) | 18(18.2%) | 5 (9.1%) | 14 (9.7%) | 12(26.1%) | 31 (12.7%) |
| Heart Failure Episode† | 1 (1.9%) | 5 (3.0%) | 2 (8.3%) | 0 | 5 (4.9%) | 3 (3.0%) | 1 (1.8%) | 3 (2.1%) | 4 (8.7%) | 8 (3.3%) |
| Thromboembolism† | 0 | 2(1.2%) | 1 (4.2%) | 0 | 2 (2.0%) | 1 (1.0%) | 0 | 0 | 3 (6.5%) | 3 (1.2%) |
| Stroke† | 1 (1.9%) | 0 | 0 | 0 | 1 (1.0%) | 0 | 0 | 1 (0.7%) | 0 | 1 (0.4%) |
|
| ||||||||||
| Pregnancy Outcomes by Adult congenital heart disease Severity | ||||||||||
|
| ||||||||||
| Outcome |
ACHD Anatomy
|
ACHD Physiologic Class *
|
mWHO Class
|
Total N=245 | ||||||
| Simple (n= 52) | Moderate (n= 169) | Complex (n= 24) | A(n=42) | B (n= 102) | C/D (n= 99) | I (n= 55) | II (II-III) (n= 144) | III/IV (n= 46) | ||
|
| ||||||||||
| Intrauterine Growth Restriction‡ | 5 (9.8%) | 12 (7.2%) | 2 (8.3%) | 4 (9.8%) | 8 (7.8%) | 7 (7.2%) | 8 (14.8%) | 7 (4.9%) | 4 (8.7%) | 19 (7.8%) |
| Small for Gestational Age | 4 (7.8%) | 2(1.2%) | 1 (4.2%) | 2 (4.9%) | 2 (2.0%) | 3 (3.1%) | 4 (7.4%) | 2 (1.4%) | 1 (2.2%) | 7 (2.9%) |
| Neonatal intensive care unit Stay | 19 (37.3%) | 34 (20.1%) | 7 (30.4%) | 15 (36.6%) | 23 (22.6%) | 22 (22.5%) | 20 (37.0%) | 26(18.1%) | 14(31.1%) | 60 (24.5%) |
| Preterm Birth‡ | 13 (25.0%) | 22 (13.0%) | 7 (29.2%) | 11(26.2%) | 17(16.7%) | 14(14.1%) | 16(29.1%) | 13 (9.0%) | 13 (28.3%) | 42(17.1%) |
| Postpartum Hemorrhage‡ | 6(11.8%) | 15 (8.9%) | 3 (13.0%) | 5(12.2%) | 12(11.8%) | 7 (7.2%) | 5 (9.3%) | 15 (10.5%) | 4 (8.9%) | 24 (9.8%) |
| Preeclampsia‡ | 7 (13.7%) | 14 (8.3%) | 2 (8.3%) | 7(17.1%) | 13(12.8%) | 3 (3.1%) | 12 (22.2%) | 9 (6.3%) | 2 (4.4%) | 23 (9.4%) |
| Cesarean Delivery | 24 (46.2%) | 74 (43.8%) | 14 (58.3%) | 26(61.9%) | 43(42.2%) | 43 (43.4%) | 32 (58.2%) | 53 (36.8%) | 27 (58.7%) | 112 (45.7%) |
N = 243 (physiologic class could not be determined for 2 pregnancies).
Components of composite cardiac outcome.
Components of composite pregnancy outcome.
ACHD = adult congenital heart disease; mWHO = modified World Health Organization.
Table 3.
Pregnancy outcomes by parity
| Outcomes by parity |
|||
|---|---|---|---|
| Outcome | Nulliparous(n=101) | Multiparous(n=144) | Total(N=245) |
|
| |||
| Cardiac Outcomes | |||
|
| |||
| Hospitalization | 27 (26.7%) | 27(18.9%) | 54 (22.0%) |
| Intensive Care Unit Stay | 2 (2.0%) | 5 (3.5%) | 7 (2.9%) |
| Arrhythmia* | 14 (13.9%) | 17(11.8%) | 31 (12.7%) |
| Heart Failure Episode* | 2 (2.0%) | 6 (4.2%) | 8 (3.3%) |
| Thromboembolism* | 2 (2.0%) | 1 (0.7%) | 3 (1.2%) |
| Stroke* | 0 | 1 (0.7%) | 1 (0.4%) |
| Cardiac Composite | 16 (15.8%) | 23 (16.0%) | 39 (15.9%) |
|
| |||
| Pregnancy Outcomes | |||
|
| |||
| Intrauterine Growth Restriction* | 12 (12.0%) | 7 (4.9%) | 19 (7.9%) |
| Small for Gestational Age | 7 (6.9%) | 0 | 7 (2.9%) |
| Neonatal Intensive Care Unit Stay | 31 (31.0%) | 29 (20.3%) | 60 (24.7%) |
| Preterm Birth† | 18 (17.8%) | 24(16.7%) | 42(17.14%) |
| Postpartum Hemorrhage† | 14 (14.0%) | 10 (7.0%) | 24 (9.9%) |
| Preeclampsia† | 15 (14.9%) | 8 (5.6%) | 23 (9.5%) |
| Cesarean Delivery | 55 (54.5%) | 57 (39.6%) | 112 (45.7%) |
| Pregnancy Composite | 40 (39.6%) | 40 (27.8%) | 80 (32.7%) |
Components of composite cardiac outcome.
Components of composite pregnancy outcome.
In the primary analysis assessing the association between the composite cardiac outcome and ACHD anatomy, there was a 2.9-fold increased risk for the composite adverse cardiac outcome among those with complex ACHD (adjusted incidence rate ratio [aIRR] 2.90, 95% CI 1.08 to 7.81) (Table 4). There was a 9.4-fold increased risk for the composite adverse cardiac outcome among those with ACHD physiologic class C or D (aIRR 9.37, 95% CI 1.28 to 68.79) and a fourfold increased risk among those in mWHO class III/IV (aIRR 3.99, 95% CI 1.53 to 10.40). Assessing cardiac outcome-specific risks, there were elevated risks for arrhythmia associated with increasing severity as defined by anatomy (complex aIRR 2.85, 95% CI 0.93 to 8.75), physiologic class (C or D aIRR 7.88, 95% CI 1.05 to 58.99), and mWHO class (III/IV aIRR 3.08, 95% CI 1.12 to 8.52).
Table 4.
Association Between composite outcomes (cardiac and pregnancy) and adult Congenital Heart Disease severity
| Variable | ACHD Status | Outcome | Unadjusted incidence rate ratio(95% CI) | Adjusted* incidence rate ratio(95% CI) |
|---|---|---|---|---|
|
| ||||
| Composite Cardiac Outcome | ||||
|
| ||||
| ACHD Anatomy | ||||
| Simple | 52 (22.2%) | 6(11.5%) | REF | REF |
| Moderate | 169 (69.0%) | 26 (15.4%) | 1.37(0.59–3.16) | 1.41 (0.61–3.25) |
| Complex | 24 (9.8%) | 7 (29.2%) | 2.74 (1.04–7.21) | 2.90 (1.08–7.81) |
| ACHD Physiologic Class | ||||
| A | 42 (17.3%) | 1 (2.4%) | REF | REF |
| B | 102 (42.0%) | 16 (15.7%) | 6.36 (0.86–46.93) | 6.31 (0.85–46.57) |
| C/D | 99 (40.7%) | 22 (22.2%) | 9.33 (1.27–68.30) | 9.37 (1.28–68.79) |
| mWHO Class | ||||
| I | 55 (22.4%) | 5 (9.0%) | REF | REF |
| II/II-III | 144 (58.8%) | 18 (12.5%) | 1.37 (0.53–3.56) | 1.43 (0.53–3.83) |
| III/IV | 46(18.8%) | 16 (34.8%) | 3.87 (1.48–10.09) | 3.99 (1.53–10.40) |
|
| ||||
| Composite Pregnancy Outcome | ||||
|
| ||||
| ACHD Anatomy | ||||
| Simple | 52 (22.2%) | 20 (38.5%) | REF | REF |
| Moderate | 169 (69.0%) | 51 (30.2%) | 0.81 (0.51–1.29) | 0.82 (0.54–1.27) |
| Complex | 24 (9.8%) | 9 (37.5%) | 0.98 (0.47–2.03) | 0.92 (0.44–1.92) |
| ACHD Physiologic Class | ||||
| A | 42 (17.3%) | 16(38.1%) | REF | REF |
| B | 102 (42.0%) | 35 (34.3%) | 0.93 (0.55–1.58) | 0.93 (0.56–1.55) |
| C/D | 99 (40.7%) | 29 (29.3%) | 0.77 (0.44–1.36) | 0.78 (0.46–1.34) |
| mWHO Class | ||||
| I | 55 (22.4%) | 27 (49.1%) | REF | REF |
| II/II-III | 144 (58.8%) | 35 (24.3%) | 0.51 (0.34–0.77) | 0.54 (0.36–0.79) |
| III/IV | 46(18.8%) | 18 (30.4%) | 0.74 (0.44–1.23) | 0.74 (0.44–1.23) |
Boldface indicates statistically significant at p <0.05.
Adjusted for age at pregnancy and adverse event(s) in prior pregnancy.
ACHD = adult congenital heart disease; CI, confidence interval; mWHO = modified World Health Organization; REF = referent.
In analyses assessing pregnancy outcomes, compared with mWHO class I (Table 4), there was a 46% lower risk for the composite adverse pregnancy outcome among those in mWHO class II or II to III (aIRR 0.54, 95% CI 0.36 to 0.79). There was no significant association between mWHO group III/IV and the composite pregnancy outcome (aIRR 0.74, 95% CI 0.44 to 1.23). There was no significant association between the composite pregnancy outcome and either ACHD anatomy or physiologic class.
In the sensitivity analyses in which the role of parity in the associations between ACHD severity and outcomes was evaluated, the results for all exposures and the composite cardiac and pregnancy outcomes were similar to the primary analyses (Supplementary Table 2). Unadjusted analysis for the composite cardiac outcome by mWHO class stratified by physiologic class revealed a possible association for patients with ACHD of medium severity (class B, II/II to III: incidence rate ratio [IRR] 0.61, 95% CI 0.18 to 2.12 vs class B, III/IV: IRR 2.90, 95% CI 0.91 to 9.21; class C or D, II/II to III: IRR 0.64, 95% CI 0.10 to 3.95 vs class C or D, III/IV: IRR 1.26, 95% CI 0.21 to 7.56). We were unable to further evaluate this finding in adjusted analyses because of the limited sample size. In the same analyses for the composite pregnancy outcome, estimates were closer to null than in the primary analysis (Supplementary Table 3).
Discussion
We evaluated the association between the severity of ACHD, assessed using 3 different classification systems, and adverse cardiac and pregnancy outcomes. There was a dose-response effect for increased risk of adverse cardiac outcomes with more severe ACHD irrespective of the risk classification system. Pregnancy outcomes demonstrated variable and unexpected relations.
ACHD physiologic classification9 may allow for more specific risk assessment because it takes into account the current hemodynamic impacts. As in this study, the underlying ACHD anatomy is unlikely to change but physiology does, and patients in various physiologic and mWHO classes were present within each anatomic group. For example, a patient with tetralogy of Fallot (anatomy “moderate”) could be in physiologic group B (mWHO class II) if the repair is stable but could also be in group D (mWHO class IV) if there is severe cardiac dysfunction. We found similar relations in adverse outcomes when we used physiologic class as the exposure compared with when we used anatomy and mWHO class, but the risk ratios using physiologic class were much larger. This may suggest that this classification system is more accurate for risk assessment. We were unable to assess joint impacts of anatomy and physiology because of the small sample size.
The most common adverse cardiac outcome was arrhythmia. However, details like arrhythmia type and consequences were not included in these data. Arrhythmia is a recognized challenge for pregnancy in women with ACHD and is included in some risk scores. When present as a comorbidity, arrhythmias are likely to recur in pregnancy,11 posing treatment dilemmas given the risks of medications and procedures such as cardioversion. Antepartum arrhythmias are also believed to influence the occurrence of other adverse events such as preterm birth and small for gestational age neonates.5,11,12
In the assessment of adverse pregnancy outcomes, the findings were unexpected. Many trends were U-shaped with the lowest risk in moderate cardiac disease (i.e., neonatal ICU admission). At times, the trends were the opposite of what was expected with more adverse events in cases with less severe disease (i.e., preeclampsia). Adverse outcomes seemed more prevalent than for the general population at our institution (cesarean delivery rate 40%, gestational hypertension or preeclampsia 15%, postpartum hemorrhage 15%). We could not attribute this to parity or gestational age at the initiation of prenatal care. It is possible that patients with severe disease by quantifiable risk scales have relatively less severe disease than others who may have miscarried, could not become pregnant, or who chose not to attempt pregnancy. This finding may also be related to cardiac intervention or “tuning up” before pregnancy or increased surveillance during pregnancy. Conversely, patients with less severe disease may have had less surveillance and may have been treated more like patients without heart disease, leading to more adverse outcomes. The best model for comprehensive ACHD pregnancy care is to facilitate shared care between a high-risk obstetrician and an ACHD cardiologist,2,13,14 utilizing formalized testing protocols and common risk evaluation structures.
Future studies (ideally longitudinal, multicenter registry studies utilizing prospectively collected data) should more deeply examine the unexpected patterns for pregnancy outcomes seen in this study. Assessment of larger cohorts could investigate patient cardiac and pregnancy outcomes, include later pregnancies, and expand comparison with other risk models. Specific attention should be paid to evaluating the overlapping effects between models and to answer the clinical question of whether anatomy or physiology matters more.
There are notable strengths of this study. First, we assessed cardiac and pregnancy outcomes using multiple risk classification systems, particularly the newly proposed AP classification. Second, we used statistical methods that accounted for between-pregnancy correlation rather than assuming independence or analyzing only the first pregnancy. Finally, these data are from a large ACHD care center in which a substantial proportion of patients receive lifelong care. Our center also has a long history of expertise in cardio-obstetrics, including management of high-risk deliveries.
Limitations include a modest sample size, rare adverse outcomes, and lack of granularity for some variables, which limited our ability to assess the associations between specific adverse outcomes and interactions between conditions. This was most evident in the extremes of disease, in some subgroups (i.e., third pregnancy), and in determining whether ACHD physiologic class has a finer ability to assess risk. Similarly, we could not assess pregnancies for which care was fragmented among multiple medical systems. The study period initiation was determined by electronic medical record availability. However, sensitivity analyses limited to first pregnancies do not suggest that these led to major bias. Finally, most patients included in this study were White, ensured, and had access to subspecialty care; therefore, these results may not be fully generalizable.
In conclusion, the ACHD AP and mWHO risk classification systems all seem to perform adequately in assessing the potential for adverse cardiac outcomes during pregnancy; however, physiologic classification may be the best. Efforts to optimize the hemodynamic impact of ACHD and therefore the physiologic class before pregnancy may help mitigate the risks of complex anatomy.
Supplementary Material
Acknowledgments
This work was supported by the Alpha Phi Foundation (Evanston, Illinois). The funding source was not involved in the design, completion, or submission of the study. Assistance with data collection was provided by the University of Washington Institute of Translational Health Sciences (Seattle, Washington) under award number UL1 TR002319, the National Center for Advancing Translational Sciences (Bethesda, Maryland), and the National Institutes of Health (Bethesda, Maryland).
Footnotes
Disclosures
The authors have no conflicts of interest to disclose.
Supplementary materials
Supplementary material associated with this article can be found in the online version at https://doi.org/10.1016/j.amjcard.2021.08.037.
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