Pregnancy outcomes in women with a systemic right ventricle and transposition of the great arteries results from the ESC-EORP Registry of Pregnancy and Cardiac disease (ROPAC).

OBJECTIVE: Cardiac disease is a major cause of maternal mortality. Data regarding pregnancy outcomes in women with a systemic right ventricle (sRV) are scarce. We studied pregnancy outcomes in women with an sRV after the atrial switch procedure for transposition of the great arteries (TGA) or congenitally corrected TGA (CCTGA). METHODS: The ESC EORP Registry of Pregnancy and Cardiac Disease is an international prospective registry of pregnant women with cardiac disease. Pregnancy outcomes (maternal/fetal) in all women with an sRV are described. The primary end point was a major adverse cardiac event (MACE) defined as maternal death, supraventricular or ventricular arrhythmias requiring treatment, heart failure, aortic dissection, endocarditis, ischaemic coronary event and other thromboembolic events. RESULTS: Altogether, 162 women with an sRV (TGA n=121, CCTGA n=41, mean age 28.8±4.6 years) were included. No maternal mortality occurred. In 26 women, at least one MACE occurred, heart failure in 16 (9.8%), arrhythmias (atrial 5, ventricular 6) in 11 (6.7%) and others in 4 (2.5%). Prepregnancy signs of heart failure as well as an sRV ejection fraction <40% were predictors of MACE. One woman experienced fetal loss, while no neonatal mortality was observed. No significant differences were found between women with CCTGA and TGA. In the subset of women who had an echocardiogram before and after pregnancy, no clear deterioration in sRV was observed. CONCLUSION: The majority of women with an sRV tolerated pregnancy well with a favourable maternal and fetal outcome. Heart failure and arrhythmias were the most common MACE.

Cardiomyopathy and Pregnancy: Considerations for Women With Severely Reduced Left Ventricular Dysfunction.

Women with dilated cardiomyopathy or left ventricular (LV) dysfunction (LV ejection fraction [LVEF] < 40%) from other etiology are at increased risk of maternal and fetal mortality and morbidity. They should undergo preconception evaluation, risk assessment, and treatment modification including discontinuation and replacement of contraindicated medications. A close follow-up and treatment by a multidisciplinary team is recommended at all stages: preconception, gestation, delivery, and postpartum. An early gestational and delivery plan has to be prepared to face complications and to achieve a successful delivery and outcome. Long-term postpartum cardiac follow-up is recommended anticipating potential adverse effects of pregnancy. The recommended mode of delivery for most patients is vaginal. The indications for cesarian section are mainly obstetric, unless the patient is in severely decompensated heart failure or urgent delivery if the patient is receiving warfarin therapy. Cardiac events during pregnancy or in the first months postpartum occur in 32%-60% of patients. Prepregnancy signs of heart failure, atrial fibrillation, and New York Heart Association functional classification (NYHA FC) > II were associated with a poor cardiac outcome. Predictors of deterioration during pregnancy that are considered very high risk and should be advised to avoid pregnancy are: patients with NYHA FC III/IV unless improved under treatment and LVEF < 20%. Predictors for high risk of adverse outcome include: LVEF < 30%, NYHA FC II, ventricular tachyarrhythmias (including patients with implantable cardioverter defibrillator or cardiac resynchronization therapy defibrillator),atrial fibrillation with rapid ventricular rate, severe mitral regurgitation, significant right ventricular failure, and hypotension. Overall, despite a high rate of complications, most women with LV dysfunction can undergo a successful pregnancy.

Mechanical heart valves and pregnancy: Issues surrounding anticoagulation. Experience from two obstetric cardiac centres.

BACKGROUND: Pregnant women with mechanical heart valves are at significant risk of obstetric/cardiac complications. This study compares the anticoagulation management in two obstetric cardiac centres. METHODS: Retrospective case-note review from Chelsea and Westminster/Royal Brompton Hospitals (CR) and Erasmus Medical Centre (EMC). Main outcome measure was mechanical heart valve thrombosis. RESULTS: Nineteen pregnancies from CR and 25 pregnancies from EMC were included. Most women were on low-molecular-weight heparin (LMWH) throughout pregnancy at CR, whereas at EMC most had LMWH in the first trimester and vitamin K antagonists in subsequent trimesters. Peak anti-factor Xa were performed monthly at CR, levels 0.39-1.51 IU/mL (mean 0.82 IU/mL). Anticoagulation management peri-partum was inconsistent. Delivery was mainly by caesarean section at CR (74%) and vaginal delivery at EMC (64%). No maternal deaths and only one mechanical heart valve thrombosis at CR. Two mechanical heart valve thromboses and one maternal death at EMC. CONCLUSION: Peri-partum anticoagulation strategies, anticoagulation monitoring and mode of delivery inconsistencies reported.

Pregnancy outcome in thoracic aortic disease data from the Registry Of Pregnancy And Cardiac disease.

BACKGROUND: Cardiovascular disease is the leading cause of death during pregnancy with thoracic aortic dissection being one of the main causes. Thoracic aortic disease is commonly related to hereditary disorders and congenital heart malformations such as bicuspid aortic valve (BAV). Pregnancy is considered a high risk period in women with underlying aortopathy. METHODS: The ESC EORP Registry Of Pregnancy And Cardiac disease (ROPAC) is a prospective global registry that enrolled 5739 women with pre-existing cardiac disease. With this analysis, we aim to study the maternal and fetal outcome of pregnancy in women with thoracic aortic disease. RESULTS: Thoracic aortic disease was reported in 189 women (3.3%). Half of them were patients with Marfan syndrome (MFS), 26% had a BAV, 8% Turner syndrome, 2% vascular Ehlers-Danlos syndrome and 11% had no underlying genetic defect or associated congenital heart defect. Aortic dilatation was reported in 58% of patients and 6% had a history of aortic dissection. Four patients, of whom three were patients with MFS, had an acute aortic dissection (three type A and one type B aortic dissection) without maternal or fetal mortality. No complications occurred in women with a history of aortic dissection. There was no significant difference in median fetal birth weight if treated with a beta-blocker or not (2960 g (2358-3390 g) vs 3270 g (2750-3570 g), p value 0.25). CONCLUSION: This ancillary analysis provides the largest prospective data review on pregnancy risk for patients with thoracic aortic disease. Overall pregnancy outcomes in women with thoracic aortic disease followed according to current guidelines are good.

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.

Acute Coronary Syndrome and Ischemic Heart Disease in Pregnancy: Data From the EURObservational Research Programme-European Society of Cardiology Registry of Pregnancy and Cardiac Disease.

Background The prevalence of ischemic heart disease (IHD) in women of child-bearing age is rising. Data on pregnancies however are scarce. The objective is to describe the pregnancy outcomes in these women. Methods and Results The European Society of Cardiology-EURObservational Research Programme ROPAC (Registry of Pregnancy and Cardiac Disease) is a prospective registry in which data on pregnancies in women with heart disease were collected from 138 centers in 53 countries. Pregnant women with preexistent and pregnancy-onset IHD were included. Primary end point were maternal cardiac events. Secondary end points were obstetric and fetal complications. There were 117 women with IHD, of which 104 had preexisting IHD. Median age was 35.5 years and 17.1% of women were smoking. There was no maternal mortality, heart failure occurred in 5 pregnancies (4.8%). Of the 104 women with preexisting IHD, 11 women suffered from acute coronary syndrome during pregnancy. ST-segment‒elevation myocardial infarction were more common than non‒ST-segment‒elevation myocardial infarction, and atherosclerosis was the most common etiology. Women who had undergone revascularization before pregnancy did not have less events than women who had not. There were 13 women with pregnancy-onset IHD, in whom non‒ST-segment‒elevation myocardial infarction was the most common. Smoking during pregnancy was associated with acute coronary syndrome. Caesarean section was the primary mode of delivery (55.8% in preexisting IHD, 84.6% in pregnancy-onset IHD) and there were high rates of preterm births (20.2% and 38.5%, respectively). Conclusions Women with IHD tolerate pregnancy relatively well, however there is a high rate of ischemic events and these women should therefore be considered moderate- to high-risk. Ongoing cigarette smoking is associated with acute coronary syndrome during pregnancy.

Pregnant Women With Uncorrected Congenital Heart Disease: Heart Failure and Mortality.

OBJECTIVES: The purpose of this work was to study maternal and fetal outcomes of women with uncorrected congenital heart disease (CHD). BACKGROUND: Globally, CHD is an important cause of maternal morbidity and mortality in women reaching reproductive stage. Data are lacking from larger cohorts of women with uncorrected CHD. METHODS: The 10-year data from the European Society of Cardiology EORP ROPAC (EURObservational Research Programme Registry of Pregnancy and Cardiac disease) registry of women with uncorrected CHD were analyzed. RESULTS: Of 5,739 pregnancies in 53 countries, 3,295 women had CHD, 1,059 of which were uncorrected cases. Of these, 41.4% were from emerging countries. There were marked differences between the cardiac defects in uncorrected cases versus those in corrected CHD cases with primary shunt lesions (44.7% vs. 32.4%, respectively), valvular abnormalities (33.5% vs. 12.6%, respectively), and Tetralogy of Fallot and pulmonary atresia (0.8% vs. 20.3%, respectively; p < 0.001). In patients with uncorrected CHD, 6.8% were in modified World Health Organization risk class IV, approximately 10% had pulmonary hypertension (PH), and 3% were cyanotic prior to pregnancy. Maternal mortality and heart failure (HF) in the women with uncorrected CHD were 0.7% and 8.7%, respectively. Eisenmenger syndrome was associated with a very high risk of cardiac events (65.5%), maternal mortality (10.3%), and HF (48.3%). Coming from an emerging country was associated with higher pre-pregnancy signs of HF, PH, and cyanosis (p < 0.001) and worse maternal and fetal outcomes, with a 3-fold higher rate of hospital admissions for cardiac events and intrauterine growth retardation (p < 0.001). CONCLUSIONS: Marked differences between cardiac conditions in pregnant women with uncorrected CHD and those in corrected CHD were found, with a markedly worse outcome, particularly in women with Eisenmenger syndrome and from emerging countries.

Aortic Stenosis: What Risks Do the Stresses of Noncardiac Surgery or Pregnancy Pose and How Should They Be Managed?

Studies suggest that patients with aortic stenosis have increased risk in pregnancy and delivery and during anesthesia and surgery, although there are significant degrees of uncertainty as to the exact risks and best way to manage such patients. This article reviews current literature regarding impact of aortic stenosis on pregnancy and anesthesia during noncardiac surgery. There are shortcomings in the scientific evidence. Most of the available studies are observational and often retrospective and therefore there is a great deal of bias. This leads to difficulty in drawing conclusions in terms of how to apply the published information to clinical management.

Peripartum cardiomyopathy: disease or syndrome?

Peripartum cardiomyopathy (PPCM) is a rare form of pregnancy-associated heart failure and is considered to be a diagnosis of exclusion. There are many hypotheses on the aetiology of PPCM; however, the exact pathophysiological mechanism remains unknown. It shows many resemblances to other conditions, such as familial dilated cardiomyopathy or myocarditis, and therefore it can be hard to make a definite diagnosis. We describe four cases of peripartum-onset heart failure in women who were suspected of having PPCM. We discuss the differential diagnosis, pathophysiological mechanisms and various diagnostic modalities.

Pregnancy outcomes in women with cardiovascular disease: evolving trends over 10 years in the ESC Registry Of Pregnancy And Cardiac disease (ROPAC).

AIMS: Reducing maternal mortality is a World Health Organization (WHO) global health goal. Although maternal deaths due to haemorrhage and infection are declining, those related to heart disease are increasing and are now the most important cause in western countries. The aim is to define contemporary diagnosis-specific outcomes in pregnant women with heart disease. METHODS AND RESULTS: From 2007 to 2018, pregnant women with heart disease were prospectively enrolled in the Registry Of Pregnancy And Cardiac disease (ROPAC). Primary outcome was maternal mortality or heart failure, secondary outcomes were other cardiac, obstetric, and foetal complications. We enrolled 5739 pregnancies; the mean age was 29.5. Prevalent diagnoses were congenital (57%) and valvular heart disease (29%). Mortality (overall 0.6%) was highest in the pulmonary arterial hypertension (PAH) group (9%). Heart failure occurred in 11%, arrhythmias in 2%. Delivery was by Caesarean section in 44%. Obstetric and foetal complications occurred in 17% and 21%, respectively. The number of high-risk pregnancies (mWHO Class IV) increased from 0.7% in 2007-2010 to 10.9% in 2015-2018. Determinants for maternal complications were pre-pregnancy heart failure or New York Heart Association >II, systemic ejection fraction <40%, mWHO Class 4, and anticoagulants use. After an increase from 2007 to 2009, complication rates fell from 13.2% in 2010 to 9.3% in 2017. CONCLUSION: Rates of maternal mortality or heart failure were high in women with heart disease. However, from 2010, these rates declined despite the inclusion of more high-risk pregnancies. Highest complication rates occurred in women with PAH.

Pregnancy in women with pre-existent ischaemic heart disease: a systematic review with individualised patient data.

INTRODUCTION: Studies on pregnancy risk in women with ischaemic heart disease (IHD) have mainly excluded pregnancies in women with pre-existent IHD. There is a need for better information about the pregnancy risks in these women and their offspring. METHODS: We performed a systematic review searching the PubMed/MEDLINE public database for pregnancy in women with pre-existent IHD analysing the cardiac, obstetric and fetal/neonatal outcome of pregnancy in women with pre-existing IHD. Individual patient data were requested from large series. The primary outcome endpoints was a composite of ischaemic complications including maternal death, acute coronary syndrome and ventricular tachycardia. RESULTS: 116 women with pre-existent IHD had 124 pregnancies including one twin pregnancy. They had a 21% chance of having an uncomplicated pregnancy (completed pregnancy without cardiovascular, obstetric or fetal/neonatal complications, n=26). Primary (ischaemic) endpoints occurred in 9% (n=11). Women with atherosclerosis had more cardiovascular complications compared with pregnancies in women with other underlying pathology for IHD (50%vs23%, P=0.02) but no significant difference in occurrence of primary endpoints (13% vs 9%, P=0.53). There were two maternal cardiac deaths (2%), one of which occurred in the 18th week of pregnancy and the other postpartum. Obstetric complications occurred in 58% (n=65) of pregnancies and fetal/neonatal complications in 42% (n=47). CONCLUSION: Pregnancies in women with pre-existing IHD are high-risk pregnancies. These women have a high risk of ischaemic cardiovascular complications including 2% maternal mortality. The risk of ischaemic complications is especially high among women with atherosclerotic coronary artery disease.

Ischaemic heart disease and pregnancy.

Although ischaemic heart disease is currently rarely encountered in pregnancy, occurring between 2.8 and 6.2 per 100 000 deliveries, it is becoming more common as women delay becoming pregnant until later life, when medical comorbidities are more common, and because of the higher prevalence of obesity in the pregnant population. In addition, chronic inflammatory diseases, which are more common in women, may contribute to greater rates of acute myocardial infarction (AMI). Pregnancy itself seems to be a risk factor for AMI, although the exact mechanisms are not clear. AMI in pregnancy should be investigated in the same manner as in the non-pregnant population, not allowing for delays, with investigations being conducted as they would outside of pregnancy. Maternal morbidity following AMI is high as a result of increased rates of heart failure, arrhythmia and cardiogenic shock. Delivery in women with history of AMI should be typically guided by obstetric indications not cardiac ones.

The association between systolic blood pressure and in-hospital mortality in older emergency department patients who are hospitalised with a suspected infection.

OBJECTIVE: In existing risk stratification and resuscitation guidelines for sepsis, a hypotension threshold of systolic blood pressure (SBP) below 90-100 mmHg is typically used. However, for older patients, the clinical relevance of a SBP in a seemingly 'normal' range (>100 mmHg) is still poorly understood, as they may need higher SBP for adequate tissue perfusion due to arterial stiffening. We therefore investigated the association between SBP and mortality in older emergency department (ED) patients hospitalised with a suspected infection. METHODS: In this observational multicentre study in the Netherlands, we interrogated an existing prospective database of consecutive ED patients hospitalised with a suspected infection between 2011 and 2016. We investigated the association between SBP categories (≤100, 101-120, 121-139, ≥140 mmHg) and in-hospital mortality in patients of 70 years and older. We adjusted for demographics, comorbidity, disease severity and admission to ward/intensive care using multivariable logistic regression. RESULTS: In the 833 included older patients, unadjusted in-hospital mortality increased from 4.7% (n=359) in SBP ≥140 mmHg to 20.8% (n=96) in SBP ≤100 mmHg. SBP categories were linearly associated with case-mix-adjusted in-hospital mortality. The adjusted ORs (95% CI) for ≤100, 101-120 and 121-139 mmHgcompared with the reference of ≥140 mmHg were 3.8 (1.8 to 7.8), 2.8 (1.4 to 5.5) and 1.9 (0.9 to 3.7), respectively. CONCLUSION: In older ED patients hospitalised with a suspected infection, we found an inverse linear association between SBP and case-mix-adjusted in-hospital mortality. Our data suggest that the commonly used threshold for hypotension is not clinically meaningful for risk stratification of older ED patients with a suspected infection.

Orgasm induced torsades de pointes in a patient with a novel mutation with long-QT syndrome type 2: a case report.

INTRODUCTION: Congenital long-QT (LQT) syndrome can lead to torsades de pointes (TdP), which can deteriorate into ventricular fibrillation resulting in sudden death. Thus far, more than 16 genes have been linked to the LQT syndrome. We report an orgasm-induced TdP in a patient with LQT syndrome type 2 with a novel mutation in the KCNH2 gene. CASE PRESENTATION: A 24-year-old Caucasian woman with a medical history of depression, no medication use and no family history of sudden death, presented with recurrent syncope during sexual activity. Immediately after achieving orgasm during sexual intercourse she lost consciousness. Baseline 12-lead electrocardiogram revealed a wide based T-wave with a prolonged QTc-interval of 507 ms. During hospital admission runs of TdP were recorded. The patient was treated with magnesium, an oral beta-blocker, and an implantable cardioverter-defibrillator. Genetic testing (Sanger sequencing) revealed a novel mutation (c.361del) in the KCNH2 gene (chromosome 7q36). DISCUSSION: To date, orgasm-induced TdP as a first symptom in a patient with LQT2 has not been published previously. In studies with continuous blood sampling in healthy volunteers, large peaks in plasma epinephrine levels during orgasm were observed with fast post-orgasmic decline. However, in a large cohort study (402 patients of which 129 with LQT2), no patients experienced cardiac events during sexual activity, suggesting that these are indeed very rare. Nevertheless, the high levels of sympathetic adrenal hormones during orgasm may explain the timing of the TdP in our patient. The patient has remained free of syncope at 6 months of follow-up.