Iris M. van Hagen

Pregnancy in Women With a Mechanical Heart Valve Data of the European Society of Cardiology Registry of Pregnancy and Cardiac Disease (ROPAC)

Background— Pregnant women with a mechanical heart valve (MHV) are at a heightened risk of a thrombotic event, and their absolute need for adequate anticoagulation puts them at considerable risk of bleeding and, with some anticoagulants, fetotoxicity. Methods and Results— Within the prospective, observational, contemporary, worldwide Registry of Pregnancy and Cardiac disease (ROPAC), we describe the pregnancy outcome of 212 patients with an MHV. We compare them with 134 patients with a tissue heart valve and 2620 other patients without a prosthetic valve. Maternal mortality occurred in 1.4% of the patients with an MHV, in 1.5% of patients with a tissue heart valve (P=1.000), and in 0.2% of patients without a prosthetic valve (P=0.025). Mechanical valve thrombosis complicated pregnancy in 10 patients with an MHV (4.7%). In 5 of these patients, the valve thrombosis occurred in the first trimester, and all 5 patients had been switched to some form of heparin. Hemorrhagic events occurred in 23.1% of patients with an MHV, in 5.1% of patients with a tissue heart valve (P<0.001), and in 4.9% of patients without a prosthetic valve (P<0.001). Only 58% of the patients with an MHV had a pregnancy free of serious adverse events compared with 79% of patients with a tissue heart valve (P<0.001) and 78% of patients without a prosthetic valve (P<0.001). Vitamin K antagonist use in the first trimester compared with heparin was associated with a higher rate of miscarriage (28.6% versus 9.2%; P<0.001) and late fetal death (7.1% versus 0.7%; P=0.016). Conclusions— Women with an MHV have only a 58% chance of experiencing an uncomplicated pregnancy with a live birth. The markedly increased mortality and morbidity warrant extensive prepregnancy counseling and centralization of care.Background— Pregnant women with a mechanical heart valve (MHV) are at a heightened risk of a thrombotic event, and their absolute need for adequate anticoagulation puts them at considerable risk of bleeding and, with some anticoagulants, fetotoxicity. Methods and Results— Within the prospective, observational, contemporary, worldwide Registry of Pregnancy and Cardiac disease (ROPAC), we describe the pregnancy outcome of 212 patients with an MHV. We compare them with 134 patients with a tissue heart valve and 2620 other patients without a prosthetic valve. Maternal mortality occurred in 1.4% of the patients with an MHV, in 1.5% of patients with a tissue heart valve ( P =1.000), and in 0.2% of patients without a prosthetic valve ( P =0.025). Mechanical valve thrombosis complicated pregnancy in 10 patients with an MHV (4.7%). In 5 of these patients, the valve thrombosis occurred in the first trimester, and all 5 patients had been switched to some form of heparin. Hemorrhagic events occurred in 23.1% of patients with an MHV, in 5.1% of patients with a tissue heart valve ( P <0.001), and in 4.9% of patients without a prosthetic valve ( P <0.001). Only 58% of the patients with an MHV had a pregnancy free of serious adverse events compared with 79% of patients with a tissue heart valve ( P <0.001) and 78% of patients without a prosthetic valve ( P <0.001). Vitamin K antagonist use in the first trimester compared with heparin was associated with a higher rate of miscarriage (28.6% versus 9.2%; P <0.001) and late fetal death (7.1% versus 0.7%; P =0.016). Conclusions— Women with an MHV have only a 58% chance of experiencing an uncomplicated pregnancy with a live birth. The markedly increased mortality and morbidity warrant extensive prepregnancy counseling and centralization of care. # CLINICAL PERSPECTIVE {#article-title-24}

Global cardiac risk assessment in the Registry of Pregnancy and Cardiac disease: Results of a registry from the European Society of Cardiology

To validate the modified World Health Organization (mWHO) risk classification in advanced and emerging countries, and to identify additional risk factors for cardiac events during pregnancy.

Aorta pathology and pregnancy

In addition to the haemodynamic changes in pregnancy, hormones also induce changes in the aortic wall. Women with diseases like Marfan syndrome, Ehlers-Danlo syndrome, or other aortic abnormalities, have an increased risk of complications during pregnancy. Counselling and risk assessment before pregnancy is mandatory for all women with known aortic disease. Proper information should be provided about the risks of morbidity and mortality during pregnancy and information on the risks for the fetus, including the potential recurrence of disease in the offspring. Evaluation of past medical and family history, the aortic size before conception, and any increase in size before and during pregnancy, is essential to try and estimate the risk of aortic dissection. If the aorta is dilated, prophylactic repair before pregnancy may be indicated. In some cases, elective surgery during pregnancy may be warranted. In women with a severely dilated ascending aorta, caesarean section is, at present, the advised mode of delivery.

Pulmonary hypertension and pregnancy outcomes: data from the Registry Of Pregnancy and Cardiac Disease (ROPAC) of the European Society of Cardiology.

To describe the outcomes of pregnancy in women with pulmonary hypertension.

Incidence and predictors of obstetric and fetal complications in women with structural heart disease

Objective Women with cardiac disease becoming pregnant have an increased risk of obstetric and fetal events. The aim of this study was to study the incidence of events, to validate the modified WHO (mWHO) risk classification and to search for event-specific predictors. Methods The Registry Of Pregnancy And Cardiac disease is a worldwide ongoing prospective registry that has enrolled 2742 pregnancies in women with known cardiac disease (mainly congenital and valvular disease) before pregnancy, from January 2008 up to April 2014. Results Mean age was 28.2±5.5 years, 45% were nulliparous and 33.3% came from emerging countries. Obstetric events occurred in 231 pregnancies (8.4%). Fetal events occurred in 651 pregnancies (23.7%). The mWHO classification performed poorly in predicting obstetric (c-statistic=0.601) and fetal events (c-statistic=0.561). In multivariable analysis, aortic valve disease was associated with pre-eclampsia (OR=2.6, 95%CI=1.3 to 5.5). Congenital heart disease (CHD) was associated with spontaneous preterm birth (OR=1.8, 95%CI=1.2 to 2.7). Complex CHD was associated with small-for-gestational-age neonates (OR=2.3, 95%CI=1.5 to 3.5). Multiple gestation was the strongest predictor of fetal events: fetal/neonatal death (OR=6.4, 95%CI=2.5 to 16), spontaneous preterm birth (OR=5.3, 95%CI=2.5 to 11) and small-for-gestational age (OR=5.0, 95%CI=2.5 to 9.8). Conclusion The mWHO classification is not suitable for prediction of obstetric and fetal events in women with cardiac disease. Maternal complex CHD was independently associated with fetal growth restriction and aortic valve disease with pre-eclampsia, potentially offering an insight into the pathophysiology of these pregnancy complications. The increased rates of adverse obstetric and fetal outcomes in women with pre-existing heart disease should be highlighted during counselling.

Pregnancy Outcomes in Women With Rheumatic Mitral Valve Disease: Results From the Registry of Pregnancy and Cardiac Disease

Background: Cardiac disease is 1 of the major causes of maternal mortality. We studied pregnancy outcomes in women with rheumatic mitral valve disease. Methods: The Registry of Pregnancy and Cardiac Disease is an international prospective registry, and consecutive pregnant women with cardiac disease were included. Pregnancy outcomes in all women with rheumatic mitral valve disease and no prepregnancy valve replacement is described in the present study (n=390). A maternal cardiac event was defined as cardiac death, arrhythmia requiring treatment, heart failure, thromboembolic event, aortic dissection, endocarditis, acute coronary syndrome, and hospitalization for other cardiac reasons or cardiac intervention. Associations between patient characteristics and cardiac outcomes were checked in a 3-level model (patient–center–country). Results: Most patients came from emerging countries (75%). Mitral stenosis (MS) with or without mitral regurgitation (MR) was present in 273 women, isolated MR in 117. The degree of MS was mild in 20.9%, moderate in 39.2%, severe in 19.8%, and severity not classified in the remainder. Maternal death during pregnancy occurred in 1 patient with severe MS. Hospital admission occurred in 23.1% of the women with MS, and the main reason was heart failure (mild MS 15.8%, moderate 23.4%, severe 48.1%; P<0.001). Heart failure occurred in 23.1% of patients with moderate or severe MR. An intervention during pregnancy was performed in 16 patients, 14 had percutaneous balloon mitral commissurotomy, and 2 had surgical valve replacement (1 for MS, 1 for MR). In multivariable modeling, prepregnancy New York Heart Association class >1 was an independent predictor of maternal cardiac events. Follow-up at 6 months postpartum was available for 53%, and 3 more patients died (1 with severe MS, 1 with moderate MS, 1 with moderate to severe MR). Conclusions: Although mortality was only 1.9% during pregnancy, ≈50% of the patients with severe rheumatic MS and 23% of those with significant MR developed heart failure during pregnancy. Prepregnancy counseling and considering mitral valve interventions in selected patients are important to prevent these complications.

Wish to conceive and concerns to develop cardiovascular complications during pregnancy in patients with Turner syndrome

Abstract Introduction: Turner syndrome (TS) is associated with subfertility and infertility. Nevertheless, an increasing number of women become pregnant through oocyte donation. The wish to conceive may be negatively influenced by the fear of cardiovascular complications. The aim was to investigate the wish to conceive and the concerns about cardiovascular complications during pregnancy in women with TS. Methods: The patient association for TS invited all members of ≥18 years old (n = 344) to complete a specifically developed, disease-specific questionnaire, including questions about fertility, wish to conceive, attempts and concerns. Results were compared with previously published results of this questionnaire in women with congenital heart disease. Results: The questionnaire was completed by 89 women (median age 30.1 years, Q1–Q3 = 22.9–39.4). Of them, 51% had 45, X0-monosomy and 38% had ≥1 cardiac abnormality. Seventeen women (19%) had attempted to become pregnant and 12 of them succeeded to become pregnant. Women who had not undertaken attempts to conceive (81%), considered themselves mainly too young or had no partner. Of the total sample, 58% were concerned about the influence of pregnancy on their cardiovascular status. This was higher (75%) in the sample of women with TS and cardiac abnormalities, than in women with congenital heart disease from a previously published cohort (21%), (p < .001). There were no differences in concerns about pregnancy complications between women with TS who respectively had or had not attempted to become pregnant. Discussion: Women with TS, especially those with cardiac abnormalities, show serious concerns about the risks pregnancy may have. Patients should be timely counseled and specifically asked about their concerns. Psychosocial care should be provided when necessary.

Partial anomalous pulmonary venous return in Turner syndrome

PURPOSE The aim of this study is to describe the prevalence, anatomy, associations and clinical impact of partial anomalous pulmonary venous return in patients with Turner syndrome. METHODS AND RESULTS All Turner patients who presented at our Turner clinic, between January 2007 and October 2015 were included in this study and underwent ECG, echocardiography and advanced imaging such as cardiac magnetic resonance or computed tomography as part of their regular clinical workup. All imaging was re-evaluated and detailed anatomy was described. Partial anomalous pulmonary venous return was diagnosed in 24 (25%) out of 96 Turner patients included and 14 (58%) of these 24 partial anomalous pulmonary venous return had not been reported previously. Right atrial or ventricular dilatation was present in 11 (46%) of 24 partial anomalous pulmonary venous return patients. CONCLUSION When studied with advanced imaging modalities and looked for with specific attention, PAPVR is found in 1 out of 4 Turner patients. Half of these patients had right atrial and/or ventricular dilatation. Evaluation of pulmonary venous return should be included in the standard protocol in all Turner patients.

Pregnancy in Women With SMAD3 Mutation

Women with genetic aortic disease, such as Marfan syndrome, are at increased risk of pregnancy complications, in particular those with aortic dissection [(1)][1]. Aneurysms-osteoarthritis syndrome (AOS) is an autosomal-dominant syndrome caused by SMAD3 mutations, and is characterized by arterial

Influence of socioeconomic factors on pregnancy outcome in women with structural heart disease

Objective Cardiac disease is the leading cause of indirect maternal mortality. The aim of this study was to analyse to what extent socioeconomic factors influence the outcome of pregnancy in women with heart disease. Methods The Registry of Pregnancy and Cardiac disease is a global prospective registry. For this analysis, countries that enrolled ≥10 patients were included. A combined cardiac endpoint included maternal cardiac death, arrhythmia requiring treatment, heart failure, thromboembolic event, aortic dissection, endocarditis, acute coronary syndrome, hospitalisation for cardiac reason or intervention. Associations between patient characteristics, country characteristics (income inequality expressed as Gini coefficient, health expenditure, schooling, gross domestic product, birth rate and hospital beds) and cardiac endpoints were checked in a three-level model (patient–centre–country). Results A total of 30 countries enrolled 2924 patients from 89 centres. At least one endpoint occurred in 645 women (22.1%). Maternal age, New York Heart Association classification and modified WHO risk classification were associated with the combined endpoint and explained 37% of variance in outcome. Gini coefficient and country-specific birth rate explained an additional 4%. There were large differences between the individual countries, but the need for multilevel modelling to account for these differences disappeared after adjustment for patient characteristics, Gini and country-specific birth rate. Conclusion While there are definite interregional differences in pregnancy outcome in women with cardiac disease, these differences seem to be mainly driven by individual patient characteristics. Adjustment for country characteristics refined the results to a limited extent, but maternal condition seems to be the main determinant of outcome.