Titia P.E. Ruys

Outcome of pregnancy in patients with structural or ischaemic heart disease: results of a registry of the European Society of Cardiology

AIMS To describe the outcome of pregnancy in patients with structural or ischaemic heart disease. METHODS AND RESULTS In 2007, the European Registry on Pregnancy and Heart disease was initiated by the European Society of Cardiology. Consecutive patients with valvular heart disease, congenital heart disease, ischaemic heart disease (IHD), or cardiomyopathy (CMP) presenting with pregnancy were enrolled. Data for the normal population were derived from the literature. Sixty hospitals in 28 countries enrolled 1321 pregnant women between 2007 and 2011. Median maternal age was 30 years (range 16-53). Most patients were in NYHA class I (72%). Congenital heart disease (66%) was most prevalent, followed by valvular heart disease 25%, CMP 7%, and IHD in 2%. Maternal death occurred in 1%, compared with 0.007% in the normal population. Highest maternal mortality was found in patients with CMP. During pregnancy, 338 patients (26%) were hospitalized, 133 for heart failure. Caesarean section was performed in 41%. Foetal mortality occurred in 1.7% and neonatal mortality in 0.6%, both higher than in the normal population. Median duration of pregnancy was 38 weeks (range 24-42) and median birth weight 3010 g (range 300-4850). In centres of developing countries, maternal and foetal mortality was higher than in centres of developed countries (3.9 vs. 0.6%, P < 0.001 and 6.5 vs. 0.9% P < 0.001) CONCLUSION The vast majority of patients can go safely through pregnancy and delivery as long as adequate pre-pregnancy evaluation and specialized high-quality care during pregnancy and delivery are available. Pregnancy outcomes were markedly worse in patients with CMP and in developing countries.

Heart failure in pregnant women with cardiac disease: data from the ROPAC

Objective Heart failure (HF) is one of the most important complications in pregnant women with heart disease, causing maternal and fetal mortality and morbidity. Methods This is an international observational registry of patients with structural heart disease during pregnancy. Sixty hospitals in 28 countries enrolled 1321 women between 2007 and 2011. Pregnant women with valvular heart disease, congenital heart disease, ischaemic heart disease, or cardiomyopathy could be included. Main outcome measures were onset and predictors of HF and maternal and fetal death. Results In total, 173 (13.1%) of the 1321 patients developed HF, making HF the most common major cardiovascular complication during pregnancy. Baseline parameters associated with HF were New York Heart Association class ≥3, signs of HF, WHO category ≥3, cardiomyopathy or pulmonary hypertension. HF occurred at a median time of 31 weeks gestation (IQR 23–40) with the highest incidence at the end of the second trimester (34%) or peripartum (31%). Maternal mortality was higher in patients with HF (4.8% in patients with HF and 0.5% in those without HF p<0.001). Pre-eclampsia was strongly related to HF (OR 7.1, 95% CI 3.9 to 13.2, p<0.001). Fetal death and the incidence of preterm birth were higher in women with HF compared to women without HF (4.6% vs 1.2%, p=0.001; and 30% vs 13%, p=0.001). Conclusions HF was the most common complication during pregnancy, and occurred typically at the end of the second trimester, or after birth. It was most common in women with cardiomyopathy or pulmonary hypertension and was strongly associated with pre-eclampsia and an adverse maternal and perinatal outcome.

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}

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.

Pregnancy and delivery in cardiac disease

Although its prevalence is relatively low in pregnant women, heart disease is the most important cause of maternal mortality. Problems may arise due to hemodynamic burden and the hypercoagulable state of pregnancy. Heart disease may be congenital or acquired. In developed countries, the former composes the biggest part of women with heart disease. Patients with unrepaired lesions, cyanotic lesions, diminished systemic ventricular function, complex congenital heart disease, left ventricular outflow tract obstruction, pulmonary hypertension, or mechanical valves are at highest risk of developing complications during pregnancy. All patients with known cardiac disease should preferably be counseled before conception. Pre-pregnancy evaluation should include risk assessment for the mother and fetus, including medication use and information on heredity of the cardiac lesion. Management of pregnancy and delivery should be planned accordingly on individual bases. The types of complications are related to the cardiac diagnosis, with arrhythmias and heart failure being most common. Treatment options should be discussed with the future parents, as they may affect both mother and child. In general, the preferred route of delivery is vaginal. The optimal care for pregnant women with heart disease requires multidisciplinary involvement and is best concentrated in tertiary centers.

Is a planned caesarean section in women with cardiac disease beneficial

Objectives In the general population, planned caesarean section is thought to be safer in high-risk situations as it avoids the greater risk of an emergency caesarean section. Only limited data exist on the optimal mode of delivery in women with structural heart disease. We investigated the relationship between mode of delivery and pregnancy outcome in women with pre-existing heart disease. Methods The Registry on Pregnancy and Cardiac Disease is an on-going, global, prospective observational registry of women with structural heart disease. We report on 1262 deliveries, between January 2007 and June 2011. Results The caesarean section was planned in 393 women (31%): 172 (44%) for cardiac and 221 (56%) for obstetric reasons of whom 53 delivered by emergency caesarean section. Vaginal delivery was planned in 869 (69%) women, of whom 726 (84%) actually delivered vaginally and 143 (16%) had an emergency caesarean section. Perinatal mortality(1.1 vs 2.7, p=0.14) and low apgar score (11.9 vs 10.1, p=0.45) were not significantly different in women who had a caesarean section or vaginal delivery; gestational age(37 vs 38 weeks p=0.003) and birth weight (3073 vs 2870 g p<0.001) were lower in women delivered by caesarean section compared with women delivered by vaginal delivery. In those delivered by elective or emergency caesarean section, there was no difference in maternal mortality (1.8% vs 1.5%, p=1.0), postpartum heart failure (8.8% vs 8.2% p=0.79) or haemorrhage (6.2% vs 5.1% p=0.61). Conclusions These data suggest that planned caesarean section does not confer any advantage over planned vaginal delivery, in terms of maternal outcome, but is associated with an adverse fetal outcome.

Cardiac medication during pregnancy, data from the ROPAC

BACKGROUND Data on pharmacological management during pregnancy are scarce. The aim of this study was to describe the type and frequency of cardiac medication used in pregnancy in patients with cardiovascular disease and to assess the relationship between medication use and fetal outcome. METHODS AND RESULTS Between 2007 and 2011 sixty hospitals in 28 countries enrolled 1321 pregnant women. All patients had structural heart disease (congenital 66%, valvular 25% or cardiomyopathy 7% or ischemic 2%). Medication was used by 424 patients (32%) at some time during pregnancy: 22% used beta-blockers, 8% antiplatelet agents, 7% diuretics, 2.8% ACE inhibitors and 0.5% statins. Compared to those who did not take medication, patients taking medication were older, more likely to be parous, have valvular heart disease and were less often in sinus rhythm. The odds ratio of fetal adverse events in users versus non-users of medication was 2.6 (95% CI 2.0-3.4) and after adjustment for cardiac and obstetric parameter was 2.0 (95% CI 1.4-2.7). Babies of patients treated with beta-blockers had a significantly lower adjusted birth weight (3140 versus 3240 g, p = 0.002). The highest rate of fetal malformation was found in patients taking ACE inhibitors (8%). CONCLUSION One third of pregnant women with heart disease used cardiac medication during their pregnancy, which was associated with an increased rate of adverse fetal events. Birth weight was significantly lower in children of patients taking beta-blockers. A randomized trial is needed to distinguish the effects of the medication from the effects of the underlying maternal cardiac condition.

Abnormal left ventricular rotation and twist in adult patients with corrected tetralogy of Fallot

AIMS Left ventricular (LV) dysfunction is a major determinant of late adverse clinical outcome in adult patients with tetralogy of Fallot (ToF). Therefore, early detection is important. Speckle-tracking echocardiography (STE) has emerged as a quantitative technique to assess LV function. The aim of this study was to evaluate LV rotation and twist with STE in adult ToF patients and their association with right ventricular (RV) and LV dimensions and function, exercise capacity, and NT-proBNP level. METHODS Eighty-two ToF patients and 56 healthy controls matched for age and gender underwent echocardiography, electrocardiography, cardiac magnetic resonance imaging (CMR), bicycle ergometry, and NT-proBNP measurement. For STE, short-axis parasternal views were obtained at the LV base and apex. We analysed LV apical and basal rotation curves and calculated LV twist. RESULTS Of the 82 ToF patients (55% male, age 33 ± 10 years, 98% NYHA I), 58 (71%) had normal twist, but lower than the controls [12.5 (IQR: 6.6) vs. 16.9 (IQR: 8.2) degrees, P = 0.002] mainly due to decreased apical rotation. Twenty-one (26%) patients had abnormal apical rotation which was associated with larger LV dimensions and decreased systolic biventricular function. Multivariable regression analyses showed positive relations of LV twist with biventricular systolic function measured with echocardiography as well as CMR. CONCLUSION The majority of adults with corrected ToF show a reduced LV twist. Strikingly, one-quarter of these patients have an abnormal apical rotation which is associated with decreased systolic LV and RV function. These findings suggest that abnormal apical rotation is a new objective diagnostic criterion for detection of ventricular dysfunction.

Long-term Outcome and Quality of Life after Arterial Switch Operation: A Prospective Study with a Historical Comparison

AIM.: The study aims to describe the long-term cardiological and psychological results of our first surgical cohort of arterial switch operation (ASO) patients and compare the results with our earlier series of Mustard patients. METHODS.: Twenty-four survivors of ASO operated in our center (1985-1990) were evaluated by electrocardiography, echocardiography, magnetic resonance imaging, exercise testing, 24-hour Holter-monitoring, and health-related quality of life questionnaire. The results were compared with 58 adult Mustard patients who were evaluated in 2001 using the same study protocol. RESULTS.: Arterial switch operation was performed at a median age of 13 days and Mustard operation at 2 years. Median follow-up was 22 years (range 20-25) and 25 years (22-29), respectively. After ASO, survival was better (P =.04). The event-free survival after 22 years was 77% after ASO vs. 44% after Mustard (P =.03). Good systemic ventricular function was present in 93% after ASO vs. 6% after Mustard (P <.01). Exercise capacity in ASO was 85% of predicted, compared with 72% in Mustard patients (P =.01). Aortic regurgitation was found in 21% of ASO patients vs. 16% in Mustard patients. Arterial switch patients vs. Mustard patients reported significantly better quality of life and less somatic complaints. CONCLUSION.: The progression made in surgical treatment for transposition of the great arteries from Mustard to ASO has had a positive impact on survival, cardiac function, exercise capacity, and also self-reported quality of life and somatic complaints. Longer follow-up is warranted to monitor aortic regurgitation.

Pregnancy risks in women with pre-existing coronary artery disease, or following acute coronary syndrome

Objective The objective of this study was to determine outcomes in pregnant women with pre-existing coronary artery disease (CAD) or following an acute coronary syndrome (ACS) including myocardial infarction (MI). Background The physiological changes of pregnancy can contribute to myocardial ischaemia. The pregnancy risk for women with pre-established CAD or a history of ACS/MI is not well studied. Methods This was a retrospective multicentre study. Adverse maternal cardiac, obstetric and fetal/neonatal events were examined. The primary outcome was a composite endpoint of cardiac arrest, ACS/MI, ventricular arrhythmia or congestive heart failure. The prevalence of new or progressive angina during pregnancy was also examined. Results Fifty pregnancies in 43 women (mean age 35±5 years) were included. Coronary atherosclerosis (40%) and coronary thrombus (36%) were the most common underlying diagnoses. The primary outcome occurred in 10% (5/50) of pregnancies and included one maternal death secondary to cardiac arrest. Other events included ACS/MI (3/50) and heart failure (1/50). New or progressive angina occurred in 18% of pregnancies. Ischaemic complications of any type (new or progressive angina, ACS/MI, ventricular arrhythmia, cardiac arrest) occurred more commonly in women with coronary atherosclerosis compared with those without (50% vs 10%, p=0.003). A high rate of adverse obstetric (16%) and fetal/neonatal (30%) events was observed. Conclusions Pregnant women with pre-existing CAD or ACS/MI before pregnancy are at increased risk of adverse events during pregnancy. Those with coronary atherosclerosis are at highest risk of adverse maternal cardiac events due to myocardial ischaemia during pregnancy.