Pulmonary Embolism: An Update Based on the Revised AWMF-S2k Guideline.

Pulmonary embolism (PE) is the third most common acute cardiovascular disease. The risk of PE increases with age and mortality is high. Patients are stratified into hemodynamically stable versus unstable patients, as this has important implications for diagnosis and therapy. Since clinical signs and symptoms of acute PE are nonspecific, the clinical likelihood of PE is estimated to guide diagnostic pathways. D-dimer testing is performed in hemodynamically stable patients with low or intermediate probability of PE and the visualization of thromboembolism and its sequelae is commonly achieved with computed tomography pulmonary angiography (CTPA), supplemented by ultrasound techniques. With confirmed PE, another risk stratification estimates disease severity and defines intensity and setting of the ensuing treatment. The therapeutic spectrum ranges from outpatient treatment with initial oral anticoagulation to thrombolytic or interventional treatment in the intensive care unit or catheterization laboratory. In single cases, even acute surgical thrombectomy is attempted.

Post-Pulmonary Embolism Syndrome: An Update Based on the Revised AWMF-S2k Guideline.

In survivors of acute pulmonary embolism (PE), the post-PE syndrome (PPES) may occur. In PPES, patients typically present with persisting or progressive dyspnea on exertion despite 3 months of therapeutic anticoagulation. Therefore, a structured follow-up is warranted to identify patients with chronic thromboembolic pulmonary disease (CTEPD) with normal pulmonary pressure or chronic thromboembolic pulmonary hypertension (CTEPH). Both are currently understood as a dual vasculopathy, that is, secondary arterio- and arteriolopathy, affecting the large and medium-sized pulmonary arteries as well as the peripheral vessels (diameter < 50 µm). The follow-up algorithm after acute PE commences with identification of clinical symptoms and risk factors for CTEPH. If indicated, a stepwise performance of echocardiography, ventilation-perfusion scan (or alternative imaging), N-terminal prohormone of brain natriuretic peptide (NT-proBNP) level, cardiopulmonary exercise testing, and pulmonary artery catheterization with angiography should follow. CTEPH patients should be treated in a multidisciplinary center with adequate experience in the complex therapeutic options, comprising pulmonary endarterectomy, balloon pulmonary angioplasty, and pharmacological interventions.

Using Machine Learning-Based Algorithms to Identify and Quantify Exercise Limitations in Clinical Practice: Are We There Yet?

INTRODUCTION: Well-trained staff is needed to interpret cardiopulmonary exercise tests (CPET). We aimed to examine the accuracy of machine learning-based algorithms to classify exercise limitations and their severity in clinical practice compared with expert consensus using patients presenting at a pulmonary clinic. METHODS: This study included 200 historical CPET data sets (48.5% female) of patients older than 40 yr referred for CPET because of unexplained dyspnea, preoperative examination, and evaluation of therapy progress. Data sets were independently rated by experts according to the severity of pulmonary-vascular, mechanical-ventilatory, cardiocirculatory, and muscular limitations using a visual analog scale. Decision trees and random forests analyses were calculated. RESULTS: Mean deviations between experts in the respective limitation categories ranged from 1.0 to 1.1 points (SD, 1.2) before consensus. Random forests identified parameters of particular importance for detecting specific constraints. Central parameters were nadir ventilatory efficiency for CO 2 , ventilatory efficiency slope for CO 2 (pulmonary-vascular limitations); breathing reserve, forced expiratory volume in 1 s, and forced vital capacity (mechanical-ventilatory limitations); and peak oxygen uptake, O 2 uptake/work rate slope, and % change of the latter (cardiocirculatory limitations). Thresholds differentiating between different limitation severities were reported. The accuracy of the most accurate decision tree of each category was comparable to expert ratings. Finally, a combined decision tree was created quantifying combined system limitations within one patient. CONCLUSIONS: Machine learning-based algorithms may be a viable option to facilitate the interpretation of CPET and identify exercise limitations. Our findings may further support clinical decision making and aid the development of standardized rating instruments.

[Non-invasive Mechanical Ventilation in Acute Respiratory Failure. Clinical Practice Guidelines - on behalf of the German Society of Pneumology and Ventilatory Medicine]. / S2k-Leitlinie Nichtinvasive Beatmung als Therapie der akuten respiratorischen Insuffizienz.

The guideline update outlines the advantages as well as the limitations of NIV in the treatment of acute respiratory failure in daily clinical practice and in different indications.Non-invasive ventilation (NIV) has a high value in therapy of hypercapnic acute respiratory failure, as it significantly reduces the length of ICU stay and hospitalization as well as mortality.Patients with cardiopulmonary edema and acute respiratory failure should be treated with continuous positive airway pressure (CPAP) and oxygen in addition to necessary cardiological interventions. This should be done already prehospital and in the emergency department.In case of other forms of acute hypoxaemic respiratory failure with only mild or moderately disturbed gas exchange (PaO2/FiO2 > 150 mmHg) there is no significant advantage or disadvantage compared to high flow nasal oxygen (HFNO). In severe forms of ARDS NIV is associated with high rates of treatment failure and mortality, especially in cases with NIV-failure and delayed intubation.NIV should be used for preoxygenation before intubation. In patients at risk, NIV is recommended to reduce extubation failure. In the weaning process from invasive ventilation NIV essentially reduces the risk of reintubation in hypercapnic patients. NIV is regarded useful within palliative care for reduction of dyspnea and improving quality of life, but here in concurrence to HFNO, which is regarded as more comfortable. Meanwhile NIV is also recommended in prehospital setting, especially in hypercapnic respiratory failure and pulmonary edema.With appropriate monitoring in an intensive care unit NIV can also be successfully applied in pediatric patients with acute respiratory insufficiency.

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.

Protein expression profiling suggests relevance of noncanonical pathways in isolated pulmonary embolism.

Patients with isolated pulmonary embolism (PE) have a distinct clinical profile from those with deep vein thrombosis (DVT)-associated PE, with more pulmonary conditions and atherosclerosis. These findings suggest a distinct molecular pathophysiology and the potential involvement of alternative pathways in isolated PE. To test this hypothesis, data from 532 individuals from the Genotyping and Molecular Phenotyping of Venous ThromboEmbolism Project, a multicenter prospective cohort study with extensive biobanking, were analyzed. Targeted, high-throughput proteomics, machine learning, and bioinformatic methods were applied to contrast the acute-phase plasma proteomes of isolated PE patients (n = 96) against those of patients with DVT-associated PE (n = 276) or isolated DVT (n = 160). This resulted in the identification of shared molecular processes between PE phenotypes, as well as an isolated PE-specific protein signature. Shared processes included upregulation of inflammation, response to oxidative stress, and the loss of pulmonary surfactant. The isolated PE-specific signature consisted of 5 proteins: interferon-γ, glial cell line-derived neurotrophic growth factor, polypeptide N-acetylgalactosaminyltransferase 3, peptidyl arginine deiminase type-2, and interleukin-15 receptor subunit α. These proteins were orthogonally validated using cis protein quantitative trait loci. External replication in an independent population-based cohort (n = 5778) further validated the proteomic results and showed that they were prognostic for incident primary isolated PE in individuals without history of VTE (median time to event: 2.9 years; interquartile range: 1.6-4.2 years), supporting their possible involvement in the early pathogenesis. This study has identified molecular overlaps and differences between VTE phenotypes. In particular, the results implicate noncanonical pathways more commonly associated with respiratory and atherosclerotic disease in the acute pathophysiology of isolated PE.

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

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.

Riociguat for pulmonary arterial hypertension and chronic thromboembolic pulmonary hypertension: Results from a phase II long-term extension study.

BACKGROUND: Riociguat was well tolerated and improved exercise and functional capacity in patients with pulmonary arterial hypertension (PAH) and inoperable chronic thromboembolic pulmonary hypertension (CTEPH) in a 12-week Phase II trial. We present final data from the long-term extension phase of this study. METHODS: During this multicenter, open-label, uncontrolled long-term extension study, riociguat dose could be changed at the physician's discretion (range 0.5-2.5 mg three times daily). The primary outcome was long-term safety and tolerability of riociguat; secondary outcomes included 6-minute walking distance, World Health Organization functional class, survival, and clinical worsening-free survival. RESULTS: Sixty-eight patients (inoperable CTEPH, n = 41; PAH, n = 27) entered the long-term extension. Median treatment duration at the final data cut-off was 77 months. The most common adverse events were nasopharyngitis (57%) and peripheral edema (37%). Three patients (4%) experienced serious adverse events of hemoptysis: two moderate, one severe, none fatal or considered drug-related. At Month 48, 6-minute walking distance increased from baseline by 69 ± 105 m, and World Health Organization functional class improved/stabilized/worsened versus baseline in 50/45/5% of patients. Three-year survival and clinical worsening-free survival were 91% and 49%, respectively (with patients censored if they withdrew without experiencing an event). Starting a new PAH treatment was the most frequent clinical worsening event. CONCLUSIONS: Improvements in exercise and functional capacity were maintained at 4 years in patients remaining on treatment, with no new safety signals identified. These data support riociguat as a long-term treatment option for PAH and inoperable CTEPH. TRIAL REGISTERED AT: ClinicalTrials.gov. REGISTRATION NUMBER: NCT00454558.

Late outcomes after acute pulmonary embolism: rationale and design of FOCUS, a prospective observational multicenter cohort study.

Acute pulmonary embolism (PE) is a frequent cause of death and serious disability. The risk of PE-associated mortality and morbidity extends far beyond the acute phase of the disease. In earlier follow-up studies, as many as 30 % of the patients died during a follow-up period of up to 3 years, and up to 50 % of patients continued to complain of dyspnea and/or poor physical performance 6 months to 3 years after the index event. The most feared 'late sequela' of PE is chronic thromboembolic pulmonary hypertension (CTEPH), the true incidence of which remains obscure due to the large margin of error in the rates reported by mostly small, single-center studies. Moreover, the functional and hemodynamic changes corresponding to early, possibly reversible stages of CTEPH, have not been systematically investigated. The ongoing Follow-Up after acute pulmonary embolism (FOCUS) study will prospectively enroll and systematically follow, over a 2-year period and with a standardized comprehensive program of clinical, echocardiographic, functional and laboratory testing, a large multicenter prospective cohort of 1000 unselected patients (all-comers) with acute symptomatic PE. FOCUS will possess adequate power to provide answers to relevant remaining questions regarding the patients' long-term morbidity and mortality, and the temporal pattern of post-PE abnormalities. It will hopefully provide evidence for future guideline recommendations regarding the selection of patients for long-term follow-up after PE, the modalities which this follow-up should include, and the findings that should be interpreted as indicating progressive functional and hemodynamic post-PE impairment, or the development of CTEPH.

Management of patients with idiopathic pulmonary fibrosis in clinical practice: the INSIGHTS-IPF registry.

After introduction of the new international guidelines on idiopathic pulmonary fibrosis (IPF) in 2011, we investigated clinical management practices for patients with IPF according to physicians' diagnoses. A prospective, multicenter, noninterventional study with comprehensive quality measures including on-site source data verification was performed in Germany. 502 consecutive patients (171 newly diagnosed, 331 prevalent; mean±SD age 68.7±9.4 years, 77.9% males) with a mean disease duration of 2.3±3.5 years were enrolled. IPF diagnosis was based on clinical assessments and high-resolution computed tomography (HRCT) in 90.2%, and on surgical lung biopsy combined with histology in 34.1% (lavage in 61.8%). The median 6-min walk distance was 320 m (mean 268±200 m). The mean forced vital capacity was 72±20% pred and diffusing capacity of the lung for carbon monoxide was 35±15% pred. No drugs were administered in 17.9%, oral steroids in 23.7%, N-acetylcysteine in 33.7%, pirfenidone in 44.2% and other drugs in 4.6% of patients. Only 2.8% of the cohort was listed for lung transplantation. IPF patients were diagnosed in line with the new guidelines. They had more severe disease than those enrolled in recent randomised controlled trials. In addition to HRCT, the frequency of lung biopsies was surprisingly high. Treatment patterns varied substantially.

The correlation between endothelin-1 levels and spirometry in dialysis patients compared to healthy subjects.

BACKGROUND AND AIM: Several studies demonstrated a six-fold increase in plasma concentration of endothelin-1 (ET-1) in diaysis patients (hemodialysis and peritoneal dialysis) compared to healthy control subjects. However, the effects of ET-1 on respiratory function in these patients are less known. The aim of this study was to determine the potential differences in spirometric values in relation to ET-1 levels. METHODS: The study included 28 patients (15 male, 13 female, mean age 55.9 +/- 16. 2 years) with end stage renal diseases (ESRD) receiving regular hemodialysis (HD), 23 patients (10 males, 13 females, mean age 55.8 +/- 15.8 years) with ESRD treated with continuous ambulatory peritoneal dialysis (CAPD) without any cardiovascular or respiratory diseases, and 30 healthy volunteers (14 male, 16 female, mean age 51.8 +/- 15.6 years) in control group. In each of the three groups the participants were divided into two additional sub-groups according to the serum levels of ET-1. The spirometry values were recorded before the onset of hemodialysis and prior to emptying the peritoneal cavity in CAPD patients. The results were analyzed using standard statistical methods (Student's t-test). RESULTS: Patients who were treated with HD or CAPD were found to have significant difference in values of most pulmonary function parameters between subjects with ET-1 levels lower than 6.6 pg/ml and subjects with ET-1 levels higher than 6.6 pg/ml. In the control group there was no difference in pulmonary function parameters in correlation with ET-1 levels. ET-1 values in patients of both dialysis groups were significantly higher compared to healthy subjects. CONCLUSIONS: Higher levels of ET-1 in dialysis patients over healthy subjects is associated with lower parameters of lung function tests. A possible pathophysiological mechanism for deterioration of pulmonary function might be explained by progression of inflammation, pulmonary oedema also known as "uraemic lung" or/and the progression of pulmonary hypertension.

Relation of respiratory muscle strength, cachexia and survival in severe chronic heart failure.

BACKGROUND: Respiratory muscle (RM) function predicts prognosis in non-cachectic patients with chronic heart failure (CHF). We hypothesized that weakness of RM (maximum inspiratory mouth occlusion pressure, Pimax) is a function of body mass index, and that outcome is more a function of BMI than of Pimax or ventilatory drive (P0.1). SUBJECTS AND METHODS: We enrolled 249 CHF patients (11.2 % female, median age 54.2 years) at the German Heart Institute Berlin. Patients were in NYHA classes I/II/III/IV by n = 16/90/108/35. All patients underwent tests of pulmonary function, RM (Pimax, P0.1), cardiopulmonary exercise testing (peakVO2, VE/VCO2-slope), and right heart catheterization. RESULTS: Mean follow-up time was 18 (1-36) months, 47 patients (18.9 %) died or underwent cardiac assist implantation. Pimax correlated weakly with BMI (r = 0.19), peakVO2 (r = 0.15), and FEV1 (r = 0.34, all p < 0.02), and was lower in females compared to males (3.9 ± 1.7 vs. 6.6 ± 2.7 kPa; p < 0.001). P0.1 correlated with pulmonary pressure (rho = 0.2; p < 0.01) and peakVO2 (rho = -0.14; p < 0.02). Neither Pimax [hazard ratio (HR) 0.98; confidence interval (CI) 0.88-1.08] nor P0.1 (HR 0.52; 0.06-4.6) predicted survival. Multivariate regression analysis revealed gender, BMI, and FEV1 as cofactors of Pimax, with only BMI (HR 0.87; CI 0.80-0.95) predicting survival independently. The lowest quintile in BMI had the worst outcome (log-rank χ² = 13.5, p = 0.009). In CHF patients including cachexia and NYHA IV, Pimax does not predict survival. Pimax depends on gender, BMI, FEV1, and peakVO2, with only BMI and peakVO2 predicting survival. The impaired Pimax in CHF might be a result of catabolism and weight loss and is not a predictive factor in itself.

High-sensitive Troponin T increase after exercise in patients with pulmonary arterial hypertension.

BACKGROUND: The current study aimed to investigate the release of myocardial high-sensitive Troponin T (hsTnT) in patients with pulmonary arterial hypertension (PAH) in response to maximal physical exercise. METHODS: In 24 patients with PAH, symptom-limited cardiopulmonary exercise testing was performed. hsTnT was measured by the novel hsTnT assay with a lower limit of detection of 2 ng/L and a total imprecision of less than 10% at the 99th percentile value. hsTnT was related to NT-proBNP, WHO functional class and right ventricular (RV) function. Serial measurement was performed before and 30 min, 180 min, and 300 min after exercise. Healthy volunteers served as a control group. RESULTS: In 21 PAH patients, hsTnT levels were detectable before exercise with a close correlation between hsTnT and NT-proBNP. hsTnT was detectable in all PAH patients after exercise and significantly increased from 7.5 ng/L at baseline to 14.62 ng/L after 300 min, whereas levels of NT-proBNP remained constant with time. CONCLUSIONS: Using the novel hsTnT assay, the current study provides first evidence that hsTnT levels increase in PAH patients after maximal physical exercise, while levels of other biomarkers remain constant after exercise testing. This might provide new insights into pathophysiology and individual risk assessment in patients with PAH.

Exercise capacity affects quality of life in patients with pulmonary hypertension.

BACKGROUND: The objective of this prospective study was to evaluate the impact of exercise capacity, mental disorders, and hemodynamics on quality-of-life (QoL) parameters in patients with pulmonary arterial hypertension (PAH) and chronic thromboembolic pulmonary hypertension (CTEPH). METHODS: Sixty-three patients with invasively diagnosed PAH (n = 48) or CTEPH (n = 15) underwent a broad panel of assessments, including cardiopulmonary exercise testing (CPET), 6-minute walking distance (6-MWD), World Health Organization functional class (WHO-FC), and assessment of hemodynamics. QoL was evaluated by the 36-item Medical Outcome Study Short Form Health Survey Questionnaire (SF-36). Exercise capacity, hemodynamics, age, gender, and mental disorders (anxiety and depression) were assessed for association with QoL subscores by uni- and multivariate regression analyses. RESULTS: Exercise capacity, WHO-FC, oxygen therapy, symptoms of right heart failure, right atrial pressure, and mental disorders were significantly associated with QoL (p < 0.05). In the stepwise backward selection multivariate analysis, depression remained an independent parameter in seven of eight subscales of the SF-36. Furthermore, peak oxygen uptake (peakVO2) during CPET, 6-MWD, anxiety, long-term oxygen therapy, right heart failure, and age remained independent factors for QoL. Hemodynamic parameters at rest did not independently correlate with any domain of the SF-36 QoL subscores. CONCLUSIONS: Mental disorders, exercise capacity, long-term oxygen therapy, right heart failure, and age play important role in the quality of life in patients with PAH and CTEPH.

Incremental prognostic value of cardiopulmonary exercise testing and resting haemodynamics in pulmonary arterial hypertension.

BACKGROUND: Pulmonary arterial hypertension (PAH) is a fatal disease despite recent treatment advances. Individual risk stratification is important. Exercise capacity and invasive haemodynamic data are both relevant, but data on the combined prognostic power are lacking. METHODS: 226 consecutive patients with idiopathic or familial PAH were included at seven specialised tertiary centres. All patients underwent right heart catheterization and cardiopulmonary exercise testing (CPET). RESULTS: During follow-up (1508 ± 1070 days) 72 patients died and 30 underwent transplantation. On multivariate analysis percentage of predicted peak oxygen uptake (%predicted peak VO2 [risk ratio 0.95]), pulmonary vascular resistance (PVR [1.105,]) and increase in heart rate during exercise (ΔHR [0.974]) were independent prognostic predictors (all p<0.0001). Peak VO2 allowed for risk stratification with a survival of 100, 92.9, 87.4 and 69.6% at 1 year and 97.7, 63.2, 41 and 23% at 5 years for the 4th, 3rd, 2nd and 1st quartiles, respectively. Dichotomizing by median peak VO2 and intra-group median PVR showed a worse 1-year survival for patients with low peak VO2/higher PVR compared to patients with low peak VO2/low PVR, high peak VO2/high PVR and high peak VO2/low PVR (65 vs. 93, 93, 100%, p<0.001). At 10 years survival was different for all 4 subgroups (19 vs. 25 vs. 48 vs. 75%, adjusted p<0.05). CONCLUSIONS: Peak VO2, PVR and ΔHR independently predict prognosis in patients with PAH. Low peak VO2, high PVR and low ΔHR refer to poor prognosis. Combined use of peak VO2 and PVR provides accurate risk stratification underlining the complementary prognostic information from cardiopulmonary exercise testing and resting invasive haemodynamic data.

Osteopontin predicts adverse right ventricular remodelling and dysfunction in pulmonary hypertension.

BACKGROUND: Osteopontin (OPN) was found upregulated in several heart failure models and appears to play an important role in myocardial remodelling. As we have previously demonstrated that OPN predicts mortality in patients with pulmonary hypertension (PH), we now evaluated whether OPN also predicts adverse right ventricular (RV) remodelling and dysfunction in PH. METHODS: We prospectively included 71 patients with PH of different etiology in this study. OPN plasma level were determined by ELISA and assessed for correlation with RV dilatation and dysfunction determined by echocardiography. RESULTS: OPN plasma values significantly correlated with RV end-diastolic diameter, Tricuspid Annular Plane Systolic Excursion (TAPSE) and Tricuspid Annular Systolic Velocity (TASV) (r = 0·43, P = 0·0002; r = -0·46, P = 0·0006; r = -0·31, P = 0·02). Furthermore, stratification of our study population according to RV end-diastolic diameter and RV dysfunction revealed that patients with enlarged and functionally impaired RV's display higher OPN levels (956 ng/mL vs. 628 ng/mL, P = 0·0005; 1108 ng/mL vs. 792 ng/mL; P = 0·02). Next, we determined OPN cut-off values for the detection of RV remodelling and dysfunction by receiver operating curve analyses and further stratified these parameters in a multivariate analysis. Here, OPN emerged as an independent predictor of RV dilatation and dysfunction. Finally, we demonstrate synergism of OPN and NT-proBNP in the prediction of RV dilatation and dysfunction by calculation of the Rothman Synergy Index. CONCLUSION: In summary, OPN predicts adverse RV remodelling and dysfunction in PH. Together with our previously published data regarding OPN's value for the prognostication of death in PH, we believe that OPN can improve risk stratification in patients with PH beyond current assessment standards.

Changes in spirometry over time in uremic patients receiving long-term hemodialysis therapy.

Complications of respiratory system in patients suffering from chronic renal failure who are treated with regular haemodialysis are well known. However, the influence of the duration of haemodialysis on pulmonary function is less understood. The aim of this study was to determine spirometry changes in patients on chronic haemodialysis over a five-year period. We tested 21 patients, out of which 11 female and 10 male, mean age of 50 (+/- 11) years. The mean duration of haemodialysis was 52.2 (+/- 44.7) months at the time of the inclusion. We performed spirometry testings in all patients, one hour before start and one hour after completion of haemodialysis. All parameters of spirometry recorded one hour after completion of haemodialysis (FVC, FEV1, FEF75, 50, 25, % of predicted), improved significantly (p < 0.01). After five years, only FVC demonstrated significant decline and none of the recorded spirometry parameters improved significantly one hour post haemodialysis compared to pre-haemodialysis period. Analysis of post-dialysis parameters of spirometry at the study onset and following five years of haemodialysis showed that all parameters, except FEF50 (p > 0.05), significantly deteriorated (p < 0.01). Patients who are on long-term haemodialysis show a significant decline in FVC following five years of treatment. Although the spirometry changes in observed population treated with chronic haemodialysis have reversible character during the first years of renal replacement therapy, five years after these changes become irreversible.