Pregnancy in PAH Is Potentially Manageable

PHILADELPHIA—Can early delivery, an aggressive treatment strategy, and a multidisciplinary approach to managing pregnancy in patients with pulmonary arterial hypertension (PAH) counteract the condition’s high mortality risk? At the American College of Chest Physicians 2008 Annual International Scientific Assembly, Dianne L. Zwicke, MD, answered in the affirmative—although with significant caveats. She described the successful outcomes of 40 pregnant patients with PAH who underwent a high-risk management team approach with precise post-delivery care.

“I’m not encouraging anyone with PAH to get pregnant at this point,” said Dr. Zwicke, Clinical Associate Professor of Medicine at the University of Wisconsin School of Medicine and Public Health in Milwaukee. “All I say is, here are the data. You have to make the decision.”

INITIAL DATA AND RECENT STUDY RESULTS

Findings from six of the 40 patients in Dr. Zwicke’s study were first reported in 2003, and ultimately paralleled the complete 2008 results. These six patients had moderate to severe PAH and made monthly visits to a pulmonary hypertension clinic until 28 weeks’ gestation. At this point, right heart echocardiographic imaging was performed at weekly visits. Deterioration in right ventricular (RV) function determined the delivery date, and all physicians involved in the delivery were included in a pre-delivery planning meeting.

The average time of delivery for the six patients was 35 weeks; four were scheduled for vaginal delivery with epidural anesthesia, while the other two were scheduled for cesarean delivery with general anesthesia. Epoprostenol, nitric oxide, and dobutamine were used in managing the patients’ deliveries. Although three of the patients developed right heart failure symptoms before delivery, all six births were managed successfully and proceeded without adverse outcomes to either the mother or the baby.

“Weekly surveillance of RV function beginning at week 28 was critical in scheduling the timing of delivery,” Dr. Zwicke and colleagues concluded in 2003. “We attributed the successful management and survival to this close monitoring and induction of delivery before term.”

For Dr. Zwicke’s most recent report, she and her colleagues used observational data from these six patients, as well as 21 others treated at her practice, and 13 patients treated at other hospitals in the United States and abroad. Among this group, 39 patients were diagnosed with PAH after they had become pregnant, while one became pregnant after diagnosis.

Dr. Zwicke explained that the 40 patients had PAH due to a variety of reasons; the most common etiology was idiopathic (20 patients). Of the remaining cases, seven were caused by congenital heart disease, four by postmitral valve stenosis, four by lupus, two by sickle cell disease, two by exposure to drugs for anorexia, and one by pulmonary emboli. The average age of the patients was 27, and the average mean pulmonary artery pressure was 59 mm Hg. Among other PAH therapies, a high-dose calcium channel blocker was used in one patient, and 39 were on prostaglandin infusions.

Thirty-four natural births and five cesarean deliveries occurred at 36 to 37 weeks; one elective abortion was performed at 22 weeks. All mothers and the 39 infants survived post-delivery. Average maternal hospital stay was five days; one infant needed ventilator assistance for two days, while the rest were ready to be sent home by the third day, Dr. Zwicke said.

STRATEGIES FOR TREATMENT AND MANAGEMENT

Dr. Zwicke and colleagues used a multidisciplinary management technique for their study in which the subspecialties worked closely together. A cardiology/pulmonary specialist served as the team leader, joined by a high-risk obstetrician, a neonatologist, and a cardiac anesthesia specialist. Other team members included an ECG technician, labor and delivery nursing staff, and critical care nursing staff. Pre-delivery meetings with the entire team were key, Dr. Zwicke noted, as most drugs used to treat PAH were unfamiliar to the obstetricians and to the labor and delivery staff.

Also, due to the crucial importance of using RV heart function to gauge the delivery date, Dr. Zwicke emphasized that the clinician treating the patient for PAH must be permitted to dictate the timing of delivery.

“Pulling your team together is probably the most important take- home lesson from this study,” she said. “Whoever is managing the PAH has to call the delivery time, because it is directly related to the RV function. If you start to see RV dysfunction you’re uncomfortable with, and you can’t treat it, you need to get the infant delivered. Your obstetrician has to believe you. You have to have a good relationship.”

To use RV function as an indicator of delivery time, Dr. Zwicke stated, frequent right heart echocardiography should be performed by experienced technicians as often as once a week from 30 to 36 weeks’ gestation—a period that is of particularly high risk for the patient during pregnancy. She advised that delivery should be performed no later than the 36th to the 37th week.

In addition to use of an epidural and cardiac anesthesia techniques, delivery room treatment strategies used in Dr. Zwicke’s study included keeping patient fluid levels low and avoiding a prolonged Valsalva maneuver. Every milliliter of fluid in and out of the patient must be accounted for, Dr. Zwicke stressed. After delivery, the patient should be brought to the critical care unit until discharge and undergo aggressive fluid management—maintaining a negative output of eliminating 3 L a day for three days. Up to 72 hours after delivery represents another high-risk time for the patient, Dr. Zwicke said, as most maternal deaths in PAH occur during this immediate postpartum period.

Dr. Zwicke recommended that a patient who is discharged on the morning of the fourth day be prescribed low-dose diuretics for seven days, and that the clinician should follow the patient closely (weekly office visits for three weeks) to see if she is on track for stability at six to eight weeks.

“I think we still need to tread cautiously,” Dr. Zwicke emphasized, who noted that current data in the literature cite a 50% to 66% mortality rate in pregnant women with PAH. “We need more data. This is only a sample set of 40 patients, not thousands of pregnant patients with pulmonary hypertension.”

—John Merriman

Suggested Reading
Bendayan D, Hod M, Oron G, et al. Pregnancy outcome in patients with pulmonary arterial hypertension receiving prostacyclin therapy. Obstet Gynecol. 2005;106(5 Pt 2):1206-1210.
Huang S, DeSantis ER. Treatment of pulmonary arterial hypertension in pregnancy. Am J Health Syst Pharm. 2007;64(18):1922-1926.
Nahapetian A, Oudiz RJ. Serial hemodynamics and complications of pregnancy in severe pulmonary arterial hypertension. Cardiology. 2008;109(4):237-240.
Stewart R, Tuazon D, Olson G, Duarte AG. Pregnancy and primary pulmonary hypertension: successful outcome with epoprostenol therapy. Chest. 2001;119(3):973-975.

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