ACE Inhibitor and Angiotensin Receptor Blocker Use During Pregnancy: Data from the ESC Registry Of Pregnancy and Cardiac Disease (ROPAC).

Angiotensin-converting enzyme inhibitors (ACE-Is) and angiotensin receptor blockers (ARBs) are not recommended during the second and third trimester because of the significant risk of congenital anomalies associated with their use. However, data are scarce, especially regarding their use in the first trimester and about the impact of stopping just before pregnancy. Our study illustrates the profile of the women who used ACE-Is or ARBs during pregnancy and evaluates the impact on perinatal outcomes. The Registry of Pregnancy and Cardiac Disease is a prospective, global registry of pregnancies in women with structural heart disease. Outcomes were compared between women who used ACE-Is or ARBs and those who did not. Multivariable regression analysis was performed to assess the effect of ACE-I or ARB use on the occurrence of congenital anomalies. ACE-Is (n = 35) and/or ARBs (n = 8) were used in 42 (0.7%) of the 5,739 Registry of Pregnancy and Cardiac Disease pregnancies. Women who used ACE-Is or ARBs more often came from a low-or-middle-income country (57% vs 40%, p = 0.021), had chronic hypertension (31% vs 6%, p <0.001), or a left ventricular ejection fraction <40% (33% vs 4%, p <0.001). In the multivariable analysis, ACE-I use during the first trimester was associated with an increased risk of congenital anomaly (odds ratio 3.2, 95% confidence interval 1.0 to 9.6). Therefore, ACE-Is should be avoided during pregnancy, also in the first trimester, because of a higher risk of congenital anomalies. However, there is no need to stop long before pregnancy. Preconception counseling is crucial to discuss the potential risks of these medications, to evaluate the clinical condition and, if possible, to change or stop the medication.

Diuretics in pregnancy: Data from the ESC Registry of Pregnancy and Cardiac disease (ROPAC).

AIMS: Data on diuretic use in pregnancy are limited and inconsistent, and consequently it remains unclear whether they can be used safely. Our study aims to evaluate the perinatal outcomes after in-utero diuretic exposure. METHODS AND RESULTS: The Registry Of Pregnancy And Cardiac disease (ROPAC) is a prospective, global registry of pregnancies in women with heart disease. Outcomes were compared between women who used diuretics during pregnancy versus those who did not. Multivariable regression analysis was used to assess the impact of diuretic use on the occurrence of congenital anomalies and foetal growth. Diuretics were used in 382 (6.7%) of the 5739 ROPAC pregnancies, most often furosemide (86%). Age >35 years (odds ratio [OR] 1.5, 95% confidence interval [CI] 1.2-2.0), other cardiac medication use (OR 5.4, 95% CI 4.2-6.9), signs of heart failure (OR 1.7, 95% CI 1.2-2.2), estimated left ventricular ejection fraction <40% (OR 2.9, 95% CI 2.0-4.2), New York Heart Association class >II (OR 3.4, 95% CI 2.3-5.1), valvular heart disease (OR 6.3, 95% CI 4.7-8.3) and cardiomyopathy (OR 3.9, 95% CI 2.6-5.7) were associated with diuretic use during pregnancy. In multivariable analysis, diuretic use during the first trimester was not significantly associated with foetal or neonatal congenital anomalies (OR 1.3, 95% CI 0.7-2.6), and diuretic use during pregnancy was also not significantly associated with small for gestational age (OR 1.4, 95% CI 1.0-1.9). CONCLUSIONS: Our study does not conclusively establish an association between diuretic use during pregnancy and adverse foetal outcomes. Given these findings, it is essential to assess the risk-benefit ratio on an individual basis to guide clinical decisions.

Perinatal outcomes after in-utero exposure to beta-blockers in women with heart disease: Data from the ESC EORP registry of pregnancy and cardiac disease (ROPAC).

BACKGROUND: Beta-blockers are commonly used drugs during pregnancy, especially in women with heart disease, and are regarded as relatively safe although evidence is sparse. Differences between beta-blockers are not well-studied. METHODS: In the Registry of Pregnancy And Cardiac disease (ROPAC, n = 5739), a prospective global registry of pregnancies in women with structural heart disease, perinatal outcomes (small for gestational age (SGA), birth weight, neonatal congenital heart disease (nCHD) and perinatal mortality) were compared between women with and without beta-blocker exposure, and between different beta-blockers. Multivariable regression analysis was used for the effect of beta-blockers on birth weight, SGA and nCHD (after adjustment for maternal and perinatal confounders). RESULTS: Beta-blockers were used in 875 (15.2%) ROPAC pregnancies, with metoprolol (n = 323, 37%) and bisoprolol (n = 261, 30%) being the most frequent. Women with beta-blocker exposure had more SGA infants (15.3% vs 9.3%, p < 0.001) and nCHD (4.7% vs 2.7%, p = 0.001). Perinatal mortality rates were not different (1.4% vs 1.9%, p = 0.272). The adjusted mean difference in birth weight was -177 g (-5.8%), the adjusted OR for SGA was 1.7 (95% CI 1.3-2.1) and for nCHD 2.3 (1.6-3.5). With metoprolol as reference, labetalol (0.2, 0.1-0.4) was the least likely to cause SGA, and atenolol (2.3, 1.1-4.9) the most. CONCLUSIONS: In women with heart disease an association was found between maternal beta-blocker use and perinatal outcomes. Labetalol seems to be associated with the lowest risk of developing SGA, while atenolol should be avoided.

Pregnancy outcomes in women with Ebstein's anomaly: data from the Registry of Pregnancy And Cardiac disease (ROPAC).

OBJECTIVE: Ebstein's anomaly is a rare congenital cardiac condition and data regarding pregnancy outcomes in this patient group are scarce. We evaluated the maternal and perinatal risks of pregnancy in 81 women with Ebstein's anomaly. METHODS: The Registry of Pregnancy and Cardiac disease is a prospective global registry of pregnancies in women with structural cardiac disease. Pregnancy outcomes in women with Ebstein's anomaly were examined. The primary outcome was the occurrence of a major adverse cardiac event (MACE) defined as maternal mortality, heart failure, arrhythmia, thromboembolic event or endocarditis. Secondary endpoints were obstetric and perinatal outcomes and the influence of pregnancy on tricuspid valve regurgitation as well as right atrial and ventricular dimensions. RESULTS: In the 81 women with Ebstein's anomaly (mean age 29.7±6.1 years, 46.9% nulliparous), MACE occurred in 8 (9.9%) pregnancies, mostly heart failure (n=6). There were no maternal deaths. Prepregnancy signs of heart failure were predictive for MACE. Almost half of the women were delivered by caesarean section (45.7%) and preterm delivery occurred in 24.7%. Neonatal mortality was 2.5% and 4.9% of the infants had congenital heart disease. In the subgroup in which prepregnancy and postpregnancy data were available, there was no difference in tricuspid valve regurgitation grade or right atrial and ventricular dimensions before and after pregnancy. CONCLUSIONS: Most women with Ebstein's anomaly tolerate pregnancy well, but women with prepregnancy signs of heart failure are at higher risk for MACE during pregnancy and should be counselled accordingly.

Long-term quality of life after obstetric intensive care unit admission: A cross-sectional cohort study.

OBJECTIVE: To assess the long-term quality of life (QoL) after obstetric Intensive Care Unit (ICU) admission. DESIGN: Cross-sectional survey study. SETTING: Tertiary care centre. POPULATION: Women admitted to the level 3 ICU during pregnancy or ≤6 weeks postpartum, between 2000 and 2015. METHODS: Quality of life measures were compared with the population reference values. Associations with baseline ICU parameters were assessed with multivariable linear regression. Patient-reported outcome and experience measures (PROMs/PREMs) were described. MAIN OUTCOME MEASURES: Quality of life according to the Linear Analogous Scale (LAS), the Satisfaction with Life Scale (SWLS) and the SF-36 questionnaire; PROMs/PREMs using the Pregnancy and Childbirth outcome set of the International Consortium for Health Outcomes Measurement. RESULTS: Of all 265 obstetric ICU admissions, 230 were eligible and 94 (41%) were included (median follow-up time 14 years). The LAS (75.7 versus 78.7, p = 0.077) and SWLS (25.2 versus 26, p = 0.176) sum scores were not different from the population reference values. The SF-36 subdomains bodily pain (55.3 versus 73.9), general health (58.2 versus 73.9) and vitality (56.9 versus 69.1) were lower than the reference values (all p < 0.001). PROMs/PREMs were low in 46.2% for pain, 15.1% for depression, 11.8% for satisfaction with care and 52.7% for healthcare responsiveness. An indirect obstetric ICU admission diagnosis was independently associated with a reduced physical health score (B -1.7, 95% confidence interval [CI] -3.4 to -0.1) and severe neonatal morbidity with a reduced mental health score (B -6.6, 95% CI -11.3 to -1.8). CONCLUSION: Obstetric ICU admission is associated with reductions in long-term physical health QoL and in some patients with mental health QoL. We suggest multidisciplinary rehabilitation and long-term psychosocial support.

Hypertensive disorders of pregnant women with heart disease: the ESC EORP ROPAC Registry.

AIMS: Hypertensive disorders of pregnancy (HDP) occur in 10% of pregnancies in the general population, pre-eclampsia specifically in 3-5%. Hypertensive disorders of pregnancy may have a high prevalence in, and be poorly tolerated by, women with heart disease. METHODS AND RESULTS: The prevalence and outcomes of HDP (chronic hypertension, gestational hypertension or pre-eclampsia) were assessed in the ESC EORP ROPAC (n = 5739), a worldwide prospective registry of pregnancies in women with heart disease.The overall prevalence of HDP was 10.3%, made up of chronic hypertension (5.9%), gestational hypertension (1.3%), and pre-eclampsia (3%), with significant differences between the types of underlying heart disease (P < 0.05). Pre-eclampsia rates were highest in women with pulmonary arterial hypertension (PAH) (11.1%), cardiomyopathy (CMP) (7.1%), and ischaemic heart disease (IHD) (6.3%). Maternal mortality was 1.4 and 0.6% in women with vs. without HDP (P = 0.04), and even 3.5% in those with pre-eclampsia. All pre-eclampsia-related deaths were post-partum and 50% were due to heart failure. Heart failure occurred in 18.5 vs. 10.6% of women with vs. without HDP (P < 0.001) and in 29.1% of those with pre-eclampsia. Perinatal mortality was 3.1 vs. 1.7% in women with vs. without HDP (P = 0.019) and 4.7% in those with pre-eclampsia. CONCLUSION: Hypertensive disorders of pregnancy and pre-eclampsia rates were higher in women with CMP, IHD, and PAH than in the general population. Adverse outcomes were increased in women with HDP, and maternal mortality was strikingly high in women with pre-eclampsia. The combination of HDP and heart disease should prompt close surveillance in a multidisciplinary context and the diagnosis of pre-eclampsia requires hospital admission and continued monitoring during the post-partum period.

Supraventricular arrhythmia in pregnancy.

The physiological changes during pregnancy predispose a woman for the development of new-onset or recurrent arrhythmia. Supraventricular arrhythmia is the most common form of arrhythmia during pregnancy and, although often benign in nature, can be concerning. We describe three complex cases of supraventricular arrhythmia during pregnancy and review the currently available literature on the subject. In pregnancies complicated by arrhythmia, a plan for follow-up and both maternal and fetal monitoring during pregnancy, delivery and post partum should be made in a multidisciplinary team. Diagnostic modalities should be used as in non-pregnant women if there is an indication. All antiarrhythmic drugs cross the placenta, but when necessary, medical treatment should be used with consideration to the fetus and the mother's altered pharmacodynamics and kinetics. Electrical cardioversion is safe during pregnancy, and electrophysiological study and catheter ablation can be performed in selected patients, preferably with zero-fluoroscopy technique. Sometimes, delivering the fetus (if viable) is the best therapeutic option. In this review, we provide a framework for the workup and clinical management of supraventricular arrhythmias in pregnant women, including cardiac, obstetric and neonatal perspectives.

Women of reproductive age in a tertiary intensive care unit: indications, outcome and the impact of pregnancy-a retrospective cohort study.

BACKGROUND: To evaluate the indications for admission and mortality rates of women of reproductive age admitted to a tertiary Intensive Care Unit (ICU) and to compare the outcomes of obstetric and non-obstetric admissions. METHODS: A retrospective cohort study was performed, including all women aged 17-41 years admitted to a level 3 ICU in the Netherlands, between January 1, 2000 and January 1, 2016. Primary outcome was indication for admission and mortality. Mortality, length of stay (LOS), need for mechanical ventilation and APACHE II score were compared between obstetric and non-obstetric admissions. The obstetric group was further analyzed for maternal and perinatal outcomes. RESULTS: 3461 women (median age 32 years) were included, with an overall mortality rate of 13.3%. The obstetric group consisted of 265 women (7.7%). The non-obstetric group (n = 3196) was admitted most often for cardiovascular disease (19.6%), followed by oncologic disease (15%). Mortality was the highest in women with oncologic disease (23.9%). The obstetric group had lower mortality compared to the non-obstetric group (4.9% vs. 14%, p < 0.001), despite higher APACHE II score (14 vs. 11, p < 0.001) and a higher ventilation rate (47.9% vs. 39%, p = 0.004). Major surgical or endovascular interventions, besides caesarean section, were performed in 46% of the obstetric group. Perinatal death occurred in 17.2% and of the surviving infants, 63.2% were born preterm and 45.1% required Neonatal Intensive Care Unit admission. CONCLUSIONS: Cardiovascular disease is the most important indication for admission and oncologic disease is associated with highest mortality in women of reproductive age. Obstetric patients constitute a small percentage of all ICU admissions in a tertiary ICU center. They have lower mortality rates than non-obstetric young female patients, despite a more severe initial presentation. Nevertheless lasting maternal morbidity and perinatal mortality and morbidity is frequent.

Pregnancy Outcomes in Women After Arterial Switch Operation for Transposition of the Great Arteries: Results From ROPAC (Registry of Pregnancy and Cardiac Disease) of the European Society of Cardiology EURObservational Research Programme.

Background In the past 3 decades, the arterial switch procedure has replaced the atrial switch procedure as treatment of choice for transposition of the great arteries. Although survival is superior after the arterial switch procedure, data on pregnancy outcomes are scarce and transposition of the great arteries after arterial switch is not yet included in the modified World Health Organization classification of maternal cardiovascular risk. Methods and Results The ROPAC (Registry of Pregnancy and Cardiac disease) is an international prospective registry of pregnant women with cardiac disease, part of the European Society of Cardiology EURObservational Research Programme. Pregnancy outcomes in all women after an arterial switch procedure for transposition of the great arteries are described. The primary end point was a major adverse cardiovascular event, defined as combined end point of maternal death, supraventricular or ventricular arrhythmias requiring treatment, heart failure, aortic dissection, endocarditis, ischemic coronary events, and thromboembolic events. Altogether, 41 pregnant women (mean age, 26.7±3.9 years) were included, and there was no maternal mortality. A major adverse cardiovascular event occurred in 2 women (4.9%): heart failure in one (2.4%) and ventricular tachycardia in another (2.4%). One woman experienced fetal loss, whereas no neonatal mortality was observed. Conclusions Women after an arterial switch procedure for transposition of the great arteries tolerate pregnancy well, with a favorable maternal and fetal outcome. During counseling, most women should be reassured that the risk of pregnancy is low. Classification as modified World Health Organization risk class II seems appropriate.

Pregnancy outcomes in women with aortic coarctation.

OBJECTIVE: Pregnancy in women with aortic coarctation (CoA) has an estimated moderately increased risk (mWHO II-III) of adverse cardiovascular, obstetric or fetal events, but prospective data to validate this risk classification are scarce. We examined pregnancy outcomes and identified associations with adverse outcomes. METHODS: Pregnancies in women with CoA were selected from the worldwide prospective Registry of Pregnancy and Cardiac Disease (ROPAC, n=303 out of 5739), part of the European Society of Cardiology EURObservational Research Programme. The frequency of and associations with major adverse cardiac events (MACE) and hypertensive disorders (pregnancy-induced hypertension, (pre-)eclampsia or haemolysis, elevated liver enzymes and low platelets syndrome) were analysed. RESULTS: Of 303 pregnancies (mean age 30 years, pregnancy duration 39 weeks), 9.6% involved unrepaired CoA and 27.1% were in women with pre-existing hypertension. No maternal deaths or aortic dissections occurred. MACE occurred in 13 pregnancies (4.3%), of which 10 cases were of heart failure (3.3%). Univariable associations with MACE included prepregnancy clinical signs of heart failure (OR 31.8, 95% CI 6.8 to 147.7), left ventricular ejection fraction <40% (OR 10.4, 95% CI 1.8 to 59.5), New York Heart Association class >1 (OR 11.4, 95% CI 3.6 to 36.3) and cardiac medication use (OR 4.9, 95% CI 1.3 to 18.3). Hypertensive disorders of pregnancy occurred in 16 (5.3%), cardiac medication use being their only predictor (OR 3.2, 95% CI 1.1 to 9.6). Premature births were 9.1%, caesarean section was performed in 49.7% of pregnancies. Of 4 neonatal deaths, 3 were after spontaneous extreme preterm birth. CONCLUSIONS: The ROPAC data show low MACE and hypertensive disorder rates during pregnancy in women with CoA, suggesting pregnancy to be more safe and better tolerated than previously appreciated.

Pregnancy and cardiovascular disease.

Cardiovascular disease complicates 1-4% of pregnancies - with a higher prevalence when including hypertensive disorders - and is the leading cause of maternal death. In women with known cardiovascular pathology, such as congenital heart disease, timely counselling is possible and the outcome is fairly good. By contrast, maternal mortality is high in women with acquired heart disease that presents during pregnancy (such as acute coronary syndrome or aortic dissection). Worryingly, the prevalence of acquired cardiovascular disease during pregnancy is rising as older maternal age, obesity, diabetes mellitus and hypertension become more common in the pregnant population. Management of cardiovascular disease in pregnancy is challenging owing to the unique maternal physiology, characterized by profound changes to multiple organ systems. The presence of the fetus compounds the situation because both the cardiometabolic disease and its management might adversely affect the fetus. Equally, avoiding essential treatment because of potential fetal harm risks a poor outcome for both mother and child. In this Review, we examine how the physiological adaptations during pregnancy can provoke cardiometabolic complications or exacerbate existing cardiometabolic disease and, conversely, how cardiometabolic disease can compromise the adaptations to pregnancy and their intended purpose: the development and growth of the fetus.

An Exceptional Vulvar Tumor: Myeloid Sarcoma of the Labia Majora.

Vulvar malignancies are rare and have diverse origins and presentations. The majority of these tumors are squamous cell carcinoma. An ulcerating vulvar tumor was found in a 74-yr-old woman presenting with fatigue and leukocytosis. Tumor biopsy revealed infiltration of blastoid cells from myeloid origin. Through bone marrow aspiration chronic myelomonocytic leukemia was diagnosed, of which the vulvar tumor was a rare extramedullary disease manifestation termed myeloid sarcoma. Limited palliative treatment was instated with a focus on the patient's quality of life. Myeloid sarcoma (chloroma; granulocytic sarcoma) is a mass of myeloblasts occurring in cases of myeloid disease. Manifestations in most organ systems have been described. Presentation in gynecologic areas is reported in a few case reports, to which we now add our experience.