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Background: Persistent symptoms after acute coronavirus-disease-2019 (COVID-19) are common, and there is no significant correlation with the severity of the acute disease. In long-COVID (persistent symptoms >4 weeks after acute COVID-19), respiratory symptoms are frequent, but lung function testing shows only mild changes that do not explain the symptoms. Although COVID-19 may lead to an impairment of the peripheral nervous system and skeletal muscles, respiratory muscle function has not been examined in this setting. Methods: In this study, we assessed the severity of dyspnea (NYHA-function class) in long-COVID patients and analyzed its association with body mass index (BMI), FEV1, forced vital capacity, other parameters of body plethysmography, diffusing capacity for carbon monoxide (DLCO), arterial blood gases, and inspiratory muscle function, assessed by airway occlusion pressure (P0.1) and maximal inspiratory pressure (PImax) in two respiratory clinics in Germany between Oct 2020 and Aug 2021. Results: A total of 116 patients were included in the study. The mean age was 50.2 ± 14.5 years; BMI, 26.7 ± 5.87 kg/m2; NYHA class I, 19%; II, 27%; III, 41%; and IV, 14%. While lung function values and computed tomography or conventional X-ray of the chest were in the normal range, inspiratory muscle function was markedly impaired. P01 was elevated to 154 ± 83%predicted and PImax was reduced to 41 ± 25%predicted. PImax reduction was strongly associated with the severity of dyspnea but independent of BMI, time after acute COVID-19 and most of the other parameters. Conclusions: This study shows that in long-COVID patients, respiratory symptoms may be mainly caused by reduced inspiratory muscle strength. Assessment of PImax and P0.1 might better explain dyspnea than classical lung function tests and DLCO. A prospective study is needed to confirm these results. [ABSTRACT FROM AUTHOR]

Aims The presence of pulmonary hypertension (PH) severely aggravates the clinical course of heart failure with preserved ejection fraction (HFpEF). To date, neither established heart failure therapies nor pulmonary vasodilators proved beneficial. This study investigated the efficacy of chronic treatment with the oral soluble guanylate cyclase stimulator riociguat in patients with PH-HFpEF. Methods and Results The phase IIb, randomized, double-blind, placebo-controlled, parallel-group, multicentre DYNAMIC trial assessed riociguat in PH-HFpEF. Patients were recruited at five hospitals across Austria and Germany. Key eligibility criteria were mean pulmonary artery pressure ≥25 mmHg, pulmonary arterial wedge pressure >15 mmHg, and left ventricular ejection fraction ≥50%. Patients were randomized to oral treatment with riociguat or placebo (1:1). Patients started at 0.5 mg three times daily (TID) and were up-titrated to 1.5 mg TID. The primary efficacy endpoint was change from baseline to week 26 in cardiac output (CO) at rest, measured by right heart catheterization. Primary efficacy analyses were performed on the full analysis set. Fifty-eight patients received riociguat and 56 patients placebo. After 26 weeks, CO increased by 0.37 ± 1.263 L/min in the riociguat group and decreased by −0.11 ± 0.921 L/min in the placebo group (least-squares mean difference: 0.54 L/min, 95% confidence interval 0.112, 0.971; P  = 0.0142). Five patients dropped out due to riociguat-related adverse events but no riociguat-related serious adverse event or death occurred. Conclusion The vasodilator riociguat improved haemodynamics in PH-HFpEF. Riociguat was safe in most patients but led to more dropouts as compared to placebo and did not change clinical symptoms within the study period. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: Right ventricular (RV) dysfunction is a major prognostic predictor in pulmonary arterial hypertension (PAH). Objectives: The objective of this study was to assess the prognostic impact of a newly developed index merging haemodynamic parameters into 1 variable. Methods: We retrospectively assessed 2 cohorts of 248 patients (164 from Hamburg and 84 from Heidelberg) with invasively diagnosed PAH. During a median follow-up time of 3.6 years (3.1 and 4.0 years for Hamburg and Heidelberg, respectively), the composite endpoint of all-cause mortality and lung transplantation occurred in 57 patients (53 and 4 patients for Hamburg and Heidelberg, respectively). The RV index was developed in the Hamburg cohort and validated in the Heidelberg cohort: (right atrial pressure × pulmonary vascular resistance)/mixed venous oxygen saturation. Results: Patients with a high RV index had a higher incidence of the combined endpoint in Kaplan-Meier analyses in the Hamburg and Heidelberg cohort (p = 0.017 and p = 0.034, respectively). The calculated RV index cut-off value was 91 and identified patients with a worse outcome in the Hamburg cohort and showed a trend in the Heidelberg cohort (p < 0.001 and p = 0.089, respectively). The RV index in Cox regression hazard models was an independent predictor of outcomes after adjustment for sex and age in both cohorts (Hamburg: hazard ratio [HR] 1.26 [95% CI 1.08, 1.47], p = 0.0027; Heidelberg: HR 2.27 [95% CI 1.46, 3.51], p < 0.001). A nomogram based on these results allowed risk stratification. Conclusion: Merging 3 haemodynamic variables into 1 variable, the RV index increased the prognostic power up to an independent risk factor. The RV index is easy to calculate and allows the construction of a nomogram for an individualized risk assessment. [ABSTRACT FROM AUTHOR]

Objectives: This prospective study was performed to analyse whether routine clinical follow-up investigations at 12±6 months add to risk stratification and improve survival rates in patients with a first diagnosis of dilated cardiomyopathy (DCM). Methods: Four hundred and eighty consecutive patients (mean age 53.4±12.3 years, 369 males, mean NYHA class 2.4±0.8) with invasively confirmed DCM were included and followed for 3.9±3.5 years. Patients were requested to adhere to a follow up investigation within 6–18 months either at the referring physicians or at our out patient department. Two hundred and eighty-one of the 480 patients presented for follow up which consisted of a detailed evaluation of symptoms, standardized physical examination, 12-lead-electrocardiogram recording and echocardiography. Seventeen patients were lost for follow up, 182 did not seek specialized medical follow up. Patients outcome was assessed by structured telephone interviews. Results: Independent predictors of death or transplantation at initial diagnosis were LV–ejection fraction <30% (P=0.0001, risk ratio 2.25), LV–end diastolic pressure &ges;15 mmHg (P=0.002, risk ratio 2.0), age &ges;54 years, (P=0.04, risk ratio 1.55), and presence of left bundle branch block (P=0.046, risk ratio 1.53). On follow up investigations only deterioration of clinical status by at least one NYHA-class (P=0.001, risk ratio 2.6) and new onset or worsening of mitral regurgitation (P=0.02, risk ratio 1.8), remained independent prognostic factors for cardiac death. Patients who presented for routine follow up revealed significant better 5-year survival rates (n=281, 70%) than those who did not (n=153, 55%, P=0.005). Conclusions: Routine clinical follow up investigations within 6–18 months after first diagnosis of DCM adds to risk stratification and improves survival rates. [Copyright &y& Elsevier]

Background: Individuals with precapillary pulmonary hypertension (PH) experience severely impaired quality of life. A disease-specific outcome measure for PH, the Cambridge Pulmonary Hypertension Outcome Review (CAMPHOR) was developed and validated in the UK and subsequently adapted for use in additional countries. The aim of this study was to translate and assess the reliability and validity of the CAMPHOR for German-speaking populations. Methods: Three main adaptation stages involved; translation (employing bilingual and lay panels), cognitive debriefing interviews with patients and validation (assessment of the adaptation's psychometric properties). The psychometric evaluation included 107 patients with precapillary PH (60 females; age mean (standard deviation) 60 (15) years) from 3 centres in Austria, Germany and Switzerland. Results: No major problems were found with the translation process with most items easily rendered into acceptable German. Participants in the cognitive debriefing interviews found the questionnaires relevant, comprehensive and easy to complete. Psychometric analyses showed that the adaptation was successful. The three CAMPHOR scales (symptoms, activity limitations and quality of life) had excellent test-retest reliability correlations (Symptoms = 0.91; Activity limitations = 0.91; QoL = 0.90) and internal consistency (Symptoms = 0.94; Activity limitations = 0.93; QoL = 0.94). Predicted correlations with the Nottingham Health Profile provided evidence of the construct validity of the CAMPHOR scales. The CAMPHOR adaptation also showed known group validity in its ability to distinguish between participants based on perceived general health, perceived disease severity, oxygen use and NYHA classification. Conclusions: The CAMPHOR has been shown to be valid and reliable in the German population and is recommend for use in clinical practice. [ABSTRACT FROM AUTHOR]

Background: Even though specific agents for the treatment of patients with pulmonary hypertension (PH) are available, in PH patients, physical capacity and quality of life (QoL) are often restricted and survival is reduced. Objectives: This study prospectively investigated the long-term effects of respiratory and exercise training in patients with severe chronic PH regarding safety, time to clinical worsening and survival. Methods: Fifty-eight consecutive patients with severe PH on stable disease-targeted medication received exercise and respiratory training in hospital for 3 weeks and continued at home. They were prospectively followed for 24 ± 12 months. Primary endpoints were time to clinical worsening and survival. Adverse events and changes in the 6-min walking test, QoL, WHO functional class and gas exchange were secondary endpoints and were evaluated at baseline and at weeks 3 and 15. Results: All patients tolerated the exercise training well without severe adverse events. In week 15, 6-min walking test results were significantly improved compared to baseline (by 84 ± 49 m, p < 0.001), as well as QoL scores, WHO functional class (from 2.9 ± 0.5 to 2.6 ± 0.6, p < 0.01), peak oxygen consumption (from 12.5 ± 3.0 to 14.6 ± 3.9 ml/min/kg, p < 0.001), heart rate at rest (from 75 ± 12 to 61 ± 18 beats/min, p < 0.001) and maximal workload (from 65 ± 21 to 80 ± 25 W, p < 0.001). Survival at 1 and 2 years was 100 and 95%, respectively. Fifteen events occurred during the follow-up. Conclusion: This study indicates that exercise and respiratory training as add-on to medical treatment may improve exercise capacity and QoL, and that they have a good long-term safety in the described setting. Copyright © 2011 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Abstract: 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 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 non-invasive diagnosis of pulmonary hypertension. This manuscript describes in detail the results and recommendations of the working group which were last updated in October 2011. [Copyright &y& Elsevier]

Abstract: The 2009 European Guidelines on Diagnosis and Treatment of Pulmonary Hypertension (PH) 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 including PH owing to left heart disease. The guidelines point out that the drugs currently used to treat patients with PAH (prostanoids, endothelin receptor antagonists and phosphodiesterase type 5 inhibitors) have not been sufficiently investigated in other forms of PH. However, despite the lack of respective efficacy data an uncritical use of targeted PAH drugs in patients with PH associated with left heart disease is currently observed at an increasing rate. This development is a matter 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. 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 describes in detail the results and recommendations of the working group which were last updated in October 2011. [Copyright &y& Elsevier]

Abstract: The 2009 European Guidelines on Diagnosis and Treatment of Pulmonary Hypertension have been adopted for Germany. The guidelines contain detailed recommendations on the diagnosis of pulmonary hypertension (PH). 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 pulmonary arterial hypertension (PAH). This commentary describes in detail the results and recommendations of the working group on treatment of PAH which were last updated in October 2011. [Copyright &y& Elsevier]

The number of adults with congenital heart defects (CHD) is steadily rising and amounts to approximately 360,000 in Germany. CHD is often associated with pulmonary hypertension (PH), which may develop early in untreated CHD. Despite timely treatment of CHD, PH not infrequently persists or recurs in older age and is associated with significant morbidity and mortality.The revised European Society of Cardiology/European Respiratory Society 2022 guidelines for the diagnosis and treatment of PH represent a significant contribution to the optimized care of those affected. However, the topic of "adults with congenital heart disease" is addressed only relatively superficial in these guidelines. Therefore, in the present article, this topic is commented in detail from the perspective of congenital cardiology., Competing Interests: Harald Kaemmerer: Unabhängig von diesem Manuskript Sponsorship and honoraria Janssen/Johnson & Johnson; Bristol Myers Squibb. Steering Board COMPERA International.Gerhard Paul Diller: Advisory consultancy work for Janssen/Johnson & Johnson.Ingo Dähnert: Proctortätigkeit für Occlutech und Medtronic, Studien für Janssen und Novartis, Advisory Board für Actelion/Janssen.Christina A. Eichstaedt: C. A. E. ist Miterfinderin des europäischen Patents (EP3507380) “Gene panel specific for pulmonary hypertension and its uses”. CAE hat von msd Vortragshonorare erhalten, unabhängig von dieser Arbeit.Andreas Eicken: Keine Interessenkonflikte.Annika Freiberger: Keine Interessenkonflikte.Sebastian Freilinger: Keine Interessenkonflikte.Ralf Geiger: Keine Interessenkonflikte.Matthias Gorenflo: Advisory Board für Janssen.Ekkehard Grünig: E. G. hat Honorare für Vorträge/Konsultationen von Bayer/MSD, Ferrer, GEBRO, GSK, Janssen und OMT erhalten. Forschungsförderung für klinische Studien wurde von Acceleron, Actelion, BayerHealthCare, MSD, Bellerophon, GossamerBio, Janssen, Novartis, OMT, Pfizer, REATE und United Therapeutics erhalten.Alfred Hager: Unabhängig von diesem Manuskript erhielt A. H. Reisekostenerstattungen von Actelion, Pfizer, GlaxoSmithKline, Lilly und OMT; Rednergelder von Encysive, Pfizer, Actelion, Medtronic, Schiller, GlaxoSmithKline, OMT, AOP Orphan und Janssen; Autorenvergütungen von Actelion; Beraterhonorare von Actelion, Bayer, Ethypharm und GlaxoSmithKline; er hält Aktien von Merck Inc., Merck KGaA, Johnson & Johnson, Pfizer und Abbott.Michael Huntgeburth: Honorare Advisory-Board Janssen-Cilag, Johnson & Johnson.Ann-Sophie Kaemmerer-Suleiman: Keine Interessenkonflikte.Rainer Kozlik-Feldmann: Teaching-Kurse für Occlutech, Proktortätigkeit für Abbott (Amplatzer).Astrid E. Lammers: CEC chair and advisory consultancy work for Janssen/Johnson & Johnson.Nicole Nagdyman: Keine Interessenkonflikte.Sebastian Michel: Keine Interessenkonflikte.Kai Helge Schmidt: Vortragshonorare von Janssen, MSD und Abbott.Anselm Uebing: Keine Interessenkonflikte.Fabian von Scheidt: Keine Interessenkonflikte.Christian Apitz: Honorare für Vortragstätigkeit und Advisory Board für Janssen., (Thieme. All rights reserved.)

Competing Interests: Die Autorinnen/Autoren geben an, dass kein Interessenkonflikt besteht.

The number of adults with congenital heart disease (CHD) is steadily rising and amounts to approximately 360,000 in Germany. CHD is often associated with pulmonary arterial hypertension (PAH), which may develop early in untreated CHD. Despite timely treatment of CHD, PAH often persists or recurs in older age and is associated with significant morbidity and mortality.The revised European Society of Cardiology/European Respiratory Society 2022 guidelines for the diagnosis and treatment of PH represent a significant contribution to the optimized care of those affected. However, the topic of "adults with congenital heart defects" is addressed only relatively superficially in these guidelines. Therefore, this article addresses the perspective of congenital cardiology in greater depth., Competing Interests: Harald Kaemmerer: Unabhängig von diesem Manuskript Sponsorship and honoraria Janssen/Johnson & Johnson; Bristol Myers Squibb. Steering Board COMPERA International.Gerhard Paul Diller: Advisory consultancy work for Janssen/Johnson & Johnson.Ingo Dähnert: Proctortätigkeit für Occlutech und Medtronic, Studien für Janssen und Novartis, Advisory Board für Actelion/Janssen.Christina A. Eichstaedt: C.A.E. ist Miterfinderin des europäischen Patents (EP3507380) “Gene panel specific for pulmonary hypertension and its uses”. CAE hat von msd Vortragshonorare erhalten, unabhängig von dieser Arbeit.Andreas Eicken: keine Interessenkonflikte.Annika Freiberger: keine Interessenkonflikte.Sebastian Freilinger: keine Interessenkonflikte.Ralf Geiger: keine Interessenkonflikte.Matthias Gorenflo: Advisory Board für Janssen.Ekkehard Grünig: E.G. hat Honorare für Vorträge/Konsultationen von Bayer/MSD, Ferrer, GEBRO, GSK, Janssen und OMT erhalten. Forschungsförderung für klinische Studien wurde von Acceleron, Actelion, BayerHealthCare, MSD, Bellerophon, GossamerBio, Janssen, Novartis, OMT, Pfizer, REATE und United Therapeutics erhalten.Alfred Hager: Unabhängig von diesem Manuskript erhielt A.H. Reisekostenerstattungen von Actelion, Pfizer, GlaxoSmithKline, Lilly und OMT; Rednergelder von Encysive, Pfizer, Actelion, Medtronic, Schiller, GlaxoSmithKline, OMT, AOP Orphan und Janssen; Autorenvergütungen von Actelion; Beraterhonorare von Actelion, Bayer, Ethypharm und GlaxoSmithKline; er hält Aktien von Gilead, Merck Inc., Merck KGaA, Johnson &Johnson, Pfizer, Abbvie und Takeda.Ulrike Herberg: keine Interessenkonflikte.Michael Huntgeburth: Honorare Advisory-Board Janssen-Cilag, Johnson & Johnson.Ann-Sophie Kaemmerer: keine Interessenkonflikte.Rainer Kozlik-Feldmann: Teaching Kurse für Occlutech, Proktortätigkeit für Abbott (Amplatzer).Astrid E. Lammers: CEC chair and advisory consultancy work for Janssen/Johnson & Johnson.Nicole Nagdyman: keine Interessenkonflikte.Sebastian Michel: keine Interessenkonflikte.Kai Helge Schmidt: Vortragshonorare von Janssen, MSD und Abbott.Anselm Uebing: keine Interessenkonflikte.Fabian von Scheidt: keine Interessenkonflikte.Christian Apitz: Honorare Janssen., (Thieme. All rights reserved.)

In the summer of 2016, delegates from the German Respiratory Society, the German Society of Cardiology and the German Society of Pediatric Cardiology met in Cologne, Germany, to define consensus-based practice recommendations for the management of patients with pulmonary arterial hypertension (PAH). These recommendations were built on the 2015 European Pulmonary Hypertension guidelines aiming at their practical implementation, considering country-specific issues, and including new evidence, where available. To this end, a number of working groups was initiated, one of which was specifically dedicated to general measures (i.e. physical activity/supervised rehabilitation, pregnancy/contraception, elective surgery, infection prevention, psychological support, travel) and supportive therapy (i.e. anticoagulants, diuretics, oxygen, cardiovascular medications, anaemia/iron deficiency, arrhythmias) for PAH. While the European guidelines provide detailed recommendations for the use of targeted PAH therapies as well as supportive care, detailed treatment decisions in routine clinical care may be challenging, and the relevance of supportive care is often not sufficiently considered. In addition, new evidence became available, thus requiring a thorough reevaluation of specific recommendations. The detailed results and recommendations of the working group on general measures and supportive therapy for PAH, which were last updated in the spring of 2018, are summarized in this article., (Copyright © 2018 Elsevier B.V. All rights reserved.)

In the summer of 2016, delegates from the German Society of Cardiology (DGK), the German Respiratory Society (DGP), and the German Society of Pediatric Cardiology (DGPK) met in Cologne, Germany, to define consensus-based practice recommendations for the management of patients with pulmonary hypertension (PH). These recommendations were built on the 2015 European Pulmonary Hypertension guidelines, aiming at their practical implementation, considering country-specific issues, and including new evidence, where available. To this end, a number of working groups was initiated, one of which was specifically dedicated to the definition, clinical classification and initial diagnosis of PH. While the European guidelines provide a detailed clinical classification and a structured approach for diagnostic testing, their application in routine care may be challenging, particularly given the changing phenotype of PH patients who are nowadays often elderly and may present with multiple potential causes of PH, as well as comorbid conditions. Specifically, the working group addresses the thoroughness of diagnostic testing, and the roles of echocardiography, exercise testing, and genetic testing in diagnosing PH. Furthermore, challenges in the diagnostic work-up of patients with various causes of PH including "PAH with comorbidities", CTEPH and coexisting conditions are highlighted, and a modified diagnostic algorithm is provided. The detailed results and recommendations of the working group on definition, clinical classification and initial diagnosis of PH, which were last updated in the spring of 2018, are summarized in this article., (Copyright © 2018. Published by Elsevier B.V.)

The European guidelines, which focus on clinical aspects of pulmonary hypertension (PH), provide only minimal information about the pathophysiological concepts of PH. Here, we review this topic in greater detail, focusing on specific aspects in the pathobiology, pathology and genetics, which include mechanisms of vascular inflammation, the role of transcription factors, ion channels/ion channel diseases, hypoxic pulmonary vasoconstriction, genetics/epigenetics, metabolic dysfunction, and the potential future role of histopathology of PH in the modern era of PH therapy. In addition to new insights in the pathobiology of this disease, this working group of the Cologne Consensus Conference also highlights novel concepts and potential new therapeutic targets to further improve the treatment options in PAH., (Copyright © 2018. Published by Elsevier B.V.)

In the summer of 2016, delegates from the German Respiratory Society, the German Society of Cardiology and the German Society of Pediatric Cardiology met in Cologne, Germany, to define consensus-based practice recommendations for the management of patients with pulmonary arterial hypertension (PAH). These recommendations were built on the 2015 European Pulmonary Hypertension guidelines and included new evidence, where available. The treatment algorithm for PAH was modified based on the observation that there are now many patients diagnosed with IPAH who are at an advanced age and have significant cardiopulmonary comorbidities. For patients newly diagnosed with classic forms of PAH, i.e. younger patients without significant cardiopulmonary comorbidities, the consensus-based recommendation was to use initial combination therapy as the standard approach. The use of monotherapies was no longer considered appropriate in such patients. The choice of treatment strategies should be based on the risk assessment as proposed in the European guidelines. In patients presenting with a low or intermediate risk, oral combination therapy with endothelin receptor antagonists and phosphodiesterase-5 inhibitors or soluble guanylate cyclase stimulators, respectively, should be used. In high-risk patients, triple combination therapy including a subcutaneous or intravenous prostacyclin analogue should be considered. For patients who suffer from PAH and significant cardiopulmonary comorbidities, initial monotherapy is recommended and the use of combination therapies should be considered on an individual basis. The latter recommendations are based on the scarcity of evidence supporting the use of combination therapy and the higher risk of drug-related adverse events in such patients., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Background: Right ventricular (RV) dysfunction is a major prognostic predictor in pulmonary arterial hypertension (PAH)., Objectives: The objective of this study was to assess the prognostic impact of a newly developed index merging haemodynamic parameters into 1 variable., Methods: We retrospectively assessed 2 cohorts of 248 patients (164 from Hamburg and 84 from Heidelberg) with invasively diagnosed PAH. During a median follow-up time of 3.6 years (3.1 and 4.0 years for Hamburg and Heidelberg, respectively), the composite endpoint of all-cause mortality and lung transplantation occurred in 57 patients (53 and 4 patients for Hamburg and Heidelberg, respectively). The RV index was developed in the Hamburg cohort and validated in the Heidelberg cohort: (right atrial pressure × pulmonary vascular resistance)/mixed venous oxygen saturation., Results: Patients with a high RV index had a higher incidence of the combined endpoint in Kaplan-Meier analyses in the Hamburg and Heidelberg cohort (p = 0.017 and p = 0.034, respectively). The calculated RV index cut-off value was 91 and identified patients with a worse outcome in the Hamburg cohort and showed a trend in the Heidelberg cohort (p < 0.001 and p = 0.089, respectively). The RV index in Cox regression hazard models was an independent predictor of outcomes after adjustment for sex and age in both cohorts (Hamburg: hazard ratio [HR] 1.26 [95% CI 1.08, 1.47], p = 0.0027; Heidelberg: HR 2.27 [95% CI 1.46, 3.51], p < 0.001). A nomogram based on these results allowed risk stratification., Conclusion: Merging 3 haemodynamic variables into 1 variable, the RV index increased the prognostic power up to an independent risk factor. The RV index is easy to calculate and allows the construction of a nomogram for an individualized risk assessment., (© 2018 S. Karger AG, Basel.)

Purpose: Besides the established biomarker NT-proBNP, the new cardiovascular biomarkers MR-proANP, MR-proADM, Copeptin, and CT-proET-1 are promising to evaluate hemodynamics, exercise parameters, and prognosis in patients with pulmonary hypertension (PH)., Methods: 125 consecutive patients with pulmonary arterial hypertension (PAH) or chronic thromboembolic pulmonary hypertension (CTEPH) were prospectively enrolled at five German PH centers. Blood samples were taken during right heart catheterization. The primary study endpoint was the correlation between biomarkers and hemodynamic and exercise parameters. As secondary endpoint, prediction of 1-year mortality was evaluated., Results: MR-proADM showed the strongest correlations with 6MWD and VO2peak, whereas NT-proBNP showed the strongest correlations with PVR, PAPm, and CI. In multivariate analysis, only MR-proADM was independently associated with exercise variables, whereas only NT-proBNP independently predicted hemodynamic parameters. All biomarkers were associated with 1-year survival, with MR-proADM showing the highest C index of 0.78. In multivariate analysis, MR-proADM predicted survival independent of age, 6-MWD, CI, RAP, and NT-proBNP. The cut-off of 1.08 nmol/l provided a sensitivity of 83 % and specificity of 66 %., Conclusions: Different biomarkers reflect distinctive disease aspects in PH. NT-proBNP best predicts hemodynamic impairment while MR-proADM strongly correlates with exercise capacity. Additionally, MR-proADM represents a promising new marker to evaluate prognosis in patients with PAH and CTEPH. Multi-marker strategies should further be evaluated.

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.

Background: Mutations in the bone morphogenetic protein receptor 2 (BMPR2) gene can lead to idiopathic pulmonary arterial hypertension (IPAH). This study prospectively screened for BMPR2 mutations in a large cohort of PAH-patients and compared clinical features between BMPR2 mutation carriers and non-carriers., Methods: Patients have been assessed by right heart catheterization and genetic testing. In all patients a detailed family history and pedigree analysis have been obtained. We compared age at diagnosis and hemodynamic parameters between carriers and non-carriers of BMPR2 mutations. In non-carriers with familial aggregation of PAH further genes/gene regions as the BMPR2 promoter region, the ACVRL1, Endoglin, and SMAD8 genes have been analysed., Results: Of the 231 index patients 22 revealed a confirmed familial aggregation of the disease (HPAH), 209 patients had sporadic IPAH. In 49 patients (86.3% of patients with familial aggregation and 14.3% of sporadic IPAH) mutations of the BMPR2 gene have been identified. Twelve BMPR2 mutations and 3 unclassified sequence variants have not yet been described before. Mutation carriers were significantly younger at diagnosis than non-carriers (38.53 ± 12.38 vs. 45.78 ± 11.32 years, p < 0.001) and had a more severe hemodynamic compromise. No gene defects have been detected in 3 patients with HPAH., Conclusion: This study identified in a large prospectively assessed cohort of PAH- patients new BMPR2 mutations, which have not been described before and confirmed previous findings that mutation carriers are younger at diagnosis with a more severe hemodynamic compromise. Thus, screening for BMPR2 mutations may be clinically useful.

Objective: This is the first study that investigates the prevalence and actual treatment of anxiety, depression, and other mental disorders in patients with pulmonary hypertension (PH). The prevalence of mental disorders in patients with PH was compared with parallel groups of primary care patients and patients with inflammatory rheumatic diseases, and the relationship between functional status and prevalence of mental disorders was determined., Methods: The patient group with PH (70.1% female; mean age, 47.8 +/- 12.7 years) and the two comparison groups, which were matched by age and sex, consisted of 164 patients each. Patients completed self-administered instruments, including the Patient Health Questionnaire for the diagnosis of mental disorders. New York Heart Association (NYHA) functional class was assessed in all patients with PH., Results: Thirty-five percent of the patients with PH suffered from mental disorders, with the most common being major depressive disorder (15.9%) and panic disorder (10.4%). Both panic disorder and panic attacks were significantly more prevalent in patients with PH than in either patients with inflammatory rheumatic diseases or primary care patients. The prevalence of mental disorders in patients with PH increased significantly with functional impairment, from 17.7% (NYHA class I) to 61.9% (NYHA class IV). Only 24.1% of the patients with PH with mental disorders were receiving psychopharmacological or psychotherapeutic treatment., Conclusions: Anxiety and depression are frequent in patients with PH and increase as the severity of disease progresses. Given the fact that safe and efficacious treatments of mental disorders are available, greater importance should be attached to the diagnosis and treatment of these conditions in patients with PH.