ABSTRACT
Pulmonary arterial hypertension (PAH) is a rare disease that can be caused by (likely) pathogenic germline genomic variants. In addition to the most prevalent disease gene, BMPR2 (bone morphogenetic protein receptor 2), several genes, some belonging to distinct functional classes, are also now known to predispose to the development of PAH. As a consequence, specialist and non-specialist clinicians and healthcare professionals are increasingly faced with a range of questions regarding the need for, approaches to and benefits/risks of genetic testing for PAH patients and/or related family members. We provide a consensus-based approach to recommendations for genetic counselling and assessment of current best practice for disease gene testing. We provide a framework and the type of information to be provided to patients and relatives through the process of genetic counselling, and describe the presently known disease causal genes to be analysed. Benefits of including molecular genetic testing within the management protocol of patients with PAH include the identification of individuals misclassified by other diagnostic approaches, the optimisation of phenotypic characterisation for aggregation of outcome data, including in clinical trials, and importantly through cascade screening, the detection of healthy causal variant carriers, to whom regular assessment should be offered.
Subject(s)
Hypertension, Pulmonary , Pulmonary Arterial Hypertension , Humans , Genetic Counseling/methods , Pulmonary Arterial Hypertension/genetics , Hypertension, Pulmonary/diagnosis , Hypertension, Pulmonary/genetics , Hypertension, Pulmonary/therapy , Mutation , Familial Primary Pulmonary Hypertension/diagnosis , Familial Primary Pulmonary Hypertension/genetics , Genetic Testing/methods , Genetic Predisposition to DiseaseABSTRACT
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.
Subject(s)
Lung Diseases/complications , Lung/physiopathology , Physical Conditioning, Human , Pulmonary Disease, Chronic Obstructive/complications , Sports , Adult , Female , Germany , Humans , Male , OutpatientsABSTRACT
The 2015 European Guidelines on Diagnosis and Treatment of Pulmonary Hypertension (PH) are also valid for Germany. While the guidelines contain detailed recommendations regarding clinical aspects of pulmonary arterial hypertension (PAH) and other forms of PH, they contain only a relatively short paragraph on novel findings on the pathobiology, pathology, and genetics. However, these are of great importance for our understanding of this complex disease both from a clinical and scientific point of view, and they are essential for the development of novel treatment strategies. To this end, a number of current data are relevant, prompting a detailed commentary to the guidelines, and the consideration of new scientific data. 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 pathobiology, pathology and genetics of PH. This article summarizes the results and recommendations of this working group.
Subject(s)
Cardiology/standards , Hypertension, Pulmonary/diagnosis , Hypertension, Pulmonary/therapy , Practice Guidelines as Topic , Pulmonary Medicine/standards , Antihypertensive Agents/therapeutic use , Combined Modality Therapy/standards , Endarterectomy/standards , Germany , Humans , Hypertension, Pulmonary/geneticsABSTRACT
The 2015 European Guidelines on Diagnosis and Treatment of Pulmonary Hypertension are also valid for Germany. The guidelines contain detailed information about the clinical classification and diagnosis of pulmonary hypertension, and furthermore provide novel recommendations for risk stratification and follow-up assessments. 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 clinical classification and initial diagnosis of PH. This article summarizes the results and recommendations of this working group.
Subject(s)
Blood Pressure Determination/standards , Cardiology/standards , Hypertension, Pulmonary/diagnosis , Practice Guidelines as Topic , Pulmonary Medicine/standards , Terminology as Topic , Early Diagnosis , Germany , Humans , Hypertension, Pulmonary/classificationABSTRACT
The 2015 European Guidelines on Diagnosis and Treatment of Pulmonary Hypertension are also valid for Germany. The guidelines contain detailed recommendations for the targeted and supportive 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 general and supportive therapy of PAH. This article summarizes the results and recommendations of this working group.
Subject(s)
Cardiology/standards , Hypertension, Pulmonary/diagnosis , Hypertension, Pulmonary/therapy , Practice Guidelines as Topic , Pulmonary Medicine/standards , Antihypertensive Agents/therapeutic use , Blood Pressure Determination/standards , Combined Modality Therapy/standards , Endarterectomy/standards , Germany , HumansABSTRACT
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.
Subject(s)
Antihypertensive Agents/administration & dosage , Cardiology/standards , Hypertension, Pulmonary/therapy , Molecular Targeted Therapy/standards , Practice Guidelines as Topic , Pulmonary Medicine/standards , Germany , Humans , Hypertension, Pulmonary/diagnosis , Hypertension, Pulmonary/genetics , Molecular Diagnostic Techniques/standardsABSTRACT
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.
Subject(s)
Antihypertensive Agents/administration & dosage , Hypertension, Pulmonary/diagnosis , Hypertension, Pulmonary/drug therapy , Practice Guidelines as Topic , Pulmonary Medicine/standards , Dose-Response Relationship, Drug , Evidence-Based Medicine , Humans , Treatment OutcomeABSTRACT
BACKGROUND: Sudden cardiac death (SCD) accounts for approximately 30 % in patients with pulmonary arterial hypertension (PAH). The exact circumference for SCD in this patient population is still unclear. Malignant cardiac arrhythmias are reported to be rarely present. There are no systematic data concerning long-term electrocardiographic (ECG) recording in patients with PAH. OBJECTIVES: We sought to investigate the rate of potentially relevant arrhythmias in patients with pulmonary hypertension (PH). METHODS: Consecutive patients without diagnosis of known cardiac arrhythmias followed in our outpatient clinic for PH were enrolled in the study. All patients underwent a 72-h Holter ECG. Clinical data, 6-min walk distance, laboratory values, and echocardiography were collected/performed. RESULTS: Ninety-two consecutive patients (New York Heart Association class (NYHA) III/IV: 65.2 %/5.4 %, PH Group 1: 35.9 %, Group 3: 10.9 %, Group 4: 28.3 %, Group 5: 2.2 %) were investigated. Relevant arrhythmias were newly detected in 17 patients: non-sustained ventricular tachycardia (n = 12), intermittent second-degree heart block (n = 1), intermittent third-degree heart block (n= 3), and atrial flutter (n = 1). Echocardiographic systolic pulmonary pressure and diameter of the right heart were elevated in patients with relevant arrhythmias. Right heart catheterization revealed higher pulmonary vascular resistance (672 vs. 542 dyn · s · cm(-5), p = 0.247) and lower cardiac index (2.46 vs. 2.82 l/min/m(2), p = 0.184). CONCLUSIONS: Ventricular tachycardias occur more often in PH patients than previously reported. However, the prognostic relevance of non-sustained ventricular tachycardias in this cohort remains unclear. As a large number of PH patients die from SCD, closer monitoring, e.g., using implantable event recorders, might be useful to identify patients at high risk.
Subject(s)
Electrocardiography, Ambulatory/statistics & numerical data , Hypertension, Pulmonary/diagnosis , Hypertension, Pulmonary/epidemiology , Tachycardia, Ventricular/diagnosis , Tachycardia, Ventricular/epidemiology , Adult , Age Distribution , Aged , Aged, 80 and over , Asymptomatic Diseases , Causality , Comorbidity , False Negative Reactions , Female , Germany/epidemiology , Humans , Male , Middle Aged , Prevalence , Prospective Studies , Reproducibility of Results , Risk Assessment , Sensitivity and Specificity , Sex Distribution , Young AdultABSTRACT
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.
Subject(s)
Anticoagulants/therapeutic use , Antihypertensive Agents/therapeutic use , Exercise Therapy , Genetic Predisposition to Disease/genetics , Hypertension, Pulmonary/genetics , Hypertension, Pulmonary/therapy , Evidence-Based Medicine , Humans , Hypertension, Pulmonary/diagnosis , Treatment OutcomeABSTRACT
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.
Subject(s)
Guanylate Cyclase/metabolism , Hypertension, Pulmonary/drug therapy , Hypertension, Pulmonary/metabolism , Pulmonary Embolism/drug therapy , Pulmonary Embolism/metabolism , Pyrazoles/administration & dosage , Pyrimidines/administration & dosage , Receptors, Cytoplasmic and Nuclear/metabolism , Antihypertensive Agents/administration & dosage , Chronic Disease , Fibrinolytic Agents/administration & dosage , Humans , Hypertension, Pulmonary/complications , Pulmonary Embolism/complications , Pyrazoles/pharmacokinetics , Pyrimidines/pharmacokinetics , Receptors, Cytoplasmic and Nuclear/agonists , Soluble Guanylyl Cyclase , Treatment OutcomeABSTRACT
BACKGROUND AND AIM: Exercise intolerance is one of the key features of pulmonary arterial hypertension (PAH). The main determinants of exercise impairment include hypoxemia, reduced right ventricular output, perfusion/ventilation mismatch, and weakness of skeletal and breathing muscles. The aim of the current review is to describe the findings in the existing literature about respiratory and muscle dysfunction in PAH. Animal and clinical studies regarding both respiratory and peripheral skeletal muscles and the effect of exercise training on muscle function in PAH patients are analyzed. DATA SYNTHESIS: PAH myopathy is characterized by reduced skeletal muscle mass, reduced volitional and non-volitional contractility, reduced generated force, a fiber switch from type I to type II, increased protein degradation through ubiquitin-proteasome system (UPS) activation, reduced mitochondrial functioning, and impaired activation-contractility coupling. Increased inflammatory response, impaired anabolic signaling, hypoxemia, and abnormalities of mitochondrial function are involved in the pathophysiology of this process. Exercise training has been shown to improve exercise capacity, peak oxygen uptake, quality of life, and possibly clinical outcomes of PAH patients. CONCLUSIONS: The skeletal muscles of PAH patients show a wide spectrum of cellular abnormalities that finally culminate in muscle atrophy and reduced contractility. Exercise training improves muscle function and bears a positive impact on the clinical outcomes of PAH patients.
