Pregnancy outcome in women with Eisenmenger’s syndrome: a case series from west China

Pregnancy is well known to require significant hemodynamic changes in women to meet the rising metabolic demands of the mother and the fetus. The cardiovascular changes that occur during the pregnancy contribute to the high maternal morbidity in patients with Eisenmenger’s syndrome, including heart failure, dyspnea, syncope and sudden death. Therefore, ES is regarded as an absolute contraindication for pregnancy [8]. If a woman with ES chooses to continue with pregnancy, oxygen therapy, aggressive use of pulmonary vasodilator therapies, and care by a specialist multidisciplinary team may help to minimize mortality [11].

In this study, most patients with ES were rural residents in west China, with low educational level and poor physical status. They suffered from cardiac lesions over a long period with chronic tolerance to CHD, or no symptoms. Perhaps as a result of lack of general and special medical knowledge, these rural patients all refused cardiac surgery and were not followed up by cardiologists. Most of them were not sufficiently conscious of the increased risks and mortality of pregnancy with ES, and there was lack of pre-conception counseling nor regular care with the cardiologist and obstetrician during pregnancy. Although early pregnancy termination was recommended for patients with known ES, none of them chose to discontinue pregnancy in the first trimester. After 32 gestational weeks, the hemodynamic burden of pregnancy peaks, with the highest risk for maternal and fetal life, especially in the presence of a large VSD. In this study, five cases with heart failure presented at this stage, and four of those women eventually died with uncontrollable heart failure.

From this study, we found that patients with pulmonary infection and/or SP were more likely to succumb to heart failure and death. Such complications likely further exacerbate cardiovascular and pulmonary vascular demands. In our study, PABP in all patients was very high. Pulmonary hypertension is associated with high morbidity and mortality during pregnancy. For patients with aggressive PAH in pregnancy, hypertension reduction using sildenafil or prostacyclin analogs has not been the primary therapeutic regimen because of associated adverse effects [12]. However, Rao et al. deemed that for women with pulmonary hypertension who do become pregnant and do not wish to terminate pregnancy, it is important to continue pre-pregnancy management such as anticoagulation, prostacyclin analogs, and sildenafil [13]. Because of limited evidence with only a few published case series, there is no consensus on the use of such therapies for ES patients in pregnancy. In our hospital, sildenafil or prostacyclin analogs were not given to ES patients with aggressive PAH throughout pregnancy. Although large intrapulmonary thrombi occur in up to a quarter of patients with Eisenmenger syndrome, no evidence of thrombi was identified in our study and no anticoagulation was performed.

Close pregnancy monitoring and supportive care for these patients are essential, especially for cases with aggressive PAH. To monitor cardiac and hemodynamic status of ES patients, arterial line, central venous catheter or right-sided catheterization may be of use. However, invasive monitoring is not routinely recommended to pregnant women because of the increased risk of pulmonary artery rupture or thrombosis, unless the patient is unstable or with high-risk lesions. Therefore, monthly echocardiograms and weekly examination for these women are needed. If PABP aggravates during early trimester, the prognosis of continuing pregnancy may be particularly bad, and therapeutic abortion is recommended. If these patients insist on continuing pregnancy, hospitalization in the second trimester is highly recommended [14]. They should be admitted in a tertiary center, with a multidisciplinary team approach.

Due to few reports, it should be noted that the ideal mode of delivery in ES patients with PAH is controversial [7, 15]. Compared with cesarean delivery, although vaginal delivery is associated with less risk of haemorrhage, infection and venous thromboembolism, vaginal delivery is associated with increased basal cardiac output and increased output with every uterine contraction,which would promote cardiac arrhythmia and worsen heart failure. Furthermore, ES patients with PAH will be delivered early due to serious disease condition with unfavourable cervix and labour induction is likely to be difficult in these patients. Advantages of cesarean delivery include that time and opportunity of delivery can be controllable, and presence of senior staff can usually be ensured [16, 17]. Since our cases had ES with high PAH, we thought CS was suitable; our cases in third trimester were all delivered by cesarean section, except for one death before delivery. As far as blood loss and time of operation were concerned, no case lost more than 300 ml and all operations were completed within an hour. Because of the greater stability of hemodynamics, CS may be safer than vaginal delivery for these patients with severe baseline hemodynamic abnormalities.

In our study, 6/9 ES patients underwent CS under general anesthesia, whereas most of the previous reported ES patients were given epidural anesthesia or combined spinal epidural anesthesia [16, 18]. Either epidural or general anesthesia has been used with successful outcomes. Gurumurthy et al. reported general anesthesia in patient with ES undergoing cesarean section [19]. We hold to the same opinion as Gurumurthy’s: general anesthesia could allow for adequate control of pain and early initiation of thromboprophylaxis. Moreover, it allows for placement of an esophageal ultrasound probe after trachea cannulation for ultrasonic monitoring.

The presence of maternal cardiovascular disease places the fetus and neonate at greater risk. Increased rates of miscarriage, SGA, prematurity, intrauterine fetal demise, and neonatal death are present in many forms of maternal CHD whether repaired or unrepaired [20]. ES with PAH in pregnancy presents an increased risk of fetal complications such as stillbirth, SGA and preterm delivery [6]. Our study supports these findings and suggests that severe PAH in ES patients is likely to cause even higher risk. Our findings support that ES patients with severe PAH should be counseled regarding the discouraging outcomes and options for termination, especially in low income countries as reported by Lin et al. [21].

More women with ES are surviving in recent years because of advances in medicine and neonatal care. However, the prognosis for a pregnant woman with ES has not improved. Gleicher et al. reviewed 44 published cases and 52% pregnancy-associated mortality with ES, with 36.1% mortality on first pregnancy, 26.7% on second pregnancy and 33.3% on third pregnancy [4]. Our study indicated that the maternal mortality was 50% on first pregnancy, 50% on second pregnancy and the delivery frequency was higher in group II. Drenthen et al. reported that in pregnant ES patients, the occurrence of heart failure was 21%, prematurity rate 64.7%, SGA 37.5%, fetal mortality 9.5 %, and death within the first year of life 18.2% [22]. Stoddart et al. reviewed 30 cases and found that maternal mortality was 39%; the incidence of preterm deliveries, perinatal death, and total fetal wastage was respectively 44, 14 and 44% [23]. Alvira et al. reported maternal mortality was 33% according to a prospective study of 12 cases [5]. Yentis et al. studied 15 cases and identified that maternal mortality, fetal mortality and prematurity rate was respectively 40, 8 and 85% [6]. In our study, the incidence of maternal HF, maternal mortality, preterm birth, SGA, fetal mortality and neonatal mortality were respectively 45, 36, 88, 83, 27 and 25% respectively. Our maternal outcomes were similar to the other reports, whereas fetal outcome was worse than other reports. Most of our cases were from the rural areas of west China where there is a less developed medical system, and rejection of regular prenatal care with obstetricians and cardiologists is common. The development of SP may be an additional risk factor in ES. Phupong et al. recently performed a small review of five cases of ES with preeclampsia, and found that maternal mortality and premature delivery rate were respectively 80 and 60% [24], substantially higher than those without SP. Wang and Liu presented four cases of pregnancy complicated with HELLP syndrome in the setting of ES: three of the mothers died [25]. In our study, the incidence of SP in group II (maternal death) was higher than group I. It seems highly likely that SP or HELLP may aggravate the dangers of pregnancy in ES.

There have been few reports suggesting particular success in pregnancy with ES. Wang et al. recently reported perinatal outcome in 13 cases with ES and found maternal mortalityto be 7.7% (1/13), while infant loss was 38.5% and prematurity rate was 100%. The only maternal death occurred 17 days after delivery etc., resulting from HELLP syndrome, lung infection and heart failure [16]. However, optimistic reports of maternal survival rates are rare. We think in Wang’s study the lower maternal mortality may result from the higher delivery rate before 28 weeks (38.5%; 5/13). The progressive hemodynamic changes from second trimester to the third trimester add to the burden of a compromised right ventricle. Further studies with more cases will be needed to confirm this. In our study, 76.9% (10/11) cases delivered beyond 28 weeks’gestation and the maternal mortality rate was 36%, similar to other reports.