Cardiac operation under cardiopulmonary bypass during pregnancy.

Background Certain pregnant women suffer from cardiac pathology,and a few of them need cardiac operations under cardiopulmonary bypass during pregnancy. Feto-neonatal and maternal outcomes have not been sufficiently described. Methods We conducted a retrospective review of 22 cases of women undergoing cardiac operations under cardiopulmonary bypass during pregnancy in our hospital from Jan.2014 to Mar.2019. Results All 22 patients were alive after treatment. The types of cardiac disorders included congenital heart defects, rheumatic heart disease,infective endocarditis,aortic dissection, obstruction and/or thrombosis of a prosthetic valve. Only one case was a twin pregnancy,and the other 21 cases were singletons. Four fetuses died in the utero after surgery. Three patients chose termination of the pregnancy after the cardiac operations: one fetus was detected abnormity of the brain and the other two patients abandoned pregnancy. Fourteen fetuses were alive and born without any abnormity. Two fetuses suffered from neonatal intracranial hemorrhage and died after birth. Conclusions Cardiac operation under cardiopulmonary bypass during pregnancy is a challenge for physicians in multidisciplinary teams. Strictly evaluating the indication is vital. On the other hand, some patients can benefit from this management.


Background
Heart disease complicates more than 1% of pregnancies and is now the leading cause of indirect maternal deaths [1]. Pregnancy creates a great burden on the cardiovascular system and can result in decompensation in women with underlying cardiac disease. To minimize the maternal and fetal risks, the first choice of treatment should be medical. In cases that are refractory to medical treatment, however, corrective cardiac operations should be undertaken [2]. As the Guangdong provincial obstetrical cardiology intensive care center in China, our hospital has accumulated a significant amount of clinical data of pregnant women with heart disease receiving cardiac operations under cardiopulmonary bypass during pregnancy. To investigate fetoneonatal and maternal outcomes, we conducted this study.

Subject
We searched in our medical record database from Jan.2014 to Mar.2019. The search terms included "pregnancy", "cardiopulmonary bypass" and "cardiac operation". We obtained 22 copies of the patients' medical materials containing the entire pregnancy course and fetal outcomes with their consent.

NYHA classes
The NYHA classification was developed in 1928 to describe an overall cardiac appraisal of the status of a patient with heart disease. It was divided into four classes [3]: Class I: Patients with cardiac disease but without resulting limitation of physical activity. Ordinary physical activity does not cause undue fatigue, palpitation, dyspnea, or anginal pain. Class II: Patients with cardiac disease resulting in a slight limitation of physical activity. They are comfortable at rest. Ordinary physical activity results in fatigue, palpitation, dyspnea, or anginal pain. Class III: Patients with cardiac disease resulting in marked limitation of physical activity. They are comfortable at rest. Less than ordinary activity causes fatigue, palpitation, dyspnea, or anginal pain. Class IV:Patients with cardiac disease resulting in inability to carry on any physical activity without discomfort. Symptoms of heart failure or anginal syndrome may be present even at rest. If any physical activity is undertaken, discomfort increases.

Cardioplegia technique
Adequate myocardial protection is essential for achieving successful outcomes of any surgical procedure necessitating cardiac arrest. The Del Nido solution (blood and crystalloid mixed formula) was used in all the cardiac operations of our study. The route of administration was antegrade or combined antegrade & retrograde.

Cardiac surgical procedures
Corrective cardiac operations consisted of mitral or/and tricuspid valve repair, aortic valve replacement (AVR), mitral valve replacement (MVR), ruptured sinus of Valsalva repair, atrial septal defect closure, ventricular septal defect closure, right ventricle outlet obstruction repair, prosthetic mitral/aortic valve thrombectomy and Betall procedure.

Maternal, fetal and neonatal complications after operation
The most common maternal complication was arrhythmia after operation. Fetal and neonatal complications included stillbirth, preterm delivery (< 37 weeks of gestation), neonatal intracranial hemorrhage and death.

Statistical analysis
A retrospective analysis was performed. Measurement data and enumeration data were expressed as mean ± standard deviation (SD) or frequencies.

Patient general information
The average age of the patients was 29.5 ± 5.4 years, with an age range of 21 to 42 years. Half the patients were nulliparous (n = 12, 54.5%). There was one twin pregnancy(n = 1, 4.5%)and the other patients were singletons(n = 21, 95.5%). The patient's characteristics are listed in Table 1.
Cardiac surgical procedure, intraoperatory parameters and fetal outcomes There were 22 patients with different types of heart diseases who received cardiac operations under cardiopulmonary bypass during pregnancy. The composition and proportion distribution of these patients by the type of heart disease,weeks of gestation during operation, NYHA functional classification, cardiac surgical procedure, intraoperatory parameters and fetal outcomes are presented in Table 1, Table 2 and Table 3.

Feto-neonatal and maternal outcomes
All 22 patients were alive after treatment. Three cases were complicated by arrhythmia after operations, especially atrial fibrillation, which needed medications. Four fetuses died in the utero after operations. Three patients chose termination of the pregnancy: one fetus was detected a brain abnormity and the other two patients abandoned pregnancy. Fourteen fetuses were alive and born without any abnormity. Two fetuses had complicated neonatal intracranial hemorrhage and died after birth. Feto-neonatal outcomes and mode of delivery are presented in Table 4.

Discussion
Heart disease is the primary cause of maternal and fetal death in 1-4% of pregnancies. Pregnancy creates an increased burden on the maternal cardiovascular system and can result in decompensation in women with underlying cardiac disease. To minimize the maternal and fetal risks, the first choice of treatment should be medical. However, in some cases, medical therapy is not always sufficient,and open heart operation might be necessary [4]. In 1958, Leyse and colleagues [5] first used cardiopulmonary bypass (CPB) in a heart operation during pregnancy. After the initial trials, pregnant women have been recognized to tolerate CPB as well as non-pregnant women, but the effects of CPB on the fetus have varied [6]. Several review articles, reported the maternal mortality rate ranged from 1.5 to 5%, and the fetal mortality rate has ranged from 16 to 33% [4,6]. Currently, reported maternal mortality for cardiac operations is similar to the mortality rate for non-pregnant female patients [7]. Therefore, CPB during pregnancy has a greater effect on the fetus than mother. In our report, the maternal mortality rate was 0%,and fetal mortality rate was 18.2%, as same as the above mentioned reviews.
The present study demonstrated that mitral and/or aortic valve disorders were the most common surgical indications for CPB during pregnancy, although it has been recognized that coronary arterial disease is increasingly prevalent in gynecological patients [8]. The latter, however, could be managed interventionally in most patients, avoiding the risk associated with CPB for fetoneo-natal outcomes. In our report, the indications for surgical procedure under CPB during pregnancy consisted of congenital heart defect (ASD, DCRV, VSD), rheumatic heart disease (mitral or aortic valve disorders),infective endocarditis,aortic dissection, obstruction and thrombosis of the prosthetic valve. Seven patients (all with a congenital heart defect)accompanied moderate to severe PAH, which could result in sudden death and greatly increase the maternal and fetal risk. Consequently, we performed cardiac operations during pregnancy to maintain the pregnancy and to decrease the risk of adverse feto-neonatal outcomes. Other indications were life-threatening diseases, such as severe MS/AR, infective endocarditis,aortic dissection (Stanford type A), obstruction and thrombosis of the prosthetic valve. All patients were alive,and 3 cases had complicated arrhythmia after operations, especially atrial fibrillation. There were no other complications. The results indicate that cardiac operations can be performed during pregnancy with remarkable safety for mothers.
Pregnant women who have cardiac operations requiring CPB must face a nonphysiologic hemodynamic status where the tolerance is not clearly known, which can adversely affect the fetus [4]. CPB can compromise utero-placental perfusion and fetal development by potential adverse effects such as coagulation and blood component alterations, the release of vasoactive substances from leukocytes, complement activation, particulate and air embolism, nonpulsatile flow, hypothermia and hypotension [2].Three main pathophysiological changes can occur in pregnant patients under CPB: uterine contraction, placental hypo-perfusion and fetal hypoxia. Utero-placental hypo-perfusion and fetal hypoxia subjected to sustained uterine contractions during CPB are considered risk factors for fetal death [9]. Despite the limited experimental data regarding the effect of CPB on uterine/placental blood flow and its effect on the fetus, it has been postulated that pulsatile, high-flow, high-pressure, normothermic bypass poses the least risk to the fetus [10,11].According to the above theories we

Conclusion
In conclusion, the decision to subject a pregnant woman to operation must be made by a team composed of an obstetrician, a cardiologist, an anesthesiologist and a neonatologist. Cardiac operation under CPB during pregnancy is a challenge for physicians in multidisciplinary teams. Strictly evaluating the indication is vital. On the other hand, some patients can benefit from this form of case management.  Cesarean section 14 (63.6%) 14 fetuses were alive without any abnormity(9 fetuses were term deliveries, and the other 5 were preterm deliveries). One fetus manifested intracranial hemorrhage at 36 weeks of gestation and died after birth.