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BACKGROUND: Riociguat and phosphodiesterase-5 inhibitors (PDE5i), approved for the treatment of pulmonary arterial hypertension (PAH), act on the same pathway via different mechanisms. Riociguat might be an alternative option for patients with PAH who do not respond sufficiently to treatment with PDE5i, but comparisons of the potential benefits of riociguat and PDE5i in these patients are needed. The aim of this trial was to assess the effects of switching to riociguat from PDE5i therapy versus continued PDE5i therapy in patients with PAH at intermediate risk of 1-year mortality.METHODS: Riociguat rEplacing PDE5i therapy evaLuated Against Continued PDE5i thErapy (REPLACE) was an open-label, randomised controlled trial in 81 hospital-based pulmonary hypertension centres in 22 countries. The study enrolled patients aged 18-75 years with symptomatic PAH at intermediate risk of 1-year mortality (based on the European Society for Cardiology-European Respiratory Society guideline thresholds for WHO functional class and 6-min walk distance [6MWD]) who were receiving treatment with a PDE5i with or without an endothelin receptor antagonist for at least 6 weeks before randomisation. Patients were excluded if they had been previously treated with riociguat, had used prostacyclin analogues or prostacyclin receptor agonists within 30 days before randomisation, had clinically significant restrictive or obstructive parenchymal lung disease, or had left heart disease. Patients were randomly assigned (1:1) to remain on PDE5i treatment (oral sildenafil [≥60 mg per day] or oral tadalafil [20-40 mg per day]; the PDE5i group) or to switch to oral riociguat (up to 2·5 mg three times per day; the riociguat group), using an interactive voice and web response system, stratified by cause of PAH. The primary endpoint was clinical improvement by week 24, defined as an absence of clinical worsening and prespecified improvements in at least two of three variables (6MWD, WHO functional class, and N-terminal prohormone of brain natriuretic peptide), analysed using last observation carried forward in all randomly assigned patients with observed values at baseline and week 24 who received at least one dose of study medication (the full analysis set). Secondary endpoints included clinical worsening events. The trial has been completed and is registered with ClinicalTrials.gov, NCT02891850.FINDINGS: Between Jan 11, 2017, and July 31, 2019, 293 patients were screened, of which 226 patients were randomly assigned to the riociguat group (n=111) or to the PDE5i group (n=115). 211 patients completed the study and 14 patients discontinued (seven in each group). One patient assigned to the PDE5i group did not receive treatment, so 225 patients were included in the safety analysis, and one further patient in the PDE5i group had missing components of the composite primary endpoint at baseline, so 224 patients were included in the full analysis set. The primary endpoint was met by 45 (41%) of 111 patients in the riociguat group and 23 (20%) of 113 patients in the PDE5i group; odds ratio [OR] 2·78 (95% CI 1·53-5·06; p=0·0007). Clinical worsening events occurred in one (1%) of 111 patients in the riociguat group (hospitalisation due to worsening PAH) and 10 (9%) of 114 patients in the PDE5i group (hospitalisation due to worsening PAH [n=9]; disease progression [n=1]; OR 0·10 [0·01-0·73]; p=0·0047). The most frequently occurring adverse events were hypotension (15 [14%]), headache (14 [13%]), and dyspepsia (10 [9%]) in the riociguat group, and headache (eight [7%]), cough (seven [6%]), and upper respiratory tract infection (seven [6%]) in the PDE5i group. Serious adverse events were reported in eight (7%) of 111 patients in the riociguat group and 19 (17%) of 114 patients in the PDE5i group. During the study, four patients died in the PDE5i group, one of them during the safety follow-up period.INTERPRETATION: Switching to riociguat from PDE5i treatment, both of which act via the nitric oxide-soluble guanylate cyclase-cyclic guanosine monophosphate pathway, could be a strategic option for treatment escalation in patients with PAH at intermediate risk of 1-year mortality.FUNDING: Bayer AG, Merck Sharp & Dohme.

To improve acceptance and use of physical training by patients with chronic lung diseases, recommendations for performing lung exercises on an outpatient basis in a group setting are given by experts in physical training, sports therapists and pulmonologists. The evidence-based positive effects of physical training were analyzed for asthma , COPD, interstitial lung diseases, cystic fibrosis, lung carcinoma, and pulmonary hypertension. The requirements for lung exercises in outpatient groups as well as compensation by care providers were given on the basis of legal regulations. Furthermore, the main items of the training units as well as supervision by specially trained group leaders in relation to the severity of the underlying lung disease are described. Finally, aspects of safety of the participating patients are discussed, including the prevention of infection with corona-2-virus.Um der zu selten genutzten Behandlungsoption „Bewegungstherapie“ bei Patienten mit chronischen Lungenkrankheiten eine bessere Nutzung und eine größere Verbreitung zu ermöglichen, wurden von einer Expertengruppe aus Sportwissenschaftlern, Sporttherapeuten und Pneumologen Empfehlungen zur Durchführung von ambulantem, wohnortnahem Lungensport in Gruppen verfasst. Die positiven Effekte von Sport und körperlichem Training bei Asthma, COPD, interstitiellen Lungenkrankheiten, Mukoviszidose, Lungenkarzinom und pulmonaler Hypertonie werden dargestellt. Unter Berücksichtigung der gesetzlichen Grundlagen werden die notwendigen Voraussetzungen der Patienten für die Teilnahme am ambulanten Lungensport, den Aufbau von Übungseinheiten sowie die Überwachung der Teilnehmer durch speziell ausgebildete Übungsleiter in Abhängigkeit von Schwere und Art der Lungenkrankheit dargestellt. Hinweise für den Aufbau, die Organisation und die Kostenerstattung von Lungensportgruppen sollen die Verbreitung des ambulanten Lungensports fördern. Schließlich wird auch auf Sicherheitsaspekte der teilnehmenden Patienten unter Einschluss des Infektionsrisikos mit dem Corona-2-Virus eingegangen.

BackgroundThe delay of the diagnosis of pulmonary hypertension (PH) in patients with systemic sclerosis (SSc) leads to severe impairment of survival.ObjectivesThe objective of this study was to investigate the prognostic impact of right ventricular (RV) function at rest and during exercise on survival in patients with SSc presenting for screening for PH.MethodsData from SSc patients who underwent routinely performed examinations for PH screening including echocardiography and right heart catheterization at rest and during exercise were analyzed. Uni- and multivariable analyses were performed to identify prognostic parameters in SSc and to compare them to known prognostic predictors.ResultsOut of 285 SSc patients screened for PH, 225 patients (81.3% female, mean age 58.1±13.0 years, 68% limited cutaneous SSc, WHO-FC II-III 74%, 24 manifest PH) were included in the analysis. During an observation period of 3.2±2.7 (median 2.6) years 35 patients died. Tricuspid annular plane systolic excursion ≤18 mm (p=0.0004), increase of cardiac index (CI) during exercise ≤ 2 l/min (p=0.0002), RV output reserve >3 mmHg/l/min (p=0.001), peak CI ≤ 5.5l/min (p=0.01), pulmonary arterial compliance >2 ml/mmHg (p=0.0005) and qualitative RV function at rest (p2 were identified as independent prognostic predictors and had >70% sensitivity and specificity to predict development of pulmonary vascular disease (PVD) during follow-up.ConclusionThis study demonstrates that assessment of RV function at rest and during exercise may provide crucial information to identify SSc patients who are at a high risk of an impaired survival and development of PVD.References[1]Brown ZR, et al. Screening for pulmonary arterial hypertension in systemic sclerosis: Now or never!. Eur J Rheumatol. 2020;7(Suppl 3):S187-S192.Disclosure of InterestsPanagiota Xanthouli Speakers bureau: MSD and OMT, outside the submitted work, Julia Miazgowski: None declared, Nicola Benjamin Speakers bureau: Actelion pharmaceuticals, Bayer HealthCare and MSD outside the submitted work., Ojan Gordjani: None declared, Benjamin Egenlauf Speakers bureau: Actelion, MSD, Bayer and OMT (less than $10,000 each)., Satenik Harutyunova Speakers bureau: Bayer, MSD, Actelion and GSK, outside the submitted work., Rebekka Seeger: None declared, Alberto Marra Speakers bureau: MSD, Norbert Blank Speakers bureau: MSD, GSK, Actelion and Bayer Vital., Hanns-Martin Lorenz Speakers bureau: AbbVie, BMS, Pfizer, Cellgene, Medac, GSK, Roche, Chugai, Novartis, UCB, Janssen-Cilag, AstraZeneca, and Lilly (less than $10,000 each) and research support from AbbVie, MSD, BMS, Cellgene, Medac, GSK, Roche, Chugai, Novartis, UCB, Janssen-Cilag, AstraZeneca, Lilly, Baxter, SOBI, Biogen, Actelion, Bayer Vital, Shire, Octapharm, Sanofi, Hexal, Mundipharm, and Thermo Fisher, Consultant of: AbbVie, BMS, Pfizer, Cellgene, Medac, GSK, Roche, Chugai, Novartis, UCB, Janssen-Cilag, AstraZeneca, and Lilly (less than $10,000 each) and research support from AbbVie, MSD, BMS, Cellgene, Medac, GSK, Roche, Chugai, Novartis, UCB, Janssen-Cilag, AstraZeneca, Lilly, Baxter, SOBI, Biogen, Actelion, Bayer Vital, Shire, Octapharm, Sanofi, Hexal, Mundipharm, and Thermo Fisher, Ekkehard Grünig Speakers bureau: Actelion, Bayer AG, and MSD; grants from GSK, Novartis, and United Therapeutics; and personal fees from SCOPE, OrPha Swiss GmbH, and Zurich Heart House, Consultant of: Actelion, Bayer AG, and MSD; grants from GSK, Novartis, and United Therapeutics; and personal fees from SCOPE, OrPha Swiss GmbH, and Zurich Heart House, Christina Eichstaedt: None declared

BackgroundIron deficiency is frequent among patients with systemic sclerosis (SSc), particularly among those with pulmonary hypertension (PH). First data indicate prognostic importance of hypochromic erythrocytes (HRC) >2% among patients with PH1. Hence, the aim of this study was to investigate the predictive value of HRC in SSc patients screened for PH.ObjectivesThe objective of this study was to investigate the predictive value of HRC in SSc patients screened for PH.MethodsIn this retrospective, single-center cohort study SSc patients screened for PH were included. Clinical characteristics, laboratory and pulmonary functional parameters associated with the prognosis of SSc were analysed using uni- and multivariable analysis.ResultsA total of 280 SSc patients were screened, 171 were included in the analysis having complete data of iron metabolism (79% female, 61.0±12.9 years of age, 73.2% limited cutaneous SSc, 56 manifest PH and 112 pulmonary fibrosis). The patients were followed for 2.4±1.8 (median 2.4) years. HRC >2% at baseline was significantly associated with worse survival in the uni- (p=0.018) and multivariable analysis (p2% was identified as independent predictor of mortality, for patients with and without pulmonary manifestations of SSc.ConclusionThis study detected for the first time that HRC >2% is an independent prognostic predictor and can possibly be used as a biomarker among SSc-patients. Further studies are needed to confirm these results.References[1]Xanthouli P, Theobald V, Benjamin N, Marra AM, D’Agostino A, Egenlauf B, Shaukat M, Ding C, Cittadini A, Bossone E, Kögler M, Grünig E, Muckenthaler MU, Eichstaedt CA. Prognostic impact of hypochromic erythrocytes in patients with pulmonary arterial hypertension. Respir Res. 2021 Nov 9;22(1):288. doi: 10.1186/s12931-021-01884-9.Disclosure of InterestsPanagiota Xanthouli Speakers bureau: MSD and OMT, outside the submitted work, Ojan Gordjani: None declared, Christina Eichstaedt: None declared, Nicola Benjamin Speakers bureau: Actelion pharmaceuticals, Bayer HealthCare and MSD., Benjamin Egenlauf Speakers bureau: Actelion, MSD, Bayer and OMT outside the submitted work, Satenik Harutyunova Speakers bureau: Bayer, MSD, Actelion and GSK, outside the submitted work., Alberto Marra Speakers bureau: Bayer/MSD outside the submitted work, Vivienne Theobald: None declared, Nicklas Milde: None declared, Christian Nagel Speakers bureau: Actelion, MSD, Boehringer, Novartis, Bayer, and AstraZeneca, Norbert Blank Speakers bureau: MSD, GSK, Actelion and Bayer Vital., Consultant of: MSD, GSK, Actelion and Bayer Vital., Hanns-Martin Lorenz Speakers bureau: AbbVie, BMS, Pfizer, Cellgene, Medac, GSK, Roche, Chugai, Novartis, UCB, Janssen-Cilag, AstraZeneca, and Lilly (less than $10,000 each) and research support from AbbVie, MSD, BMS, Cellgene, Medac, GSK, Roche, Chugai, Novartis, UCB, Janssen-Cilag, AstraZeneca, Lilly, Baxter, SOBI, Biogen, Actelion, Bayer Vital, Shire, Octapharm, Sanofi, Hexal, Mundipharm, and Thermo Fisher, Consultant of: AbbVie, BMS, Pfizer, Cellgene, Medac, GSK, Roche, Chugai, Novartis, UCB, Janssen-Cilag, AstraZeneca, and Lilly (less than $10,000 each) and research support from AbbVie, MSD, BMS, Cellgene, Medac, GSK, Roche, Chugai, Novartis, UCB, Janssen-Cilag, AstraZeneca, Lilly, Baxter, SOBI, Biogen, Actelion, Bayer Vital, Shire, Octapharm, Sanofi, Hexal, Mundipharm, and Thermo Fisher, Ekkehard Grünig Speakers bureau: Actelion, Bayer AG, and MSD; grants from GSK, Novartis, and United Therapeutics; and personal fees from SCOPE, OrPha Swiss GmbH, and Zurich Heart House, Consultant of: Actelion, Bayer AG, and MSD; grants from GSK, Novartis, and United Therapeutics; and personal fees from SCOPE, OrPha Swiss GmbH, and Zurich Heart House

BackgroundOxygenated hemoglobin (OxyHem)1 in arterial blood may reflect disease severity in patients with systemic sclerosis (SSc), particularly among those with pulmonary manifestations such as pulmonary hypertension (PH).ObjectivesHence, the aim of this study was to analyze the predictive value of OxyHem in SSc patients screened for PH.MethodsSSc patients were screened for PH including right heart catheterisation, laboratory and clinical assessment. They were followed for 3.2±2.6 (median 3.0) years. OxyHem was measured by multiplying the concentration of hemoglobin with oxygen saturation assessed in arterialized capillary blood. Kaplan-Meier analysis was performed using the defined threshold from Receiver Operating characteristic. Prognostic power was compared with known parameters of prognostic significance in SSc using uni- and multivariable analysis. Clinical parameters of patients with high and low OxyHem were compared by student’s t-test.ResultsA total of 280 SSc patients were screened, 267 were included in the analysis (82% female, 59.8±13.4 years, 73.8% limited cutaneous SSc), 56 patients had manifest PH and 112 interstitial lung disease (ILD). Low OxyHem ≤12.5g/dl at baseline was significantly associated with a worse survival (p=0.046) among SSc patients. In the multivariable analysis the presence of ILD, age ≥60 years and diffusion capacity (DLCO) ≤65% were associated with worse survival among SSc patients. The combination of low DLCO and low OxyHem at baseline could predict the development of early pulmonary vascular disease at follow- up (sensitivity 79.6%).ConclusionThis study detected for the first time that an OxyHem level ≤12.5 g/dl is a prognostic predictor in SSc- patients. Further studies are needed to confirm these results.References[1]Trudzinski, F. C., R. A. Jörres, P. Alter, K. Kahnert, B. Waschki, C. Herr, C. Kellerer, A. Omlor, C. F. Vogelmeier, S. Fähndrich, H. Watz, T. Welte, B. Jany, S. Söhler, F. Biertz, F. Herth, H. U. Kauczor and R. Bals (2020). “Associations of oxygenated hemoglobin with disease burden and prognosis in stable COPD: Results from COSYCONET.” Sci Rep10(1): 10544.Disclosure of InterestsPanagiota Xanthouli Speakers bureau: MSD and OMT, outside the submitted work, Ojan Gordjani: None declared, Christina Eichstaedt: None declared, Nicola Benjamin Speakers bureau: Actelion pharmaceuticals, Bayer HealthCare and MSD outside the submitted work, Franziska Trudzinski: None declared, Benjamin Egenlauf Speakers bureau: Actelion, MSD, Bayer and OMT outside the submitted work, Satenik Harutyunova Speakers bureau: Bayer, MSD, Actelion and GSK, outside the submitted work., Alberto Marra Speakers bureau: Bayer/MSD outside the submitted work, Nicklas Milde: None declared, Christian Nagel Speakers bureau: from Actelion, MSD, Boehringer, Novartis, Bayer, and AstraZeneca outside the submitted work, Norbert Blank Speakers bureau: MSD, GSK, Actelion and Bayer Vital outside the submitted work, Hanns-Martin Lorenz Speakers bureau: AbbVie, BMS, Pfizer, Cellgene, Medac, GSK, Roche, Chugai, Novartis, UCB, Janssen-Cilag, AstraZeneca, and Lilly (less than $10,000 each) and research support from AbbVie, MSD, BMS, Cellgene, Medac, GSK, Roche, Chugai, Novartis, UCB, Janssen-Cilag, AstraZeneca, Lilly, Baxter, SOBI, Biogen, Actelion, Bayer Vital, Shire, Octapharm, Sanofi, Hexal, Mundipharm, and Thermo Fisher outside the submitted work, Consultant of: AbbVie, BMS, Pfizer, Cellgene, Medac, GSK, Roche, Chugai, Novartis, UCB, Janssen-Cilag, AstraZeneca, and Lilly (less than $10,000 each) and research support from AbbVie, MSD, BMS, Cellgene, Medac, GSK, Roche, Chugai, Novartis, UCB, Janssen-Cilag, AstraZeneca, Lilly, Baxter, SOBI, Biogen, Actelion, Bayer Vital, Shire, Octapharm, Sanofi, Hexal, Mundipharm, and Thermo Fisher outside the submitted work, Ekkehard Grünig Speakers bureau: Actelion, Bayer AG, and MSD; grants from GSK, Novartis, and United Therapeutics; and personal fees from SCOPE, OrPha Swiss GmbH, and Zurich Heart House (less than $10,000 each) outside the submitted work., Consultant of: Actelion, Bayer AG, and MSD; grants from GSK, Novartis, and United Therapeutics; and personal fees from SCOPE, OrPha Swiss GmbH, and Zurich Heart House (less than $10,000 each).

Background: Oral treprostinil (TRE) decreased the risk of adjudicated clinical worsening (CW) compared to placebo (PBO) in FREEDOM-EV (HR 0.74; 95% CI 0.56,0.97; p=0.0391). This prespecified analysis hypothesized that changes in NT-proBNP, World Health Organization Functional Class (FC), Borg dyspnea score (BDS), and 6-minute walk distance (6MWD) would be dose-dependent. Methods: Participants with pulmonary arterial hypertension (PAH) taking one PAH medication were randomized to TRE or PBO and titrated to 12 mg thrice daily (TID). Results are compared for TRE Results: Baseline characteristics were similar. More than half (54%) assigned to TRE reached ≥3 mg TID at W24; median dose was 3.6 mg TID. The ≥3 mg TID group had greater clinical response compared to PBO and Conclusions: Higher TRE dose facilitated greater clinical improvements at W24 in this a priori analysis. Although 6MWD effect with ≥3 mg TID was modest, it was coupled with a significant reduction in BDS. AEs did not appear dose dependent. A dose ≥3 mg TID may be a reasonable initial target in clinical practice.

The 2015 European Guidelines on Diagnosis and Treatment of Pulmonary Hypertension are also valid for Germany. The guidelines contain detailed recommendations for the targeted treatment of pulmonary arterial hypertension (PAH). However, the practical implementation of the European Guidelines in Germany requires the consideration of several country-specific issues and already existing novel data. This requires a detailed commentary to the guidelines, and in some aspects an update already appears necessary. 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 Pediatric Cardiology (DGPK) was held in Cologne, Germany. This conference aimed to solve practical and controversial issues surrounding the implementation of the European Guidelines in Germany. To this end, a number of working groups was initiated, one of which was specifically dedicated to the targeted therapy of PAH. This article summarizes the results and recommendations of the working group on targeted treatment of PAH.

Die pulmonal-arterielle Hypertonie (PAH) betrifft haufig junge Patienten, fur die eine lebenslange Antikoagulation eine einschneidende Entscheidung darstellen kann. Daher ist es wichtig, die zum Teil widerspruchlichen klinischen und wissenschaftlichen Befunde zu dieser Therapie zu analysieren. PAH wird haufig aufgrund der endothelialen Dysfunktion, vor allem der kleinen Pulmonalarteriolen mit prothrombotischer und verminderter antifibrinolytischer Aktivitat, von Thrombose und Thromboembolien der Lungenstrombahn begleitet. Messbare Veranderungen von Gerinnungsfaktoren sind von prognostischer Bedeutung. Zudem ist die Funktion der Thrombozyten gestort. Die meisten Patienten mit PAH haben daruber hinaus eine Rechtsherzinsuffizienz mit vergrosertem rechtem Ventrikel und verlangsamtem Blutfluss. Neben diesen pathophysiologischen Befunden begrunden 4 nichtrandomisierte klinische Studien, die eine verbesserte Prognose durch Phenprocoumontherapie vermuten lassen, die Rationale zur Antikoagulation bei PAH und die Empfehlungen der nationalen und internationalen Leitlinien. Klinische Studien zu Alternativen wie der Gabe von Acetylsalicylsaure stehen aus. Es sollten alle Anstrengungen unternommen werden, die Erkrankung fruher zu diagnostizieren, um durch eine fruhe Therapie u. a. die Veranderung der Gerinnung und Thrombozytenfunktion rasch korrigieren zu konnen.

Pulmonary hypertension (PH) is classified into five distinct groups according to the fifth world conference in Nice 2013. Pulmonary arterial hypertension (PAH) comprises idiopathic PAH, hereditary PAH, drug-induced and associated PAH. Right heart catheterization is essential for the diagnosis of PH and should precede initiation of a targeted PAH therapy. Besides general measures and supportive therapy, four different classes of targeted drugs have been approved for the treatment of PAH. Combination therapy, either sequential or initial (up-front), is increasingly gaining recognition. Risk stratification and treatment goals have been defined to guide therapeutic decisions. However, cure is still far from reach and lung transplantation is an important treatment option for patients with end-stage disease under optimal supportive and targeted drug therapy.

Pulmonary hypertension (PH) is a severe disease, which is usually only recognized at a late stage. It is characterized by dyspnea and right heart insufficiency. In some forms of pulmonary hypertension, such as the rare pulmonary arterial hypertension (PAH) and PAH associated with congenital heart defects, genetic factors have been identified. This article summarizes the general and supportive therapies for PH, targeted pharmaceutical treatment for PAH and non-operable chronic thromboembolic pulmonary hypertension. To achieve acceptable survival rates, it is essential to transfer patients to an expert center at an early stage for further differential diagnostics and therapy.

Riociguat is the first clinically available soluble Guanylate-cyclase stimulator (sGC) and representative of a completely new class of drugs. Riociguat is approved for pulmonary arterial hypertension (PAH) and non-operable or recurrent/persistent chronic thromboembolic pulmonary hypertension (CTEPH). Moreover, Riociguat is currently under investigation for a wider spectrum of diseases. This article focusses on its mode of action and clinical trial data. Finally, based on these data, the status of approval, as well as the costs a proposal is given how Riociguat can be integrated in the current treatment of PAH and CTEPH.

The therapeutic options for pulmonary arterial hypertension (PAH) have significantly improved in the last few years. But the disease is still too often diagnosed late in its course. In more than 80% of patients the diagnosis is made and treatment started when the condition is already in NYHA class III-IV with a very poor prognosis. According to the EARLY study, beginning treatment 3 - 6 months earlier can improve prognosis and progression of the PHT. Late diagnosis is first of all due to the fact that it is asymptomatic in the early stages, such symptoms as dyspnoea, peripheral edema or syncope frequently occurring only when there are already signs of heart failure. Secondly, there is as yet no method for the early diagnosis of PHT. But echocardiography and magnetic resonance imaging (MRI) are non-invasive modes that are important for screening and follow-up. Among noninvasive methods echocardiography shows the greatest diagnostic sensitivity and specificity. It should be undertaken in all patients in whom pulmonary hypertension (PHT) is suspected. But because of the particular geometry of the right ventricle its examination is difficult. New diagnostic techniques allow for assessment of additional information of right ventricular function. Right heart catheterization is essential for further elucidating PHT.

The diagnosis of acute myocardial infarction is straightforward when anginal pain is accompanied by typical ECG changes and in these patients measurements of cardiac markers are unnecessary in deciding whether thrombolytic therapy is appropriate. Cardiac markers in patients with acute ischaemic coronary syndromes, however, may serve to identify a high risk subgroup of patients with small acute infarctions or minor myocardial damage. In many patients with chest pain a valid diagnosis of myocardial cell injury depends on the result of biochemical assays. In 30% of patients with unstable angina, troponin T is elevated although myocardial infarction was ruled out by cardiac enzymes and ECG recordings. The outcome of these patients at 4 weeks and 6 months follow-up is not different from that of patients with definite myocardial infarction. To guide therapeutic decisions on these patients a troponin T test result needs to be available rapidly. The rapid troponin T test strip assay, which allows the determination of troponin T levels in whole blood at the patient's bedside, can be performed conveniently in the emergency room or in laboratories with less sophisticated equipment and has the potential to aid in the triage of chest pain patients and the selection of therapeutic strategies.

The 2009 European Guidelines on Diagnosis and Treatment of Pulmonary Hypertension have been adopted for Germany. While the guidelines contain detailed recommendations regarding pulmonary arterial hypertension (PAH), they contain only a relatively short paragraph on other, much more frequent forms of PH such as PH due to left heart disease. Despite the lack of data, targeted PAH treatments are increasingly being used for PH associated with left heart disease. This development is of concern. On the other hand, PH is a frequent problem that is highly relevant for morbidity and mortality in patients with left heart disease, so that it may be speculated whether selected patients may benefit from targeted PH therapy. It that sense, the practical implementation of the European Guidelines in Germany requires the consideration of several specific issues and already existing novel data. This requires a detailed commentary to the guidelines, and in some aspects an update already appears necessary. In June 2010, 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 Pediatric Cardiology (DGPK) was held in Cologne, Germany. This conference aimed to solve practical and controversial issues surrounding the implementation of the European Guidelines in Germany. To this end, a number of working groups was initiated, one of which was specifically dedicated to PH due to left heart disease. This commentary summarizes the results and recommendations of this working group.

The 2009 European Guidelines on Diagnosis and Treatment of Pulmonary Hypertension have been adopted for Germany. The guidelines contain detailed recommendations for the diagnosis of pulmonary hypertension. However, the practical implementation of the European Guidelines in Germany requires the consideration of several country-specific issues and already existing novel data. This requires a detailed commentary to the guidelines, and in some aspects an update y appears necessary. In June 2010, 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 Pediatric Cardiology (DGPK) was held in Cologne, Germany. This conference aimed to solve practical and controversial issues surrounding the implementation of the European Guidelines in Germany. To this end, a number of working groups was initiated, one of which was specifically dedicated to non-invasive diagnosis of PH. This commentary summarizes the results and recommendations of the working group on treatment of PAH.

The 2009 European Guidelines on Diagnosis and Treatment of Pulmonary Hypertension have been adopted for Germany. The guidelines contain detailed recommendations for the treatment of pulmonary arterial hypertension (PAH). However, the practical implementation of the European Guidelines in Germany requires the consideration of several country-specific issues and already existing novel data. This requires a detailed commentary to the guidelines, and in some aspects an update already appears necessary. In June 2010, 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 Pediatric Cardiology (DGPK) was held in Cologne, Germany. This conference aimed to solve practical and controversial issues surrounding the implementation of the European Guidelines in Germany. To this end, a number of working groups was initiated, one of which was specifically dedicated to the treatment of PAH. This commentary summarizes the results and recommendations of the working group on treatment of PAH.

In pulmonary arterial hypertension (PAH), thrombosis and thromboembolism occurs as a consequence of pulmonary microvasculopathy with a change of pulmonary vascular microenviroment toward a procoagulant, prothrombotic and antifibrinolytic pattern. Circulating antiphospholipid antibodies, increased plasma levels of platelet aggregating agents (serotonin, thromboxane), adhesion molecules (P selectin, von Willebrand factor), antifibrinolytic enzymes (plasminogen activator inhibitor 1) and prothrombotic cytokines have been identified in PAH patients so far. Thrombogenic pulmonary vasculopathy has been documented in many patients with PAH. Furthermore, most patients will not be diagnosed until right heart enlargement and impaired right ventricular function has developed. Thus, there is clear rationale for a treatment with anticoagulation. In four uncontrolled studies Warfarin improved the prognosis of patients with idiopathic and other forms of PAH. However, so far there are no prospective randomised studies evaluating the role of anticoagulants in the treatment of PAH. This review summarizes the current data and guidelines concerning anticoagulation in PAH.

The therapeutic options for pulmonary arterial hypertension (PAH) have significantly improved in the last few years. But the disease is still too often diagnosed late in its course. In more than 80% of patients the diagnosis is made and treatment started when the condition is already in NYHA class III-IV with a very poor prognosis. According to the EARLY study, beginning treatment 3 - 6 months earlier can improve prognosis and progression of the PHT. Late diagnosis is first of all due to the fact that it is asymptomatic in the early stages, such symptoms as dyspnoea, peripheral edema or syncope frequently occurring only when there are already signs of heart failure. Secondly, there is as yet no method for the early diagnosis of PHT. But echocardiography and magnetic resonance imaging (MRI) are non-invasive modes that are important for screening and follow-up. Among noninvasive methods echocardiography shows the greatest diagnostic sensitivity and specificity. It should be undertaken in all patients in whom pulmonary hypertension (PHT) is suspected. But because of the particular geometry of the right ventricle its examination is difficult. New diagnostic techniques allow for assessment of additional information of right ventricular function. Right heart catheterization is essential for further elucidating PHT.

Dilative cardiomyopathy is a heterogeneous myocardial disease characterized by a depressed contractile function and ventricular dilation. The exercise intolerance of patients with dilative cardiomyopathy is partly explained by changes of metabolism and composition of skeletal muscle, whereas the physical findings result from progressive heart failure and cardiac remodeling. The clinical course of the disease is highly variable and prognostic indicators of progressive heart failure or cardiac arrhythmias are of little value in the assessment of cardiac risk in an individual patient. During recent years the mortality of patients with dilative cardiomyopathy was 5-15%, which appears to be lower than previously reported. The differences in mortality today and in previous years may be explained by a more precise and earlier diagnosis of the disease and possibly better treatment strategies. Patients with a severely depressed left ventricular function but a stable clinical course, a good hemodynamic response to therapy, and an oxygen uptake of12 ml/kg min can be followed without heart transplantation. It can be expected that the definition of the molecular causes of dilative cardiomyopathy will lead to a better classification of the patients and the development of more efficient treatment strategies.