Pulmonary Hypertension in Patients with Chronic Fibrosing Idiopathic Interstitial Pneumonias

Background Pulmonary hypertension (PH) is a common finding in patients with chronic fibrosing idiopathic interstitial pneumonias (IIP). Little is known about the response to pulmonary vasodilator therapy in this patient population. COMPERA is an international registry that prospectively captures data from patients with various forms of PH receiving pulmonary vasodilator therapies. Methods We retrieved data from COMPERA to compare patient characteristics, treatment patterns, response to therapy and survival in newly diagnosed patients with idiopathic pulmonary arterial hypertension (IPAH) and PH associated with IIP (PH-IIP). Results Compared to patients with IPAH (n = 798), patients with PH-IIP (n = 151) were older and predominantly males. Patients with PH-IIP were treated predominantly with phosphodiesterase-5 inhibitors (88% at entry, 87% after 1 year). From baseline to the first follow-up visit, the median improvement in 6MWD was 30 m in patients with IPAH and 24.5 m in patients with PH-IIP (p = 0.457 for the difference between both groups). Improvements in NYHA functional class were observed in 22.4% and 29.5% of these patients, respectively (p = 0.179 for the difference between both groups). Survival rates were significantly worse in PH-IIP than in IPAH (3-year survival 34.0 versus 68.6%; p<0.001). Total lung capacity, NYHA class IV, and mixed-venous oxygen saturation were independent predictors of survival in patients with PH-IIP. Conclusions Patients with PH-IIP have a dismal prognosis. Our results suggest that pulmonary vasodilator therapy may be associated with short-term functional improvement in some of these patients but it is unclear whether this treatment affects survival

Riociguat treatment in patients with pulmonary arterial hypertension: Final safety data from the EXPERT registry

Objective The soluble guanylate cyclase stimulator riociguat is approved for the treatment of adult patients with pulmonary arterial hypertension (PAH) and inoperable or persistent/recurrent chronic thromboembolic pulmonary hypertension following Phase 3 randomized trials. The EXPosurE Registry RiociguaT in patients with pulmonary hypertension (EXPERT) study was designed to monitor the long-term safety of riociguat in clinical practice. Methods EXPERT was an international, multicenter, prospective, uncontrolled, non-interventional cohort study of patients treated with riociguat. Patients were followed for at least 1 year and up to 4 years from enrollment or until 30 days after stopping riociguat treatment. Primary safety outcomes were adverse events (AEs) and serious adverse events (SAEs) coded using Medical Dictionary for Regulatory Activities preferred terms and System Organ Classes version 21.0, collected during routine clinic visits (usually every 3–6 months) and collated via case report forms. Results In total, 326 patients with PAH were included in the analysis. The most common AEs in these patients were dizziness (11.7%), right ventricular (RV)/cardiac failure (10.7%), edema/peripheral edema (10.7%), diarrhea (8.6%), dyspnea (8.0%), and cough (7.7%). The most common SAEs were RV/cardiac failure (10.1%), pneumonia (6.1%), dyspnea (4.0%), and syncope (3.4%). The exposure-adjusted rate of hemoptysis/pulmonary hemorrhage was 2.5 events per 100 patient-years. Conclusion Final data from EXPERT show that in patients with PAH, the safety of riociguat in clinical practice was consistent with clinical trials, with no new safety concerns identified and a lower exposure-adjusted rate of hemoptysis/pulmonary hemorrhage than in the long-term extension of the Phase 3 trial in PAH

Die Subanalyse von Rheuma-VOR zeigt den erheblichen Bedarf der rheumatologischen Versorgung auf

Background: Early diagnosis and treatment of inflammatory rheumatic diseases can prevent consequential damage such as permanently limited mobility and joint or organ damage. Simultaneously, there is an increasing deficit in medical care owing to the lack of rheumatological capacity. Rural regions are particularly affected. Objectives: The available unconfirmed diagnoses of the study Rheuma-VOR were analysed regarding another definitive inflammatory rheumatic disease. Materials and methods: The returned questionnaires of the rheumatologists participating in Rheuma-VOR were screened for definitive inflammatory rheumatic diseases other than the required diagnosis of rheumatoid arthritis, psoriatic arthritis or spondyloarthritis. Results: Of 910 unconfirmed diagnoses, in 245 patients another definitive diagnosis could be confirmed. A total of 29.8% of the diagnoses corresponded to degenerative joint changes or chronic pain syndrome, whereas 26.1% involved different forms of inflammatory arthritis. The majority of diagnoses (40.5%) were collagenosis or vasculitis, Discussion: The available data show that a rheumatological presentation was indicated for the majority of patients. Owing to the increasing deficits in medical care a prior selection of the patients is crucial to make optimal use of restricted rheumatological capacities.Hintergrund: Eine frühe Diagnose und Behandlung entzündlich-rheumatischer Erkrankungen kann Folgeschäden wie dauerhafte Einschränkungen der Mobilität und Gelenk- oder Organschäden verhindern. Gleichzeitig besteht ein größer werdendes Versorgungsdefizit aufgrund fehlender rheumatologischer Kapazitäten. Betroffen sind besonders die ländlichen Regionen. Ziel der Arbeit: Die vorliegenden nicht bestätigten Diagnosen der Studie Rheuma-VOR wurden hinsichtlich des Vorliegens einer anderen definitiven entzündlich-rheumatischen Erkrankung analysiert. Material und Methoden: Die eingegangenen Fragebögen der an der Rheuma-VOR-Studie teilnehmenden Rheumatolog:innen wurden nach Vermerken anderer entzündlich-rheumatischer Erkrankungen als der geforderten Diagnose einer rheumatoiden Arthritis, Psoriasis-Arthritis oder Spondyloarthritis gescreent. Ergebnisse: Von 910 „nicht bestätigten“ Diagnosen waren bei 245 Patient:innen andere gestellte Diagnosen auszuwerten. Insgesamt 29,8 % der Diagnosen entsprechen degenerativen Gelenkveränderungen oder chronischen Schmerzsyndromen, bei 26,1 % lagen verschiedene Formen entzündlicher Arthritiden vor. Der Großteil der Diagnosen (40,5 %) entfiel auf Kollagenosen und Vaskulitiden, wobei die Polymyalgia rheumatica mit 20 % am häufigsten diagnostiziert wurde (49 Patient:innen). Diskussion: Die vorliegenden Daten zeigen, dass bei einem Großteil der Patient:innen die rheumatologische Vorstellung indiziert war. Aufgrund der ambulanten Versorgungsdefizite ist eine vorherige Selektion des Patientenguts essenziell, um die eingeschränkten Kapazitäten bestmöglich zu nutzen

Riociguat treatment in patients with chronic thromboembolic pulmonary hypertension: Final safety data from the EXPERT registry

Objective: The soluble guanylate cyclase stimulator riociguat is approved for the treatment of adult patients with pulmonary arterial hypertension (PAH) and inoperable or persistent/recurrent chronic thromboembolic pulmonary hypertension (CTEPH) following Phase 3 randomized trials. The EXPosurE Registry RiociguaT in patients with pulmonary hypertension (EXPERT) study was designed to monitor the long-term safety of riociguat in clinical practice. Methods: EXPERT was an international, multicenter, prospective, uncontrolled, non-interventional cohort study of patients treated with riociguat. Patients were followed for at least 1 year and up to 4 years from enrollment or until 30 days after stopping riociguat treatment. Primary safety outcomes were adverse events (AEs) and serious adverse events (SAEs) coded using Medical Dictionary for Regulatory Activities preferred terms and System Organ Classes version 21.0, collected during routine clinic visits and collated via case report forms. Results: In total, 956 patients with CTEPH were included in the analysis. The most common AEs in these patients were peripheral edema/edema (11.7%), dizziness (7.5%), right ventricular (RV)/cardiac failure (7.7%), and pneumonia (5.0%). The most common SAEs were RV/cardiac failure (7.4%), pneumonia (4.1%), dyspnea (3.6%), and syncope (2.5%). Exposure-adjusted rates of hemoptysis/pulmonary hemorrhage and hypotension were low and comparable to those in the long-term extension study of riociguat (Chronic Thromboembolic Pulmonary Hypertension Soluble Guanylate Cyclase–Stimulator Trial [CHEST-2]). Conclusion: Data from EXPERT show that in patients with CTEPH, the safety of riociguat in routine practice was consistent with the known safety profile of the drug, and no new safety concerns were identified

Long-term results from the EARLY study of bosentan in WHO functional class II pulmonary arterial hypertension patients.

Abstract BACKGROUND: The double-blind phase of the EARLY study of bosentan remains the only randomized controlled trial of a PAH-targeted therapy in World Health Organization functional class (FC) II patients. We report on the efficacy, safety, disease worsening, survival and prognostic factors in mildly symptomatic pulmonary arterial hypertension (PAH) patients treated with bosentan in the open-label extension phase of the EARLY study. METHODS: Exploratory efficacy outcomes included 6-minute walk distance (6 MWD) and WHO FC. Adverse events were recorded. Kaplan-Meier analysis was used to estimate time to first PAH worsening event (death, initiation of intravenous or subcutaneous prostanoids, atrial septostomy or lung transplantation) and survival. Cox regression analysis determined factors prognostic of survival. RESULTS: Median exposure to bosentan (n=173) was 51 months. At the end of the bosentan-treatment assessment period, 77.8% of patients were in WHO FC I/II. Adverse events led to discontinuation of bosentan in 20.2% of patients. Aminotransferase elevations>3× upper limit of normal occurred in 16.8%. Four-year PAH-event-free survival and survival were 79.5% (95% confidence intervals [95% CI] 73.4, 85.6) and 84.8% [95% CI 79.4, 90.2], respectively. Low 6 MWD, low mixed venous oxygenation, high N-terminal pro hormone of brain natriuretic peptide levels and PAH associated with connective tissue disease were associated with a higher risk of death. CONCLUSIONS: The majority of patients exposed to long-term bosentan maintained or improved their functional class. Approximately 20% of the patients discontinued treatment because of adverse events, which were most commonly PAH worsening and elevated liver enzymes

Metacognitive Short-Term Intervention in Patients With Mental Disorders Following Cardiovascular Events

Background: Mental disorders are common among patients with severe cardiovascular diseases (CVD). Yet, there is a lack of easily accessible evidence-based treatments. Recent research indicates elevated prevalence of dysfunctional metacognitions in patients with mental disorders following cardiovascular events. As metacognitive therapy (MCT) is an established treatment to modify metacognitions, we tested if a brief metacognitive intervention via videotelephony is effective in this patient group. Methods: A brief MCT treatment was tailored to CVD patients and designed as a face-to-face internet-based intervention. Five patients with CVDs and comorbid mental disorders underwent a psychocardiological examination and diagnostic approach. Each patient participated in eight 50 min sessions via encrypted video messenger service. Metacognitions, depression and anxiety symptoms and quality of life were assessed by self-report measures pre- and post-treatment. Patients rated dysfunctional thought processes, current psychological impairment, and treatment satisfaction after each session. Intended follow-up measures were not reported due to missing data. Results: For most patients, the brief metacognitive intervention was associated with a decrease in dysfunctional metacognitions and a reduction of symptoms of anxiety and depression post-treatment. Psychological and physiological quality of life improved. Patients reported high satisfaction with the tailored treatment. Conclusion: Our results suggest that a brief internet-based metacognitive treatment may be a promising tool for patients with CVDs and comorbid mental disorders. Feasibility and acceptance of the intervention was rated high by the patients. Further research is necessary to support the preliminary findings and to adapt and evaluate the intervention in a controlled clinical trial setting. Copyright © 2022 Gebhardt, Caldarone, Westhoff-Bleck, Olsson, Hoeper, Park, Stapel, Breitner, Werth, Heitland and Kahl

Use of responder threshold criteria to evaluate the response to treatment in the phase III CHEST-1 study

BackgroundIn the Chronic Thromboembolic Pulmonary Hypertension Soluble Guanylate Cyclase - Stimulator Trial 1 (CHEST-1) study, riociguat improved 6-minute walking distance (6MWD) vs placebo in patients with inoperable chronic thromboembolic pulmonary hypertension or persistent/recurrent pulmonary hypertension after pulmonary endarterectomy. In this study, the proportion of patients who achieved responder thresholds that correlate with improved outcome in patients with pulmonary arterial hypertension was determined at baseline and at the end of CHEST-1.MethodsPatients received placebo or riociguat individually adjusted up to 2.5 mg 3 times a day for 16 weeks. Response criteria were defined as follows: 6MWD increase ≥40 m, 6MWD ≥380 m, cardiac index ≥2.5 liters/min/m2, pulmonary vascular resistance <500 dyn∙sec∙cm−5, mixed venous oxygen saturation ≥65%, World Health Organization functional class I/II, N-terminal pro-brain natriuretic peptide <1,800 pg/ml, and right atrial pressure <8 mm Hg.ResultsRiociguat increased the proportion of patients with 6MWD ≥380 m, World Health Organization functional class I/II, and pulmonary vascular resistance <500 dyn∙sec∙cm−5 from 37%, 34%, and 25% at baseline to 58%, 57%, and 50% at Week 16, whereas there was little change in placebo-treated patients (6MWD ≥380 m, 43% vs 44%; World Health Organization functional class I/II, 29% vs 38%; pulmonary vascular resistance <500 dyn∙sec∙cm−5, 27% vs 26%). Similar changes were observed for thresholds for cardiac index, mixed venous oxygen saturation, N-terminal pro-brain natriuretic peptide, and right atrial pressure.ConclusionsIn this exploratory analysis, riociguat increased the proportion of patients with inoperable chronic thromboembolic pulmonary hypertension or persistent/recurrent pulmonary hypertension after pulmonary endarterectomy achieving criteria defining a positive response to therapy

Comparison of hemodynamic parameters in treatment-naïve and pre-treated patients with pulmonary arterial hypertension in the randomized phase III PATENT-1 study

Background Detailed hemodynamic data from the phase III PATENT-1 study of riociguat in patients with pulmonary arterial hypertension (PAH) were investigated. Methods Patients with PAH who were treatment naïve or pre-treated with endothelin receptor antagonists or non-intravenous prostanoids were randomly assigned to riociguat up to 2.5 mg 3 times a day or placebo. Hemodynamic parameters were assessed at baseline and week 12. Results Riociguat significantly decreased pulmonary vascular resistance in treatment-naïve (n = 221; least squares [LS] mean difference −266 dyne∙sec∙cm−5 [95% confidence interval (CI) −357 to −175; p < 0.0001]) and pre-treated (n = 222; LS mean difference −186 dyne∙sec ∙cm−5 [95% CI −252 to −120; p < 0.0001]) patients and significantly increased cardiac index (LS mean difference +0.7 [95% CI 0.5 to 0.8] and +0.5 [95% CI 0.3 to 0.7], respectively [both p < 0.0001]). Mean pulmonary artery pressure (p = 0.0056 and p = 0.0019 for treatment-naïve and pre-treated patients, respectively), mean arterial pressure (both p < 0.0001), and systemic vascular resistance (both p < 0.0001) were significantly reduced, and there was an increase in mixed venous oxygen saturation (p < 0.0001 and p = 0.0004, respectively). Results were similar in patients pre-treated with endothelin receptor antagonists and patients pre-treated with non-intravenous prostanoids. Improvements in 6-minute walking distance correlated very weakly with improvements in pulmonary vascular resistance (r = −0.21 [95% CI −0.30 to −0.11; p < 0.0001]) and cardiac index (r = 0.16 [95% CI 0.06 to 0.25; p < 0.0016]). Conclusions Riociguat significantly improved hemodynamic parameters in pre-treated and treatment-naïve patients with PAH