Prostacyclin Therapy, Expert Care Help in Pregnancy With PAH

Despite a high-risk of serious complications, 10 women with moderate to severe pulmonary arterial hypertension (PAH) had a successful pregnancy and delivery, according to a single center study.

The patients were managed with prostacyclin therapy in addition to PAH-specific treatments during pregnancy and specialized care. Most transitioned to oral PAH therapy after giving birth.

The study “Medical Management Of Pulmonary Arterial Hypertension In Pregnancy: A Single Center Experience” was published in International Journal of Cardiology Congenital Heart Disease.

Pregnancy poses an extra burden to the heart and circulatory system, with an increase in blood volume and, consequently, the need for the heart to pump more blood.

Although treatment advances have reduced the risk of complications and death among patients who get pregnant, such risk is still high and pregnancy is not advised for women with PAH, this study’s researchers noted, continuing to recommend against pregnancy for this patient group.

Some women, however, chose to continue a high-risk pregnancy. Others are diagnosed with PAH while pregnant, with the changes induced by a developing fetus precipitating symptoms.

No official guidelines currently exist for managing pregnant women with PAH, and data on PAH pregnancy outcomes is limited to small observational studies, the researchers at Ohio State University wrote.

To identify a way of better managing pregnancy in these women, the researchers conducted a retrospective study of PAH patients who continued with a pregnancy while being treated at the local Wexner Medical Center between 2004 and 2018.

They analyzed data covering 10 women (mean age, 28) with moderate to severe WHO Group 1 PAH. Most (70%) had been diagnosed with PAH before the pregnancy, while two were diagnosed during pregnancy and one after delivery.

In half of these cases, PAH was caused by congenital (since birth) heart disease; one case was due to portopulmunary hypertension — a form of PAH associated with high blood pressure in the portal vein that carries blood to the liver. In four cases the cause was unknown, or idiopathic.

Three patients had Eisenmenger syndrome, a congenital heart defect that affects blood circulation from the heart to the lungs.

Women diagnosed with PAH before pregnancy were using combinations of phosphodiesterase 5 inhibitors, which include as Adcirca (taladafil) and Revatio (sildenafil); endothelin receptor antagonists, which include Opsumit (macitentan); and prostacyclin analogues, which include Flolan and Veletri.

Five patients were not on any PAH-specific medication prior to their pregnancy, but began treatment upon pregnancy or PAH diagnosis.

Cardiac examination showed that all women had a moderate or severe dilation of the heart’s right ventricle, with eight (80%) showing right ventricle systolic dysfunction, a prognostic factor in heart failure and PH. 

PAH was diagnosed using echocardiography, a non-invasive imaging exam of the heart, using several criteria including a mean pulmonary artery pressure (mPAP) of 48 mmHg (above the limit of 20 mmHg).

Nine women underwent an invasive test before delivery, with five during pregnancy and four before conception. According to average test results, patients were categorized as having moderate to severe PAH — an mPAP of 50 mmHg, and a pulmonary vascular resistance, which evaluates the internal resistance to blood flow within the pulmonary arteries, of 7.5 Wood Units.

All were managed with anticoagulants and PAH-targeted therapy. Anticoagulant treatment consisting of heparin, a blood thinner, was used by eight patients.

Eight women (80%) were given prostacyclin therapy intravenously (IV, into the vein) at 29 weeks of gestation. One patient, diagnosed postpartum, started on prostacyclin following a cardiogenic shock — a life-threatening condition in which the heart suddenly cannot pump enough blood to meet the body’s needs.

The women were tapered off prostacyclin therapy after being treated for a mean of 37 weeks. Two continued on prostacyclin therapy for a longer period.

Seven women (70%) delivered by cesarean section. Bleeding requiring laparotomy — an exam that looks to the inside of the abdomen — occurred in two women with Eisenmenger syndrome.

Four women delivered their babies preterm (before 37 weeks of gestation): two due to fetal growth restriction, one due to pre-eclampsia (high blood pressure and other complications related to pregnancy), and another due to a prior cesarean delivery. These four infants required intensive care.

No deaths were reported among patients or their children.

Four women (40 %) experienced heart failure, and five developed other (not heart-related) complications. Two patients were readmitted to the hospital after delivery, due to a catheter-related infection and an intraperitoneal (abdomen) hematoma.

Postpartum monitoring, including echocardiogram and 6-minute walking test (an exercise capacity assessment), showed their pulmonary arterial pressure continued to be stable.

After pregnancy, all the women opted for contraception,  and none had subsequent pregnancies.

Overall, “in this cohort of 10 women with moderate to severe PAH who proceeded with pregnancy, there was no maternal or fetal mortality,” the researchers wrote.

“All women received IV prostacyclin therapy and received close hemodynamic monitoring during labor and delivery and the postpartum period. The majority of women were successfully transitioned to oral PAH specific therapy,” they added.

“Women with PAH who undertake high risk pregnancy require management at an expert center by a specialized team of pulmonary vascular medicine, maternal-fetal medicine and anesthesiology,” the team concluded. “While maternal outcomes appear to be improving in the current era of PAH medical therapies, until more robust studies on this topic can be performed, pregnancy in PAH should be considered prohibitively high risk.

“Large, multi-center observational studies are warranted.”