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Background: Dissecting the determinants of functional capacity during long-term follow-up after acute pulmonary embolism (PE) can help to better characterize a patient population with persisting limitation., Methods: In a prospective cohort study, consecutive unselected survivors of acute PE underwent 3- and 12-month follow-up, including six-minute walking distance (6MWD) and dyspnea assessment with the modified Medical Research Council (mMRC) scale. We used reference equations adjusting for age, sex, and anthropometric measurements to define abnormal 6MWD., Results: Overall, 323 of 363 (89.0%) patients had at least one recorded 6MWD value at one year. At 3 months, the prevalence of abnormal 6MWD was 21.9% and at 12 months it was 18.3%. At 3 and 12 months, 58.8% and 52.1% with abnormal 6MWD did not report dyspnea, respectively. On average and during follow-up, 6MWD significantly improved with time, while the mMRC dyspnea scale did not. Abnormal 6MWD was associated with younger age (odds ratio per decade, 0.91; 95% CI, 0.88-0.94), higher body mass index (1.10; 1.03-1.17), smoking (3.53; 1.34-9.31), intermediate- or high-risk PE (3.21; 1.21-8.56), and higher mMRC grading (2.28; 1.59-3.27). Abnormal 6MWD at 3 months was associated with the prospectively defined endpoint of post-PE impairment (3.72; 1.50-9.28) and with poor disease-specific and generic health-related quality of life., Conclusion: Three months after PE, 37% of patients reported dyspnea and 22% had abnormal 6MWD. After a year, 20% still had abnormal 6MWD. Dyspnea correlated with abnormal 6MWD, but over 50% of patients with abnormal 6MWD did not report dyspnea. Abnormal 6MWD predicted subsequent post-pulmonary embolism impairment and worse long-term quality of life., Clinical Trial Registration: German Clinical Trials Register Identifier DRKS00005939., Competing Interests: Declaration of competing interests I.T.F. reports no conflicts of interest. L.V. reports no conflicts of interest. S.B. reports grants or contracts from Bayer, INARI, Boston Scientific, Medtronic, Bard, SANOFI, and Concept Medical; consulting fees from INARI; payment or honoraria from INARI, Boston Scientific, and Concept Medical; and support for attending meetings and/or travel from Bayer and Daiichi Sankyo. K.C.C. reports no conflicts of interest. R.E. reports lecture fees from Boehringer Ingelheim, OMT, Novartis, Janssen-Cilag, United Therapeutics, AstraZeneca, Berlin Chemie, research funding from Boehringer Ingelheim, OMT, Janssen-Cilag, and consulting fees from BetaPharm, OMT, Lungpacer Medical. G.G. reports personal lecture/advisory fees from Bayer HealthCare, Pfizer and LeoPharma. M.H. reports honoraria for lectures and advisory board activities from Astra Zeneca, Bayer HealthCare, Berlin Chemie, Boehringer Ingelheim, Bristol Myers Squibb, Daichi Sankyo, Janssen, MSD, OMT, Pfizer, Santis. L.H. reports consulting fees from MSD and Janssen. K.K. reports no conflicts of interest. H.W. reports lecture and consulting fees from Actelion/Janssen, GSK, Bayer HealthCare, Daiichi Sanchyo, Biotest, Boehringer Ingelheim, MSD and Roche. S.R. reports grants or contracts from Actelion, AstraZeneca, Bayer, Janssen, and Novartis; consulting fees from Abbott, Acceleron, Actelion, Bayer, Janssen, MSD, Novartis, Pfizer, United Therapeutics, and Vifor; payment or honoraria from Actelion, Bayer, BMS, Ferrer, GSK, Janssen, MSD, Novartis, Pfizer, United Therapeutics, and Vifor. S.V.K. reports grants or contracts from Bayer AG; consulting fees from Bayer AG, Daiichi Sankyo, and Boston Scientific; and payment or honoraria from Bayer AG, MSD, Pfizer, and Bristol-Myers Squibb., (Copyright © 2023. Published by Elsevier Inc.)

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., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

We aimed to characterise the association of pulmonary hypertension due to hypoventilation and exercise capacity, and the haemodynamic and functional changes under noninvasive ventilation. A retrospective analysis was carried out to assess haemodynamics and functional capacity in 18 patients with daytime pulmonary hypertension, due to hypoventilation, at baseline and after 3 months of noninvasive ventilation. Patients presented with a mean±SD pulmonary artery pressure of 49±13 mmHg, preserved cardiac index (3.2±0.66 L·min(-1)·m(-2)), 6-min walking distance of 303±134 m and severely elevated N-terminal pro-brain natriuretic peptide (NT-proBNP) levels. Mean pulmonary artery pressure correlated negatively with maximum work rate (R= -0.72; p=0.03) and 6-min walking distance (R= -0.62; p=0.01). Following noninvasive ventilation we found a significant reduction of mean pulmonary artery pressure (-18 mmHg; p<0.001) and NT-proBNP levels (-2110 pg·mL(-1); p=0.001), and improvement in the 6-min walking distance (+66 m; p=0.008) and maximum work rate (+18 W; p=0.028). Changes in work rate correlated inversely with pulmonary artery pressure (R= -0.75; p=0.031). In this specific cohort with hypoventilation and severe pulmonary hypertension, pulmonary hypertension was associated with reduced exercise capacity. Following noninvasive ventilation, haemodynamics and exercise capacity improved significantly.

Pulmonary hypertension (PH) is a common consequence of COPD. It has been speculated that patients showing serious PH and vascular remodeling without severe airway obstruction might benefit from vasoactive treatment. There is no approved drug available for COPD-induced PH. Most trials assessing the efficacy of vasoactive drugs in PH have had a follow-up of 12-16 weeks. We report on 4 subjects with COPD and PH. Pulmonary arterial hypertension associated diseases and pulmonary embolism were ruled out. PH persisted despite optimized treatment of underlying COPD and comorbidities, so bosentan was started in all 4 subjects. With bosentan the mean pulmonary artery pressure improved. The average gains in 6-min walk distance at 2-3 months and 8-9 months were 36 m and 145 m, respectively. The maximum gains in 6-min walk distance of the individual subjects were at the 9th, 13th, and 18th month. Oxygenation was stable, and no side effects were observed. We suggest from this experience that in clinical trials of PH in COPD, a follow-up of 16 weeks might cause underestimation of the treatment effects.

Background: The Global initiative for chronic Obstructive Lung Disease (GOLD) defines COPD as a fixed post-bronchodilator ratio of forced expiratory volume in 1 second and forced vital capacity (FEV1/FVC) below 0.7. Age-dependent cut-off values below the lower fifth percentile (LLN) of this ratio derived from the general population have been proposed as an alternative. We wanted to assess the diagnostic accuracy and prognostic capability of the GOLD and LLN definition when compared to an expert-based diagnosis., Methods: In a prospective cohort study, 405 patients aged ≥ 65 years with a general practitioner's diagnosis of COPD were recruited and followed up for 4.5 (median; quartiles 3.9; 5.1) years. Prevalence rates of COPD according to GOLD and three LLN definitions and diagnostic performance measurements were calculated. The reference standard was the diagnosis of COPD of an expert panel that used all available diagnostic information, including spirometry and bodyplethysmography., Results: Compared to the expert panel diagnosis, 'GOLD-COPD' misclassified 69 (28%) patients, and the three LLNs misclassified 114 (46%), 96 (39%), and 98 (40%) patients, respectively. The GOLD classification led to more false positives, the LLNs to more false negative diagnoses. The main predictors beyond the FEV1/FVC ratio for an expert diagnosis of COPD were the FEV1 % predicted, and the residual volume/total lung capacity ratio (RV/TLC). Adding FEV1 and RV/TLC to GOLD or LLN improved the diagnostic accuracy, resulting in a significant reduction of up to 50% of the number of misdiagnoses. The expert diagnosis of COPD better predicts exacerbations, hospitalizations and mortality than GOLD or LLN., Conclusions: GOLD criteria over-diagnose COPD, while LLN definitions under-diagnose COPD in elderly patients as compared to an expert panel diagnosis. Incorporating FEV1 and RV/TLC into the GOLD-COPD or LLN-based definition brings both definitions closer to expert panel diagnosis of COPD, and to daily clinical practice.