The adult population of patients with congenital heart disease (CHD) is growing rapidly as a result of progress in cardiologic and surgical interventions. At least a million women with CHD are alive in the western world and many of them wish to become pregnant. During pregnancy, plasma volume and cardiac output increase by 30-50%, while systemic vascular resistance is reduced. Thus, the circulatory burden of pregnancy may not be well tolerated in women with CHD. Relatively little data on this subject are available in the literature, although several have presented data at this Congress.
Previous research has indicated that women with CHD have an increased risk of cardiac complications – mainly arrhythmias and heart failure. Their offspring has a greater risk for premature delivery, intrauterine growth restriction and recurrence of congenital heart disease. Predictors of increased maternal risk are pre-pregnancy NYHA-class, cyanosis, left-sided obstructive heart disease, systemic ventricular ejection fraction <40%, heart failure, transient ischaemic attack/cerebrovascular accident or arrhythmia.
Predictors of an increased foetal risk are maternal NYHA-class and cyanosis, left-sided obstructive heart disease, smoking during pregnancy, use of anticoagulation, and multiple pregnancy (Siu SC, Circulation 2001). Pulmonary hypertension is also associated with an increased maternal and foetal risk, as the Buenos Aires group of Professor Vazquez Blanco described in their poster presentation on Sunday (P506).
Cardiac contraindications to pregnancy are severe pulmonary hypertension, severe obstructive lesions, class III/IV congestive heart failure and Marfan syndrome with aortic root >40 mm.
Recently the Dutch ZAHARA study (pregnancy in CHD study) has added a significant amount of disease-specific information to the literature. This study used the nationwide registry of patients with CHD in the Netherlands, called CONCOR. Unexpected findings from the study were the high cardiovascular complication rate (40%) in women with atrioventricular septal defects (in part attributable to worsening of left atrioventricular valve regurgitation) and the high incidence of pre-eclampsia in some patient groups. High miscarriage rates, high numbers of premature deliveries and of small for gestational age children, and high fetal/neonatal mortality were not restricted to complex CHD but also occurred in simple CHD. Fetal/neonatal mortality was related to premature delivery and to recurrence of CHD. At this Congress, several investigators have reported maternal mortality rates of 0-2% (R.Brooks, V. Stangl, L.Hudsmith).
On Sunday a Dutch study (FP 1092) reported the pooled data of 1302 completed (>20 weeks) pregnancies in 1802 women from the ZAHARA study, the largest series ever. In addition to the previously noted predictors for maternal complications, several others were identified: valvular regurgitation, use of cardiac medication, and presence of a mechanical prosthetic valve.
Valvular regurgitation
Because of the fall in systemic vascular resistance, valvular regurgitation has been regarded as relatively harmless for the mother. So it was surprising that in the ZAHARA study atrioventricular valve regurgitation predicted maternal cardiac complications, with a predictive power comparable to NYHA-class. However, left-sided obstructive valvular lesions are a more powerful predictor for cardiac complications in the ZAHARA study, and this is also illustrated in the presentation of Dr Stangl.
Fig.1: In women with simple atrial septal defect (ASD), pregnancy is usually well tolerated, but cardiac and neonatal complications occur more frequently than in healthy women. The outcome of 243 pregnancies in women with ASD was presented to the Congress by Dr S.C. Yap on behalf of the ZAHARA investigators. Illustration: J.P.M. Hamer
Thromboembolic complications
Pregnancy results in a hypercoagulable state. In our recent literature review of 2491 pregnancies, thromboembolic complications occurred in one out of every 50 pregnancies of women with CHD (normal rate is 1 per 1000-2000 pregnancies).
The hypercoagulable state poses an extra problem in women with a mechanical valve prosthesis. In the ZAHARA study, mechanical valve prosthesis predicted both maternal and neonatal complications. The literature reports maternal mortality of 3-4% in women with mechanical prosthetic valves. Continued use of oral anticoagulants throughout pregnancy is the safest regimen for the mother but has a high risk of fetal loss (±35%) and embryopathy (±6%, dose-dependent). Therefore, oral coagulants are often replaced by heparin from 6-12 weeks of pregnancy, but this results in a significantly increased number of (sometimes fatal) thromboembolic complications both with unfractionated and low-molecular-weight heparin.
Cardiac medication
The use of cardiac medication predicts a poorer outcome of pregnancy, both for the mother and the foetus. This is probably related more to a worse pre-pregnancy condition of the mother than to direct negative effects of the medication. Many cardiac medications are relatively safe for the fetus (diuretics, beta-blocking agents, digoxin); other medications must be avoided (ACE inhibitors). Both pre-pregnancy counselling and management of pregnant women with CHD continue to be a challenge to cardiologists and obstetricians. Prospective studies are needed to improve risk stratification and to elucidate the mechanisms responsible for maternal,obstetric and foetal/neonatal complications.