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.

Background— Impaired endothelial homeostasis underlies the pathophysiology of pulmonary arterial hypertension (PAH). We speculated that PAH patients are deficient in circulating endothelial progenitor cells (EPCs), potentially contributing to endothelial dysfunction and disease progression. Methods and Results— We recruited 41 patients with Eisenmenger syndrome (13 with Down syndrome), 55 with idiopathic PAH, and 47 healthy control subjects. Flow cytometry and in vitro assays were used to quantify EPCs and to assess cell function. The number of circulating CD34 + , CD34 + /AC133 + , CD34 + /KDR + , and CD34 + /AC133 + /KDR + progenitor cells was low in Eisenmenger patients compared with healthy control subjects, and those with Down syndrome displayed even fewer EPCs. Reductions in EPC numbers correlated with New York Heart Association functional class, 6-minute walk distance, and plasma brain-type natriuretic peptide levels. The capacity of cultured peripheral blood mononuclear cells to form colonies and incorporate into tube-like structures was impaired in Eisenmenger patients. Idiopathic PAH patients had reduced numbers of EPCs, and the number of circulating EPCs correlated with invasive hemodynamic parameters in this cohort. Levels of immune inflammatory markers, cGMP, stable nitric oxide oxidation products, and asymmetric dimethylarginine were abnormal in patients with PAH and related to numbers of EPCs. Within the idiopathic PAH population, treatment with the phosphodiesterase inhibitor sildenafil was associated with a dose-dependent rise in EPC numbers, resulting in levels consistently above those found with other therapies. Conclusions— Circulating EPC numbers are reduced in 2 well-characterized forms of PAH, which also exhibit raised levels of inflammatory mediators. Sildenafil treatment may represent a pharmacological means of increasing circulating EPC numbers long-term.

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