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A Successful Pregnancy and Delivery after Heart Transplantation: The First Case Report from Korea

Pregnancy following heart transplantation is a high-risk condition, requiring adequate maintenance of immunosuppressive drugs that enable proper graft function for optimal maternal and fetal outcomes. Here, we present the first case of successful child delivery in a patient who underwent heart transplantation in Korea. The 35-year-old female patient had become pregnant at 4 years after heart transplantation. The pregnancy progressed uneventfully, and the infant was healthy.


INTRODUCTION
Heart transplantation is a widely accepted procedure for patients with end-stage heart disease who are refractory to medical therapy. The number of women of childbearing age who have received heart transplants has risen partly due to the overall increase in heart transplantation in adults as well as increased rate of pediatric heart transplant recipients surviving to childbearing age (1). After receiving transplantation, most patients regain fertility and may consider pregnancy (2). However, pregnancy in heart transplant recipients imposes significant risks to the mother, graft, and the fetus(3). Such pregnancies carry increased risk of obstetric complications including pre-eclampsia, spontaneous abortions, low birth weight, and intrauterine growth re-striction (IUGR) (4,5).
In South Korea, a total of 1,354 transplantations have been performed since 2000; of those, female cardiac transplant recipient population accounts for 32% of all recipients, and 38% of them are of childbearing age (6). However, there has been no reported case of successful child delivery in Korean heart transplant recipients. This may be because transplantation and immunosuppressive drugs can act as major limitations to the success of a pregnancy, the latter of which is essential for maintaining graft function and recipient survival (7). We here report the first Korean case of successful child delivery in a patient who underwent heart transplantation.

CASE REPORT
A 35-year-old patient in the 38th week of her first pregnancy was admitted to the obstetrics clinic at Asan Medical Center due to IUGR. At the age of 26, the patient had been diagnosed with dilated cardiomyopathy; her family medical history revealed that her older brother died from sudden cardiac death before the age of 18, and that her mother also Based on the blood level, the dosage of tacrolimus was progressively increased to 9 mg/day from 4 mg/day before pregnancy (Table 1) During pregnancy, blood volume increases significantly by an average of 40%. This increase begins in the 6th week of pregnancy and reaches a peak in the 32nd week of pregnancy. Cardiac output increases by 30% to 50% and heart rate also increases by 10 to 20 bpm. Systemic blood pressure decreases in the first and second trimesters, and is restored to pre-gestational levels at the end of pregnancy.
The most evident change is elevation in end-diastolic volume (17). In transplant recipients, cardiac output is usually reduced and ventricular compliance is smaller than that in the normal ventricle, which is maintained by the high central venous pressure (18). Intracardiac pressures are normal at rest, but ventricular diastolic pressure drastically increases during physical exertion. If such changes occur in a pregnant transplant recipients, they can adversely affect the heart in terms of increase in cardiac contractility, central venous pressure, blood volume, and cardiac output (19,20).
These hemodynamic changes are usually well tolerated by transplant recipients during pregnancy (21).
Most immunosuppressive agents are designated as category C by the U.S. FDA in terms of their safety for use in pregnant women (8); nevertheless, immunosuppressive agents must be administered to transplant recipients during pregnancy (15). Currently, treatment with azathioprine, tacrolimus, glucocorticoids, and cyclosporin is allowed in pregnant women (22,23), and blood levels of immunosuppressive drugs should be monitored closely and adjusted on a case-by-case basis. We recommend that the target im- Kim et al. (27) reported that a 20% to 25% dose increase in CNIs is necessary during the gestational period. To adjust the immunosuppressive dosage based on stable blood level before pregnancy is our feasible experience. We would suggest even more frequent CNI trough levels in the first two trimesters to minimize the risk of significantly reduced levels culminating in rejection. Mycophenolate mofetil and sirolimus should be discontinued approximately 6 weeks before planned pregnancy in order to avoid the risk of fatal congenital defects (27). Statins remain contraindicated and should be stopped (28,29 There is no consensus on immunosuppressant drug levels in breast milk, but breastfeeding is generally discouraged in order to avoid the risk of passing immunosuppressive drugs, particularly cyclosporine and tacrolimus, to the baby (33).
The American Society of Transplantation stated that breastfeeding need not be viewed as absolutely contraindicated (3).
The International Society for Heart and Lung Transplantation guidelines note that it is uncertain whether the risks of infant drug exposure outweigh the benefits of breastfeeding, and they do not recommend that heart transplant recipients breastfeed (9).
To our knowledge, this is the first successful case of parturition by a heart transplant recipient in Korea. The successful outcome of this case can be attributed to the involvement of an interdisciplinary team as well as good cooperation by the patient.