Pulmonary arterial hypertension (PAH) is a rare disease characterised by pulmonary vascular remodelling and elevated pulmonary pressure, which eventually leads to right heart failure and death. Registries worldwide have noted a female predominance of the disease, spurring particular interest in hormonal involvement in the disease pathobiology. Several experimental models have shown both protective and deleterious effects of oestrogens, suggesting that complex mechanisms participate in PAH pathogenesis. In fact, oestrogen metabolites as well as receptors and enzymes implicated in oestrogen signalling pathways and associated conditions such asBMPR2mutation contribute to PAH penetrance more specifically in women. Conversely, females have better right ventricular function, translating to a better prognosis. Along with right ventricular adaptation, women tend to respond to PAH treatment differently from men. As some young women suffer from PAH, contraception is of particular importance, considering that pregnancy in patients with PAH is strongly discouraged due to high risk of death. When contraception measures fail, pregnant women need a multidisciplinary team-based approach. This article aims to review epidemiology, mechanisms underlying the higher female predominance, but better prognosis and the intricacies in management of women affected by PAH.

Pulmonary hypertension is a term used to describe a complex multifactorial group of conditions diagnosed by an elevated mean pulmonary artery pressure of 20 mm Hg or higher on right heart catheterization. The diagnosis of pulmonary hypertension in pregnancy is important, as it is associated with high rates of maternal morbidity and mortality, even with modern management. Diagnostic testing is important for establishing the diagnosis, type, and severity of pulmonary hypertension, which in turn, dictates treatment options. Echocardiographic assessment is the first step in diagnosis and the gold standard for monitoring right heart function in patients with pulmonary hypertension. Supportive therapy for pulmonary hypertension includes monitored exercise, vaccination, and avoidance of certain activities. Therapies for pulmonary hypertension are considered conventional or targeted. Conventional therapy includes preventative care, anticoagulation, and calcium channel blockers for appropriate patients. Targeted therapy is usually reserved for patients with World Health Organization group 1 pulmonary arterial hypertension (including idiopathic, heritable, drug-induced or associated with congenital heart disease) and involves different types of direct pulmonary vasodilators. Right heart failure is the end result of pulmonary hypertension and the options for management include medical optimization, support with extracorporeal membrane oxygenation, and combined heart-lung transplantation. With pregnancy, management must be individualized, and patients should be cared for as part of an experienced multidisciplinary team. There are few studies addressing, timing and mode of delivery, including anesthetic considerations. In this review, the natural history of pulmonary hypertension in pregnancy and outcomes are summarized and current evidence-based management is discussed.

The aim of this study was to evaluate the pregnancy feasibility of women with mild pulmonary hypertension according to pregnancy outcomes.

To determine the outcomes in women with pulmonary hypertension (PH) and determine the factors related to adverse outcomes.

To analyze the risk factors for complications in pregnancy associated with pulmonary hypertension (PH) and to develop a logistic regression model to predict cardiac outcomes.A retrospective analysis was performed on 249 women with PH, who were followed at the Beijing Anzhen Hospital, Affiliated to the Capital Medical University, from January 2012 to March 2015. All pregnancies were recorded. Overall, 214 cases of pulmonary arterial hypertension were identified. Univariate analysis and multivariate analysis were performed to determine the risk factors occurring during or after pregnancy in women with PH. Ultimately, six independent risk factors for cardiac events were determined.There were 70 cases of cardiac complications (28.1%) with PH, including 7 cases of maternal death (2.81%). Independent risk factors were rapid progression of symptoms [OR=3.044, 95%CI (1.042-8.895), P<0.05], brain natriuretic peptide (BNP) plasma levels ≥300pg/mL [OR=5.543, 95%CI (1.403-21.896), P<0.05], severe pulmonary hypertension (PAP≥80mmHg, 1mmHg=0.133kPa) [OR=6.769, 95%CI (2.748-16.677), P<0.05], World Health Organization functional class (WHO-FC) III-IV [OR=6.053, 95%CI (2.638-13.886), P<0.05], PH pre-pregnancy [OR=5.434, 95%CI (1.298-22.738), P<0.05], and delivery ≥28weeks gestation [OR=10.876, 95%CI (3.957-29.893), P<0.05].Early advice on contraception for patients with PH, and the need for patients to undergo a comprehensive assessment of cardiac function pre-pregnancy are suggested from the results of the present study.Copyright © 2017 International Society for the Study of Hypertension in Pregnancy. Published by Elsevier B.V. All rights reserved.

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.

Data regarding pregnancy outcome in women with congenital heart disease (CHD) are limited.In 1802 women with CHD, 1302 completed pregnancies were observed. Independent predictors of cardiac, obstetric, and neonatal complications were calculated using logistic regression. The most prevalent cardiac complications during pregnancy were arrhythmias (4.7%) and heart failure (1.6%). Factors independently associated with maternal cardiac complications were the presence of cyanotic heart disease (corrected/uncorrected) (P < 0.0001), the use of cardiac medication before pregnancy (P < 0.0001), and left heart obstruction (P < 0.0001). New characteristics were mechanical valve replacement (P = 0.0014), and systemic (P = 0.04) or pulmonary atrioventricular valve regurgitation related with the underlying (moderately) complex CHD (P = 0.03). A new risk score for cardiac complications is proposed. The most prevalent obstetric complications were hypertensive complications (12.2%). No correlation of maternal characteristics with adverse obstetric outcome was found. The most prevalent neonatal complications were premature birth (12%), small for gestational age (14%), and mortality (4%). Cyanotic heart disease (corrected/uncorrected) (P = 0.0003), mechanical valve replacement (P = 0.03), maternal smoking (P = 0.007), multiple gestation (P = 0.0014), and the use of cardiac medication (P = 0.0009) correlated with adverse neonatal outcome.In our tertiary CHD cohort, cardiac, obstetric, and neonatal complications were frequently encountered, and (new) correlations of maternal baseline data with adverse outcome are reported. A new risk score for adverse cardiac complications is proposed, although prospective validation remains necessary.

Pregnant women with pulmonary hypertension (PH) have higher mortality rates and poor foetal/neonatal outcomes. Tools to assess these risk factors are not well established.

Managing contraception for women at high risk for thrombosis poses unique challenges. Combined estrogen and progestin contraceptives increase the risk of both venous and arterial thrombosis. They are contraindicated in women with a history of thrombosis and in other women at high risk for thrombosis. However, progestin-only contraceptives are generally considered safe in this patient population. This paper reviews the evidence linking hormonal contraception and clotting risk, outlines appropriate contraceptive methods for women at high risk for thrombosis, discusses surgical risk for sterilization in the setting of current or past thrombosis, and includes a review of the safety of hormonal methods for women who are fully anticoagulated. In general, long-acting reversible contraception is safe for women with a history of thrombosis and may offer additional noncontraceptive benefits for women who are on anticoagulant therapy, such as improved bleeding profiles.

Severe early onset fetal growth restriction caused by placental dysfunction leads to high rates of perinatal mortality and neonatal morbidity. The phosphodiesterase 5 inhibitor, sildenafil, inhibits cyclic guanosine monophosphate hydrolysis, thereby activating the effects of nitric oxide, and might improve uteroplacental function and subsequent perinatal outcomes.

Available literature on pregnant women with severe pulmonary hypertension (PH) relies mainly on anecdotal case reports and two series only.

Pregnancies in patients with pulmonary arterial hypertension (PAH) are associated with serious complications and mortality rates of more than 50%. Advanced medical therapies for PAH have been developed during the past years resulting in improved hemodynamics, exercise capacity, quality of life, and outcome. However, despite these advances, pregnancy in women with PAH is still associated with excessive maternal mortality. Consequently, all current guidelines strongly discourage pregnancy and recommend an effective method of contraception in women of childbearing age. If this fails, early pregnancy termination is advised. Those patients who choose to continue pregnancy should be treated with targeted PAH therapies including prostacyclin analogues and/or phosphodiesterase type 5 inhibitors. The care of the pregnant women with PAH requires a planned, multidisciplinary approach, preferably in a dedicated pulmonary hypertension referral center, focusing on close monitoring before, during and after delivery. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Pregnancy in women with pulmonary arterial hypertension (PAH) is considered to be associated with prohibitive maternal mortality. During the past decade, new advanced therapies for PAH have emerged and progress in high-risk pregnancy management has been made. We examined whether these changes have improved outcomes in parturients with PAH. A systematic review of all cases of parturients with idiopathic pulmonary hypertension (iPAH), congenital heart disease associated with PAH (CHD-PAH), or PAH of other aetiology (oPH) published in the past decade (1997-2007) was performed. Outcome data from this study were then compared with relevant data published between 1978 and 1996. Forty-eight case reports or case series met the inclusion criteria, totalling 73 parturients with PAH. Seventy-two per cent of patients with iPAH were receiving advanced therapies, compared with 52% of CHD-PAH and 47% of oPH. Although a publication bias cannot be excluded, overall maternal mortality was significantly lower compared with previous era (25 vs. 38%, P = 0.047) and was 17% in iPAH, 28% in CHD-PAH, and 33% in oPH. Seventy-eight per cent of deaths occurred within the first month after delivery. Primigravidae and parturients who received general anaesthesia were at higher risk of death (OR 3.70, 95% CI 1.15-12.5, P = 0.03 and OR 4.37, 95% CI 1.28-16.50, P = 0.02, respectively). Maternal mortality in parturients with PAH remains prohibitively high, despite lower death rates than previous decades. Early advice on pregnancy risks, including contraception, remains paramount. Women with PAH who become pregnant warrant a multidisciplinary approach with consideration of advanced therapies.

We describe the management of a parturient with severe primary pulmonary hypertension who underwent caesarean section. A multi-disciplinary approach was used. She was admitted to the intensive care unit perioperatively for invasive monitoring and trial of inhaled nitric oxide. Anaesthesia was provided by combined spinal-epidural block. We discuss controversies about the management of obstetric patients with this rare and serious condition.

Cardiovascular disease complicating pregnancy is rising in prevalence secondary to advanced maternal age, cardiovascular risk factors, and the successful management of congenital heart disease conditions. The physiological changes of pregnancy may alter drug properties affecting both mother and fetus. Familiarity with both physiological and pharmacological attributes is key for the successful management of pregnant women with cardiac disease. This review summarizes the published data, available guidelines, and recommendations for use of cardiovascular medications during pregnancy. Care of the pregnant woman with cardiovascular disease requires a multidisciplinary team approach with members from cardiology, maternal fetal medicine, anesthesia, and nursing.Copyright © 2019 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.