No abstract

When performed in experienced centers, right heart catheter procedures in patients with pulmonary hypertension are associated with low morbidity and mortality rates.

Novel treatments, such as prostanoids or endothelin receptor antagonists, have been introduced for various forms of pulmonary arterial hypertension, but the long-term effects of these treatments on portopulmonary hypertension (PPHT) are unknown.In a retrospective analysis, the present authors assessed the safety and efficacy of inhaled iloprost, a prostacyclin analogue, and bosentan, an endothelin receptor antagonist, in patients with PPHT. In total, 31 consecutive patients with Child class A or B cirrhosis and severe PPHT were treated for up to 3 yrs with either inhaled iloprost (n513) or bosentan (n518), and the effects on exercise capacity, haemodynamics and survival were evaluated.In the iloprost group, the survival rates at 1, 2 and 3 yrs were 77, 62 and 46%, respectively. In the bosentan group, the respective survival rates were 94, 89 and 89%. Event-free survival rates, i.e. survival without transplantation, right heart failure or clinical worsening requiring the introduction of a new treatment for pulmonary hypertension, was also significantly better in the bosentan group. Bosentan had significantly better effects than inhaled iloprost on exercise capacity, as determined by the 6-min walk test, as well as on haemodynamics. Both treatments proved to be safe, especially in regards of liver function.In the present series of patients with well-preserved liver function and severe portopulmonary hypertension, treatment with both inhaled iloprost and bosentan appeared to be safe. Patients treated with bosentan had higher survival rates, but prospective controlled studies are required to confirm these findings.

BackgroundAim of this prospective study was to evaluate the effects of exercise training in patients with inoperable or residual chronic thromboembolic pulmonary hypertension (CTEPH).MethodsThirty-five consecutive patients with invasively confirmed inoperable or residual CTEPH (16 women;19 men; mean age 61±15 years, mean pulmonary artery pressure, 63±20 mmHg; primary inoperable n = 33, persisting pulmonary hypertension after pulmonary endarterectomy n = 2) on stable disease-targeted medication received exercise training in-hospital for 3 weeks and continued at home for 15 weeks. Medication remained unchanged during the study period. Efficacy parameters have been evaluated at baseline, after 3 and 15 weeks by blinded-observers. Survival rate has been evaluated in a follow-up period of median 36.4 months (interquartile range 26.6–46.6 months).ResultsAll patients tolerated exercise training without severe adverse events. Patients significantly improved the mean distance walked in 6 minutes compared to baseline by 61±54 meters after 3 weeks (p<0.001) and by 71±70 meters after 15 weeks (p = 0.001), as well as scores of quality-of-life questionnaire, peak oxygen consumption and maximal workload. NT-proBNP improved significantly after 3 weeks of exercise training (p = 0.046). The 1-year survival rate was 97%, 2-year survival rate was 94% and the 3-year-survival 86% respectively.ConclusionTraining as add-on to medical therapy may be effective in patients with CTEPH to improve work capacity, quality of life and further prognostic relevant parameters and possibly improves the 1-, 2- and 3-year survival rate. Further multicentric randomized controlled studies are needed to confirm these promising results.Trial RegistrationClinicalTrials.gov NCT01398345

The dual endothelin receptor antagonist bosentan has been approved in several countries for pulmonary arterial hypertension, and patients with portopulmonary hypertension (PPHTN) have not specifically been excluded. However, no data have been published on the efficacy and safety of bosentan in this patient population. Here, the first clinical experiences with bosentan in patients with Child A cirrhosis and severe PPHTN are reported.In total, 11 consecutive patients with cirrhosis and severe PPHTN in New York Heart Association Functional Classes III and IV were treated for .1 yr with bosentan.After 1 yr of treatment with bosentan, all patients showed improved symptoms and exercise capacity. The 6-min walking distance increased from 310¡102 m at baseline to 388¡81 m at 1 yr. Cardiopulmonary exercise testing disclosed a significant increase in peak oxygen uptake, from 12.6¡3.5 to 16.6¡2.8 mL?min -1 ?kg -1 . Pulmonary vascular resistance fell from 944¡519 to 635¡321 dynes?s?L -1. The medication was well tolerated by all patients, and there was no evidence of drug-related liver injury.In conclusion, bosentan proved to be efficacious and safe in a small number of patients with portopulmonary hypertension.

We conducted an international, prospective, 3-year questionnaire-based survey among 11 pulmonary hypertension centres to assemble data from patients with pulmonary arterial hypertension (PAH) undergoing noncardiac and nonobstetric surgery.Data were collected between July 2007 and June 2010 from 114 patients with PAH (70% female, mean age 57 years) who underwent major surgery. At the time of surgery, 43% were in functional class III/IV. 82% of the interventions were performed under general anaesthesia and 18% under spinal anaesthesia. Major complications occurred in seven (6.1%) of the patients, of whom four died, resulting in an overall perioperative mortality rate of 3.5%. The mortality rate was 15% (two out of 13) in emergency procedures, compared with 2% (two out of 101) in nonemergency procedures (p50.01). Risk factors for major complications were an elevated right atrial pressure (OR 1.1, 95% CI 1.0-1.3; p50.01), a 6-min walking distance ,399 m at the last preoperative assessment (OR 2.2, 95% CI 1.1-3.7; p50.04), the perioperative use of vasopressors (OR 1.5, 95% CI 1.2-2.7; p50.03) and the need for emergency surgery (OR 2.4, 95% CI 1.4-3.6; p50.01).Major surgery in patients with PAH continues to be a high-risk procedure, particularly when emergency interventions are needed.

Analysis of breath condensate (BC) has received interest recently due to the need for easy and repetitive monitoring or airway and pulmonary disease. While many authors have used custom built systems, commercial systems are now available and will probably be used more widely. Early studies of markers and mediators in BC have reported concentrations following varying periods of sampling time. However, factors that influence the generation of BC have not been analysed and it is unclear whether breathing rate, tidal volume, lung function, body weight, height or age influence the amount of BC collected. We therefore studied the influence of these factors on breath condensate volume and breath condensate urea and protein concentrations in 22 healthy volunteers and 23 COPD patients. A strong correlation of total respired volume and breath condensate volume was observed for both groups (volunteers: r=0.952, p < 0.0001, COPD: r=0.883, p < 0.001) while no significant correlation existed for breath condensate volume and TLC, RV, Vc, FEV1, R(tot), height or body weight, As long as ventilation remained fairly constant, breath condensate volume increased linearly with time. The fraction of breath condensate extracted from total vapour contained in the exhalate was estimated by measuring relative atmospheric humidity before and after the collecting tube. The amount calculated by the change in temperature and saturation corresponded closely to the amount actually collected. We conclude from these results that breath condensate volume is primarily dependent on V(E), and does not seem to depend on lung function parameters. For standardisation it is suggested to report breath condensate measurements per volume respired. Both, urea and protein are present in measurable quantities in breath condensate and protein as well as BCV may be helpful denominators for comparison with e.g. cytokines in lung disease.

The present study demonstrates significant improvement of exercise capacity and clinical symptoms without relevant safety concerns during ambrisentan treatment in patients with PoPH.