Rehabilitation in patients with pulmonary arterial hypertension.

Exertional dyspnoea is a leading symptom in patients with pulmonary arterial hypertension (PAH). Patients suffering from PAH report poor quality of life, have skeletal muscle dysfunction and in the absence of advanced medical therapy deteriorate progressively due to right heart failure which can lead to death. For decades, patients with PAH were advised to avoid exercise in fear of exacerbated right heart failure.

Exercise training improves peak oxygen consumption and haemodynamics in patients with severe pulmonary arterial hypertension and inoperable chronic thrombo-embolic pulmonary hypertension: a prospective, randomized, controlled trial.

Aims: The impact of exercise training on the right heart and pulmonary circulation has not yet been invasively assessed in patients with pulmonary hypertension (PH) and right heart failure. This prospective randomized controlled study investigates the effects of exercise training on peak VO2/kg, haemodynamics, and further clinically relevant parameters in PH patients.

Methods And Results: Eighty-seven patients with pulmonary arterial hypertension and inoperable chronic thrombo-embolic PH (54% female, 56 ± 15 years, 84% World Health Organization functional class III/IV, 53% combination therapy) on stable disease-targeted medication were randomly assigned to a control and training group.

Mutation in BMPR2 Promoter: A 'Second Hit' for Manifestation of Pulmonary Arterial Hypertension?

Background: Hereditary pulmonary arterial hypertension (HPAH) can be caused by autosomal dominant inherited mutations of TGF-β genes, such as the bone morphogenetic protein receptor 2 (BMPR2) and Endoglin (ENG) gene. Additional modifier genes may play a role in disease manifestation and severity. In this study we prospectively assessed two families with known BMPR2 or ENG mutations clinically and genetically and screened for a second mutation in the BMPR2 promoter region.

Stress Doppler echocardiography for early detection of systemic sclerosis-associated pulmonary arterial hypertension.

Introduction: In patients with systemic sclerosis (SSc), associated pulmonary arterial hypertension (SSc-APAH) is the leading cause of death. The objective of this prospective screening study was to analyse sensitivity and specificity of stress Doppler echocardiography (SDE) in detecting pulmonary hypertension (PH).

Methods: Pulmonary artery pressures and further parameters of PH were assessed by echocardiography and right heart catheterisation (RHC) at rest and during exercise in patients with SSc.

Change of right heart size and function by long-term therapy with riociguat in patients with pulmonary arterial hypertension and chronic thromboembolic pulmonary hypertension.

Background: Riociguat is a soluble guanylate cyclase stimulator approved for pulmonary arterial hypertension (PAH) and chronic thromboembolic pulmonary hypertension (CTEPH). The objective of this study was to evaluate the change of right heart size and function assessed by echocardiography during long-term treatment with riociguat.

Methods: We assessed patients who started riociguat treatment (1.

Reference ranges for and determinants of right ventricular area in healthy adults by two-dimensional echocardiography.

Background: The right ventricular (RV) area is important for diagnosis and follow-up in patients with various diseases, such as in pulmonary hypertension.

Objectives: The aim of this study was to define the reference ranges of the end-diastolic RV area in healthy adults and to assess the determining factors.

Methods: In the first part of the study 860 healthy subjects (37.

Principles of rehabilitation and reactivation: pulmonary hypertension.

Most recently, a specialized and carefully monitored exercise training and rehabilitation program has been recommended as add-on to medical treatment in patients with pulmonary arterial hypertension (class I, level of evidence A). Three prospective randomized, controlled trials, 10 prospective uncontrolled trials, 2 retrospective studies and 2 case series in more than 470 patients with severe pulmonary hypertension (PH) and right heart failure reported beneficial effects of a specialized exercise training and rehabilitation program, i.e.

Endoscopic lung volume reduction with endobronchial valves in patients with severe emphysema and established pulmonary hypertension.

Background: One of the most common forms of pulmonary hypertension (PH) is that associated with chronic obstructive pulmonary disease (COPD). So far, patients with severe emphysema and established PH have been excluded from endoscopic lung volume reduction (ELVR) therapy due to the risk of right heart decompensation.

Objective: The aim of this pilot study was to evaluate the feasibility and efficacy of ELVR using one-way endobronchial valves (EBV) in this specific group of patients.

Safety and long-term efficacy of transition from sildenafil to tadalafil due to side effects in patients with pulmonary arterial hypertension.

Introduction: Two phosphodiesterase-type 5 (PDE-5) inhibitors, sildenafil and tadalafil, are approved for treatment of pulmonary arterial hypertension (PAH). It has not yet been observed if transition from sildenafil to tadalafil is beneficial in patients suffering from adverse reactions. Aim of this study was to analyze safety and long-term effects in PAH patients whose treatment was transitioned from sildenafil to tadalafil due to intolerable side-effects.

Identification of a new intronic BMPR2-mutation and early diagnosis of heritable pulmonary arterial hypertension in a large family with mean clinical follow-up of 12 years.

Background: Mutations in the bone morphogenetic protein receptor 2 (BMPR2) gene can lead to hereditary pulmonary arterial hypertension (HPAH) and are detected in more than 80% of cases with familial aggregation of the disease. Factors determining disease penetrance are largely unknown.

Methods: A mean clinical follow-up of 12 years was accomplished in 46 family members including echocardiography, stress-Dopplerechocardiography and genetic analysis of TGF-β pathway genes.

Economic evaluation of exercise training in patients with pulmonary hypertension.

Purpose: Exercise training as an add-on to medical therapy has been shown to improve exercise capacity, quality of life, and possibly prognosis in patients with pulmonary hypertension (PH). The purpose of this study was to analyze the impact of exercise training on healthcare costs in PH.

Methods: Estimated healthcare costs have been compared between patients with severe PH under optimized medical therapy only (control group) versus patients who received exercise training as an add-on to medical therapy (training group).

The combination of exercise and respiratory training improves respiratory muscle function in pulmonary hypertension.

Purpose: Increased dyspnea and reduced exercise capacity in pulmonary arterial hypertension (PAH) can be partly attributed to impaired respiratory muscle function. This prospective study was designed to assess the impact of exercise and respiratory training on respiratory muscle strength and 6-min walking distance (6MWD) in PAH patients.

Methods: Patients with invasively confirmed PAH underwent 3 weeks of in-hospital exercise and respiratory training, which was continued at home for another 12 weeks.

Anxiety and depression disorders in patients with pulmonary arterial hypertension and chronic thromboembolic pulmonary hypertension.

Background: The objective of this prospective study was to assess the prevalence of anxiety and depression disorders and their association with quality of life (QoL), clinical parameters and survival in patients with pulmonary hypertension (PH).

Methods: We prospectively assessed 158 patients invasively diagnosed with pulmonary arterial hypertension (n = 138) and inoperable chronic thromboembolic PH (n = 20) by clinical measures including quality of life (QoL, SF-36 questionnaire), cardiopulmonary exercise testing and six minute walking distance and by questionnaires for depression (PHQ-9) and anxiety (GAD-7). According to the results of the clinical examination and the questionnaires for mental disorders (MD) patients were classified into two groups, 1) with moderate to severe MD (n = 36, 22,8%), and 2) with mild or no MD (n = 122).

Assessment and prognostic relevance of right ventricular contractile reserve in patients with severe pulmonary hypertension.

Background: This study sought to analyze a new approach to assess exercise-induced pulmonary artery systolic pressure (PASP) increase by means of stress Doppler echocardiography as a possible measure of right ventricular contractile reserve in patients with severe pulmonary hypertension and right heart failure.

Methods And Results: In this prospective study, patients with invasively diagnosed pulmonary arterial hypertension or inoperable chronic thromboembolic pulmonary hypertension and impaired right ventricular pump function despite a stable targeted pulmonary arterial hypertension medication underwent a broad panel of noninvasive assessments, including stress echocardiography and cardiopulmonary exercise testing. On the basis of the assumption that exercise-induced PASP is a measure of right ventricular contractile reserve, patients were classified into 2 groups according to an exercise-induced PASP increase above or below the median.

Hemodynamic and genetic analysis in children with idiopathic, heritable, and congenital heart disease associated pulmonary arterial hypertension.

Background: Aim of this prospective study was to compare clinical and genetic findings in children with idiopathic or heritable pulmonary arterial hypertension (I/HPAH) with children affected with congenital heart defects associated PAH (CHD-APAH).

Methods: Prospectively included were 40 consecutive children with invasively diagnosed I/HPAH or CHD-APAH and 117 relatives. Assessment of family members, pedigree analysis and systematic screening for mutations in TGFß genes were performed.

Reference values for and determinants of right atrial area in healthy adults by 2-dimensional echocardiography.

Background: Right atrial (RA) size is important in screening, diagnosis, and follow-up assessment in patients with pulmonary hypertension. The objective of this study was to define normal reference values for RA area by echocardiography in a large population of athletic versus sedentary healthy subjects.

Methods And Results: In the first part of the study, 880 healthy adult subjects (mean age, 28±6 years; 38% women; 395 top-level endurance athletes, 255 strength athletes, and 230 nonathletes) were prospectively assessed.

Efficacy of exercise training in pulmonary arterial hypertension associated with congenital heart disease.

Background: The objective of this prospective study was to assess the efficacy of exercise training as add-on to medical therapy in patients with congenital heart disease associated pulmonary arterial hypertension (CHD-APAH).

Methods: Patients with invasively confirmed CHD-APAH received in-hospital exercise training for 3 weeks and continued at home. Efficacy parameters were evaluated at baseline, after 3 and 15 weeks.

The German adaptation of the Cambridge Pulmonary Hypertension Outcome Review (CAMPHOR).

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.

Magnetic resonance imaging to assess the effect of exercise training on pulmonary perfusion and blood flow in patients with pulmonary hypertension.

Objectives: To evaluate whether careful exercise training improves pulmonary perfusion and blood flow in patients with pulmonary hypertension (PH), as assessed by magnetic resonance imaging (MR).

Methods: Twenty patients with pulmonary arterial hypertension or inoperable chronic thromboembolic PH on stable medication were randomly assigned to control (n = 10) or training groups (n = 10). Training group patients received in-hospital exercise training; patients of the sedentary control group received conventional rehabilitation.

Exercise training improves exercise capacity and quality of life in patients with inoperable or residual chronic thromboembolic pulmonary hypertension.

Background: Aim of this prospective study was to evaluate the effects of exercise training in patients with inoperable or residual chronic thromboembolic pulmonary hypertension (CTEPH).

Methods: Thirty-five consecutive patients with invasively confirmed inoperable or residual CTEPH (16 women;19 men; mean age 61±15 years, mean pulmonary artery pressure, 63±20 mmHg; primary inoperable n = 33, persisting pulmonary hypertension after pulmonary endarterectomy n = 2) on stable disease-targeted medication received exercise training in-hospital for 3 weeks and continued at home for 15 weeks. Medication remained unchanged during the study period.

Exercise training in pulmonary arterial hypertension associated with connective tissue diseases.

Introduction: The objective of this prospective study was to assess short- and long-term efficacy of exercise training (ET) as add-on to medical therapy in patients with connective tissue disease-associated pulmonary arterial hypertension (CTD-APAH).

Methods: Patients with invasively confirmed CTD-APAH received ET in-hospital for 3 weeks and continued at home for 12 weeks. Efficacy parameters have been evaluated at baseline and after 15 weeks by blinded-observers.

Safety and efficacy of exercise training in various forms of pulmonary hypertension.

The objective of this prospective study was to assess safety and efficacy of exercise training in a large cohort of patients with different forms and World Health Organization (WHO) functional classes of chronic pulmonary hypertension (PH). 183 patients with PH (pulmonary arterial hypertension (PAH), chronic thromboembolic PH and PH due to respiratory or left heart diseases received exercise training in hospital for 3 weeks and continued at home. Adverse events have been monitored during the in-hospital training programme.

Hemodynamic and clinical onset in patients with hereditary pulmonary arterial hypertension and BMPR2 mutations.

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.

Effect of exercise and respiratory training on clinical progression and survival in patients with severe chronic pulmonary hypertension.

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.

Stress Doppler echocardiography in relatives of patients with idiopathic and familial pulmonary arterial hypertension: results of a multicenter European analysis of pulmonary artery pressure response to exercise and hypoxia.

Background: This large, prospective, multicentric study was performed to analyze the distribution of tricuspid regurgitation velocity (TRV) values during exercise and hypoxia in relatives of patients with idiopathic and familial pulmonary arterial hypertension (PAH) and in healthy control subjects. We tested the hypothesis that relatives of idiopathic/familial PAH patients display an enhanced frequency of hypertensive TRV response to stress and that this response is associated with mutations in the bone morphogenetic protein receptor II (BMPR2) gene.

Methods And Results: TRV was estimated by Doppler echocardiography during supine bicycle exercise in normoxia and during 120 minutes of normobaric hypoxia (FIO(2)=12%; approximately 4500 m) in 291 relatives of 109 PAH patients and in 191 age-matched control subjects.