Symposium review: high altitude travel with pulmonary vascular disease.

Pulmonary arterial hypertension and chronic thromboembolic pulmonary hypertension are the main precapillary forms of pulmonary hypertension (PH) summarized as pulmonary vascular diseases (PVD). PVDs are characterized by exertional dyspnoea and oxygen desaturation, and reduced quality of life and survival. Medical therapies improve life expectancy and physical performance of PVD patients, of whom many wish to participate in professional work and recreational activities including traveling to high altitude. The exposure to the hypobaric hypoxic environment of mountain regions incurs the risk of high altitude adverse events (AEHA) due to severe hypoxaemia exacerbating symptoms and further increase in pulmonary artery pressure, which may lead to right heart decompensation. Recent prospective and randomized trials show that altitude-induced hypoxaemia, pulmonary haemodynamic changes and impairment of exercise performance in PVD patients are in the range found in healthy people. The vast majority of optimally treated stable PVD patients who do not require long-term oxygen therapy at low altitude can tolerate short-term exposure to moderate altitudes up to 2500 m. PVD patients that reveal persistent severe resting hypoxaemia ( S p O 2 ${{S}_{{\mathrm{p}}{{{\mathrm{O}}}_{\mathrm{2}}}}}$  <80% for >30 min) at 2500 m respond well to supplemental oxygen therapy. Although there are no accurate predictors for AEHA, PVD patients with unfavourable risk profiles at low altitude, such as higher WHO functional class, lower exercise capacity with more pronounced exercise-induced desaturation and more severely impaired haemodynamics, are at increased risk of AEHA. Therefore, doctors with experience in PVD and high-altitude medicine should counsel PVD patients before any high-altitude sojourn. This review aims to summarize recent literature and clinical recommendations about PVD patients travelling to high altitude.

The effect of high altitude (2500†m) on incremental cycling exercise in patients with pulmonary arterial hypertension and chronic thromboembolic pulmonary hypertension: a randomised controlled crossover trial.

BACKGROUND: Our objective was to investigate the effect of a day-long exposure to high altitude on peak exercise capacity and safety in stable patients with pulmonary arterial hypertension (PAH) and chronic thromboembolic pulmonary hypertension (CTEPH). METHODS: In a randomised controlled crossover trial, stable patients with PAH or distal CTEPH without resting hypoxaemia at low altitude performed two incremental exercise tests to exhaustion: one after 3-5 h at high altitude (2500 m) and one at low altitude (470 m). RESULTS: In 27 patients with PAH/CTEPH (44% females, mean±sd age 62±14 years), maximal work rate was 110±64 W at 2500 m and 123±64 W at 470 m (-11%, 95% CI -16- -11%; p<0.001). Oxygen saturation measured by pulse oximetry and arterial oxygen tension at end-exercise were 83±6% versus 91±6% and 6.1±1.9 versus 8.6±1.9 kPa (-8% and -29%; both p<0.001) at 2500 versus 470 m, respectively. Maximal oxygen uptake was 17.8±7.5 L·min-1·kg-1 at high altitude versus 20±7.4 L·min-1·kg-1 at low altitude (-11%; p<0.001). At end-exercise, the ventilatory equivalent for carbon dioxide was 43±9 at 2500 m versus 39±9 at 470 m (9%, 95% CI 2-6%; p=0.002). No adverse events occurred during or after exercise. CONCLUSIONS: Among predominantly low-risk patients with stable PAH/CTEPH, cycling exercise during the first day at 2500 m was well tolerated, but peak exercise capacity, blood oxygenation and ventilatory efficiency were lower compared with 470 m.

Effects of 5-Week Oral Acetazolamide on Incremental Cycling Exercise in Pulmonary Arterial and Chronic Thromboembolic Pulmonary Hypertension: A Randomized Placebo-Controlled, Double-Blinded, Crossover Trial.

INTRODUCTION: Acetazolamide (AZA) improves nocturnal and daytime blood oxygenation in patients with pulmonary vascular disease (PVD), defined as pulmonary arterial and distal chronic thromboembolic pulmonary hypertension (CTEPH), and may improve exercise performance. METHODS: We investigated the effect of 5 weeks of AZA (250 mg bid) versus placebo on maximal load during incremental cycling ramp exercise in patients with PVD studied in a randomized controlled, double-blind, crossover design, separated by > 2 weeks of washout. RESULTS: Twenty-five patients (12 pulmonary arterial hypertension, 13 CTEPH, 40% women, age 62 ± 15 years) completed the trial according to the protocol. Maximum load was similar after 5 weeks of AZA versus placebo (113 ± 9 vs. 117 ± 9 watts [W]), mean difference -4 W (95% CI: -9 to 1, p = 0.138). With AZA, maximum (max)-exercise partial pressure of O2 (PaO2) was significantly higher by 1.1 kPa (95% CI: 0.5-1.8, p = 0.003), while arterial pH and partial pressure of CO2 were significantly lower. Gas exchange threshold was reached at a higher load with AZA (108 ± 8 W vs. 97 ± 8 W) and was therefore delayed by 11 W (95% CI: 3-19, p = 0.013), while the ventilatory equivalent for O2 and CO2 were significantly higher at both the max-exercise and gas exchange threshold with AZA versus placebo. CONCLUSION: AZA for 5 weeks did not significantly change maximum exercise capacity in patients with PVD despite a significant increase in PaO2. The beneficial effects of increased blood oxygenation may have been diminished by increased ventilation due to AZA-induced metabolic acidosis and increased dyspnea.

Mechanisms underlying the health benefits of intermittent hypoxia conditioning.

Intermittent hypoxia (IH) is commonly associated with pathological conditions, particularly obstructive sleep apnoea. However, IH is also increasingly used to enhance health and performance and is emerging as a potent non-pharmacological intervention against numerous diseases. Whether IH is detrimental or beneficial for health is largely determined by the intensity, duration, number and frequency of the hypoxic exposures and by the specific responses they engender. Adaptive responses to hypoxia protect from future hypoxic or ischaemic insults, improve cellular resilience and functions, and boost mental and physical performance. The cellular and systemic mechanisms producing these benefits are highly complex, and the failure of different components can shift long-term adaptation to maladaptation and the development of pathologies. Rather than discussing in detail the well-characterized individual responses and adaptations to IH, we here aim to summarize and integrate hypoxia-activated mechanisms into a holistic picture of the body's adaptive responses to hypoxia and specifically IH, and demonstrate how these mechanisms might be mobilized for their health benefits while minimizing the risks of hypoxia exposure.

Oxygen Therapy in Pulmonary Vascular Disease: A Systematic Review, Meta-Analysis, and Comment.

Main pulmonary vascular diseases (PVD) with precapillary pulmonary hypertension (PH) are pulmonary arterial and chronic thromboembolic PH. Guidelines recommend supplemental oxygen therapy (SOT) for severely hypoxemic patients with PH, but evidence is scarce. The authors performed a systematic review and where possible meta-analyses on the effects of SOT on hemodynamics and exercise performance in patients with PVD. In PVD, short-term SOT significantly improved mean pulmonary artery pressure and exercise performance. There is growing evidence on the benefit of long-term SOT for selected patients with PVD regarding exercise capacity and maybe even survival.

[Targeted therapy for pulmonary arterial hypertension in patients without comorbidities]. / Gezielte medikamentöse Therapie der pulmonalarteriellen Hypertonie bei Patient*innen ohne Komorbiditäten.

The 2022 guidelines on pulmonary hypertension from the European Society of Cardiology (ESC) and the European Respiratory Society (ERS) provide therapeutic strategies that account for the variability in the clinical presentation of newly diagnosed patients. We summarize treatment recommendations for pulmonary arterial hypertension (PAH) in patients without significant comorbidities, particularly for idiopathic, hereditary, drug/toxin-induced, or connective tissue disease-associated PAH. In this group of patients, multidimensional assessments for short-term mortality risk guide initial treatment decisions and treatment decisions during follow-up. Upfront dual combination therapy (phosphodiesterase type-5 inhibitor and endothelin receptor antagonist) is recommended for low- and intermediate-risk patients, and triple therapy including a parenteral prostacyclin should be considered in high- or intermediate-high-risk patients. If a low or intermediate-low-risk profile cannot be achieved during therapy, sequential add-on therapy escalation with parenteral prostacyclin or a prostacyclin receptor agonist should be considered, and switching from a phosphodiesterase type-5 inhibitor to a guanylate cyclase stimulator may also be considered.

[General measures and management of pulmonary arterial hypertension]. / Allgemeine Maßnahmen und Management der pulmonalarteriellen Hypertonie.

Care of patients with pulmonary arterial hypertension (PAH) needs a multi-facetet concept and measures, including management of adverse reactions, right heart insufficiency as well as information on pregnancy, travels by air, psychosocial support, physical exercise training and prophylaxis by vaccination.Positive study results led to an higher recommendation of specialized exercise training in pulmonary hypertension. Also, the recommendation on iron substitution was amended according to the current evidence.In the current guidelines, special focus was given to the elaboration of recommendations regarding pregnancy, including patient information, contraception and patient management in case of pregnancy.This article aims to provide an overview on the recommendations of general measuremes, special circumstances and patient management according to the ESC/ERS guidelines. Amendments to the guideline recommendations are given as comments from the authors of this article.

[Medication treatment in pulmonary arterial hypertension with comorbidities - Which phenotypes and points to consider]. / Medikamentöse Therapie der pulmonalarteriellen Hypertonie mit Komorbiditäten ­ Welche Phänotypen gibt es, was gibt es zu beachten?

Within the last decade, the age at diagnosis of patients with pulmonary arterial hypertension has increased, which led to a change of the clinical phenoype being associated with more comorbidities. Cluster analyses of registry data have identified cardiac, cardio-pulmonary and classical phenotypes of pulmonary arterial hypertension.Subgroup analyses of randomised controlled trials and registry data indicate, that in patients with pulmonary arterial hypertension and cardiac comorbidities, especially the left-heart phenotype, a closely supervised combination treatment may be considered. The 4-strata model may be used for monitoring and risk stratification in these patients. Individual treatment decisions should be made in the pulmonary hypertension centre. Factors such as hemodynamics, age, phenotype, number and severity of comorbidities, therapy response, adverse reactions and the wish of the patient should be considered.Prospective, randomized studies to assess the efficacy and safety profile of pulmonary arterial hypertension treatments are desirable. Patients with a mainly pulmonary phenotype (smoking, diffusion capacity of the lung < 45 % and/or lung parenchymal changes) may have less benefit of oral medication.

Differential effects of high-altitude exposure on markers of oxidative stress, antioxidant capacity, and iron profiles.

High-altitude (HA) exposure may stimulate significant physiological and molecular changes, resulting in HA-related illnesses. HA may impact oxidative stress, antioxidant capacity, and iron homeostasis, yet it is unclear how both repeated exposure and HA acclimatization may modulate such effects. Therefore, we assessed the effects of weeklong repeated daily HA exposure (2,900-5,050 m) in altitude-naïve individuals (n = 21 individuals, 13 females, mean ± SD, 25.3 ± 3.7 yr) to mirror the working schedule of HA workers (n = 19 individuals, all males, 41.1 ± 9.4 yr) at the Atacama Large Millimeter Array (ALMA) Observatory (San Pedro de Atacama, Chile). Markers of oxidative stress, antioxidant capacity, and iron homeostasis were measured in blood plasma. Levels of protein oxidation (P < 0.001) and catalase activity (P = 0.023) increased and serum iron (P < 0.001), serum ferritin (P < 0.001), and transferrin saturation (P < 0.001) levels decreased with HA exposure in both groups. HA workers had lower levels of oxidative stress, and higher levels of antioxidant capacity, iron supply, and hemoglobin concentration as compared with altitude-naïve individuals. On a second week of daily HA exposure, changes in levels of protein oxidation, glutathione peroxidase, and nitric oxide metabolites were lower as compared with the first week in altitude-naïve individuals. These results indicate that repeated exposure to HA may significantly alter oxidative stress and iron homeostasis, and the degree of such changes may be dependent on if HA is visited naïvely or routinely. Further studies are required to fully elucidate differences in HA-induced changes in oxidative stress and iron homeostasis profiles among visitors of HA.

Intracerebral endotheliitis and microbleeds are neuropathological features of COVID-19.

Coronavirus disease 19 (COVID-19) is a rapidly evolving pandemic caused by the coronavirus Sars-CoV-2. Clinically manifest central nervous system symptoms have been described in COVID-19 patients and could be the consequence of commonly associated vascular pathology, but the detailed neuropathological sequelae remain largely unknown. A total of six cases, all positive for Sars-CoV-2, showed evidence of cerebral petechial hemorrhages and microthrombi at autopsy. Two out of six patients showed an elevated risk for disseminated intravascular coagulopathy according to current criteria and were excluded from further analysis. In the remaining four patients, the hemorrhages were most prominent at the grey and white matter junction of the neocortex, but were also found in the brainstem, deep grey matter structures and cerebellum. Two patients showed vascular intramural inflammatory infiltrates, consistent with Sars-CoV-2-associated endotheliitis, which was associated by elevated levels of the Sars-CoV-2 receptor ACE2 in the brain vasculature. Distribution and morphology of patchy brain microbleeds was clearly distinct from hypertension-related hemorrhage, critical illness-associated microbleeds and cerebral amyloid angiopathy, which was ruled out by immunohistochemistry. Cerebral microhemorrhages in COVID-19 patients could be a consequence of Sars- CoV-2-induced endotheliitis and more general vasculopathic changes and may correlate with an increased risk of vascular encephalopathy.

Cardiac function and pulmonary hypertension in Central Asian highlanders at 3250†m.

THE QUESTION ADDRESSED BY THE STUDY: Chronic exposure to hypoxia increases pulmonary artery pressure (PAP) in highlanders, but the criteria for diagnosis of high-altitude pulmonary hypertension (HAPH) are debated. We assessed cardiac function and PAP in highlanders at 3250 m and explored HAPH prevalence using different definitions. PATIENTS AND METHODS: Central Asian highlanders free of overt cardiorespiratory disease, permanently living at 2500-3500 m compared to age-matched lowlanders living <800 m. Participants underwent echocardiography close to their altitude of residence (at 3250 m versus 760 m). RESULTS: 173 participants (97 highlanders, 76 lowlanders), mean±sd age 49±9 years (49% females) completed the study. Results in lowlanders versus highlanders were systolic PAP (23±5 versus 30±10 mmHg), right ventricular fractional area change (42±6% versus 39±8%), tricuspid annular plane systolic excursion (2.1±0.3 versus 2.0±0.3 cm), right atrial volume index (20±6 versus 23±8 mL·m-2), left ventricular ejection fraction (62±4% versus 57±5%) and stroke volume (64±10 versus 57±11 mL); all between-group comparisons p<0.05. Depending on criteria, HAPH prevalence varied between 6% and 35%. THE ANSWER TO THE QUESTION: Chronic exposure to hypoxia in highlanders is associated with higher PAP and slight alterations in right and left heart function compared to lowlanders. The prevalence of HAPH in this large highlander cohort varies between 6% according to expert consensus definition of chronic high-altitude disease to 35% according to the most recent definition of pulmonary hypertension proposed for lowlanders.

Haemodynamic phenotypes and survival in patients with systemic sclerosis: the impact of the new definition of pulmonary arterial hypertension.

BACKGROUND: In this study, we investigated the impact of the new haemodynamic definition of pulmonary arterial hypertension (PAH) as proposed by the 6th PH World Symposium on phenotypes and survival in patients with systemic sclerosis (SSc). METHODS: In SSc patients who were prospectively and consecutively screened for PAH including right heart catheterisation in Heidelberg or Zurich, haemodynamic and clinical variables have been reassessed according to the new PAH definition. Patients have been followed for 3.7±3.7 (median 3.4) years; Kaplan-Meier survival analysis was performed. Patients with significant lung or left heart disease were excluded from comparative analyses. RESULTS: The final dataset included 284 SSc patients, 146 patients (49.2%) had mean pulmonary arterial pressure (mPAP) ≤20 mm Hg, 19.3% had mPAP 21-24 mm Hg and 29.4% had mPAP ≥25 mm Hg. In the group of mildly elevated mPAP, only four patients (1.4% of the whole SSc cohort) had pulmonary vascular resistance (PVR) values ≥3 Wood Units (WU) and could be reclassified as manifest SSc-APAH. Twenty-eight (9.8%) patients with mPAP of 21-24 mm Hg and PVR ≥2 WU already presented with early pulmonary vascular disease with decreased 6 min walking distance (6MWD) (p<0.001), TAPSE (p=0.004) and pulmonary arterial compliance (p<0.001). A PVR ≥2 WU was associated with reduced long-term survival (p=0.002). PVR and 6MWD were independent prognostic predictors in multivariate analysis. CONCLUSION: The data of this study show that a PVR threshold ≥3 WU is too high to enable an early diagnosis of PAH. A PVR threshold ≥2 WU was already associated with pulmonary vascular disease, significantly reduced survival and would be more appropriate in SSc patients with mild PAH.

Effect of Breathing Oxygen-Enriched Air on Exercise Performance in Patients with Chronic Obstructive Pulmonary Disease: Randomized, Placebo-Controlled, Cross-Over Trial.

BACKGROUND: Patients with chronic obstructive pulmonary disease (COPD) experience dyspnea and hypoxemia during exercise. OBJECTIVE: The aim of this study was to evaluate the effects of breathing oxygen-enriched air on exercise performance and associated physiological changes in patients with COPD. METHODS: In a randomized, placebo-controlled, single-blind, cross-over trial, 20 patients with COPD (11 women, age 65 ± 6 years, FEV1 64 ± 19% pred., resting SpO2 ≥90%) performed 4 cycle ergospirometries to exhaustion using an incremental exercise test (IET) and a constant work rate (at 75% maximal workload with air) exercise test (CWRET), each with ambient (FiO2 0.21) and oxygen-enriched (FiO2 0.5) air. The main outcomes were the change in maximal workload in the IET and the change in exercise duration in the CWRET with oxygen versus air. Electrocardiogram, pulmonary gas exchange, thoracic volumes by inductance plethysmography, arterial blood gases, and cerebral and quadriceps muscle tissue oxygenation (CTO and MTO) were additionally measured. RESULTS: In the IET, maximal workload increased from 96 ± 21 to 104 ± 28 W with oxygen. In the CWRET, exercise duration increased from 605 ± 274 to 963 ± 444 s with oxygen. At end-exercise with oxygen, CTO, MTO, PaO2, and PaCO2 were increased, while V'E/V'CO2 was reduced and thoracic volumes were similar. At the corresponding time to end of exercise with ambient air, oxygen decreased heart rate, respiratory rate, minute ventilation, and V'E/V'CO2, while oxygenation was increased. CONCLUSION: In COPD patients without resting hypoxemia, breathing oxygen-enriched air improves exercise performance. This relates to a higher arterial oxygen saturation promoting oxygen availability to muscle and cerebral tissue and an enhanced ventilatory efficiency. COPD patients may benefit from oxygen therapy during exercise training.

Effect of domiciliary oxygen therapy on exercise capacity and quality of life in patients with pulmonary arterial or chronic thromboembolic pulmonary hypertension: a randomised, placebo-controlled trial.

STUDY QUESTION: We investigated whether domiciliary oxygen therapy (DOXT) increases exercise capacity and quality of life in patients with pulmonary arterial or distal chronic thromboembolic pulmonary hypertension (PAH/CTEPH) presenting with mild resting hypoxaemia and exercise-induced oxygen desaturation. MATERIALS AND METHODS: 30 patients with PAH/CTEPH, mean±sd age 60±15 years, pulmonary artery pressure 39±11 mmHg, resting arterial oxygen saturation measured by pulse oximetry (S pO2 ) ≥90%, S pO2 drop during a 6-min walk test ≥4%, on pulmonary hypertension-targeted medication, were randomised in a double-blind crossover protocol to DOXT and placebo (ambient air) treatment, each over 5 weeks, at 3 L·min-1 via nasal cannula overnight and when resting during the day. Treatment periods were separated by 2 weeks of washout. Co-primary outcomes were changes in 6-min walk distance (6MWD, breathing ambient air) and physical functioning scale of the 36-item short-form medical outcome questionnaire during treatment periods. RESULTS: DOXT increased the 6MWD from baseline 478±113 m by a mean (95% CI) of 19 (6-32) m, and physical functioning from 52±29 by 4 (0-8) points. Corresponding changes with placebo were 1 (-11-13) m in 6MWD and -2 (-6-2) points in physical functioning. Between-treatment differences in changes were 6MWD 18 (1-35) m (p=0.042) and physical functioning 6 (1-11) points (p=0.029). DOXT significantly improved the New York Heart Association functional class versus placebo. ANSWER TO THE QUESTION: This first randomised trial in PAH/CTEPH patients with exercise-induced hypoxaemia demonstrates that DOXT improves exercise capacity, quality of life and functional class. The results support large long-term randomised trials of DOXT in PAH/CTEPH.

Right and Left Heart Function in Lowlanders with COPD at Altitude: Data from a Randomized Study.

BACKGROUND: Changes in pulmonary hemodynamics and cardiac function in patients with chronic obstructive pulmonary disease (COPD) traveling to altitude have not been assessed despite an increasing prevalence of the disease. OBJECTIVES: We hypothesized that pulmonary artery pressure (PAP) significantly increases and cardiac function deteriorates during exposure to hypobaric hypoxia as encountered by traveling to moderate altitude or air flight. METHODS: A total of 37 patients (17 female; median age [quartiles] 66 years [60; 69] with COPD GOLD grade 2-3 [FEV1 57% predicted (49; 71)]) living < 800 m underwent echocardiography in Zurich (490 m) and after 1 night at Davos Jakobshorn (2,590 m) in a randomized order of allocation. RESULTS: The transtricuspid pressure gradient increased from 23 mm Hg (18; 29) to 32 mm Hg (25; 41) (p < 0.0001; Δmedian [95% CI] 7.5 [2.0; 13.0]), the right ventricular fractional area change decreased from 45% (39; 49) to 38% (33; 43) (p = 0.002), while the heart rate and systolic blood pressure increased from 70 bpm (64; 78) to 82 bpm (70; 86) (p < 0.0001) and from 133 mm Hg (123; 141) to 136 mm Hg (126; 148) (p = 0.002), respectively, and left ventricular diastolic dysfunction was more prevalent (24-54%, p = 0.02). CONCLUSIONS: This is a first study assessing changes in pulmonary hemodynamics and cardiac function in patients with COPD during a short altitude sojourn. Despite the increase in PAP and indications of change in cardiac function, the exposure was well tolerated. None of the patients had to descend to lower altitude for symptomatic altitude-related disease.

Real-Life Experience with Selexipag as an Add-On Therapy to Oral Combination Therapy in Patients with Pulmonary Arterial or Distal Chronic Thromboembolic Pulmonary Hypertension: A Retrospective Analysis.

BACKGROUND: Patients with pulmonary arterial hypertension (PAH) and distal chronic thromboembolic pulmonary hypertension (CTEPH) who still reveal risk factors of worse prognosis on double combination therapy may benefit from add-on therapy with the novel oral selective prostacyclin receptor agonist selexipag. METHODS: We reviewed all patients with PAH/distal CTEPH in the Zurich cohort who received selexipag as add-on to oral combination therapy and retrieved New York Heart Association (NYHA) functional class, 6-min walk distance (6MWD), NT-pro-BNP, quality of life questionnaires (CAMPHOR and EuroQoL), tricuspid pressure gradient (TPG) by echocardiography and cardiopulmonary exercise test parameters (power output and oxygen uptake). RESULTS: Twenty-three patients with PAH/CTEPH (20/3), 14 females, median (quartiles) age 56 (46; 66) years received an oral triple therapy containing selexipag at a median dose of 2000 (1600; 3100) mcg during 221 (113; 359) days. The following parameters were stabilized from baseline to last FU: 6MWD (440 (420; 490) to 464 (420; 526) m), NYHA class (three to two), NT-pro-BNP (326 (167; 1725) to 568 (135; 1856)  ng/l), TPG, power output, and oxygen uptake. Quality of life reflected by the CAMPHOR and EuroQoL improved. CONCLUSIONS: Early initiation of triple oral combination therapy including selexipag in PAH/CTEPH with intermediate risk factor profile may help to stabilize functional class, exercise performance, and pulmonary hemodynamics in a real-life setting and potentially improves quality of life. Whether these beneficial effects can be truly attributed to the addition of selexipag should be addressed in future randomized controlled trials.

Physical activity in incident patients with pulmonary arterial and chronic thromboembolic hypertension.

INTRODUCTION: The cardinal symptom of pulmonary hypertension (PH) is dyspnea on exertion, leading to decreased activity in daily living. The aim of this study was to analyze daily physical activity in incident patients with arterial or chronic thromboembolic PH (PAH/CTEPH) and to investigate its correlation with pulmonary hemodynamics, symptoms, exercise capacity, and other outcomes. METHODS: Incident patients with PAH/CTEPH had a 1-week activity assessment by the arm-worn accelerometer SenseWear within - 3 months/+ 2 weeks of the diagnostic right heart catheterization (RHC) and baseline assessments including 6-minute walking distance (6MWD). Activity was correlated to RHC data at rest and exercise and to other outcomes. RESULTS: Thirty-nine PH-patients (24 PAH, 15 CTEPH, 23 females, 65(54;73) years, mean pulmonary artery pressure (mPAP) 38(30;46) mmHg, cardiac output (CO) 5.2(4.6;6.3) l/min, 6MWD 458(300;593) m) were included. 64% had a sedentary lifestyle ( < 5000 steps/day), 26% were moderately active (5000-9999 steps/day), and 10% were active. In a multivariate stepwise regression analysis including age, gender, 6MWD and hemodynamics at rest and during exercise (heart rate, mPAP, stroke volume), the 6MWD was the only independent predictor of steps/day (B = 16.8 (95% CI 11.6-22.0), p < 0.001). CONCLUSION: Daily physical activity as steps/day assessed in incident patients with PAH/CTEPH did not well correlate with invasive hemodynamics at rest or during exercise, but very well with the 6MWD. Whether daily activity assessments provide additional information to simple walk distance on risk factor profiles during follow-up in patients with PAH/CTEPH remains to be clarified.

Asthma rehabilitation at high vs. low altitude: randomized parallel-group trial.

BACKGROUND: To investigate the effect of asthma rehabilitation at high altitude (3100 m, HA) compared to low altitude (760 m, LA). METHODS: For this randomized parallel-group trial insufficiently controlled asthmatics (Asthma Control Questionnaire (ACQ) > 0.75) were randomly assigned to 3-week in-hospital rehabilitation comprising education, physical-&breathing-exercises at LA or HA. Co-primary outcomes assessed at 760 m were between group changes in peak expiratory flow (PEF)-variability, and ACQ) from baseline to end-rehabilitation and 3 months thereafter. RESULTS: 50 asthmatics were randomized [median (quartiles) LA: ACQ 2.7(1.7;3.2), PEF-variability 19%(14;33); HA: ACQ 2.0(1.6;3.0), PEF-variability 17%(12;32)]. The LA-group improved PEF-variability by median(95%CI) -7%(- 14 to 0, p = 0.033), ACQ - 1.4(- 2.2 to - 0.9, p < 0.001), and after 3 months by - 3%(- 18 to 2, p = 0.103) and - 0.9(- 1.3 to - 0.3, p = 0.002). The HA-group improved PEF-variability by - 10%(- 21 to - 3, p = 0.004), ACQ - 1.1(- 1.3 to - 0.7, p < 0.001), and after 3 months by - 9%(- 10 to - 3, p = 0.003) and - 0.2(- 0.9 to 0.4, p = 0.177). The additive effect of HA vs. LA directly after the rehabilitation on PEF-variability was - 6%(- 14 to 2), on ACQ 0.3(- 0.4 to 1.1) and after 3 months - 5%(- 14 to 5) respectively 0.4(- 0.4 to 1.1), all p = NS. CONCLUSION: Asthma rehabilitation is highly effective in improving asthma control in terms of PEF-variability and symptoms, both at LA and HA similarly. TRIAL REGISTRATION: Clinicaltrials.gov: NCT02741583, Registered April 18, 2016.