Riociguat for the treatment of chronic thromboembolic pulmonary hypertension.

BACKGROUND: Riociguat, a member of a new class of compounds (soluble guanylate cyclase stimulators), has been shown in previous clinical studies to be beneficial in the treatment of chronic thromboembolic pulmonary hypertension. METHODS: In this phase 3, multicenter, randomized, double-blind, placebo-controlled study, we randomly assigned 261 patients with inoperable chronic thromboembolic pulmonary hypertension or persistent or recurrent pulmonary hypertension after pulmonary endarterectomy to receive placebo or riociguat. The primary end point was the change from baseline to the end of week 16 in the distance walked in 6 minutes. Secondary end points included changes from baseline in pulmonary vascular resistance, N-terminal pro-brain natriuretic peptide (NT-proBNP) level, World Health Organization (WHO) functional class, time to clinical worsening, Borg dyspnea score, quality-of-life variables, and safety. RESULTS: By week 16, the 6-minute walk distance had increased by a mean of 39 m in the riociguat group, as compared with a mean decrease of 6 m in the placebo group (least-squares mean difference, 46 m; 95% confidence interval [CI], 25 to 67; P<0.001). Pulmonary vascular resistance decreased by 226 dyn · sec · cm-5in the riociguat group and increased by 23 dyn · sec · cm-5in the placebo group (least-squares mean difference, -246 dyn · sec · cm-5; 95% CI, -303 to -190; P<0.001). Riociguat was also associated with significant improvements in the NT-proBNP level (P<0.001) and WHO functional class (P = 0.003). The most common serious adverse events were right ventricular failure (in 3% of patients in each group) and syncope (in 2% of the riociguat group and in 3% of the placebo group). CONCLUSIONS: Riociguat significantly improved exercise capacity and pulmonary vascular resistance in patients with chronic thromboembolic pulmonary hypertension. (Funded by Bayer HealthCare; CHEST-1 and CHEST-2 ClinicalTrials.gov numbers, NCT00855465 and NCT00910429, respectively.) Copyright © 2013 Massachusetts Medical Society

Monitoring of lung edema by microwave reflectometry during lung ischemia-reperfusion injury in vivo

It is still unclear whether lung edema can be monitored by microwave reflectometry and whether the measured changes in lung dry matter content (DMC) are accompanied by changes in PaO(2) and in pro-to anti-inflammatory cytokine expression (IFN-gamma and IL-10). Right rat lung hili were cross-clamped at 37 degrees C for 0, 60, 90 or 120 min ischemia followed by 120 min reperfusion. After 90 min (DMC: 15.9 +/- 1.4%; PaO(2): 76.7 +/- 18 mm Hg) and 120 min ischemia (DMC: 12.8 +/- 0.6%; PaO(2): 43 +/- 7 mm Hg), a significant decrease in DMC and PaO(2) throughout reperfusion compared to 0 min ischemia (DMC: 19.5 +/- 1.11%; PaO(2): 247 +/- 33 mm Hg; p < 0.05) was observed. DMC and PaO(2) decreased after 60 min ischemia but recovered during reperfusion (DMC: 18.5 +/- 2.4%; PaO(2) : 173 +/- 30 mm Hg). DMC values reflected changes on the physiological and molecular level. In conclusion, lung edema monitoring by microwave reflectometry might become a tool for the thoracic surgeon. Copyright (c) 2006 S. Karger AG, Basel

Aortic valve replacement performed twice through ministernotomy 15 years after lung transplantation.

After transplantation, steroids and calcineurin inhibitors together with end-stage renal failure may lead to associated cardiovascular diseases, particularly in long-term survivors. We present a case of aortic valve replacement 15 years after lung transplantation, followed by reoperative valve replacement for late infective endocarditis. Lung compliance and gas exchange were excellent during recovery. Despite adequate prophylaxis, immunosuppression and hemodialysis likely contributed to repeated episodes of sepsis, which caused detachment of the first aortic prosthesis. Despite the high mortality of prosthetic valve endocarditis, the postoperative course was uneventful and the patient is doing well at 24-month follow-up

Airway bleeding during pulmonary endarterectomy: the "bubbles" technique.

Pulmonary endarterectomy (PEA) is a technically demanding operation, currently performed in few centers worldwide. 1 A bloodless surgical field is mandatory to identify the correct arterial dissection plane, which has to be extended toward subsegmental branches with limited visibility. Vessel perforation is a rare but potentially fatal complication, leading to uncontrollable airway bleeding. A general algorithm for the approach to pulmonary hemorrhage has been proposed by the group from the University of California at San Diego,2 whereas alternative managements are only briefly mentioned in the literature.3 Extracorporeal life support unloads pulmonary circulation but invariably requires anticoagulation, which is detrimental in pulmonary hemorrhage. We describe a novel technique for the treatment of intraoperative airway bleeding during PEA

Lung retransplantation 3 yrs after heart-lung transplantation.

The main long-term complication after lung transplantation is chronic rejection in terms of obliterative bronchiolitis; when therapy does not arrest the progression of the airflow obstruction, lung retransplantation seems to be. at present, the only strategy in the management of chronic rejection. We report the 12 month follow-up of a single lung retransplantation in a 21 yr old female who had received a heart-lung transplantation 35 months previously for Eisenmenger syndrome. The patient had excellent first allograft function and quality of life for 26 months, then progressively deteriorated due to the occurrence of obliterative bronchiolitis, and further worsened in the following 9 months. At that time, she underwent left lung retransplantation, based on her negative history of infection, low rate of acute rejection, ambulatory status, and young age. She is now doing well at 12 months after retransplantation and her forced expiratory volume in one second is still improving, p thus justifying both retransplantation and hopeful expectatio