Pulmonary arterial hypertension in pregnancy and the right ventricle–placenta axis: A systematic review integrating targeted pulmonary arterial hypertension therapies, advanced right ventricular imaging, and maternal–fetal hemodynamic adaptation in the era of evolving guidelines

Pulmonary arterial hypertension (PAH) has long been regarded as an almost absolute contraindication to pregnancy, a position shaped by historical reports of extreme maternal mortality and compounded by limited understanding of right ventricular (RV) adaptation and placental perfusion. Over the past decade, however, the landscape has shifted. Targeted PAH therapies, advances in RV imaging, and evolving guideline frameworks have created a narrow but real space in which pregnancy is no longer uniformly fatal, yet remains profoundly high risk. Against this backdrop, we conducted a systematic review to integrate contemporary evidence through a unifying physiological lens that has not been previously formalized: The right ventricle–placenta axis. We systematically searched major databases and clinical trial registers in accordance with PRISMA 2020 guidance, identifying 34 eligible studies encompassing observational cohorts, systematic reviews, and expert syntheses. Data were extracted on maternal hemodynamics, RV structure and function, PAH-directed therapies, placental and fetal outcomes, and peripartum management. Rather than treating maternal and fetal outcomes as parallel endpoints, we synthesized findings mechanistically, examining how RV maladaptation propagates through systemic and uteroplacental circulations. Across studies, maternal outcomes were closely linked to markers of RV dysfunction rather than pulmonary pressures alone. Impaired RV–pulmonary artery coupling, reduced forward cardiac output, and rising biomarkers were consistently associated with uteroplacental hypoperfusion, abnormal Doppler indices, fetal growth restriction, and iatrogenic prematurity. Pregnancy-compatible PAH therapies appeared to mitigate, but not eliminate, this cascade in carefully selected patients. Advanced imaging modalities and longitudinal monitoring emerged as critical tools for dynamic risk stratification. This review reframes PAH in pregnancy as a disorder of coupled maternal–placental physiology. Recognizing and targeting the RV–placenta axis may offer a more coherent foundation for counseling, surveillance, and future research in this exceptionally complex field.