Search

Background: Pulmonary hypertension (PH) is a heterogeneous disease with a poor prognosis. Accurate risk stratification is essential for guiding treatment decisions in pulmonary arterial hypertension (PAH). Although various risk models have been developed for PAH, their comparative prognostic potential requires further exploration. Additionally, the applicability of risk scores in PH groups beyond group 1 remains to be investigated., Research Question: Are risk scores originally developed for PAH predictive in PH groups 1 through 4?, Study Design and Methods: We conducted a comprehensive analysis of outcomes among patients with incident PH enrolled in the multicenter worldwide Pulmonary Vascular Research Institute GoDeep meta-registry. Analyses were performed across PH groups 1 through 4 and further subgroups to evaluate the predictive value of PAH risk scores, including the Registry to Evaluate Early and Long-Term PAH Disease Mangement (REVEAL) Lite 2, REVEAL 2.0, European Society of Cardiology/European Respiratory Society 2022, Comparative, Prospective Registry of Newly Initiated Therapies for Pulmonary Hypertension (COMPERA) 3-strata, and COMPERA 4-strata., Results: Eight thousand five hundred sixty-five patients were included in the study, of whom 3,537 patients were assigned to group 1 PH, whereas 1,807 patients, 1,635 patients, and 1,586 patients were assigned to group 2 PH, group 3 PH, and group 4 PH, respectively. Pulmonary hemodynamics were impaired with median mean pulmonary arterial pressure of 42 mm Hg (interquartile range, 33-52 mm Hg) and pulmonary vascular resistance of 7 Wood units (WU) (interquartile range, 4-11 WU). All risk scores were prognostic in the entire PH population and in each of the PH groups 1 through 4. The REVEAL scores, when used as continuous prediction models, demonstrated the highest statistical prognostic power and granularity; the COMPERA 4-strata risk score provided subdifferentiation of the intermediate-risk group. Similar results were obtained when separately analyzing various subgroups (PH subgroups 1.1, 1.4.1, and 1.4.4; PH subgroups 3.1 and 3.2; group 2 with isolated postcapillary PH vs combined precapillary and postcapillary PH; patients of all groups with concomitant cardiac comorbidities; and severe [> 5 WU] vs nonsevere PH)., Interpretation: This comprehensive study with real-world data from 15 PH centers showed that PAH-designed risk scores possess predictive power in a large PH cohort, whether considered as common to the group or calculated separately for each PH group (1-4) and various subgroups., Trial Registry: ClinicalTrials.gov; No.: NCT05329714; URL: www., Clinicaltrials: gov., Competing Interests: Financial/Nonfinancial Disclosures The authors have reported to CHEST the following: A. Y. has received personal fees from MSD. H. G. has received personal fees from Actelion, AstraZeneca, Bayer, BMS, GossamerBio, GSK, Janssen-Cilag, Lilly, MSD, Novartis, OMT, Pfizer, and United Therapeutics. M. R. W. reports personal fees from MorphogenIX, Janssen, Chiesi, and Aerami; grants from British Heart Foundation and NIHR; and personal fees from MSD, Benevolent AI, and Tiakis Biotech, outside the submitted work. L. H. reports personal fees and nonfinancial support from Janssen and personal fees from MSD, Gossamer, and Altavant. D. G. K. reports support for the present manuscript from the Sheffield Biomedical Research Centre and consulting fees and other payments from Jansen Pharmaceuticals, Ferrer, Altavant, MSD, and United therapeutics. P. M. H. reports personal fees from Merck Co. S. Y. C. reports personal fees from Janssen, Bayer, Pfizer, United Therapeutics, and Acceleron Pharma and is a director, officer, and shareholder of Synhale Therapeutics. S. O. reports personal fees from MSD, Janssen, and Gallenica-Ferrer. H. A. G. has received fees from Actelion, AstraZeneca, Bayer, GSK, Janssen-Cilag, Lilly, Novartis, OMT, Pfizer, and United Therapeutics. M. J. R. has received support from Janssen Pharmaceutica and Bayer Pharma AG and speaker fees from Janssen Pharmaceutica and OMT. S. S. reports personal fees from Gossamer Bio, Merck, Keros, Janssen, United Therapeutics, and Liquidia. K. T. has received personal fees from Bayer, AstraZeneca, and Gossamer. W. S. has received consultancy fees from United Therapeutics, Tiakis Biotech AG, Liquidia, Pieris Pharmaceuticals, Abivax, Pfitzer, and Medspray BV. None declared (M. Fünderich, A.L., Y. S., O. T., A. J. S., R. T. Z., P. G. W., M. Frauendorf, A. Arvanitaki, G. G., K. S., H. R. C., R. F., I. A. G., E. B., J. S. A., A. P., S. G., A. Anthi, R. W. M., J. W., F. G.), (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Few therapies exist to treat severe COVID-19 respiratory failure once it develops. Given known diffuse pulmonary microthrombi on autopsy studies of COVID-19 patients, we hypothesized that tissue plasminogen activator (tPA) may improve pulmonary function in COVID-19 respiratory failure., Methods: A multicenter, retrospective, observational study of patients with confirmed COVID-19 and severe respiratory failure who received systemic tPA (alteplase) was performed. Seventy-nine adults from seven medical centers were included in the final analysis after institutional review boards' approval; 23 were excluded from analysis because tPA was administered for pulmonary macroembolism or deep venous thrombosis. The primary outcome was improvement in the PaO 2 /FiO 2 ratio from baseline to 48 h after tPA. Linear mixed modeling was used for analysis., Results: tPA was associated with significant PaO 2 /FiO 2 improvement at 48 h (estimated paired difference = 23.1 ± 6.7), which was sustained at 72 h (interaction term p  < 0.00). tPA administration was also associated with improved National Early Warning Score 2 scores at 24, 48, and 72 h after receiving tPA (interaction term p  = 0.00). D-dimer was significantly elevated immediately after tPA, consistent with lysis of formed clot. Patients with declining respiratory status preceding tPA administration had more marked improvement in PaO 2 /FiO 2 ratios than those who had poor but stable (not declining) respiratory status. There was one intracranial hemorrhage, which occurred within 24 h following tPA administration., Conclusions: These data suggest tPA is associated with significant improvement in pulmonary function in severe COVID-19 respiratory failure, especially in patients whose pulmonary function is in decline, and has an acceptable safety profile in this patient population., (© 2022 The Authors. Research and Practice in Thrombosis and Haemostasis published by Wiley Periodicals LLC on behalf of International Society on Thrombosis and Haemostasis (ISTH).)

Objectives: Sepsis-3 definitions generated controversies regarding their general applicability. The Sepsis-3 Task Force outlined the need for validation with emphasis on the quick Sequential Organ Failure Assessment (qSOFA) score. This was done in a prospective cohort from a different healthcare setting., Methods: Patients with infections and at least two signs of systemic inflammatory response syndrome (SIRS) were analysed. Sepsis was defined as total SOFA ≥2 outside the intensive care unit (ICU) or as an increase of ICU admission SOFA ≥2. The primary endpoints were the sensitivity of qSOFA outside the ICU and sepsis definition both outside and within the ICU to predict mortality., Results: In all, 3346 infections outside the ICU and 1058 infections in the ICU were analysed. Outside the ICU, respective mortality with ≥2 SIRS and qSOFA ≥2 was 25.3% and 41.2% (p <0.0001); the sensitivities of qSOFA and of sepsis definition to predict death were 60.8% and 87.2%, respectively. This was 95.9% for sepsis definition in the ICU. The sensitivity of qSOFA and of ≥3 SIRS criteria for organ dysfunction outside the ICU was 48.7% and 72.5%, respectively (p <0.0001). Misclassification outside the ICU with the 1991 and Sepsis-3 definitions into stages of lower severity was 21.4% and 3.7%, respectively (p <0.0001) and 14.9% and 3.7%, respectively, in the ICU (p <0.0001). Adding arterial pH ≤7.30 to qSOFA increased sensitivity for prediction of death to 67.5% (p 0.004)., Conclusions: Our analysis positively validated the use of SOFA score to predict unfavourable outcome and to limit misclassification into lower severity. However, qSOFA score had inadequate sensitivity for early risk assessment., (Copyright © 2016 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Background: Several reports have shown that homocysteine promotes thrombosis by disturbing the procoagulant-anticoagulant balance, whereas alterations in coagulation and fibrinolysis have been suggested as important pathogenetic and prognostic determinants of mortality in acute lung injury (ALI)/acute respiratory distress syndrome (ARDS). The objective of the study was to evaluate the effect of plasma homocysteine levels on the outcomes of patients with ALI/ARDS., Methods: Sixty-nine consecutive ventilated patients with ALI/ARDS were studied. Blood samples were drawn within 3 days of clinical recognition of ARDS. Measurement of plasma homocysteine, vitamin B12, folate, creatinine, protein C and plasminogen-activator inhibitor-1 antigen levels, and genotyping of the methylenetetrahydrofolate reductase gene C677T and A1298C polymorphisms were carried out. The primary outcomes were 28- and 90-day mortality, whereas secondary outcomes included nonpulmonary organ failure-free days, liberation from mechanical ventilation up to day 28, and ventilator-free days during the 28 days after enrollment., Results: In the multivariable analysis, plasma homocysteine concentration adjusted for age, Acute Physiology and Chronic Health Evaluation II score, methylenetetrahydrofolate reductase C677T and A1298C polymorphisms, and levels of plasminogen-activator inhibitor-1 antigen, protein C, creatinine, vitamin B12, and folate was not found to affect significantly mortality at 28 and 90 days (P = 0.39 and P = 0.83, respectively), days without organ failure besides lungs (P = 0.38), the probability of being free from mechanical ventilation at day 28 (P = 0.63), and days without ventilation assistance (P = 0.73)., Conclusion: Our data suggest that increased plasma homocysteine levels, either alone or in synergy with other thrombophilic risk factors, do not seem to adversely affect the prognosis in patients with ALI/ARDS.

Background: Chronic thromboembolic pulmonary hypertension (CTEPH) causes physical plugging of large pulmonary arteries as well as a distal micro-vasculopathy. Pulmonary endothelium is an active metabolic tissue in normal humans. The effects of CTEPH on pulmonary endothelial metabolism are unknown., Objectives: We studied pulmonary capillary endothelium-bound angiotensin converting enzyme (ACE) activity as an index of endothelial metabolism in patients with CTEPH., Patients/methods: We measured single-pass transpulmonary per cent metabolism (%M) and hydrolysis of an ACE synthetic substrate and calculated functional capillary surface area (FCSA), normalized to body surface area (BSA), in 13 patients with CTEPH and 23 controls., Results: Mean %M for CTEPH (71.6 +/- 4.0% SE) was similar to controls (74.7 +/- 2.7%). Substrate hydrolysis (v) was similar for CTEPH (1.47 +/- 0.22) and controls (1.51 +/- 0.11). However, FCSA/BSA was reduced (P < 0.01) for CTEPH (1530 +/- 218 mL min(-1)*m(-2)) as compared with controls (2948 +/- 245)., Conclusions: The metabolically functional pulmonary capillary bed is reduced in CTEPH. However, because %M and hydrolysis are preserved, this points to a reduction in functional capillary surface area rather than reduced ACE activity on the pulmonary capillary endothelial cell. The reduction in functional capillary surface area may just be a result of decreased capillary recruitment because of upstream vascular plugging by chronic organized thrombus.