Aims This study investigated the relationship between right ventricular (RV) structure and function and survival in idiopathic pulmonary arterial hypertension (IPAH). Methods and resultsIn 64 patients, cardiac magnetic resonance, right heart catheterization, and the six-minute walk test (6MWT) were performed at baseline and after 1-year follow-up. RV structure and function were analysed as predictors of mortality. During a mean follow-up of 32 months, 19 patients died. A low stroke volume (SV), RV dilatation, and impaired left ventricular (LV) filling independently predicted mortality. In addition, a further decrease in SV, progressive RV dilatation, and further decrease in LV end-diastolic volume (LVEDV) at 1-year follow-up were the strongest predictors of mortality. According to Kaplan-Meier survival curves, survival was lower in patients with an inframedian SV index 25 mL/m 2 , a supramedian RV end-diastolic volume index !84 mL/m 2 , and an inframedian LVEDV 40 mL/m 2 . Conclusions The RV contains prognostic information in IPAH. A large RV volume, low SV, and a reduced LV volume are strong independent predictors of mortality and treatment failure.

After PAH-targeted therapy, RV function can deteriorate despite a reduction in PVR. Loss of RV function is associated with a poor outcome, irrespective of any changes in PVR.

The efficacy and safety of combining bosentan, an orally active dual endothelin receptor antagonist and epoprostenol, a continuously infused prostaglandin, in the treatment of pulmonary arterial hypertension (PAH) was investigated.In this double-blind, placebo-controlled prospective study, 33 patients with PAH started epoprostenol treatment (2 ng?kg -1 min -1 starting dose, up to 14 ¡ 2 ng?kg -1 min -1 at week 16) and were randomised for 16 weeks in a 2:1 ratio to bosentan (62.5 mg b.i.d for 4 weeks then 125 mg b.i.d) or placebo. Haemodynamics, exercise capacity and functional class improved in both groups at week 16. In the combination treatment group, there was a trend for a greater (although nonsignificant) improvement in all measured haemodynamic parameters. There were four withdrawals in the bosentan/epoprostenol group (two deaths due to cardiopulmonary failure, one clinical worsening, and one adverse event) and one withdrawal in the placebo/epoprostenol group (adverse event).This study showed a trend but no statistical significance towards haemodynamics or clinical improvement due to the combination of bosentan and epoprostenol therapy in patients with pulmonary arterial hypertension. Several cases of early and late major complications were reported. Additional information is needed to evaluate the risk/benefit ratio of combined bosentan-epoprostenol therapy in pulmonary arterial hypertension. Pulmonary arterial hypertension (PAH) is an uncommon disease characterised by a progressive increase in pulmonary vascular resistance leading to right ventricular failure and death [1]. PAH can be idiopathic (referred to as primary pulmonary hypertension-PPH), or occur as a complication of various conditions, including scleroderma [2] or systemic lupus erythematosus [3]. The pathogenesis of PAH involves multiple and complex mechanisms triggered by endothelial dysfunction in the pulmonary bed, resulting in pulmonary vasoconstriction and vascular remodelling. An imbalance between vasoconstrictor/vasodilator activities in favour of vasoconstriction could be responsible for altered pulmonary vascular tone and structure [4]. In PAH patients, relaxing factors such as prostacyclin [5] are decreased and nitric oxide synthesis is impaired [6], whereas constricting factors including thromboxane [7], serotonin [8], and endothelin [9] are increased. Restoration of this imbalance by targeted therapies such as prostacyclin and endothelin receptor antagonists should further improve treatment options for the management of PAH.Prostacyclin (epoprostenol), a potent pulmonary vasodilator, decreases pulmonary vascular resistance and improves the survival of patients with severe PAH [10][11][12][13][14][15]. Despite major improvements in prognosis, mortality in patients with severe PAH treated with epoprostenol is still high, emphasising the need for novel therapeutic approaches in this patient population. In addition, epoprostenol is associated with dose-related side-effects (e.g. diarrhoea, flushing, headache, jaw pain, hypot...

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Systemic and pulmonary RAAS activities are increased in patients with iPAH and are associated with increased pulmonary vascular remodeling. Chronic inhibition of RAAS by losartan is beneficial in experimental PAH.

We determined the physiological effects of exercise training on exercise capacity and quadriceps muscle function in patients with idiopathic pulmonary arterial hypertension (iPAH).In total, 19 clinically stable iPAH patients (New York Heart Association II-III) underwent a supervised exercise training programme for the duration of 12 weeks. Maximal capacity, endurance capacity and quadriceps function were assessed at baseline and after 12 weeks. In 12 patients, serial quadriceps muscle biopsies were obtained.6-min walk distance and peak exercise capacity did not change after training. However, endurance capacity improved significantly after training, demonstrated by a shift of the anaerobic threshold to a higher workload (from 32¡5 to 46¡6 W; p50.003) together with an increase in exercise endurance time (p,0.001). Moreover, exercise training increased quadriceps strength by 13% (p50.005) and quadriceps endurance by 34% (p50.001).Training enhanced aerobic capacity of the quadriceps, by increasing capillarisation (1.36¡0.10 to 1.78¡0.13 capillaries per muscle fibre; p,0.001) and oxidative enzyme activity, especially of the type-I (slow) muscle fibres. No changes were found in cross-sectional area and fibre type distribution.Exercise training in iPAH improves exercise endurance and quadriceps muscle function, which is also reflected by structural changes of the quadriceps.

The aims of this study were to assess the prevalence of iron deficiency in idiopathic pulmonary arterial hypertension (IPAH) and investigate whether oral iron supplementation has effects in iron-deficient patients.Iron parameters were measure for all IPAH patients attending our centre (VU University Medical Center, Amsterdam, the Netherlands) between May 2009 and February 2010. Iron data were related to clinical parameters, including 6-min walking distance (6MWD), and haemodynamic parameters measured during right heart catheterisation. In a subset of iron-deficient patients, the uptake of iron from the bowel was studied after administering oral iron for 4 weeks.Iron deficiency was found in 30 (43%) out of 70 patients. 6MWD was reduced in iron-deficient patients compared with iron-sufficient patients (mean¡SD 390¡138 versus 460¡143 m; p,0.05) irrespective of the existence of anaemia. In a subset of 18 patients that received oral iron, ferritin levels were significantly increased, although eight patients only slightly increased their iron storage.This study shows that iron deficiency is frequently present in IPAH and is associated with a lower exercise capacity. The small response to oral iron in 44% of the treated patients suggests impaired iron absorption in these patients.

During therapy for PH, R and C remain inversely related. Therefore, changes in both R and C better explain changes in cardiac index than either of them alone. Not only resistance but also compliance plays a prominent role in PH especially in an early stage of the disease.