Positive Vasoreactivity Testing in Pulmonary Arterial Hypertension: Therapeutic Consequences, Treatment Patterns, and Outcomes in the Modern Management Era.

BACKGROUND: Among patients with pulmonary arterial hypertension (PAH), acute vasoreactivity testing during right heart catheterization may identify acute vasoresponders, for whom treatment with high-dose calcium channel blockers (CCBs) is recommended. However, long-term outcomes in the current era remain largely unknown. We sought to evaluate the implications of acute vasoreactivity response for long-term response to CCBs and other outcomes. METHODS: Patients diagnosed with PAH between January 1999 and December 2018 at 15 pulmonary hypertension centers were included and analyzed retrospectively. In accordance with current guidelines, acute vasoreactivity response was defined by a decrease of mean pulmonary artery pressure by ≥10 mm Hg to reach <40 mm Hg, without a decrease in cardiac output. Long-term response to CCBs was defined as alive with unchanged initial CCB therapy with or without other initial PAH therapy and World Health Organization functional class I/II and/or low European Society of Cardiology/European Respiratory Society risk status at 12 months after initiation of CCBs. Patients were followed for up to 5 years; clinical measures, outcome, and subsequent treatment patterns were captured. RESULTS: Of 3702 patients undergoing right heart catheterization for PAH diagnosis, 2051 had idiopathic, heritable, or drug-induced PAH, of whom 1904 (92.8%) underwent acute vasoreactivity testing. A total of 162 patients fulfilled acute vasoreactivity response criteria and received an initial CCB alone (n=123) or in combination with another PAH therapy (n=39). The median follow-up time was 60.0 months (interquartile range, 30.8-60.0), during which overall survival was 86.7%. At 12 months, 53.2% remained on CCB monotherapy, 14.7% on initial CCB plus another initial PAH therapy, and the remaining patients had the CCB withdrawn and/or PAH therapy added. CCB long-term response was found in 54.3% of patients. Five-year survival was 98.5% in long-term responders versus 73.0% in nonresponders. In addition to established vasodilator responder criteria, pulmonary artery compliance at acute vasoreactivity testing, low risk status and NT-proBNP (N-terminal pro-B-type natriuretic peptide) levels at early follow-up correlated with long-term response and predicted survival. CONCLUSIONS: Our data display heterogeneity within the group of vasoresponders, with a large subset failing to show a sustained satisfactory clinical response to CCBs. This highlights the necessity for comprehensive reassessment during early follow-up. The use of pulmonary artery compliance in addition to current measures may better identify those likely to have a good long-term response.

Treatment strategies and survival of patients with connective tissue disease and pulmonary arterial hypertension: a COMPERA analysis.

OBJECTIVES: Pulmonary arterial hypertension (PAH) occurs in various connective tissue diseases (CTDs). We sought to assess contemporary treatment patterns and survival of patients with various forms of CTD-PAH. METHODS: We analysed data from COMPERA, a European pulmonary hypertension registry, to describe treatment strategies and survival in patients with newly diagnosed PAH associated with SSc, SLE, MCTD, UCTD and other types of CTD. All-cause mortality was analysed according to the underlying CTD. For patients with SSc-PAH, we also assessed survival according to initial therapy with endothelin receptor antagonists (ERAs), phosphodiesterase type 5 inhibitors (PDE5is) or a combination of these two drug classes. RESULTS: This analysis included 607 patients with CTD-PAH. Survival estimates at 1, 3 and 5 years for SSc-PAH (n = 390) were 85%, 59% and 42%; for SLE-PAH (n = 34) they were 97%, 77% and 61%; for MCTD-PAH (n = 33) they were 97%, 70% and 59%; for UCTD-PAH (n = 60) they were 88%, 67% and 52%; and for other CTD-PAH (n = 90) they were 92%, 69% and 55%, respectively. After multivariable adjustment, the survival of patients with SSc-PAH was significantly worse compared with the other conditions (P = 0.001). In these patients, the survival estimates were significantly better with initial ERA-PDE5i combination therapy than with initial ERA or PDE5i monotherapy (P = 0.016 and P = 0.012, respectively). CONCLUSIONS: Mortality remains high in patients with CTD-PAH, especially for patients with SSc-PAH. However, for patients with SSc-PAH, our results suggest that long-term survival may be improved with initial ERA-PDE5i combination therapy compared with initial monotherapy.

[Ruptured pulmonary Echinococcus granulosus cyst: A rare cause of severe pneumogenic sepsis]. / Rupturierte pulmonale Echinococcus granulosus-Zyste ­ Eine seltene Ursache für eine schwere pneumogene Sepsis.

Parasitic infections by Echinococcus granulosus are rare in Germany, and predominantly affect individuals with a migration background. Liver and lungs are the most commonly affected organs. Pulmonary cysts often remain asymptomatic until rupture, at which point symptoms may manifest. The diagnostic approach typically involves a combination of imaging modalities and serological tests, occasionally supplemented by molecular genetic methods. Given the global movements of migration, considerations of the epidemiology of common diseases in the country of origin should also be taken into account in the differential diagnosis. We present the unusual case of a pneumogenic sepsis in a young man from Syria, where the combination of medical history alongside radiological, serological, and molecular genetic investigations ultimately led to the diagnosis of a severe pulmonary echinococcosis with rupture.

[Task Force Dyspnoe unit (DU)]. / Task Force Dyspnoe Unit (DU).

Acute dyspnoea is one of the most common internal medicine symptoms in the emergency department. It arises from an acute illness or from the exacerbation of a chronic illness. Symptom-related emergency structures and corresponding structural guidelines already exist in the stroke and chest pain units for dealing with the leading symptoms of acute stroke and acute chest pain. These are lacking in Germany for the key symptom of dyspnoea, although the benefits of these structures have already been proven in other countries. The German Society for Pneumology and Respiratory Medicine (DGP) has now set up a task force together with the Association of Pneumology Clinics (VPK), in order to deal with the topic and develop appropriate structural guidelines for such "dyspnoea units" in Germany. At the end of the process, the certification of such units at German hospitals is optional.

Cardiopulmonary exercise testing during follow-up after acute pulmonary embolism.

BACKGROUND: Cardiopulmonary exercise testing (CPET) may provide prognostically valuable information during follow-up after pulmonary embolism (PE). Our objective was to investigate the association of patterns and degree of exercise limitation, as assessed by CPET, with clinical, echocardiographic and laboratory abnormalities and quality of life (QoL) after PE. METHODS: In a prospective cohort study of unselected consecutive all-comers with PE, survivors of the index acute event underwent 3- and 12-month follow-ups, including CPET. We defined cardiopulmonary limitation as ventilatory inefficiency or insufficient cardiocirculatory reserve. Deconditioning was defined as peak O2 uptake (V'O2 ) <80% with no other abnormality. RESULTS: Overall, 396 patients were included. At 3 months, prevalence of cardiopulmonary limitation and deconditioning was 50.1% (34.7% mild/moderate; 15.4% severe) and 12.1%, respectively; at 12 months, it was 44.8% (29.1% mild/moderate; 15.7% severe) and 14.9%, respectively. Cardiopulmonary limitation and its severity were associated with age (OR per decade 2.05, 95% CI 1.65-2.55), history of chronic lung disease (OR 2.72, 95% CI 1.06-6.97), smoking (OR 5.87, 95% CI 2.44-14.15) and intermediate- or high-risk acute PE (OR 4.36, 95% CI 1.92-9.94). Severe cardiopulmonary limitation at 3 months was associated with the prospectively defined, combined clinical-haemodynamic end-point of "post-PE impairment" (OR 6.40, 95% CI 2.35-18.45) and with poor disease-specific and generic health-related QoL. CONCLUSIONS: Abnormal exercise capacity of cardiopulmonary origin is frequent after PE, being associated with clinical and haemodynamic impairment as well as long-term QoL reduction. CPET can be considered for selected patients with persisting symptoms after acute PE to identify candidates for closer follow-up and possible therapeutic interventions.

Chronic thromboembolic pulmonary hypertension and impairment after pulmonary embolism: the FOCUS study.

AIMS: To systematically assess late outcomes of acute pulmonary embolism (PE) and to investigate the clinical implications of post-PE impairment (PPEI) fulfilling prospectively defined criteria. METHODS AND RESULTS: A prospective multicentre observational cohort study was conducted in 17 large-volume centres across Germany. Adult consecutive patients with confirmed acute symptomatic PE were followed with a standardized assessment plan and pre-defined visits at 3, 12, and 24 months. The co-primary outcomes were (i) diagnosis of chronic thromboembolic pulmonary hypertension (CTEPH), and (ii) PPEI, a combination of persistent or worsening clinical, functional, biochemical, and imaging parameters during follow-up. A total of 1017 patients (45% women, median age 64 years) were included in the primary analysis. They were followed for a median duration of 732 days after PE diagnosis. The CTEPH was diagnosed in 16 (1.6%) patients, after a median of 129 days; the estimated 2-year cumulative incidence was 2.3% (1.2-4.4%). Overall, 880 patients were evaluable for PPEI; the 2-year cumulative incidence was 16.0% (95% confidence interval 12.8-20.8%). The PPEI helped to identify 15 of the 16 patients diagnosed with CTEPH during follow-up (hazard ratio for CTEPH vs. no CTEPH 393; 95% confidence interval 73-2119). Patients with PPEI had a higher risk of re-hospitalization and death as well as worse quality of life compared with those without PPEI. CONCLUSION: In this prospective study, the cumulative 2-year incidence of CTEPH was 2.3%, but PPEI diagnosed by standardized criteria was frequent. Our findings support systematic follow-up of patients after acute PE and may help to optimize guideline recommendations and algorithms for post-PE care.

[Spontaneous pneumomediastinum (Hamman's syndrome) with pneumorrhachis as a rare cause of acute chest pain in a young patient with acute asthma exacerbation]. / Spontanes Pneumomediastinum (Hamman-Syndrom) mit Pneumorrhachis als seltene Ursache für akuten Thoraxschmerz bei einem jungen Patienten mit akut exazerbiertem Asthma bronchiale.

Pneumomediastinum, defined as abnormal presence of air in the mediastinum, is a rare cause of acute chest pain. The condition may occur spontaneously as well as a secondary consequence of trauma or medical interventions. The spontaneous pneumomediastinum (Hamman's syndrome) is associated with a good prognosis, even without intervention. However, undelying severe conditions such as gastrointestinal perforations should be excluded. Diagnosis might be made using conventionell chest x-ray; a CT scan may give additional useful information. A subcutanous emphysema is a common finding in patients with pneumomediastinum. The presence of air in the epidural space of the spinal canal (pneumorrhachis) is a rarely seen but likewise mostly benign complication. We report a case of a young man with Hamman's syndrome and pneumorrhachis, provoked by acute asthma exacerbation; despite pronounced symptoms, his condition could be treated conservatively.

[Diagnostic Algorithm and Screening of Pulmonary Hypertension]. / Diagnose Algorithmus der pulmonalen Hypertonie und Screening-Verfahren.

The new guidelines for the diagnosis and treatment of pulmonary hypertension include a new diagnostic algorithm and provide specific recommendations for the required diagnostic procedures, including screening methods. These recommendations are commented on by national experts under the auspices of the DACH. These comments provide additional decision support and background information, serving as a further guide for the complex diagnosis of pulmonary hypertension.

[Pulmonary hypertension associated with lung disease]. / Pulmonale Hypertonie assoziiert mit Lungenerkrankungen.

Lung diseases and hypoventilation syndromes are often associated with pulmonary hypertension (PH). In most cases, PH is not severe. This is defined hemodynamically by a mean pulmonary arterial pressure (PAPm) > 20 mmHg, a pulmonary arterial wedge pressure (PAWP) ≤ 15 mmHg and a pulmonary vascular resistance of ≤ 5 Wood units (WU). Both the non-severe (PVR ≤ 5 WU) and much more the severe PH (PVR > 5 WU) have an unfavorable prognosis.If PH is suspected, it is recommended to primarily check whether risk factors for pulmonary arterial hypertension (PAH, group 1 PH) or chronic thromboembolic pulmonary hypertension (CTEPH, group 4 PH) are present. If risk factors are present or there is a suspicion of severe PH in lung patients, it is recommended that the patient should be presented to a PH outpatient clinic promptly.For patients with severe PH associated with lung diseases, personalized, individual therapy is recommended - if possible within the framework of therapy studies. Currently, a therapy attempt with PH specific drugs should only be considered in COPD patients if the associated PH is severe and a "pulmonary vascular" phenotype (severe precapillary PH, but typically only mild to moderate airway obstruction, no or mild hypercapnia and DLCO < 45 % of predicted value) is present. In patients with severe PH associated with interstitial lung disease phosphodiesterase-5-inhibitors may be considered in individual cases. Inhaled treprostinil may be considered also in non-severe PH in this patient population.

[Chronic thromboembolic pulmonary hypertension]. / Chronisch thromboembolische pulmonale Hypertonie (Gruppe 4).

Chronic thromboembolic pulmonary disease (CTEPD) is an important late complication of acute pulmonary embolism, in which the thrombi transform into fibrous tissue, become integrated into the vessel wall, and lead to chronic obstructions. CTEPD is differentiated into cases without pulmonary hypertension (PH), characterized by a mean pulmonary arterial pressure up to 20 mmHg and a form with PH. Then, it is still referred to as chronic thromboembolic pulmonary hypertension (CTEPH).When there is suspicion of CTEPH, initial diagnostic tests should include echocardiography and ventilation/perfusion scan to detect perfusion defects. Subsequently, referral to a CTEPH center is recommended, where further imaging diagnostics and right heart catheterization are performed to determine the appropriate treatment.Currently, three treatment modalities are available. The treatment of choice is pulmonary endarterectomy (PEA). For non-operable patients or patients with residual PH after PEA, PH-targeted medical therapy, and the interventional procedure of balloon pulmonary angioplasty (BPA) are available. Increasingly, PEA, BPA, and pharmacological therapy are combined in multimodal concepts.Patients require post-treatment follow-up, preferably at (CTE)PH centers. These centers are required to perform a minimum number of PEA surgeries (50/year) and BPA interventions (100/year).

COMPERA 2.0: a refined four-stratum risk assessment model for pulmonary arterial hypertension.

BACKGROUND: Risk stratification plays an essential role in the management of patients with pulmonary arterial hypertension (PAH). The current European guidelines propose a three-stratum 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 four risk categories, with intermediate risk subdivided into intermediate-low and intermediate-high risk. METHODS: We analysed data from the Comparative, Prospective Registry of Newly Initiated Therapies for Pulmonary Hypertension (COMPERA), a European pulmonary hypertension registry, and calculated risk at diagnosis and first follow-up based on World Health Organization functional class, 6-min walk distance (6MWD) and serum levels of brain natriuretic peptide (BNP) or N-terminal pro-BNP (NT-proBNP), using refined cut-off values. Survival was assessed using Kaplan-Meier analyses, log-rank testing and Cox proportional hazards models. RESULTS: Data from 1655 patients with PAH were analysed. Using the three-stratum model, most patients were classified as intermediate risk (76.0% at baseline and 63.9% at first follow-up). The refined four-stratum 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 three-stratum model and in 49.2% with the four-stratum 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 four-stratum model based on refined cut-off levels for functional class, 6MWD and BNP/NT-proBNP was more sensitive to prognostically relevant changes in risk than the original three-stratum model.

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

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 extent 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 looked at annualised data and at cumulated data comparing the periods 2010-2014 and 2015-2019. RESULTS: A total of 2531 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 nonsignificant 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.

Anxiety, Depression and Quality of Life in Pulmonary Hypertension: A Comparison of Incident and Prevalent Cases.

INTRODUCTION: Anxiety and depression are common in pulmonary hypertension (PH) and health-related quality of life (HRQoL) is reduced. Sufficient analyses in incident and prevalent patients are lacking, so we provide a comparative analysis of these groups with focus on anxiety, depression and HRQoL. METHODS: Depression, anxiety and HRQoL were retrospectively analyzed by Hospital Anxiety and Depression Scale (HADS) and Short Form 36 questionnaire in 91 prevalent and 21 incident PH outpatients from a German tertiary care center specialized in PH. The acquired data as well as hemodynamic and functional parameters of prevalent and incident cases were compared. RESULTS: HRQoL was reduced in both cohorts of patients. Incident patients had significantly worse HRQoL in physical dominated scales than prevalent patients (physical component summary score: p = 0.02; physical role performance: p < 0.01). Depression and anxiety were more pronounced in prevalent patients (elevated depression scales: 28.6% of incident group, 35.2% of prevalent group, elevated anxiety scores: 28.6% of incident group, 39.6% of prevalent group). The groups did not differ in hemodynamic data, but incident patients had significantly lower cardiac biomarkers such as NT-proBNP (p = 0.016) and hs-troponin (p = 0.017). The time since diagnosis was a predictor of the subscale physical role performance (p < 0.001). CONCLUSION: Physical domains of HRQoL seem to be more limited in incident patients with PH. Anxiety and depression are frequent in both groups. A screening for anxiety and depression is important from the onset of the diagnosis, and patients should receive appropriate therapy to improve HRQoL, anxiety and depression.

[Functional characterization of patients with isolated post-capillary or combined post-capillary and pre-capillary pulmonary hypertension]. / Funktionelle Charakterisierung von Patienten mit isoliert postkapillärer oder kombiniert post- und präkapillärer pulmonaler Hypertonie.

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.

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

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.

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

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.

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.

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.

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.

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 (D LCO) 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% versus 46% and 62% versus 21%, respectively, for patients with versus 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 D LCO 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 D LCO.

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

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 DLCO% 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 DLCO % 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 DLCO. 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.

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

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 (peakVO2) and ventilation/carbon dioxide (VE/VCO2)-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), peakVO2 < 15.6 mL∙kg- 1∙min- 1, and VE/VCO2-slope > 35. Age (hazard ratio HR = 1.23; 95% confidence interval CI: 1.14;1.41), VE/VCO2-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 peakVO2 (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 peakVO2 < 15.6 mL∙kg- 1∙min- 1 (< 64.5% of predicted peakVO2) and VE/VCO2-slope > 35.