Gert Hoeffken

Combining inhaled iloprost with bosentan in patients with idiopathic pulmonary arterial hypertension

Addition of inhaled iloprost to bosentan may have beneficial effects in patients with idiopathic pulmonary arterial hypertension (IPAH). A multicentre, open, randomised, controlled trial was performed to assess the safety and efficacy of inhaled iloprost in patients with IPAH who had already been treated with bosentan. The trial was terminated early after a futility analysis predicted failure with respect to the predetermined sample size. At that time, 40 patients were randomised to receive either bosentan alone (control group) or bosentan plus inhaled iloprost (combination group) for a 12-week period. The primary end-point, change in 6-min walking distance, was not met (mean changes +1 m and -9 m in the control and combination group, respectively). These results may have been skewed by three outliers in the iloprost group who presented with severe clinical worsening. None of the secondary end-points including functional class, peak oxygen uptake, and time to clinical worsening differed significantly between groups. The current study failed to show a positive effect of adding inhaled iloprost to bosentan in idiopathic pulmonary arterial hypertension patients. Further studies involving larger sample sizes and long-term follow-up are needed to determine the efficacy of adding inhaled iloprost to bosentan in patients with idiopathic pulmonary arterial hypertension.

Bosentan therapy for portopulmonary hypertension

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.

Use of aerosolized inhaled iloprost in the treatment of portopulmonary hypertension

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Combination therapy for portopulmonary hypertension with intravenous iloprost and oral bosentan.

SummarySevere portopulmonary hypertension (PPHTN) is a rare complication of liver cirrhosis and carries a poor prognosis. In the last years, intravenous (IV) epoprostenol has been suggested to be the optimal medical treatment for PPHTN, and recently oral bosentan has been shown to be efficacious and safe in selected patients with PPHTN. We report a case of PPHTN suffering from recurrent right heart failure while on treatment with IV iloprost, which was successfully managed by combination therapy with IV iloprost plus oral bosentan, providing sustained cardiopulmonary stabilization for at least two years. This report documents the first case of a patient with PPHTN successfully treated with the combination of IV iloprost and oral bosentan over an extended period. Thus, combination therapy with IV iloprost and oral bosentan might be a promising new option for selected patients suffering from PPHTN and recurrent right heart failure.ZusammenfassungDie schwere portopulmonale Hypertonie (PPHTN) ist eine seltene Komplikation einer Leberzirrhose und ist mit einer schlechten Prognose assoziiert. In den letzten Jahren wurde die intravenöse (i.v.) Epoprostenol-Therapie als die medikamentöse Standardtherapie angesehen. Kürzlich konnte gezeigt werden, dass orales Bosentan bei ausgewählten Patienten mit PPHTN wirksam und sicher ist. Wir berichten über einen Patienten mit PPHTN, der wiederholt Rechtsherzdekompensationen unter einer i.v. Therapie mit Iloprost erlitt und unter einer Kombinationstherapie mit i.v. Iloprost plus oralem Bosentan seit über zwei Jahren kardiopulmonal stabil ist. Dieser Bericht dokumentiert zum ersten Mal, dass ein Patient mit PPHTN erfolgreich mit der Kombinationstherapie von i.v. Iloprost plus oralem Bosentan über einen längeren Zeitraum therapiert wurde. Daher stellt die Kombinationstherapie bestehend aus i.v. Iloprost plus oralem Bosentan eine vielversprechende Alternative bei rezidivierendem Rechtsherzversagen bei ausgewählten Patienten mit PPHTN dar.

Haemoptysis due to pulmonary venous stenosis

Haemoptysis is a potentially life-threatening condition with the need for prompt diagnosis. In about 10–20% of all cases the bleeding source remains unexplained with the standard diagnostic approach. The aim of this article is to show the necessity of widening the diagnostic approach to haemoptysis with consideration of pulmonary venous stenosis as a possible cause of even severe haemoptysis and haemoptoe. A review of the literature was performed using the Medline/PubMed database with the terms: “pulmonary venous stenosis”, “pulmonary venous infarction” and “haemoptysis”. Further references from the case reports were considered. 58 case reports and case collections about patients with haemoptysis due to pulmonary venous stenosis were detected. This review gives an overview about the case reports and discusses the underlying pathophysiology and the pros and cons of different imaging techniques for the detection of pulmonary venous stenosis. Several conditions predispose to the obstruction of the mediastinal pulmonary veins. Clinical findings are unspecific and may be misleading. Pulmonary venous stenosis can be detected using several imaging techniques, yet three-dimensional magnetic resonance-angiography and three-dimensional contrast-enhanced computed tomography are the most appropriate. Pulmonary venous stenosis should be considered in patients with haemoptysis.

Riociguat dose titration in patients with chronic thromboembolic pulmonary hypertension (CTEPH) or pulmonary arterial hypertension (PAH)

Clinical background Despite recent advances, the prognosis for patients with pulmonary hypertension remains poor. Riociguat (BAY 63-2521) is a novel oral stimulator of the nitric oxide (NO) receptor soluble guanylate cyclase, and synergizes with low levels of bioavailable NO. Its safety and efficacy in dose titration were studied in patients with PAH (n = 33) or CTEPH (n = 42) in this multicenter open-label uncontrolled phase 2 trial.