Statement on pregnancy in pulmonary hypertension from the Pulmonary Vascular Research Institute

Abstract

Pregnancy outcomes in patients with pulmonary hypertension remain poor despite advanced therapies. Although consensus guidelines recommend against pregnancy in pulmonary hypertension, it may nonetheless occasionally occur. This guideline document sought to discuss the state of knowledge of pregnancy effects on pulmonary vascular disease and to define usual practice in avoidance of pregnancy and pregnancy management. This guideline is based on systematic review of peer-reviewed, published literature identified with MEDLINE. The strength of the literature was graded, and when it was inadequate to support high-level recommendations, consensus-based recommendations were formed according to prespecified criteria. There was no literature that met standards for high-level recommendations for pregnancy management in pulmonary hypertension. We drafted 38 consensus-based recommendations on pregnancy avoidance and management. Further, we identified the current state of knowledge on the effects of sex hormones during pregnancy on the pulmonary vasculature and right heart and suggested areas for future study. There is currently limited evidence-based knowledge about both the basic molecular effects of sex hormones and pregnancy on the pulmonary vasculature and the best practices in contraception and pregnancy management in pulmonary hypertension. We have drafted 38 consensus-based recommendations to guide clinicians in these challenging topics, but further research is needed in this area to define best practices and improve patient outcomes.

Figure 1

Changes in cardiac output (CO), mean arterial pressure (MAP), and systemic vascular resistance (SVR) during pregnancy. Values above dotted line represent an increase from baseline, while values below dotted line depict a decrease.

Figure 2

Adaptation of the pulmonary vascular system and the right ventricle (RV) to increased pulmonary blood flow during pregnancy in a healthy patient and in pulmonary vascular disease. Note that the diseased pulmonary vasculature in pulmonary arterial hypertension (PAH; characterized by vasoconstriction, pulmonary vascular remodeling with lumen obliteration, and in situ thrombosis) is unable to accommodate the increased cardiac output, thus leading to RV strain, dilation, and eventually decompensation. PE: pulmonary embolism.

Figure 3

Pathophysiology of pulmonary hypertension (PH) and right ventricular (RV) dysfunction in pregnancy. Items in red represent the underlying preexisting alterations in PH; items in blue represent pregnancy-related modifiers that may aggravate these alterations. Potential contributions of sex hormones are shown in yellow (derived from studies in normal animals as well as PH models). Decreased pulmonary vasodilation and vascular recruitment, as well as hypervolemia and volume shifts, are the major contributors to RV dysfunction and failure in pregnant PH patients. Volume shifts are primarily due to intermittent mechanical compression of the inferior vena cava, effects of respiration-induced changes in intrathoracic pressure on venous return, autotransfusion during and after delivery, and postpartum blood loss. Hypotension, hypoxemia, and arrhythmias may further worsen RV failure and initiate a vicious cycle. DHEA: dehydroepiandrosterone. *Whether worsening pulmonary vascular remodeling contributes to worsening of PH and RV function during pregnancy remains unknown. ^#The contribution of 17β-estradiol (E2) to pulmonary vascular remodeling in PAH is unknown, and inhibitory as well as stimulatory effects may exist, depending on the clinical context.

Figure 4

Recommended evaluation of and follow-up for a pregnant patient with pulmonary arterial hypertension (PAH). BNP: brain natriuretic peptide; ETRA: endothelin receptor antagonist; FC: World Health Organization function class; ICU: intensive care unit; LMWH: low-molecular-weight heparin; PH: pulmonary hypertension; RV: right ventricular; 6MWT: 6-minute walk test.