Prospective validation and assessment of cardiovascular and offspring risk models for pregnant women with congenital heart disease.

OBJECTIVES: Adequate prepregnancy prediction of maternal cardiovascular and offspring risk is important for counselling and management of pregnancy in women with congenital heart disease (CHD). Therefore we performed a study to identify the optimal assessment strategy for estimating the risk of pregnancy in women with CHD. METHODS: In this prospective study, we determined the outcomes of 213 pregnancies in 203 women with CHD. The ZAHARA I (Zwangerschap bij Aangeboren HARtAfwijkingen I) and CARPREG (CARdiac disease in PREGnancy) risk scores were calculated for each pregnancy, as was the total number of cardiovascular (TPc) or offspring risk predictors (TPo) from these and other studies combined. Pregnancies were also classified according to the modified WHO classification of maternal cardiovascular risk and according to disease complexity (DC). RESULTS: Maternal cardiovascular events occurred during 22 pregnancies (10.3%). Offspring events occurred during 77 pregnancies in 81 children (37.3%). Cardiovascular and offspring event rates increased with higher risk scores, higher TPc or TPo, higher WHO class and greater DC. The highest area under the curve (AUC) for maternal cardiovascular risk was achieved by the WHO class (AUC: 0.77, p<0.0001). AUC for the ZAHARA I risk score was 0.71 (p=0.001), and for the CARPREG risk score 0.57 (p=0.32). All models performed insufficiently in predicting offspring events (AUC≤0.6). CONCLUSIONS: The WHO classification is the best available risk assessment model for estimating cardiovascular risk in pregnant women with CHD. None of the offspring prediction models perform adequately in our cohort.

Uteroplacental blood flow, cardiac function, and pregnancy outcome in women with congenital heart disease.

BACKGROUND: Pregnant women with congenital heart disease (CHD) are susceptible to cardiovascular, obstetric, and offspring complications. In women with CHD, cardiac dysfunction may compromise uteroplacental flow and contribute to the increased incidence of obstetric and offspring events. METHODS AND RESULTS: We performed a prospective multicenter cohort study of pregnant women with CHD and healthy pregnant women. We compared clinical, laboratory, echocardiographic, and uteroplacental Doppler flow (UDF) parameters at 20 and 32 weeks gestation, and pregnancy outcome. We related cardiovascular parameters to UDF parameters and pregnancy outcome in women with CHD. We included 209 women with CHD and 70 healthy women. Cardiovascular parameters (N-terminal pro-B-type natriuretic peptide, left and right ventricular function) differed between both groups. UDF parameters were impaired in CHD women (umbilical artery pulsatility and resistance index at 32 weeks in CHD versus healthy women, P=0.0085 and P=0.017). The following cardiovascular parameters prepregnancy and at 20 weeks gestation were associated with UDF (umbilical artery resistance index) at 32 weeks at multivariable analysis: (1) right ventricular function (tricuspid annular plane systolic excursion) (P=0.002), (2) high N-terminal pro-B-type natriuretic peptide (P=0.085), (3) systemic (P=0.001), and (4) pulmonary (P=0.045) atrioventricular valve regurgitation. Women with CHD had more obstetric (58.9% versus 32.9%, P<0.0001) and offspring events (35.4% versus 18.6%, P=0.008) than healthy women. Impaired UDF was associated with adverse obstetric and offspring outcome. CONCLUSIONS: UDF parameters are abnormal in pregnant women with CHD. Cardiovascular function is associated with an abnormal pattern of UDF. Compromised UDF may be a key factor in the high incidence of offspring and obstetric complications in this population.

Associations between cardiovascular parameters and uteroplacental Doppler (blood) flow patterns during pregnancy in women with congenital heart disease: Rationale and design of the Zwangerschap bij Aangeboren Hartafwijking (ZAHARA) II study.

BACKGROUND: Previous research has shown that women with congenital heart disease (CHD) are more susceptible to cardiovascular, obstetric, and offspring events. The causative pathophysiologic mechanisms are incompletely understood. Inadequate uteroplacental circulation is an important denominator in adverse obstetric events and offspring outcome. The relation between cardiac function and uteroplacental perfusion has not been investigated in women with CHD. Moreover, the effects of physiologic changes on pregnancy-related events are unknown. In addition, long-term effects of pregnancy on cardiac function and exercise capacity are scarce. METHODS: Zwangerschap bij Aangeboren Hartafwijking (ZAHARA) II, a prospective multicenter cohort study, investigates changes in and relations between cardiovascular parameters and uteroplacental Doppler flow patterns during pregnancy in women with CHD compared to matched healthy controls. The relation between cardiovascular parameters and uteroplacental Doppler flow patterns and the occurrence of cardiac, obstetric, and offspring events will be investigated. At 20 and 32 weeks of gestation, clinical, neurohumoral, and echocardiographic evaluation and fetal growth together with Doppler flow measurements in fetal and maternal circulation are performed. Maternal evaluation is repeated 1 year postpartum. IMPLICATIONS: By identifying the factors responsible for pregnancy-related events in women with CHD, risk stratification can be refined, which may lead to better pre-pregnancy counseling and eventually improve treatment of these women.

Pregnancy in women with corrected tetralogy of Fallot: occurrence and predictors of adverse events.

BACKGROUND: In women with corrected tetralogy of Fallot (ToF), pregnancy is associated with maternal cardiac, obstetric, and offspring complications. Our aim is to investigate the magnitude and determinants of pregnancy outcome in women with corrected ToF. METHODS: In this retrospective international multicenter study using 2 congenital heart disease registries, 204 women with corrected ToF were identified. Within this group, 74 women had 157 pregnancies, including 30 miscarriages and 4 terminations of pregnancy. Detailed information on each completed pregnancy (n = 123) was obtained using medical records and supplementary interviews. RESULTS: Cardiovascular events occurred during 10 (8.1%) pregnancies, mainly (supra)ventricular arrhythmias. Obstetric and offspring events occurred in 73 (58.9%) and 42 (33.9%) pregnancies, respectively, including offspring mortality in 8 (6.4%). The most important predictor was use of cardiac medication before pregnancy (odds ratio for cardiac events 11.7, 95% CI 2.2-62.7; odds ratio for offspring events 8.4, 95% CI 1.4-48.6). In pregnancies with cardiovascular events, significantly more small-for-gestational-age children were born (P value < .01). CONCLUSIONS: Cardiovascular, obstetric, and offspring events occur frequently during pregnancies in women with ToF. Maternal use of cardiovascular medication is associated with pregnancy outcome, and maternal cardiovascular events during pregnancy are highly associated with offspring events.

Predictors of pregnancy complications in women with congenital heart disease.

AIMS: Data regarding pregnancy outcome in women with congenital heart disease (CHD) are limited. METHODS AND RESULTS: In 1802 women with CHD, 1302 completed pregnancies were observed. Independent predictors of cardiac, obstetric, and neonatal complications were calculated using logistic regression. The most prevalent cardiac complications during pregnancy were arrhythmias (4.7%) and heart failure (1.6%). Factors independently associated with maternal cardiac complications were the presence of cyanotic heart disease (corrected/uncorrected) (P < 0.0001), the use of cardiac medication before pregnancy (P < 0.0001), and left heart obstruction (P < 0.0001). New characteristics were mechanical valve replacement (P = 0.0014), and systemic (P = 0.04) or pulmonary atrioventricular valve regurgitation related with the underlying (moderately) complex CHD (P = 0.03). A new risk score for cardiac complications is proposed. The most prevalent obstetric complications were hypertensive complications (12.2%). No correlation of maternal characteristics with adverse obstetric outcome was found. The most prevalent neonatal complications were premature birth (12%), small for gestational age (14%), and mortality (4%). Cyanotic heart disease (corrected/uncorrected) (P = 0.0003), mechanical valve replacement (P = 0.03), maternal smoking (P = 0.007), multiple gestation (P = 0.0014), and the use of cardiac medication (P = 0.0009) correlated with adverse neonatal outcome. CONCLUSION: In our tertiary CHD cohort, cardiac, obstetric, and neonatal complications were frequently encountered, and (new) correlations of maternal baseline data with adverse outcome are reported. A new risk score for adverse cardiac complications is proposed, although prospective validation remains necessary.

Menstrual cycle and its disorders in women with congenital heart disease.

OBJECTIVES: To investigate the age at menarche, the prevalence of menstrual cycle (interval) disorders, and determinants in women with congenital heart disease (CHD). DESIGN: Using two CHD registries, 1802 (82%) of the 2196 women with CHD contacted (aged 18-58 years) provided written informed consent. After exclusion of patients with genetic disorders known to be associated with menstrual cycle disorders, 1593 eligible patients remained. Interviews by telephone and reviews of medical records were conducted. RESULTS: Overall, the age at menarche was slightly increased in women with CHD (13.3 vs. 13.1 years in the general population), mainly attributable to an increased prevalence of primary amenorrhea (n = 147; 9.2%). Other menstrual cycle disorders were documented: secondary amenorrhea (n = 181, 11.4%), polymenorrhea (n = 103, 6.5%), oligomenorrhea (n = 90, 5.6%), and menorrhagia (n = 117, 6.5%). The occurrence of these disorders also depended on the presence of cyanotic heart disease, surgical status, the number of surgical interventions, and the severity of CHD. DISCUSSION: Menstrual cycle disturbances, in particular primary amenorrhea, were frequently observed in this population. Patients with complex (cyanotic) heart disease needing repeated surgical interventions prior to menarche are especially at risk.

Fertility, pregnancy and delivery in women after biventricular repair for double outlet right ventricle.

OBJECTIVES: To investigate outcome of pregnancy and fertility in women with double outlet right ventricle (DORV). METHODS: Using 2 congenital heart disease registries, 21 female patients with DORV (aged 18-39 years) were retrospectively identified. Detailed recordings of each patient and their completed (>20 weeks gestation) pregnancies were recorded. RESULTS: Overall, 10 patients had 19 pregnancies, including 3 spontaneous miscarriages (16%). During the 16 live birth pregnancies, primarily (serious) noncardiac complications were observed, e.g. premature labor/delivery (n = 7 and n = 3, respectively), small for gestational age (n = 4), preeclampsia (n = 2) and recurrence of congenital heart disease (n = 2). Except for postpartum endocarditis and deterioration of subpulmonary obstruction, only mild cardiac complication pregnancies were recorded. Two women with children reported secondary female infertility. Several menstrual cycle disorders were reported: secondary amenorrhea (n = 4), primary amenorrhea (n = 3) and oligomenorrhea (n = 2). CONCLUSION: Successful pregnancy in women with DORV is possible. Primarily noncardiac complications were observed and only few (minor) cardiac complications. Infertility and menstrual cycle disorders appear to be more prevalent.

Severe pregnancy-induced deterioration of truncal valve regurgitation in an adolescent patient with repaired truncus arteriosus.

Truncus arteriosus, a rare and complex congenital heart disease, is hallmarked by a single great vessel (truncus) that arises over a large ventricular septal defect and provides both the pulmonary and systemic circulation. Pregnancy reports after repair for truncus arteriosus are scarce. Therefore, the maternal and offspring outcomes are unknown. We report the outcome of a pregnancy in an 18-year-old woman with repaired truncus arteriosus. Despite severe and symptomatic deterioration of truncal valve regurgitation, she successfully delivered a healthy child, and the valve function recovered within 2 weeks postpartum.

Smoking and its effects on mortality in adults with congenital heart disease.

AIMS: To describe smoking habits in adults with congenital heart disease (ACHD) and to assess the relationship between smoking exposure and cardiovascular mortality. METHODS: Data on smoking history and cardiovascular mortality were extracted from the Euro Heart Survey on adult congenital heart disease - a retrospective cohort study, that included patients diagnosed with 1 of 8 subgroups of ACHD (Atrial Septal Defects, Ventricular Septal Defects, Marfan Syndrome, Aortic Coarctation, Tetralogy of Fallot (ToF), Transposition of the Great Arteries (TGA), Fontan circulation, and Cyanotic disease). RESULTS: Complete data of 3375 ACHD patients (median age 28 years) were available for analysis. At inclusion, 9.3% (n=314) were current smokers and 4.2% (n=142) of the patients had smoked in the past. During a median follow-up of 5.1 years, 101 patients (3%) died. In the majority of cases the cause of death was cardiovascular (n=81; 80%). Kaplan-Meier and Cox survival analysis for each of the defects separately showed a significantly increased age and sex-adjusted cardiovascular mortality associated with smoking exposure in TGA patients (Hazard ratio 4.2 (95% CI 1.0-16.8); P=0.044). Also in ToF mortality was higher amongst smokers, though not significantly (HR 3.4 (95% CI 0.6-18.5); P=0.15). In the remaining defects no relationship between smoking and cardiovascular mortality was observed. CONCLUSION: The prevalence of smoking amongst ACHD patients is relatively low. Smoking exposure is associated with increased cardiovascular mortality in patients with TGA. Prospective long-term follow-up studies are necessary.

Risk of complications during pregnancy in women with congenital aortic stenosis.

BACKGROUND: Pregnancy in women with congenital aortic stenosis (AS) is associated with increased cardiac complications. Data on non-cardiac complications are limited, and this information is crucial for prenatal counselling and perinatal care. The aim of this study was to present the maternal and perinatal outcome of pregnancy in women with congenital AS. METHODS: By review of the Dutch CONCOR national registry and a local Belgian tertiary care centre database, 35 women with congenital AS with a history of completed pregnancy before aortic valve replacement were enrolled in this study. Medical history and maternal and perinatal outcome were determined. RESULTS: Thirty-five women had 58 pregnancies resulting in 53 successful pregnancies, three miscarriages, and two abortions. The most serious cardiac complications were heart failure (n=2, 3.8%) and atrial arrhythmia (n=3, 5.7%). Although cardiac complications were present (9.4%), obstetric (22.6%) and perinatal (24.5%) complications were observed more often. A total of six pregnancies (11.3%) were complicated by hypertension-related disorders, including one case of eclampsia. Furthermore, 7 premature births (13.2%) and 7 small-for-gestational-age births (13.2%) were encountered. Pregnancy in women with severe AS was characterized by an increased incidence of heart failure and premature labour, and shorter pregnancy duration. Older women (>30 years) were at increased risk of perinatal events (odds ratio 4.38, 95% confidence interval 1.02 to 18.81). CONCLUSIONS: Pregnancy is generally well tolerated in women with congenital AS. Importantly, an excess of obstetric and perinatal complications was found, requiring more meticulous attention.

Outcome of pregnancy in women after pulmonary autograft valve replacement for congenital aortic valve disease.

BACKGROUND AND AIM OF THE STUDY: The pulmonary autograft has been recommended as the valve of choice for aortic valve replacement (AVR) in young women contemplating pregnancy. However, current information on maternal and perinatal outcome of pregnancy in women with pulmonary autograft valve replacement is limited. METHODS: Using a nationwide Dutch registry (CONCOR) and a local Belgian tertiary care center database, 17 women (age range: 18 to 45 years) with pulmonary autograft valve replacement were enrolled into the study. Twelve pregnancies were observed among five different women, including one miscarriage and one elective abortion. RESULTS: Clinically significant (non-)cardiac complications were documented in two of 10 completed pregnancies. Complications included: (i) placental abruption necessitating Cesarean delivery at 29 weeks' gestation, further complicated by postpartum hemorrhage; and (ii) preterm premature rupture of the membranes resulting in premature delivery at 29 weeks' gestation with postpartum demise of the immature born child. Two women reported primary female infertility, but both became pregnant after hormonal substitution therapy. Four women reported irregularities of their natural menstrual cycle (menorrhagia, dysmenorrhea, polymenorrhea, oligomenorrhea, or amenorrhea). CONCLUSION: Successful pregnancy in women with pulmonary autograft valve replacement is possible, although serious and clinically significant events occurred during gestation. Infertility and menstrual cycle disorders appear to be more prevalent.

Outcome of pregnancy in women with congenital heart disease: a literature review.

A search of peer-reviewed literature was conducted to identify reports that provide data on complications associated with pregnancy in women with structural congenital heart disease (CHD). This review describes the outcome of 2,491 pregnancies, including 377 miscarriages (15%) and 114 elective abortions (5%). Important cardiac complications were seen in 11% of the pregnancies. Obstetric complications do not appear to be more prevalent. In complex CHD, premature delivery rates are high, and more children are small for gestational age. The offspring mortality was high throughout the spectrum and was related to the relatively high rate of premature delivery and recurrence of CHD.

Outcome of implantable cardioverter defibrillators in adults with congenital heart disease: a multi-centre study.

AIMS: To investigate outcome and complications of implantable cardioverter defibrillators (ICDs) in adults with congenital heart disease (CHD) and to identify predictors of (in-) appropriate shocks. METHODS AND RESULTS: Sixty-four CHD patients >/= 18 years at first ICD implantation [63% tetralogy of Fallot (TOF) and age at implantation 37 +/- 13 years] were identified using the Dutch adult CHD registry and a Belgian tertiary care centre database. Median follow-up duration was 3.7 years. Early complications included pocket haematoma (n = 3), lead failure (n = 2), and pneumothorax (n = 2). Late complications occurred in 11 (17%) patients, including lead failure (n = 6) and and electrical storm (n = 3). Overall, 30 device-related re-interventions were performed in 20 patients (31%), including four premature generator changes and seven lead replacements. Half of the patients received one or more shocks, and 46 shocks in 15 patients (23%) were classified as appropriate. One hundred and sixty shocks in 26 patients (41%) were classified as inappropriate. No predictors of (in-)appropriate shocks were identified, except TOF being associated with less appropriate shocks than patients with other CHD (HR 0.29, P = 0.02). CONCLUSION: The ICD provided effective therapy in a quarter of adults with CHD with low complication rates. The incidence of inappropriate shocks, however, appeared to be excessive and warrants further attention.

Three live-birth pregnancies in a woman with Williams syndrome.

OBJECTIVE: Maternal Williams syndrome with their associated (cardiac) malformations is rarely encountered during pregnancy. METHODS: We report on a patient with Williams syndrome who has had 3 live-birth pregnancies. RESULTS: Several noncardiac, mainly fetal, complications need to be anticipated: premature labor, intrauterine growth restriction with subsequent small-for-gestational-age offspring, and recurrence of congenital heart disease or similar syndromes. CONCLUSION: The present case report illustrates that multiple live-birth pregnancies are possible in women with Williams syndrome, and it advocates the need for regular multidisciplinary assessments prior to and during pregnancy.

Fertility, pregnancy, and delivery after biventricular repair for pulmonary atresia with an intact ventricular septum.

The objective of the present study to investigate fertility, pregnancy, and delivery in women with biventricular repair for pulmonary atresia with an intact ventricular septum (PAIVS). Using a nationwide registry (CONCOR), 37 patients with pulmonary atresia were identified, 6 of whom (aged 21 to 34 years) had biventricular repair for PAIVS. Three PAIVS patients had a total of 5 pregnancies, including 1 abortion and 1 ectopic pregnancy. Besides minor noncardiac complications, the 3 live-birth pregnancies were successful. None of the women reported infertility or irregularities (hypermenorrhea, dysmenorrhea, polymenorrhoea, oligomenorrhea, or amenorrhea) of their natural menstrual cycle. In conclusion, successful pregnancy in women with biventricular repair for PAIVS is possible, and only minor complications were observed. Infertility and menstrual cycle disorders do not appear to be more prevalent than usual.

Pregnancy after biventricular repair for pulmonary atresia with ventricular septal defect.

Information on pregnancy and delivery in women with biventricular repair for isolated noncomplex pulmonary atresia with a ventricular septal defect (PAVSD) is limited. Using a nationwide congenital heart disease registry (CONgenital CORvitia [CONCOR]), 9 women with biventricular repair for PAVSD (aged 21 to 38 years) were identified. Ten pregnancies were observed in 5 different women with PAVSD, including 3 spontaneous miscarriages. Clinically significant (non)cardiac complications were documented in 3 of 7 completed pregnancies. These complications were: (1) atrioventricular reentry tachycardia with symptomatic right-sided heart failure; (2) eclampsia with hemolysis, elevated liver enzymes, and low platelets syndrome further complicated by abruptio placentae leading to premature delivery of a small-for-gestational-age child; and (3) premature delivery due to cervical insufficiency with antepartum demise of an immature child. Furthermore, none of the women reported infertility. Moreover, none of the women reported irregularities of their natural menstrual cycle (age at menarche 13 years; cycle duration 28 days), with the exception of delayed menarche (>16 years) in 2 patients. In conclusion, successful pregnancy in patients with biventricular repair of PAVSD is possible, although often complicated by serious clinically significant events. Infertility and menstrual cycle disorders do not appear to be more prevalent, except for a high incidence of primary amenorrhea.

Obstetric complications in Marfan syndrome.

OBJECTIVE: To investigate the obstetric maternal and neonatal outcome of pregnancy in women with Marfan syndrome. METHODS: Retrospective observational multi-center study based on congenital heart disease registry. RESULTS: Sixty-three of the 122 enrolled women with Marfan syndrome had been pregnant 142 times (including 111 pregnancies>20 weeks, 28 (20%) miscarriages and 3 elective abortions). In 40% of all completed pregnancies an obstetric and/ or neonatal complication occurred. The most important complications were an increased percentage of premature deliveries (n=17, 15%) mainly due to preterm premature rupture of membranes and cervical incompetence and a markedly increased combined fetal and neonatal mortality of 7.1%. An obstetric and/or neonatal complication occurred in a similar proportion of pregnancies in women with a diagnosis of Marfan syndrome before pregnancy versus women with a diagnosis of Marfan syndrome after pregnancy (39% vs. 41%, p=0.85, respectively). CONCLUSION: In addition to cardiovascular complications, pregnancy in women with Marfan syndrome is associated with a high rate of premature deliveries, preterm premature rupture of membranes and increased mortality in the offspring.

Cardiac complications relating to pregnancy and recurrence of disease in the offspring of women with atrioventricular septal defects.

AIMS: In most pregnancy reports, atrioventricular septal defects (AVSD) are not differentiated from more simple septal defects, thus underestimating the risks of pregnancy. To investigate the magnitude and determinants of risk during pregnancy in female patients with balanced AVSD. METHODS AND RESULTS: Using a nation-wide registry (CONCOR), 79 female patients with balanced/isolated AVSD were identified. A total of 29 patients had 62 pregnancies, including 12 miscarriages (19%) and two elective abortions. Detailed recordings of each completed (>20 weeks gestation) pregnancy (n=48, 26 women) were obtained. Cardiovascular events complicated almost 40% of the completed pregnancies. In particular, post-partum persistence of pregnancy-related New York Heart Association (NYHA) class deterioration [23% mainly patients with residual atrial septal defects (ASD)] and deterioration of pre-existing left AV-valvular regurgitation (17%) were frequently recorded. Additional cardiac complications were arrhythmias (19%) and symptomatic heart failure (2%). Congenital heart disease (CHD) recurred in six children (12%): AVSD (n=4, three with left-sided hypoplasia), patent ductus arteriosus (n=1), and ASD (n=1). Three children died including two children with left-sided hypoplasia. CONCLUSION: Pregnancy is not always well tolerated in women with AVSD, predominantly due to NYHA class deterioration and worsening of pre-existing AV-valvular regurgitation. Offspring mortality is high (6.3%), primarily due to recurrence of complex CHD.

Risk of complications during pregnancy after Senning or Mustard (atrial) repair of complete transposition of the great arteries.

AIMS: To investigate magnitude and determinants of risks during pregnancy in women with Mustard or Senning repair for complete transposition of the great arteries (TGA). METHODS AND RESULTS: Using a nationwide registry (CONCOR), 70 women with Senning (23%) or Mustard (77%) repair for TGA were enrolled. A total of 28 patients had 69 pregnancies (two twins), including 17 spontaneous miscarriages and three elective abortions. During 39 of the 49 completed pregnancies, complications were observed. The most important cardiac complication was clinically significant arrhythmia (n=11, 22%), especially occurring in patients with a prior history of arrhythmia. Important general pregnancy complications were preeclampsia (n=5, 10.2%) and pregnancy-induced hypertension (n=4, 8.2%). Obstetric complications included premature rupture of membranes (n=7, 14.3%), premature labour (n=12, 24.4%), premature delivery (n=16, 31.4%), and thrombo-embolic complications (n=2, 4.1%). Mean (singleton) pregnancy duration was 36+/-5 weeks. Eleven of the 51 children (21.6%) were small for gestational age. Foetal and neonatal mortality combined was 11.8% (n=6). No recurrence of congenital heart disease in the offspring was documented. CONCLUSION: In this largest report on pregnancy in women with atrial-corrected TGA to date, a high incidence of obstetric complications and mortality in the offspring was observed.