The effect of sildenafil on maternal mortality in pulmonary arterial hypertension associated with congenital heart disease

Abstract

Abstract Background Maternal mortality in pulmonary arterial hypertension (PAH) is very high, around 30–56%, so that patients with PAH and congenital heart disease (CHD) are advised to prevent pregnancy with class I-C recommendations. If the pregnancy continues, it must be handled by a multidisciplinary team with pulmonary hypertension (PH) experts, at the PH referral center. One of the PH-specific drug included in the FDA criteria B for pregnant women available in Indonesia is sildenafil. Sildenafil was reported to improve clinical symptoms and pregnancy outcomes in pregnant women with mild-moderate PAH. Sildenafil also had a tendency to reduce all-cause mortality although it was not statistically significant. Pulmonary hypertension specific drugs could reduce maternal mortality15.8% in subjects with PAH. However, research on sildenafil in maternal clinical outcomes is still very limited. Purpose This study aims to determine the effect of sildenafil on maternal mortality with PAH associated with CHD. Methods This study is an analytic observational study with a retrospective cohort method. Patient data were taken from the maternal registry, the Congenital HeARt Disease in adult and Pulmonary Hypertension (COHARD-PH) registry, and from the medical records of our general hospital who met the research criteria from August 2015 to December 2022. We assess the effect of sildenafil compared with controlled (without sildenafil) group. The clinical outcome of the study was maternal death during pregnancy and/or after delivery up to 42 days due to all causes (all causes mortality). Results Of 68 pregnant women who met the inclusion and exclusion criteria there were 32 subjects in the sildenafil group and 36 subjects in the control group. Maternal mortality was found to be higher (17.6%) in the group without sildenafil vs 9.7% in the sildenafil group. The majority causes of death were HP crisis (7 patients), 1 patient died from thromboembolism (HELLP syndrome), and 1 patient died from massive bleeding due to retained placenta. In the bivariate analysis, it was found that the NYHA functional class had a significant effect on maternal mortality with a p value <0.05, but not significantly from multivariate analysis. In the bivariate and multivariate analysis, general anesthesia had a statistically significant effect on maternal mortality with p=0.018. Of the 9 pregnant women who died, 5 patients received general anesthesia. Of the five patients, NYHA III-IV was found in 4 subjects (4/5 = 80%) and the other patient was NYHA II but subject came in at 63% saturation. All of the subjects are Eisenmeinger syndrome. Conclusion Sildenafil can reduce maternal mortality by 45% although it is not statistically significant. Further studies with larger data are needed to confirm this result.Basic Characteristics of SubjectsRelationship of Sildenafil with Maternal