Potential impact of specific therapy on pregnant women with pulmonary arterial hypertension without cardiac shunt: a descriptive study in northern China

Abstract

Background: Pregnancy in women with pulmonary arterial hypertension (PAH) is a fatal condition, despite the effectiveness of PAH-specific therapies. The coverage status and effect of specific therapies in pregnant patients with PAH without cardiac shunts in China remain unclear. To investigate this issue, we conducted a multicenter retrospective study in northern China.

Methods: The study included 85 patients who were admitted to 4 clinical centers in Shandong Province between October 2010 and August 2020. Maternal endpoint events included (1) maternal death and/or (2) major adverse cardiac events, both occurring during pregnancy or within 6 weeks postpartum.

Results: Although the overall mortality rate was encouraging (11.8%), the number of patients receiving PAH-specific therapies was extremely low (28.2%). Moreover, only 15.3% of patients received adequate duration of PAH-specific therapy (≥4 weeks) before delivery, and this subgroup showed the lowest major adverse cardiac events rate (7.7%) compared with that in the untreated (19.7%) and short-time treated groups (<4 weeks; 54.5%).

Conclusion: Pregnant patients with PAH without cardiac shunts face significantly increased mortality risks. Short-term PAH-specific therapy does not guarantee favorable maternal outcomes. Prepregnancy screening, early identification, and timely intervention are expected to improve maternal outcomes in pregnant women with PAH.

Keywords

Major adverse cardiac events / Maternal mortality / Pregnancy outcome / Pulmonary arterial hypertension / Specific therapy

Conflict of interest statement

The authors declare no conflict of interest.

Author contributions

Cui X was involved in study conceptualization, data curation and interpretation, and manuscript writing, revision, and final approval; Li M was involved in data collection and interpretation; Ji F was involved in data collection and interpretation; Feng H was involved in data interpretation and formal analyses; Li G was involved in data collection and interpretation; Ji Q was involved in data interpretation, data validation, formal analysis, and manuscript writing; Zhang H was involved in data collection, interpretation, and validation and formal analysis; Lu W was involved in study conceptualization, data collection, formal analysis, manuscript writing, and final approval.

Funding

This study was supported by grants from Shandong Provincial Natural Science Foundation (ZR2021MH111 for Cui X and ZR2020MH033 for Zhang H) and Doctoral Program of Shandong Provincial Natural Science Foundation (ZR2017BH047 for Lu W).

Ethical approval of studies and informed consent

The study followed the principles of the Declaration of Helsinki as revised in 2013. This research was approved by the steering committee of Institutional Human Ethics Committee of Qilu Hospital (reference no. 2018-155) and was approved by the ethics committee at each participating center. Written informed consent was waived owing to the anonymized retrospective nature of the analysis.

Acknowledgments

None.

References

[1] Olsson KM, Channick R. Pregnancy in pulmonary arterial hypertension. Eur Respir Rev. 2016; 25(142):431-437. doi:10.1183/16000617.0079-2016

[2] Martin SR, Edwards A. Pulmonary hypertension and pregnancy. Obstet Gynecol. 2019; 134(5):974-987. doi:10.1097/aog.0000000000003549

[3] Galiè N, Humbert M, Vachiery JL, et al. 2015 ESC/ERS guidelines for the diagnosis and treatment of pulmonary hypertension: the Joint Task Force for the Diagnosis and Treatment of Pulmonary Hypertension of the European Society of Cardiology (ESC) and the European Respiratory Society (ERS): endorsed by: Association for European Paediatric and Congenital Cardiology (AEPC), International Society for Heart and Lung Transplantation (ISHLT). Eur Heart J. 2016;37(1):67-119. doi:10.1093/eurheartj/ehv317

[4] Humbert M, Kovacs G, Hoeper MM, et al. 2022 ESC/ERS guidelines for the diagnosis and treatment of pulmonary hypertension. Eur Heart J. 2022; 43(38):3618-3731. doi:10.1093/eurheartj/ehac237

[5] Luo J, Shi H, Xu L, Su W, Li J. Pregnancy outcomes in patients with pulmonary arterial hypertension: a retrospective study. Medicine. 2020; 99(23):e20285. doi:10.1097/md.0000000000020285

[6] Keepanasseril A, Pillai AA, Yavanasuriya J, Raj A, Satheesh S, Kundra P. Outcome of pregnancies in women with pulmonary hypertension: a single-centre experience from South India. BJOG. 2019; 126(Suppl 4):43-49. doi:10.1111/1471-0528.15681

[7] Duarte AG, Thomas S, Safdar Z, et al. Management of pulmonary arterial hypertension during pregnancy: a retrospective, multicenter experience. Chest. 2013; 143(5):1330-1336. doi:10.1378/chest.12-0528

[8] Li Q, Dimopoulos K, Liu T, et al. Peripartum outcomes in a large population of women with pulmonary arterial hypertension associated with congenital heart disease. Eur J Prev Cardiol. 2019; 26(10):1067-1076. doi:10.1177/2047487318821246

[9] Bédard E, Dimopoulos K, Gatzoulis MA. Has there been any progress made on pregnancy outcomes among women with pulmonary arterial hypertension? Eur Heart J. 2009; 30(3):256-265. doi:10.1093/eurheartj/ehn597

[10] Kiely DG, Condliffe R, Webster V, et al. Improved survival in pregnancy and pulmonary hypertension using a multiprofessional approach. BJOG. 2010; 117(5):565-574. doi:10.1111/j.1471-0528.2009.02492.x

[11] Easterling TR, Ralph DD, Schmucker BC. Pulmonary hypertension in pregnancy: treatment with pulmonary vasodilators. Obstet Gynecol. 1999; 93(4):494-498. doi:10.1016/s0029-7844(98)00524-9

[12] Curry RA, Fletcher C, Gelson E, et al. Pulmonary hypertension and pregnancy—a review of 12 pregnancies in nine women. BJOG. 2012; 119(6):752-761. doi:10.1111/j.1471-0528.2012.03295.x

[13] McMillan E, Martin WL, Waugh J, et al. Management of pregnancy in women with pulmonary hypertension secondary to SLE and anti-phospholipid syndrome. Lupus. 2002; 11(6):392-398. doi:10.1191/0961203302lu216xx

[14] Pillutla P, Nguyen T, Markovic D, Canobbio M, Koos BJ, Aboulhosn JA. Cardiovascular and neonatal outcomes in pregnant women with high-risk congenital heart disease. Am J Cardiol. 2016; 117(10):1672-1677. doi:10.1016/j.amjcard.2016.02.045

[15] Rex S, Devroe S. Anesthesia for pregnant women with pulmonary hypertension. Curr Opin Anaesthesiol. 2016; 29(3):273-281. doi:10.1097/ACO.0000000000000310

[16] Sliwa K, van Hagen IM, Budts W, et al. Pulmonary hypertension and pregnancy outcomes: data from the Registry of Pregnancy and Cardiac Disease (ROPAC) of the European Society of Cardiology. Eur J Heart Fail. 2016; 18(9):1119-1128. doi:10.1002/ejhf.594

[17] Dolgun ZN, Inan C, Sayin NC. Maternal and fetal outcomes in pregnancies with pulmonary hypertension: experience of a tertiary center. Taiwan J Obstet Gynecol. 2018; 57(1):13-17. doi:10.1016/j.tjog.2017.10.032

[18] Ghofrani HA, Voswinckel R, Reichenberger F, et al. Differences in hemodynamic and oxygenation responses to three different phosphodiesterase-5 inhibitors in patients with pulmonary arterial hypertension: a randomized prospective study. J Am Coll Cardiol. 2004; 44(7):1488-1496. doi:10.1016/j.jacc.2004.06.060

[19] Zhang J, Lu J, Zhou X, et al. Perioperative management of pregnant women with idiopathic pulmonary arterial hypertension: an observational case series study from China. J Cardiothorac Vasc Anesth. 2018; 32(6):2547-2559. doi:10.1053/j.jvca.2018.01.043

[20] Thomas E, Yang J, Xu J, Lima FV, Stergiopoulos K. Pulmonary hypertension and pregnancy outcomes: insights from the National Inpatient Sample. J Am Heart Assoc. 2017; 6(10):e006144. doi:10.1161/JAHA.117.006144

[21] Ghofrani HA, Galiè N, Grimminger F, et al. Riociguat for the treatment of pulmonary arterial hypertension. N Engl J Med. 2013; 369(4):330-340. doi:10.1056/NEJMoa1209655

[22] Marra AM, Halank M, Benjamin N, et al. Right ventricular size and function under riociguat in pulmonary arterial hypertension and chronic thromboembolic pulmonary hypertension (the RIVER study). Respir Res. 2018; 19(1):258. doi:10.1186/s12931-018-0957-y

[23] Vizza CD, Sastry BK, Safdar Z, et al. Efficacy of 1, 5, and 20 mg oral sildenafil in the treatment of adults with pulmonary arterial hypertension: a randomized, double-blind study with open-label extension. BMC Pulm Med. 2017;17(1): 44. doi:10.1186/s12890-017-0374-x

[24] Lan WF, Deng Y, Wei B, et al. Echocardiographic evaluation of initial ambrisentan plus phosphodiesterase type 5 inhibitor on right ventricular pulmonary artery coupling in severe pulmonary arterial hypertension patients. Front Cardiovasc Med. 2022; 9:843606. doi:10.3389/fcvm.2022.843606