Publications by authors named "Matthias Held"

65 Publications

COMPERA 2.0: A refined 4-strata risk assessment model for pulmonary arterial hypertension.

Eur Respir J 2021 Nov 4. Epub 2021 Nov 4.

Department of Respiratory Medicine, Eppendorf University Hospital, Hamburg, Germany.

Background: Risk stratification plays an essential role in the management of patients with pulmonary arterial hypertension (PAH). The current European guidelines propose a 3-strata model to categorise risk as low, intermediate, or high, based on the expected 1-year mortality. However, with this model, most patients are categorised as intermediate risk. We investigated a modified approach based on 4 risk categories with intermediate risk subdivided into intermediate-low and intermediate-high risk.

Methods: We analysed data from COMPERA, a European pulmonary hypertension registry, and calculated risk at diagnosis and first follow-up based on functional class (FC), 6 min walking distance (6 MWD) and serum levels of brain natriuretic peptide (BNP) or N-terminal fragment of pro-BNP (NT-proBNP), using refined cut-off values. Survival was assessed with Kaplan-Meier analyses, log-rank testing, and Cox proportional hazards models.

Results: Data from 1,655 patients with PAH were analysed. Using the 3-strata model, most patients were classified as intermediate risk (76.0% at baseline and 63.9% at first follow-up). The refined 4-strata risk model yielded a more nuanced separation and predicted long-term survival, especially at follow-up assessment. Changes in risk from baseline to follow-up were observed in 31.1% of the patients with the 3-strata model and in 49.2% with the 4-strata model. These changes, including those between the intermediate-low and intermediate-high strata, were associated with changes in long-term mortality risk.

Conclusions: Modified risk stratification using a 4-strata model based on refined cut-off levels for FC, 6MWD and BNP/NT-proBNP was more sensitive to prognostically relevant changes in risk than the original 3-strata model.
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http://dx.doi.org/10.1183/13993003.02311-2021DOI Listing
November 2021

Temporal trends in pulmonary arterial hypertension: Results from the COMPERA registry.

Eur Respir J 2021 Oct 21. Epub 2021 Oct 21.

Clinic for General and Interventional Cardiology and Angiology, Herz- und Diabeteszentrum NRW, Ruhr-Universität Bochum, Bad Oeynhausen, Germany.

Background: Since 2015, the European pulmonary hypertension guidelines recommend the use of combination therapy in most patients with pulmonary arterial hypertension (PAH). However, it is unclear to what extend this treatment strategy is adopted in clinical practice and if it is associated with improved long-term survival.

Methods: We analysed data from COMPERA, a large European pulmonary hypertension registry, to assess temporal trends in the use of combination therapy and survival of patients with newly diagnosed PAH between 2010 and 2019. For survival analyses, we look at annualized data and at cumulated data comparing the periods 2010-2014 and 2015-2019.

Results: A total of 2,531 patients were included. The use of early combination therapy (within 3 months after diagnosis) increased from 10.0% in patients diagnosed with PAH in 2010 to 25.0% in patients diagnosed with PAH in 2019. The proportion of patients receiving combination therapy 1 year after diagnosis increased from 27.7% to 46.3%. When comparing the 2010-2014 and 2015-2019 periods, 1-year survival estimates were similar (89.0% [95% CI, 87.2%, 90.9%] and 90.8% [95% CI, 89.3%, 92.4%]), respectively, whereas there was a slight but non-significant improvement in 3-year survival estimates (67.8% [95% CI, 65.0%, 70.8%] and 70.5% [95% CI, 67.8%, 73.4%]), respectively.

Conclusions: The use of combination therapy increased from 2010 to 2019, but most patients still received monotherapy. Survival rates at 1 year after diagnosis did not change over time. Future studies need to determine if the observed trend suggesting improved 3-year survival rates can be confirmed.
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http://dx.doi.org/10.1183/13993003.02024-2021DOI Listing
October 2021

[Functional characterization of patients with isolated post-capillary or combined post-capillary and pre-capillary pulmonary hypertension].

Dtsch Med Wochenschr 2021 Oct 20;146(21):e88-e94. Epub 2021 Oct 20.

Medizinische Klinik mit Schwerpunkt Pneumologie und Beatmungsmedizin, Standort Missioklinik, Klinikum Würzburg Mitte gGmbH.

Background:  The World Conference on PH recommended differentiation of isolated postcapillary (Ipc) and combined post- and precapillary (Cpc) PH according to pulmonary vascular resistance alone. The aim of this study was the haemodynamic and functional characterization of patients diagnosed IpcPH and CpcPH according to the current recommendation of the latest World Symposium on Pulmonary Hypertension (PH) with an exploratory data analysis.

Methods:  We evaluated all consecutive patients presenting at the PH outpatient clinic of Mission Medical Hospital from 2008-2015. All received a complete diagnostic work-up according to the guidelines. We analyzed data of patients with mPAP≥ 25 mmHg and pulmonary capillary wedge pressure (PCWP) > 15 mmHg. We compared anthropometric, hemodynamic and functional data of six-minute walking test (6 MWT), cardiopulmonary exercise testing (CPET) and echocardiography of patients with IpcPH and CpcPH.

Results:  Out of 726 patients 58 showed a postcapillary PH: IpcPH: n = 20; CpcPH: n = 38. Patients with IpcPH had a significantly lower mPAP and PVR than patients with CpcPH. Cardiac index was lower in the Cpc-PH group compared to the IpcPH group. Functional capacity did not differ. CpcPH patients showed a higher right/left atrial area (RA/LA)-ratio.

Discussion And Conclusion:  Although CpcPH patients showed higher values of mPAP and PVR functional capacity was not worse than in patients with IpcPH. In patients with PH due to left heart disease an elevated RA/LA ratio may indicate CpcPH and invasive diagnostic work-up should be considered.
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http://dx.doi.org/10.1055/a-1555-0345DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8550820PMC
October 2021

Technical Innovations in Pneumology: E-Health, Screening, Diagnostics, and Therapy.

Respiration 2021 7;100(10):1009-1015. Epub 2021 May 7.

Institute of Pneumology at the University of Cologne, Clinic of Pneumology and Allergology, Bethanien Hospital, Solingen, Germany.

At the 2020 "Luftschlösser" (castles in the air) conference, experts from a wide range of pneumological fields discussed technical innovations in pneumology, which can be seen in many different areas of the field, including e-health, screening, diagnostics, and therapy. They contribute to substantial advancements ranging from the innovative use of diagnostic tools to novel treatments for chronic lung diseases. Artificial intelligence enables broader screening, which can be expected to have beneficial effects on disease progression and overall prognosis. There is still a high demand for clinical trials to investigate the usefulness and risk-benefit ratio. Open questions remain especially about the quality and utility of medical apps in an inadequately regulated market. This article weighs the pros and cons of technical innovations in specific subspecialties of pneumology based on the lively exchange of ideas among various pneumological experts.
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http://dx.doi.org/10.1159/000516335DOI Listing
May 2021

Impact of the new definition of pulmonary hypertension according to world symposium of pulmonary hypertension 2018 on diagnosis of post-capillary pulmonary hypertension.

Int J Cardiol 2021 07 3;335:105-110. Epub 2021 Apr 3.

Department of Internal Medicine, Respiratory Medicine and Ventilatory Support, Medical Mission Hospital, Central Clinic Würzburg, Academic Teaching Hospital of the Julius Maximilian University of Würzburg, Würzburg, Germany.

Background: The World Symposium on Pulmonary Hypertension (WSPH) in 2018 recommended new definitions of pulmonary hypertension (PH). We investigated the impact of the updated definition on prevalence of PH due to left heart disease (PH-LHD).

Methods: The data of right heart catheterizations in patients with suspected PH-LHD between January 2008 and July 2015 was retrospectively analyzed applying different definitions. The number of patients diagnosed by the updated WSPH hemodynamic criteria of a mean pulmonary artery pressure (mPAP) > 20 mmHg was compared to the number of patients using mPAP ≥ 25 mmHg. The differentiation between patients with isolated post-capillary (Ipc) and combined post-capillary and pre-capillary (Cpc) PH was analyzed comparing the ESC/ERS guidelines, the recommendation of Cologne Consensus Conference (CCC) and WSPH.

Results: Of the 726 patients with a suspected PH, 58 patients met the diagnostic criteria of the ESC/ERS guidelines for PH-LHD with 32.8% Ipc-cases, 34.4% Cpc-PH-cases and 32.8% unclassifiable cases. Overall, 58 patients were diagnosed by the CCC criteria, with 34.5% classified as Cpc-PH and 65.5% as Icp-PH. Using the criteria of WSPH, the number of PH-LHD rose by one patient. According to the new definition, 64.4% of the patients were classified as Cpc-PH and had a significantly higher right to left atrial area (RA/LA) ratio than Ipc-PH patients.

Conclusion: Applying the new recommendation, the number of diagnosed patients with PH-LHD increases marginally. There is, however, a relevant shift in the number of Cpc-PH cases. An elevated RA/LA ratio might help to identify patients for invasive diagnostic work-up.
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http://dx.doi.org/10.1016/j.ijcard.2021.04.006DOI Listing
July 2021

Pirfenidone in patients with progressive fibrotic interstitial lung diseases other than idiopathic pulmonary fibrosis (RELIEF): a double-blind, randomised, placebo-controlled, phase 2b trial.

Lancet Respir Med 2021 05 30;9(5):476-486. Epub 2021 Mar 30.

Center for Interstitial and Rare Lung Diseases, Justus-Liebig University Giessen, Giessen, Germany; Member of the German Center for Lung Research and Cardiopulmonary Institute, and Agaplesion Lung Clinic Waldhof-Elgershausen, Greifenstein, Germany.

Background: Pirfenidone has been shown to slow disease progression in patients with idiopathic pulmonary fibrosis (IPF). However, there are few treatment options for progressive fibrotic interstitial lung diseases (ILDs)) other than IPF. In view of the pathomechanistic and clinical similarities between IPF and other progressive fibrotic ILDs, we aimed to assess the efficacy and safety of pirfenidone in patients with four non-IPF progressive fibrotic ILDs.

Methods: We did a multicentre, double-blind, randomised, placebo-controlled, parallel phase 2b trial (RELIEF) in 17 centres with expertise in ILD in Germany. Eligible participants were patients aged 18-80 years with progressive fibrotic ILD due to four diagnoses: collagen or vascular diseases (ie, connective tissue disease-associated ILDs), fibrotic non-specific interstitial pneumonia, chronic hypersensitivity pneumonitis, or asbestos-induced lung fibrosis. Other eligibility criteria included a forced vital capacity (FVC) of 40-90% predicted, a diffusing capacity of the lung for carbon monoxide of 10-90% predicted, and an annual decline of FVC of at least 5% predicted despite conventional therapy, based on at least three measurements within 6-24 months before enrolment. Patients who had received any previous antifibrotic therapy were excluded. We randomly assigned patients (1:1) to either oral pirfenidone (267 mg three times per day in week 1, 534 mg three times per day in week 2, and 801 mg three times per day thereafter) or matched placebo, added to their ongoing medication. Randomisation was done centrally using permuted block randomisation with varying block sizes stratified by the four diagnostic groups. Patients, investigators, statisticians, monitors, and the study coordinator were masked to treatment assignment until database closure. The placebo-controlled study period was 48 weeks (including up-titration). The primary endpoint was absolute change in percentage of predicted FVC (FVC % predicted) from baseline to week 48 in the intention-to-treat population, with imputation of missing data by the smallest sum of squared differences and attribution of deceased patients to the lowest rank in a rank ANCOVA model. Additionally, we did linear mixed-model repeated measures slope analyses of FVC % predicted longitudinal data over the course of the study as a prespecified sensitivity analysis and post-hoc sensitivity analyses of the primary endpoint in the intention-to-treat population using imputation methods of last observation carried forward [LOCF] and a regression-based multiple imputation procedure. Safety was assessed in all patients who received at least one dose of study medication. This trial is registered with EudraCT 2014-000861-32; DRKS00009822 and is no longer recruiting.

Findings: Between April 5, 2016, and Oct 4, 2018, we randomly assigned 127 patients to treatment: 64 to pirfenidone, 63 to placebo. After 127 patients had been randomised, the study was prematurely terminated on the basis of an interim analysis for futility triggered by slow recruitment. After 48 weeks and in the overall population of 127 patients, rank ANCOVA with diagnostic group included as a factor showed a significantly lower decline in FVC % predicted in the pirfenidone group compared with placebo (p=0·043); the result was similar when the model was stratified by diagnostic group (p=0·042). A significant treatment effect was also observed when applying the LOCF and multiple imputation methods to analyses of the primary endpoint. The median difference (Hodges-Lehmann estimate) between pirfenidone and placebo groups for the primary endpoint was 1·69 FVC % predicted (95% CI -0·65 to 4·03). In the linear mixed-model repeated measures slope analysis of FVC % predicted, the estimated difference between treatment and placebo groups from baseline to week 48 was 3·53 FVC % predicted (95% CI 0·21 to 6·86) with imputation of deaths as prespecified, or 2·79 FVC % predicted (95% CI 0·03 to 5·54) without imputation. One death (non-respiratory) occurred in the pirfenidone group (2%) and five deaths (three of which were respiratory) occurred in the placebo group (8%). The most frequent serious adverse events in both groups were infections and infestations (five [8%] in the pirfenidone group, ten [16%] in the placebo group); general disorders including disease worsening (two [3%] in the pirfenidone group, seven [11%] in the placebo group); and cardiac disorders (one ([2%] in the pirfenidone group, 5 [8%] in the placebo group). Adverse events (grade 3-4) of nausea (two patients on pirfenidone, two on placebo), dyspnoea (one patient on pirfenidone, one on placebo), and diarrhoea (one patient on pirfenidone) were also observed.

Interpretation: In view of the premature study termination, results should be interpreted with care. Nevertheless, our data suggest that in patients with fibrotic ILDs other than IPF who deteriorate despite conventional therapy, adding pirfenidone to existing treatment might attenuate disease progression as measured by decline in FVC.

Funding: German Center for Lung Research, Roche Pharma.
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http://dx.doi.org/10.1016/S2213-2600(20)30554-3DOI Listing
May 2021

Haemodynamic benefit of bridging use of bosentan prior to pulmonary endarterectomy.

Eur J Cardiothorac Surg 2021 10;60(4):840-847

Department of Thoracic and Cardiovascular Surgery, Saarland University Medical Center, Homburg/Saar, Germany.

Objectives: Some patients present with excessive pulmonary hypertension (PH) prior to pulmonary endarterectomy (PEA) for chronic thromboembolic pulmonary hypertension (CTEPH). This study was performed to evaluate the clinical role of pretreatment before PEA in CTEPH patients.

Methods: A total of 370 patients with CTEPH undergoing first PEA between 2003 and 2017 were divided into those receiving pretreatment with bosentan (group B: n = 119) and those without targeted pretreatment for PH (group C: n = 251). After selecting patients given bosentan (2-8 months) and using propensity score matching, comparable patient cohorts (n = 23 each) were created from both groups. PEA was performed in the standard manner, and the median number of extracted segments was 14.

Results: There were no significant differences in perioperative demographic characteristics or 30-day mortality (overall 5.7%) between the groups before and after matching. In patients with preoperative pulmonary vascular resistance (PVR) ≥800 dynes s/cm5, a significantly larger decrease in PVR was found in group B (78%) compared to group C (68%) (P = 0.033). There was no significant difference in late survival between the groups after matching. The frequency of residual/persistent PH (mean pulmonary artery pressure >25 mmHg) was lower in group B than in group C, although the difference was not significant (22% vs 39%, respectively, P = 0.200). Advanced age and longer cardiopulmonary bypass time were independent predictors of both 30-day mortality and residual/persistent PH (odds ratio: age, 1.053, 1.013, cardiopulmonary bypass time, 1.065, 1.010, respectively).

Conclusions: Preoperative treatment of CTEPH patients with bosentan for 2-8 months can improve post-PEA PVR without adverse clinical events in patients with a high preoperative PVR. A temporary bridging regime appears beneficial in selected patients prior to PEA.
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http://dx.doi.org/10.1093/ejcts/ezab137DOI Listing
October 2021

Pulmonary Hypertension in Patients With COPD: Results From the Comparative, Prospective Registry of Newly Initiated Therapies for Pulmonary Hypertension (COMPERA).

Chest 2021 Aug 11;160(2):678-689. Epub 2021 Feb 11.

German Center of Lung Research (DZL), Germany; Centre for Pulmonary Hypertension, Thoraxklinik Heidelberg gGmbH at Heidelberg University, Hospital, Heidelberg, Germany.

Background: Pulmonary hypertension (PH) in COPD is a poorly investigated clinical condition.

Research Question: Which factors determine the outcome of PH in COPD?

Study Design And Methods: We analyzed the characteristics and outcome of patients enrolled in the Comparative, Prospective Registry of Newly Initiated Therapies for Pulmonary Hypertension (COMPERA) with moderate or severe PH in COPD as defined during the 6th PH World Symposium who received medical therapy for PH and compared them with patients with idiopathic pulmonary arterial hypertension (IPAH).

Results: The population included incident patients with moderate PH in COPD (n = 68), with severe PH in COPD (n = 307), and with IPAH (n = 489). Patients with PH in COPD were older, predominantly male, and treated mainly with phosphodiesterase-5 inhibitors. Despite similar hemodynamic impairment, patients with PH in COPD achieved a worse 6-min walking distance (6MWD) and showed a more advanced World Health Organization functional class (WHO FC). Transplant-free survival rates at 1, 3, and 5 years were higher in the IPAH group than in the PH in COPD group (IPAH: 94%, 75%, and 55% vs PH in COPD: 86%, 55%, and 38%; P = .004). Risk factors for poor outcomes in PH in COPD were male sex, low 6MWD, and high pulmonary vascular resistance (PVR). In patients with severe PH in COPD, improvements in 6MWD by ≥ 30 m or improvements in WHO FC after initiation of medical therapy were associated with better outcomes.

Interpretation: Patients with PH in COPD were functionally more impaired and had a poorer outcome than patients with IPAH. Predictors of death in the PH in COPD group were sex, 6MWD, and PVR. Our data raise the hypothesis that some patients with severe PH in COPD may benefit from PH treatment. Randomized controlled studies are necessary to explore this hypothesis further.

Trial Registry: ClinicalTrials.gov; No.: NCT01347216; URL: www.clinicaltrials.gov.
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http://dx.doi.org/10.1016/j.chest.2021.02.012DOI Listing
August 2021

Quality of Life 3 and 12 Months Following Acute Pulmonary Embolism: Analysis From a Prospective Multicenter Cohort Study.

Chest 2021 06 3;159(6):2428-2438. Epub 2021 Feb 3.

Center for Thrombosis and Hemostasis, University Medical Center of the Johannes Gutenberg University, Mainz, Germany; Department of Cardiology, Democritus University of Thrace, Alexandroupolis, Greece. Electronic address:

Background: Few data are available on the long-term course and predictors of quality of life (QoL) following acute pulmonary embolism (PE).

Research Question: What are the kinetics and determinants of disease-specific and generic health-related QoL 3 and 12 months following an acute PE?

Study Design And Methods: The Follow-up after Acute Pulmonary Embolism (FOCUS) study prospectively followed up consecutive adult patients with objectively diagnosed PE. Patients were considered for study who completed the Pulmonary Embolism Quality of Life (PEmb-QoL) questionnaire at predefined visits 3 and 12 months following PE. The course of disease-specific QoL as assessed using the PEmb-QoL and the impact of baseline characteristics using multivariable mixed effects linear regression were studied; also assessed was the course of generic QoL as evaluated by using the EuroQoL Group 5-Dimension 5-Level utility index and the EuroQoL Visual Analog Scale.

Results: In 620 patients (44% women; median age, 62 years), overall disease-specific QoL improved from 3 to 12 months, with a decrease in the median PEmb-QoL score from 19.4% to 13.0% and a mean individual change of -4.3% (95% CI, -3.2 to -5.5). Female sex, cardiopulmonary disease, and higher BMI were associated with worse QoL at both 3 and 12 months. Over time, the association with BMI became weaker, whereas older age and previous VTE were associated with worsening QoL. Generic QoL also improved: the mean ± SD EuroQoL Group 5-Dimension 5-Level utility index increased from 0.85 ± 0.22 to 0.87 ± 0.20 and the visual analog scale from 72.9 ± 18.8 to 74.4 ± 19.1.

Interpretation: In a large cohort of survivors of acute PE, the change of QoL was quantified between months 3 and 12 following diagnosis, and factors independently associated with lower QoL and slower recovery of QoL were identified. This information may facilitate the planning and interpretation of clinical trials assessing QoL and help guide patient management.

Clinical Trial Registration: German Clinical Trials Registry (Deutsches Register Klinischer Studien: www.drks.de); No.: DRKS00005939.
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http://dx.doi.org/10.1016/j.chest.2021.01.071DOI Listing
June 2021

Pulmonary vasculitis due to infection with Mycobacterium goodii: A case report.

Int J Infect Dis 2021 Mar 29;104:178-180. Epub 2020 Dec 29.

Department of Internal Medicine, Respiratory Medicine and Ventilatory Support, Medical Mission Hospital, Central Clinic Würzburg, Academic Teaching Hospital of the Julius Maximilian University of Würzburg, Würzburg, Germany.

A 57-year-old Caucasian woman suffered from dyspnea on exertion. One year following a supposed pulmonary embolism event, a chronic thromboembolic vasculopathy was diagnosed and a pulmonary thromboendarterectomy was performed. However, a granulomatous pulmonary arterial vasculitis was identified upon examination. DNA of Mycobacterium goodii was detected as the most likely causative agent. Anti-inflammatory and anti-mycobacterial therapy was initiated for more than 12 months. Regular PET-CT scans revealed improvement under therapy. The last PET-CT did not show any tracer uptake following 10 months of therapy.
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http://dx.doi.org/10.1016/j.ijid.2020.12.074DOI Listing
March 2021

Response to Badagliacca et al: Multi-dimensional assessment and cluster analysis for idiopathic pulmonary arterial hypertension phenotyping.

J Heart Lung Transplant 2021 02 15;40(2):167-168. Epub 2020 Nov 15.

Department of Internal Medicine, Respiratory Medicine and Ventilatory Support, Medical Mission Hospital, Central Clinic Würzburg, Würzburg, Germany.

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http://dx.doi.org/10.1016/j.healun.2020.11.006DOI Listing
February 2021

Idiopathic pulmonary arterial hypertension phenotypes determined by cluster analysis from the COMPERA registry.

J Heart Lung Transplant 2020 12 30;39(12):1435-1444. Epub 2020 Sep 30.

Medizinische Klinik und Poliklinik I, Universitätsklinikum Carl Gustav Carus der Technischen Universität Dresden, Dresden, Germany.

The term idiopathic pulmonary arterial hypertension (IPAH) is used to categorize patients with pre-capillary pulmonary hypertension of unknown origin. There is considerable variability in the clinical presentation of these patients. Using data from the Comparative, Prospective Registry of Newly Initiated Therapies for Pulmonary Hypertension, we performed a cluster analysis of 841 patients with IPAH based on age, sex, diffusion capacity of the lung for carbon monoxide (DLCO; <45% vs ≥45% predicted), smoking status, and presence of comorbidities (obesity, hypertension, coronary heart disease, and diabetes mellitus). A hierarchical agglomerative clustering algorithm was performed using Ward's minimum variance method. The clusters were analyzed in terms of baseline characteristics; survival; and response to pulmonary arterial hypertension (PAH) therapy, expressed as changes from baseline to follow-up in functional class, 6-minute walking distance, cardiac biomarkers, and risk. Three clusters were identified: Cluster 1 (n = 106; 12.6%): median age 45 years, 76% females, no comorbidities, mostly never smokers, DLCO ≥45%; Cluster 2 (n = 301; 35.8%): median age 75 years, 98% females, frequent comorbidities, no smoking history, DLCO mostly ≥45%; and Cluster 3 (n = 434; 51.6%): median age 72 years, 72% males, frequent comorbidities, history of smoking, and low DLCO. Patients in Cluster 1 had a better response to PAH treatment than patients in the 2 other clusters. Survival over 5 years was 84.6% in Cluster 1, 59.2% in Cluster 2, and 42.2% in Cluster 3 (unadjusted p < 0.001 for comparison between all groups). The population of patients diagnosed with IPAH is heterogenous. This cluster analysis identified distinct phenotypes, which differed in clinical presentation, response to therapy, and survival.
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http://dx.doi.org/10.1016/j.healun.2020.09.011DOI Listing
December 2020

Survival and quality of life after early discharge in low-risk pulmonary embolism.

Eur Respir J 2021 02 4;57(2). Epub 2021 Feb 4.

Emergency Dept, Clinico San Carlos Hospital, IdISSC, Madrid, Spain.

Introduction: Early discharge of patients with acute low-risk pulmonary embolism requires validation by prospective trials with clinical and quality-of-life outcomes.

Methods: The multinational Home Treatment of Patients with Low-Risk Pulmonary Embolism with the Oral Factor Xa Inhibitor Rivaroxaban (HoT-PE) single-arm management trial investigated early discharge followed by ambulatory treatment with rivaroxaban. The study was stopped for efficacy after the positive results of the predefined interim analysis at 50% of the planned population. The present analysis includes the entire trial population (576 patients). In addition to 3-month recurrence (primary outcome) and 1-year overall mortality, we analysed self-reported disease-specific (Pulmonary Embolism Quality of Life (PEmb-QoL) questionnaire) and generic (five-level five-dimension EuroQoL (EQ-5D-5L) scale) quality of life as well as treatment satisfaction (Anti-Clot Treatment Scale (ACTS)) after pulmonary embolism.

Results: The primary efficacy outcome occurred in three (0.5%, one-sided upper 95% CI 1.3%) patients. The 1-year mortality was 2.4%. The mean±sd PEmb-QoL decreased from 28.9±20.6% at 3 weeks to 19.9±15.4% at 3 months, a mean change (improvement) of -9.1% (p<0.0001). Improvement was consistent across all PEmb-QoL dimensions. The EQ-5D-5L was 0.89±0.12 at 3 weeks after enrolment and improved to 0.91±0.12 at 3 months (p<0.0001). Female sex and cardiopulmonary disease were associated with poorer disease-specific and generic quality of life; older age was associated with faster worsening of generic quality of life. The ACTS burden score improved from 40.5±6.6 points at 3 weeks to 42.5±5.9 points at 3 months (p<0.0001).

Conclusions: Our results further support early discharge and ambulatory oral anticoagulation for selected patients with low-risk pulmonary embolism. Targeted strategies may be necessary to further improve quality of life in specific patient subgroups.
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http://dx.doi.org/10.1183/13993003.02368-2020DOI Listing
February 2021

Pulmonary Hypertension in Adults with Congenital Heart Disease: Real-World Data from the International COMPERA-CHD Registry.

J Clin Med 2020 05 13;9(5). Epub 2020 May 13.

Missionsärztliche Klinik gGmbH, Abteilung für Innere Medizin, 97074 Würzburg, Germany.

Introduction: Pulmonary hypertension (PH) is a common complication in patients with congenital heart disease (CHD), aggravating the natural, post-operative, or post-interventional course of the underlying anomaly. The various CHDs differ substantially in characteristics, functionality, and clinical outcomes among each other and compared with other diseases with pulmonary hypertension.

Objective: To describe current management strategies and outcomes for adults with PH in relation to different types of CHD based on real-world data.

Methods And Results: COMPERA (Comparative, Prospective Registry of Newly Initiated Therapies for Pulmonary Hypertension) is a prospective, international PH registry comprising, at the time of data analysis, >8200 patients with various forms of PH. Here, we analyzed a subgroup of 680 patients with PH due to CHD, who were included between 2007 and 2018 in 49 specialized centers for PH and/or CHD located in 11 European countries. At enrollment, the patients´ median age was 44 years (67% female), and patients had either pre-tricuspid shunts, post-tricuspid shunts, complex CHD, congenital left heart or aortic disease, or miscellaneous other types of CHD. Upon inclusion, targeted therapies for pulmonary arterial hypertension (PAH) included endothelin receptor antagonists, PDE-5 inhibitors, prostacyclin analogues, and soluble guanylate cyclase stimulators. Eighty patients with Eisenmenger syndrome were treatment-naïve. While at inclusion the primary PAH treatment for the cohort was monotherapy (70% of patients), with 30% of the patients on combination therapy, after a median observation time of 45.3 months, the number of patients on combination therapy had increased significantly, to 50%. The use of oral anticoagulants or antiplatelets was dependent on the underlying diagnosis or comorbidities. In the entire COMPERA-CHD cohort, after follow-up and receiving targeted PAH therapy ( = 511), 91 patients died over the course of a 5-year follow up. The 5-year Kaplan-Meier survival estimate for CHD associated PH was significantly better than that for idiopathic PAH (76% vs. 54%; < 0.001). Within the CHD associated PH group, survival estimates differed particularly depending on the underlying diagnosis and treatment status.

Conclusions: In COMPERA-CHD, the overall survival of patients with CHD associated PH was dependent on the underlying diagnosis and treatment status, but was significantly better as than that for idiopathic PAH. Nevertheless, overall survival of patients with PAH due to CHD was still markedly reduced compared with survival of patients with other types of CHD, despite an increasing number of patients on PAH-targeted combination therapy.
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http://dx.doi.org/10.3390/jcm9051456DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7290703PMC
May 2020

Survival and course of lung function in the presence or absence of antifibrotic treatment in patients with idiopathic pulmonary fibrosis: long-term results of the INSIGHTS-IPF registry.

Eur Respir J 2020 08 13;56(2). Epub 2020 Aug 13.

German Center for Lung Research (DZL), Germany.

Objective: There is a paucity of observational data on antifibrotic therapy for idiopathic pulmonary fibrosis (IPF). We aimed to assess the course of disease of IPF patients with and without antifibrotic therapy under real-life conditions.

Methods: We analysed data from a non-interventional, prospective cohort study of consecutively enrolled IPF patients from 20 interstitial lung disease expert centres in Germany. Data quality was ensured by automated plausibility checks, on-site monitoring, and source data verification. Propensity scores were applied to account for known differences in baseline characteristics between patients with and without antifibrotic therapy.

Results: Among the 588 patients suitable for analysis, the mean±sd age was 69.8±9.1 years, and 81.0% were male. The mean±sd duration of disease since diagnosis was 1.8±3.4 years. The mean±sd value at baseline for forced vital capacity (FVC) and diffusion capacity ( ) were 68.6±18.8% predicted and 37.8±18.5% predicted, respectively. During a mean±sd follow-up of 1.2±0.7 years, 194 (33.0%) patients died. The 1-year and 2-year survival rates were 87% 46% and 62% 21%, respectively, for patients with without antifibrotic therapy. The risk of death was 37% lower in patients with antifibrotic therapy (hazard ratio 0.63, 95% CI 0.45; 0.87; p=0.005). The results were robust (and remained statistically significant) on multivariable analysis. Overall decline of FVC and was slow and did not differ significantly between patients with or without antifibrotic therapy.

Conclusions: Survival was significantly higher in IPF patients with antifibrotic therapy, but the course of lung function parameters was similar in patients with and without antifibrotic therapy. This suggests that in clinical practice, premature mortality of IPF patients eventually occurs despite stable measurements for FVC and .
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http://dx.doi.org/10.1183/13993003.02279-2019DOI Listing
August 2020

Prognostic value of cardiopulmonary exercise testing in patients with systemic sclerosis.

BMC Pulm Med 2019 Nov 29;19(1):230. Epub 2019 Nov 29.

Department of Internal Medicine, Medical University of Graz, Division of Pulmonology, Graz, Austria.

Background: Systemic sclerosis (SSc) is a severe rheumatic disease of the interstitial tissue, in which heart and lung involvement can lead to disease-specific mortality. Our study tests the hypothesis that in addition to established prognostic factors, cardiopulmonary exercise testing (CPET) parameters, particularly peak oxygen uptake (peakVO) and ventilation/carbon dioxide (VE/VCO)-slope, can predict survival in patients with SSc.

Subjects And Methods: We retrospectively assessed 210 patients (80.9% female) in 6 centres over 10 years with pulmonary testing and CPET. Survival was analysed with Cox regression analysis (adjusted for age and gender) by age, comorbidity (Charlson-Index), body weight, body-mass index, extensive interstitial lung disease, pulmonary artery pressure (measured by echocardiography and invasively), and haemodynamic, pulmonary and CPET parameters.

Results: Five- and ten-year survival of SSc patients was 93.8 and 86.9%, respectively. There was no difference in survival between patients with diffuse (dcSSc) and limited cutaneous manifestation (lcSSc; p = 0.3). Pulmonary and CPET parameters were significantly impaired. Prognosis was worst for patients with pulmonary hypertension (p = 0.007), 6-min walking distance < 413 m (p = 0.003), peakVO < 15.6 mL∙kg∙min, and VE/VCO-slope > 35. Age (hazard ratio HR = 1.23; 95% confidence interval CI: 1.14;1.41), VE/VCO-slope (HR = 0.9; CI 0.82;0.98), diffusion capacity (Krogh factor, HR = 0.92; CI 0.86;0.98), forced vital capacity (FVC, HR = 0.91; CI 0.86;0.96), and peakVO (HR = 0.87; CI 0.81;0.94) were significantly linked to survival in multivariate analyses (Harrell's C = 0.95). This is the first large study with SSc patients that demonstrates the prognostic value of peakVO < 15.6 mL∙kg∙min (< 64.5% of predicted peakVO) and VE/VCO-slope > 35.
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http://dx.doi.org/10.1186/s12890-019-1003-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6884803PMC
November 2019

[Hemodynamic Definition of Pulmonary Hypertension: Commentary on the Proposed Change by the 6th World Symposium on Pulmonary Hypertension].

Dtsch Med Wochenschr 2019 09 5;144(19):1367-1372. Epub 2019 Jul 5.

Klinik für Pneumologie, Medizinische Hochschule Hannover und Deutsches Zentrum für Lungenforschung (DZL).

The ESC/ERS guidelines (published at the end of 2015) and other international recommendations defined pulmonary hypertension (PH) by an invasively measured mean pulmonary arterial pressure (mPAP) ≥ 25 mmHg at rest. At the 6 World Symposium on Pulmonary Hypertension in Nice a modification of this hemodynamic definition in the sense of lowering the threshold to > 20 mmHg was proposed. A pulmonary vascular resistance (PVR) ≥ 3 Wood units (WU) is additionally required for the diagnosis of pre-capillary PH. This modification must be critically reviewed with regard to the underlying rationale and possible consequences. Therefore, a detailed explanation is required. In particular, it must be made clear that this change currently has no influence on the evidence-based and approval-compliant prescription of drugs for the targeted therapy of pulmonary arterial hypertension (PAH).
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http://dx.doi.org/10.1055/a-0918-3772DOI Listing
September 2019

Early discharge and home treatment of patients with low-risk pulmonary embolism with the oral factor Xa inhibitor rivaroxaban: an international multicentre single-arm clinical trial.

Eur Heart J 2020 01;41(4):509-518

Helios Albert-Schweitzer-Klinik, Albert-Schweitzer-Weg 1, 37154 Northeim, Germany.

Aims: To investigate the efficacy and safety of early transition from hospital to ambulatory treatment in low-risk acute PE, using the oral factor Xa inhibitor rivaroxaban.

Methods And Results: We conducted a prospective multicentre single-arm investigator initiated and academically sponsored management trial in patients with acute low-risk PE (EudraCT Identifier 2013-001657-28). Eligibility criteria included absence of (i) haemodynamic instability, (ii) right ventricular dysfunction or intracardiac thrombi, and (iii) serious comorbidities. Up to two nights of hospital stay were permitted. Rivaroxaban was given at the approved dose for PE for ≥3 months. The primary outcome was symptomatic recurrent venous thromboembolism (VTE) or PE-related death within 3 months of enrolment. An interim analysis was planned after the first 525 patients, with prespecified early termination of the study if the null hypothesis could be rejected at the level of α = 0.004 (<6 primary outcome events). From May 2014 through June 2018, consecutive patients were enrolled in seven countries. Of the 525 patients included in the interim analysis, three (0.6%; one-sided upper 99.6% confidence interval 2.1%) suffered symptomatic non-fatal VTE recurrence, a number sufficiently low to fulfil the condition for early termination of the trial. Major bleeding occurred in 6 (1.2%) of the 519 patients comprising the safety population. There were two cancer-related deaths (0.4%).

Conclusion: Early discharge and home treatment with rivaroxaban is effective and safe in carefully selected patients with acute low-risk PE. The results of the present trial support the selection of appropriate patients for ambulatory treatment of PE.
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http://dx.doi.org/10.1093/eurheartj/ehz367DOI Listing
January 2020

The clinical course of idiopathic pulmonary fibrosis and its association to quality of life over time: longitudinal data from the INSIGHTS-IPF registry.

Respir Res 2019 Mar 15;20(1):59. Epub 2019 Mar 15.

Medizinische Klinik und Poliklinik V, Klinikum der LMU, Munich, Germany.

Background: Quality of life (QoL) is profoundly impaired in patients with idiopathic pulmonary fibrosis (IPF). However, data is limited regarding the course of QoL. We therefore analysed longitudinal data from the German INSIGHTS-IPF registry.

Methods: Clinical status and QoL were assessed at enrollment and subsequently at 6- to 12-months intervals. A range of different QoL questionnaires including the St. George's Respiratory Questionnaire (SGRQ) were used.

Results: Data from 424 patients were included; 76.9% male; mean age 68.7 ± 9.1 years, mean FVC% predicted 75.9 ± 19.4, mean DL% predicted 36.1 ± 15.9. QoL worsened significantly during follow-up with higher total SGRQ scores (increased by 1.47 per year; 95% CI: 1.17 to 1.76; p < 0.001) and higher UCSD-SOBQ scores and lower EQ-5D VAS and WHO-5 scores. An absolute decline in FVC% predicted of > 10% was associated with a significant deterioration in SGRQ (increasing by 9.08 units; 95% CI: 2.48 to 15.67; p = 0.007), while patients with stable or improved FVC had no significantly change in SGRQ. Patients with a > 10% decrease of DL predicted also had a significant increase in SGRQ (+ 7.79 units; 95% CI: 0.85 to 14.73; p = 0.028), while SQRQ was almost stable in patients with stable or improved DL. Patients who died had a significant greater increase in SGRQ total scores (mean 11.8 ± 18.6) at their last follow-up visit prior to death compared to survivors (mean 4.2 ± 18.9; HR = 1.03; 95% CI: 1.01 to 1.04; p < 0.001). All QoL scores across the follow-up period were significantly worse in hospitalised patients compared to non-hospitalised patients, with the worst scores reported in those hospitalised for acute exacerbations.

Conclusions: QoL assessments in the INSIGHTS-IPF registry demonstrate a close relationship between QoL and clinically meaningful changes in lung function, comorbidities, disease duration and clinical course of IPF, including hospitalisation and mortality.
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http://dx.doi.org/10.1186/s12931-019-1020-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6420774PMC
March 2019

Risk assessment in medically treated chronic thromboembolic pulmonary hypertension patients.

Eur Respir J 2018 11 8;52(5). Epub 2018 Nov 8.

Dept of Respiratory Medicine, Hannover Medical School and German Center of Lung Research (DZL), Hannover, Germany.

Abbreviated versions of the risk stratification strategy of the European Society of Cardiology (ESC)/European Respiratory Society (ERS) pulmonary hypertension guidelines have been recently validated in patients with pulmonary arterial hypertension. We aimed to investigate their prognostic value in medically treated chronic thromboembolic pulmonary hypertension (CTEPH) patients from the COMPERA registry, which collects six variables of interest (World Health Organization Functional Class, 6-min walk distance, brain natriuretic peptide, right atrial pressure, cardiac index and mixed venous oxygen saturation).We included patients with at least one follow-up visit, no pulmonary endarterectomy and at least three of the six variables available, and classified the patients into low-, intermediate- and high-risk groups. As a secondary analysis, the number of noninvasive low-risk criteria was counted. The association between risk assessment and survival was evaluated.Data from inclusion and follow-up (median 7 months) visits were available for 561 and 231 patients, respectively. Baseline 1- and 5-year survival estimates were significantly different (p<0.0001) in the baseline low-risk (98.6% and 88.3%, respectively), intermediate-risk (94.9% and 61.8%, respectively) and high-risk (75.5% and 32.9%, respectively) cohorts. Follow-up data were even more discriminative, with 100%, 92% and 69% 1-year survival, respectively. The number of low-risk noninvasive criteria was also associated with survival.These analyses suggest that the ESC/ERS risk assessment may be applicable in patients with medically treated CTEPH.
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http://dx.doi.org/10.1183/13993003.00248-2018DOI Listing
November 2018

Definition, clinical classification and initial diagnosis of pulmonary hypertension: Updated recommendations from the Cologne Consensus Conference 2018.

Int J Cardiol 2018 Dec 27;272S:11-19. Epub 2018 Aug 27.

Center for Pulmonary Hypertension and Lung Vascular Diseases, Department of Internal Medicine, Missionsklinik Würzburg, Germany.

In the summer of 2016, delegates from the German Society of Cardiology (DGK), the German Respiratory Society (DGP), and the German Society of Pediatric Cardiology (DGPK) met in Cologne, Germany, to define consensus-based practice recommendations for the management of patients with pulmonary hypertension (PH). These recommendations were built on the 2015 European Pulmonary Hypertension guidelines, aiming at their practical implementation, considering country-specific issues, and including new evidence, where available. To this end, a number of working groups was initiated, one of which was specifically dedicated to the definition, clinical classification and initial diagnosis of PH. While the European guidelines provide a detailed clinical classification and a structured approach for diagnostic testing, their application in routine care may be challenging, particularly given the changing phenotype of PH patients who are nowadays often elderly and may present with multiple potential causes of PH, as well as comorbid conditions. Specifically, the working group addresses the thoroughness of diagnostic testing, and the roles of echocardiography, exercise testing, and genetic testing in diagnosing PH. Furthermore, challenges in the diagnostic work-up of patients with various causes of PH including "PAH with comorbidities", CTEPH and coexisting conditions are highlighted, and a modified diagnostic algorithm is provided. The detailed results and recommendations of the working group on definition, clinical classification and initial diagnosis of PH, which were last updated in the spring of 2018, are summarized in this article.
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http://dx.doi.org/10.1016/j.ijcard.2018.08.083DOI Listing
December 2018

Chronic thromboembolic pulmonary hypertension (CTEPH): Updated Recommendations from the Cologne Consensus Conference 2018.

Int J Cardiol 2018 Dec 28;272S:69-78. Epub 2018 Aug 28.

Department of Thoracic Surgery, Kerckhoff-Clinic GmbH, Benekestr. 2-8, 61231 Bad Nauheim, Germany.

Chronic thromboembolic pulmonary hypertension (CTEPH) is a subgroup of pulmonary hypertension that differs from all other forms of PH in terms of its pathophysiology, patient characteristics and treatment. For implementation of the European Guidelines on Diagnosis and Treatment of Pulmonary Hypertension in Germany, the Cologne Consensus Conference 2016 was held and last updated in spring of 2018. One of the working groups was dedicated to CTEPH, practical and controversial issues were commented and updated. In every patient with suspected PH, CTEPH or chronic thromboembolic disease (CTED, i.e. symptomatic residual vasculopathy without pulmonary hypertension) should be excluded. Primary treatment is surgical pulmonary endarterectomy (PEA) in a multidisciplinary CTEPH centre. Inoperable patients or patients with persistent or recurrent CTEPH after PEA are candidates for targeted drug therapy. There is increasing experience with balloon pulmonary angioplasty (BPA) for inoperable patients; this option, like PEA, is reserved for specialised centres with expertise in this treatment method.
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http://dx.doi.org/10.1016/j.ijcard.2018.08.079DOI Listing
December 2018

Pulmonary hypertension due to lung diseases: Updated recommendations from the Cologne Consensus Conference 2018.

Int J Cardiol 2018 Dec 11;272S:63-68. Epub 2018 Aug 11.

Medizinische Klinik und Poliklinik II, Universities of Giessen and Marburg Lung Center (UGMLC), Mitglied des Deutschen Zentrums für Lungenforschung (DZL), Gießen, Germany.

The 2015 European Guidelines on Pulmonary Hypertension did not only cover pulmonary arterial hypertension (PAH) but also some aspects of pulmonary hypertension (PH) associated with chronic lung disease. The European Guidelines point out that the drugs currently used to treat patients with PAH (prostanoids, endothelin receptor antagonists, phosphodiesterase‑5 inhibitors, sGC stimulators) have not been sufficiently investigated in other forms of PH. Therefore, the European Guidelines do not recommend the use of these drugs in patients with chronic lung disease and PH. This recommendation, however, is not always in agreement with medical ethics as physicians sometimes feel inclined to treat other forms of PH which may affect quality of life and survival of these patients in a similar manner. To this end, it is crucial to consider the severity of both PH and the underlying lung disease. In June 2016, a Consensus Conference organized by the PH working groups of the German Society of Cardiology (DGK), the German Society of Respiratory Medicine (DGP) and the German Society of Paediatric Cardiology (DGPK) was held in Cologne, Germany, to discuss open and controversial issues surrounding the practical implementation of the European Guidelines. Several working groups were created, one of which was dedicated to the diagnosis and treatment of PH in patients with chronic lung disease. The 2018 updated recommendations of this working group are summarized in the present paper.
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http://dx.doi.org/10.1016/j.ijcard.2018.08.043DOI Listing
December 2018

[Pulmonary embolism].

MMW Fortschr Med 2018 Mar;160(Suppl 1):48-56

Universitätsklinikum des Saarlandes, Homburg/Saar, Deutschland.

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http://dx.doi.org/10.1007/s15006-018-0010-6DOI Listing
March 2018

Dabigatran after Short Heparin Anticoagulation for Acute Intermediate-Risk Pulmonary Embolism: Rationale and Design of the Single-Arm PEITHO-2 Study.

Thromb Haemost 2017 12 6;117(12):2425-2434. Epub 2017 Dec 6.

Center for Thrombosis and Hemostasis, University Medical Center Mainz, Mainz, Germany.

Patients with intermediate-risk pulmonary embolism (PE) may, depending on the method and cut-off values used for definition, account for up to 60% of all patients with PE and have an 8% or higher risk of short-term adverse outcome. Although four non-vitamin K-dependent direct oral anticoagulants (NOACs) have been approved for the treatment of venous thromboembolism, their safety and efficacy as well as the optimal anticoagulation regimen using these drugs have not been systematically investigated in intermediate-risk PE. Moreover, it remains unknown how many patients with intermediate-high-risk and intermediate-low-risk PE were included in most of the phase III NOAC trials. The ongoing Pulmonary Embolism International Thrombolysis 2 (PEITHO-2) study is a prospective, multicentre, multinational, single-arm trial investigating whether treatment of acute intermediate-risk PE with parenteral heparin anticoagulation over the first 72 hours, followed by the direct oral thrombin inhibitor dabigatran over 6 months, is effective and safe. The primary efficacy outcome is recurrent symptomatic venous thromboembolism or death related to PE within the first 6 months. The primary safety outcome is major bleeding as defined by the International Society on Thrombosis and Haemostasis. Secondary outcomes include all-cause mortality, the overall duration of hospital stay (index event and repeated hospitalizations) and the temporal pattern of recovery of right ventricular function over the 6-month follow-up period. By applying and evaluating a contemporary risk-tailored treatment strategy for acute PE, PEITHO-2 will implement the recommendations of current guidelines and contribute to their further evolution.
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http://dx.doi.org/10.1160/TH17-06-0434DOI Listing
December 2017

Anxiety, Depression, and Health-Related QOL in Patients Diagnosed with PAH or CTEPH.

Lung 2017 12 9;195(6):759-768. Epub 2017 Oct 9.

Department of Internal Medicine, Academic Teaching Hospital of the Julius Maximilian University of Würzburg, Medical Mission Hospital, Salvatorstrasse 7, 97074, Würzburg, Germany.

Background: Pulmonary arterial hypertension (PAH) and chronic thromboembolic pulmonary hypertension (CTEPH) are life-threatening diseases with a high burden of symptoms. Although depression, anxiety, and reduced health related quality of life (HRQOL) have also been reported, a comparative analysis which explores these traits and their underlying factors was lacking.

Methods: A retrospective analysis of depression, anxiety, and health related QOL was conducted using a Hospital anxiety and depression scale (HADS) as well as the SF-36 HRQOL questionnaire. Results from these tools were compared with haemodynamic and functional parameters in 70 PAH and 23 CTEPH outpatients from a German tertiary care center specializing in pulmonary hypertension.

Results: Although HRQOL was reduced in both cohorts of patients, individuals diagnosed with CTEPH scored lower in nearly all SF-36 parameters. Significance was noted in both "mental health" (p = 0.01) and "mental component summary score" (MCS) (p = 0.02). Depression was also more frequent in patients with CTEPH (56%) than in patients with PAH (30%), (p = 0.03). Overall, depression and anxiety correlated with most SF-36 scales in both PAH and CTEPH. In CTEPH, depression also correlated with the Borg Dyspnea Scale (r = 0.44, p = 0.01). These patients also had significantly lower pCO levels than the PAH cohort reflecting more severe ventilation/perfusion mismatch. All other haemodynamic and functional parameters did not differ across the groups.

Conclusion: While both cohorts of patients suffer from a reduced HRQOL as well as depression and anxiety, decreases in mental health parameters are more pronounced in the CTEPH cohort. This suggests a strong effort to improve early detection, especially in dyspneic patients with classical risk factors for CTEPH and PAH and argues for mental illness interventions alongside routine clinical care provided to patients diagnosed with PAH or CTEPH.
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http://dx.doi.org/10.1007/s00408-017-0052-zDOI Listing
December 2017

Health related quality of life in patients with idiopathic pulmonary fibrosis in clinical practice: insights-IPF registry.

Respir Res 2017 07 14;18(1):139. Epub 2017 Jul 14.

Comprehensive Pneumology Center, Lungenforschungsambulanz, Klinikum der Universität München, München, Germany.

Background: The INSIGHTS-IPF registry provides one of the largest data sets of clinical data and self-reported patient related outcomes including health related quality of life (QoL) on patients with idiopathic pulmonary fibrosis (IPF). We aimed to describe associations of various QoL instruments between each other and with patient characteristics at baseline.

Methods: Six hundred twenty-three IPF patients with available QoL data (St George's Respiratory Questionnaire SGRQ, UCSD Shortness-of-Breath Questionnaire SoB, EuroQol visual analogue scale and index EQ-5D, Well-being Index WHO-5) were analysed. Mean age was 69.6 ± 8.7 years, 77% were males, mean disease duration 2.0 ± 3.3 years, FVC pred was 67.5 ± 17.8%, DL pred 35.6 ± 17%.

Results: Mean points were SGRQ total 48.3, UCSD SoB 47.8, EQ-5D VAS 66.8, and WHO-5 13.9. These instruments had a high or very high correlation (exception WHO-5 to EQ-5D VAS with moderate correlation). On bivariate analysis, QoL by SGRQ total was statistically significantly associated with clinical symptoms (NYHA; p < 0.001), number of comorbidities (p < 0.05), hospitalisation rate (p < 0.01) and disease severity (as measured by GAP score, CPI, FVC and 6-min walk test; p < 0.05 each). Multivariate analyses showed a significant association between QoL (by SGRQ total) and IPF duration, FVC, age, NYHA class and indication for long-term oxygen treatment.

Conclusions: Overall, IPF patients under real-life conditions have lower QoL compared to those in clinical studies. There is a meaningful relationship between QoL and various patient characteristics.

Trial Registration: The INSIGHTS-IPF registry is registered at Clinicaltrials.gov ( NCT01695408 ).
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http://dx.doi.org/10.1186/s12931-017-0621-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5512739PMC
July 2017

The safety and pharmacokinetics of rapid iloprost aerosol delivery via the BREELIB nebulizer in pulmonary arterial hypertension.

Pulm Circ 2017 Apr-Jun;7(2):505-513. Epub 2017 May 12.

1 Department of Internal Medicine II, University of Giessen and Marburg Lung Center and Member of the German Center of Lung Research, Giessen, Germany.

The BREELIB nebulizer was developed for iloprost to reduce inhalation times for patients with pulmonary arterial hypertension (PAH). This multicenter, randomized, unblinded, four-part study compared inhalation time, pharmacokinetics, and acute tolerability of iloprost 5 µg at mouthpiece delivered via BREELIB versus the standard I-Neb nebulizer in 27 patients with PAH. The primary safety outcome was the proportion of patients with a maximum increase in heart rate (HR) ≥ 25% and/or a maximum decrease in systolic blood pressure ≥ 20% within 30 min after inhalation. Other safety outcomes included systolic, diastolic, and mean blood pressure, HR, oxygen saturation, and adverse events (AEs). Median inhalation times were considerably shorter with BREELIB versus I-Neb (2.6 versus 10.9 min; n = 24). Maximum iloprost plasma concentration and systemic exposure (area under the plasma concentration-time curve) were 77% and 42% higher, respectively, with BREELIB versus I-Neb. Five patients experienced a maximum systolic blood pressure decrease ≥ 20%, four with BREELIB (one mildly and transiently symptomatic), and one with I-Neb; none required medical intervention. AEs reported during the study were consistent with the known safety profile of iloprost. The BREELIB nebulizer offers reduced inhalation time, good tolerability, and may improve iloprost aerosol therapy convenience and thus compliance for patients with PAH.
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http://dx.doi.org/10.1177/2045893217706691DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5467944PMC
May 2017

Diagnosis of chronic thromboembolic pulmonary hypertension.

Eur Respir Rev 2017 Jan 15;26(143). Epub 2017 Mar 15.

Medical Mission Hospital, Dept of Internal Medicine, Center for Pulmonary Hypertension and Pulmonary Vascular Disease, Academic Teaching Hospital, Julius-Maximilian University of Würzburg, Würzburg, Germany.

Chronic thromboembolic pulmonary hypertension (CTEPH) is the only potentially curable form of pulmonary hypertension. Rapid and accurate diagnosis is pivotal for successful treatment. Clinical signs and symptoms can be nonspecific and risk factors such as history of venous thromboembolism may not always be present. Echocardiography is the recommended first diagnostic step. Cardiopulmonary exercise testing is a complementary tool that can help to identify patients with milder abnormalities and chronic thromboembolic disease, triggering the need for further investigation. Ventilation/perfusion ('/') scintigraphy is the imaging methodology of choice to exclude CTEPH. Single photon emission computed tomography '/' is gaining popularity over planar imaging. Assessment of pulmonary haemodynamics by right heart catheterisation is mandatory, although there is increasing interest in noninvasive haemodynamic evaluation. Despite the status of digital subtraction angiography as the gold standard, techniques such as computed tomography (CT) and magnetic resonance imaging are increasingly used for characterising the pulmonary vasculature and assessment of operability. Promising new tools include dual-energy CT, combination of rotational angiography and cone beam CT, and positron emission tomography. These innovative procedures not only minimise misdiagnosis, but also provide additional vascular information relevant to treatment planning. Further research is needed to determine how these modalities will fit into the diagnostic algorithm for CTEPH.
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http://dx.doi.org/10.1183/16000617.0108-2016DOI Listing
January 2017

Frequency and prognostic impact of mid-expiratory flow reduction in stable patients six months after hospitalisation for heart failure with reduced ejection fraction.

Int J Cardiol 2017 Jan 28;227:727-733. Epub 2016 Oct 28.

University Hospital Würzburg and University of Würzburg, Comprehensive Heart Failure Center, Würzburg, Germany; University Hospital Würzburg, Department of Internal Medicine I, Würzburg, Germany; Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, The Netherlands.

Aim: This study investigates the prevalence and prognostic impact of central and small airways obstruction (CAO and SAO) in patients with stable heart failure (HF).

Methods & Results: Spirometry was performed in 585 outpatients (mean age 65±12years, 75% male) six months after hospitalisation for acute decompensation secondary to HF with ejection fraction <40%. We assessed forced expiratory volume in the first second (FEV1), forced vital capacity (FVC) and mid-expiratory flow (MEF) at 50% of FVC. CAO was defined by FEV1/FVC <0.7. SAO was defined by FEV1/FVC ≥0.7 plus MEF <60% of predicted value. CAO and SAO were excluded in 359 patients (61% of all). MEF <60% predicted was found in 226 patients (39% of all), among those 88 with CAO (15% of all) and 138 (24% of all) with SAO. During a twelve month follow-up, 42 patients (7.2%) died. Mortality rates of patients with CAO and SAO were comparable (12.5% and 10.9%, respectively, p=0.74), and both higher than in patients without airways obstruction (4.5%, both p<0.01). In univariable Cox regression analysis, both CAO and SAO were associated with 2-fold increased all-cause mortality risk (hazard ratios [95% confidence intervals]: 2.78 [1.33-6.19], p=0.007 and 2.51 [1.24-5.08], p=0.010, respectively). Adjustment for determinants of CAO and SAO, prognostic markers of heart failure and comorbidities attenuated the association of mortality with CAO but not with SAO.

Conclusions: SAO is more common than CAO and indicates an increased mortality risk in HF. Thus, reduced MEF may be a feature of patients at risk and merits special attention in HF management.
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http://dx.doi.org/10.1016/j.ijcard.2016.10.071DOI Listing
January 2017
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