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.

Time course of cerebral oxygenation and cerebrovascular reactivity in Kyrgyz highlanders. A five-year prospective cohort study.

Introduction: This prospective cohort study assessed the effects of chronic hypoxaemia due to high-altitude residency on the cerebral tissue oxygenation (CTO) and cerebrovascular reactivity. Methods: Highlanders, born, raised, and currently living above 2,500 m, without cardiopulmonary disease, participated in a prospective cohort study from 2012 until 2017. The measurements were performed at 3,250 m. After 20 min of rest in supine position while breathing ambient air (FiO2 0.21) or oxygen (FiO2 1.0) in random order, guided hyperventilation followed under the corresponding gas mixture. Finger pulse oximetry (SpO2) and cerebral near-infrared spectroscopy assessing CTO and change in cerebral haemoglobin concentration (cHb), a surrogate of cerebral blood volume changes and cerebrovascular reactivity, were applied. Arterial blood gases were obtained during ambient air breathing. Results: Fifty three highlanders, aged 50 ± 2 years, participated in 2017 and 2012. While breathing air in 2017 vs. 2012, PaO2 was reduced, mean ± SE, 7.40 ± 0.13 vs. 7.84 ± 0.13 kPa; heart rate was increased 77 ± 1 vs. 70 ± 1 bpm (p < 0.05) but CTO remained unchanged, 67.2% ± 0.7% vs. 67.4% ± 0.7%. With oxygen, SpO2 and CTO increased similarly in 2017 and 2012, by a mean (95% CI) of 8.3% (7.5-9.1) vs. 8.5% (7.7-9.3) in SpO2, and 5.5% (4.1-7.0) vs. 4.5% (3.0-6.0) in CTO, respectively. Hyperventilation resulted in less reduction of cHb in 2017 vs. 2012, mean difference (95% CI) in change with air 2.0 U/L (0.3-3.6); with oxygen, 2.1 U/L (0.5-3.7). Conclusion: Within 5 years, CTO in highlanders was preserved despite a decreased PaO2. As this was associated with a reduced response of cerebral blood volume to hypocapnia, adaptation of cerebrovascular reactivity might have occurred.

Long-term outcome of patients with combined post- and pre-capillary pulmonary hypertension.

Aims: Pulmonary hypertension (PH) is a complex clinical condition, and left heart disease is the leading cause. Little is known about the epidemiology and prognosis of combined post- and pre-capillary PH (CpcPH). Methods and results: This retrospective analysis of the Swiss PH Registry included incident patients with CpcPH registered from January 2001 to June 2019 at 13 Swiss hospitals. Patient baseline characteristics [age, sex, mean pulmonary artery pressure (mPAP), pulmonary artery wedge pressure (PAWP), pulmonary vascular resistance (PVR), and risk factors, including World Health Organization (WHO)-functional class (FC), 6 min walk distance (6MWD), and N-terminal pro-brain natriuretic peptide (NT-proBNP), treatment, days of follow-up, and events (death or loss to follow-up) at last visit] were analysed by Kaplan-Meier and Cox regression analyses. Two hundred and thirty-one patients (59.3% women, age 65 ± 12 years, mPAP 48 ± 11 mmHg, PAWP 21 ± 5 mmHg, PVR 7.2 ± 4.8 WU) were included. Survival analyses showed a significantly longer survival for women [hazard ratio (HR) 0.58 (0.38-0.89); P = 0.01] and a higher mortality risk for mPAP > 46 mmHg [HR 1.58 (1.03-2.43); P = 0.04] but no association with age or PVR. Patients stratified to high risk according to four-strata risk assessment had an increased mortality risk compared with patients stratified to low-intermediate risk [HR 2.44 (1.23-4.84); P = 0.01]. A total of 46.8% of CpcPH patients received PH-targeted pharmacotherapy; however, PH-targeted medication was not associated with longer survival. Conclusion: Among patients with CpcPH, women and patients with an mPAP ≤46 mmHg survived longer. Furthermore, risk stratification by using non-invasively assessed risk factors, such as WHO-FC, 6MWD, and NT-proBNP, as proposed for pulmonary arterial hypertension, stratified survival in CpcPH, and might be helpful in the management of these patients.

Hyperoxia improves exercise capacity in cardiopulmonary disease: a series of randomised controlled trials.

Background: The aim of this study was to investigate the overall and differential effect of breathing hyperoxia (inspiratory oxygen fraction (F IO2 ) 0.5) versus placebo (ambient air, F IO2 0.21) to enhance exercise performance in healthy people, patients with pulmonary vascular disease (PVD) with precapillary pulmonary hypertension (PH), COPD, PH due to heart failure with preserved ejection fraction (HFpEF) and cyanotic congenital heart disease (CHD) using data from five randomised controlled trials performed with identical protocols. Methods: 91 subjects (32 healthy, 22 with PVD with pulmonary arterial or distal chronic thromboembolic PH, 20 with COPD, 10 with PH in HFpEF and seven with CHD) performed two cycle incremental (IET) and two constant work-rate exercise tests (CWRET) at 75% of maximal load (Wmax), each with ambient air and hyperoxia in single-blinded, randomised, controlled, crossover trials. The main outcomes were differences in Wmax (IET) and cycling time (CWRET) with hyperoxia versus ambient air. Results: Overall, hyperoxia increased Wmax by +12 W (95% CI: 9-16, p<0.001) and cycling time by +6:13 min (4:50-7:35, p<0.001), with improvements being highest in patients with PVD (Wmax/min: +18%/+118% versus COPD: +8%/+60%, healthy: +5%/+44%, HFpEF: +6%/+28%, CHD: +9%/+14%). Conclusion: This large sample of healthy subjects and patients with various cardiopulmonary diseases confirms that hyperoxia significantly prolongs cycling exercise with improvements being highest in endurance CWRET and patients with PVD. These results call for studies investigating optimal oxygen levels to prolong exercise time and effects on training.

Effect of acetazolamide on visuomotor performance at high altitude in healthy people 40 years of age or older-RCT.

OBJECTIVE: Altitude travel is increasingly popular also for middle-aged and older tourists and professionals. Due to the sensitivity of the central nervous system to hypoxia, altitude exposure may impair visuomotor performance although this has not been extensively studied. Therefore, we investigated whether a sojourn at moderately high altitude is associated with visuomotor performance impairments in healthy adults, 40y of age or older, and whether this adverse altitude-effect can be prevented by acetazolamide, a drug used to prevent acute mountain sickness. METHODS: In this randomized placebo-controlled parallel-design trial, 59 healthy lowlanders, aged 40-75y, were assigned to acetazolamide (375 mg/day, n = 34) or placebo (n = 25), administered one day before ascent and while staying at high altitude (3100m). Visuomotor performance was assessed at 760m and 3100m after arrival and in the next morning (post-sleep) by a computer-assisted test (Motor-Task-Manager). It quantified deviation of a participant-controlled cursor affected by rotation during target tracking. Primary outcome was the directional error during post-sleep recall of adaptation to rotation estimated by multilevel linear regression modeling. Additionally, adaptation, immediate recall, and correct test execution were evaluated. RESULTS: Compared to 760m, assessments at 3100m with placebo revealed a mean (95%CI) increase in directional error during adaptation and immediate recall by 1.9° (0.2 to 3.5, p = 0.024) and 1.1° (0.4 to 1.8, p = 0.002), respectively. Post-sleep recall remained unchanged (p = NS), however post-sleep correct test execution was 14% less likely (9 to 19, p<0.001). Acetazolamide improved directional error during post-sleep recall by 5.6° (2.6 to 8.6, p<0.001) and post-sleep probability of correct test execution by 36% (30 to 42, p<0.001) compared to placebo. CONCLUSION: In healthy individuals, 40y of age or older, altitude exposure impaired adaptation to and immediate recall and correct execution of a visuomotor task. Preventive acetazolamide treatment improved visuomotor performance after one night at altitude and increased the probability of correct test execution compared to placebo. CLINICALTRIALS.GOV IDENTIFIER: ClinicalTrials.gov NCT03536520.

Effect of altitude and acetazolamide on postural control in healthy lowlanders 40 years of age or older. Randomized, placebo-controlled trial.

Background: Hypoxia and old age impair postural control and may therefore enhance the risk of accidents. We investigated whether acetazolamide, the recommended drug for prevention of acute mountain sickness, may prevent altitude-induced deterioration of postural control in older persons. Methods: In this parallel-design trial, 95 healthy volunteers, 40 years of age or older, living <1,000 m, were randomized to preventive therapy with acetazolamide (375 mg/d) or placebo starting 24 h before and during a 2-day sojourn at 3,100 m. Instability of postural control was quantified by a balance platform with the center of pressure path length (COPL) as primary outcome while pulse oximetry (SpO2) was monitored. Effects of altitude and treatment on COPL were evaluated by ordered logistic regression. www.ClinicalTrials.gov NCT03536429. Results: In participants taking placebo, ascent from 760 m to 3,100 m increased median COPL from 25.8 cm to 27.6 cm (odds ratio 3.80, 95%CI 2.53-5.70) and decreased SpO2 from 96% to 91% (odds ratio 0.0003, 95%CI 0.0002-0.0007); in participants taking acetazolamide, altitude ascent increased COPL from 24.6 cm to 27.3 cm (odds ratio 2.22, 95%CI 1.57-3.13), while SpO2 decreased from 96% to 93% (odds ratio 0.007, 95%CI 0.004-0.012). Altitude-induced increases in COPL were smaller with acetazolamide vs. placebo (odds ratio 0.58, 95%CI 0.34-0.99) while drops in SpO2 were mitigated (odds ratio 19.2, 95%CI 9.9-37.6). Conclusion: In healthy individuals, 40 years of age or older, postural control was impaired after spending a night at 3,100 m. The altitude-induced deterioration of postural control was mitigated by acetazolamide, most likely due to the associated improvement in oxygenation.

Prediction of maximal oxygen uptake from 6-min walk test in pulmonary hypertension.

Maximal oxygen uptake (V'O2 max), assessed by cardiopulmonary exercise testing (CPET), is an important parameter for risk assessment in patients with pulmonary hypertension (PH). However, CPET may not be available for all PH patients. Thus, we aimed to test previously published predictive models of V'O2 max from the 6-min walk distance (6MWD) for their accuracy and to create a new model. We tested four models (two by Ross et al. (2010), one by Miyamoto et al. (2000) and one by Zapico et al. (2019)). To derive a new model, data were split into a training and testing dataset (70:30) and step-wise linear regression was performed. To compare the different models, the standard error of the estimate (SEE) was calculated and the models graphically compared by Bland-Altman plots. Sensitivity and specificity for correct prediction into low-risk classification (V'O2 max >15 mL/min/kg) was calculated for all models. A total of 276 observations were included in the analysis (194/82 training/testing dataset); 6MWD and V'O2 max were significantly correlated (r=0.65, p<0.001). Linear regression showed significant correlation of 6MWD, weight and heart rate response (HRR) with V'O2 max and the best fitting prediction equation was: V'O2 max = 1.83 + 0.031 × 6MWD (m) - 0.023 × weight (kg) - 0.015 × HRR (bpm). SEEs for the different models were 3.03, 3.22, 4.36 and 3.08 mL/min/kg for the Ross et al., Miyamoto et al., Zapico et al. models and the new model, respectively. Predicted mean V'O2 max was 16.5 mL/min/kg (versus observed 16.1 mL/min/kg). 6MWD and V'O2 max reveal good correlation in all models. However, the accuracy of all models is inadequate for clinical use. Thus, CPET and 6MWD both remain valuable risk assessment tools in the management of PH.

Disease characteristics and clinical outcome over two decades from the Swiss pulmonary hypertension registry.

Pulmonary hypertension (PH), especially pulmonary arterial and chronic thromboembolic pulmonary hypertension (PAH/CTEPH), are rare and progressive conditions. Despite recent advances in treatment and prognosis, PH is still associated with impaired quality of life and survival. Long-term PH-registry data provide information on the changing PH-epidemiology and may help to direct resources to patient's needs. This retrospective analysis of the Swiss Pulmonary Hypertension Registry includes patients newly diagnosed with PH (mainly PAH/CTEPH) registered from January 2001 to June 2019 at 13 Swiss hospitals. Patient characteristics (age, body mass index, gender, diagnosis), hemodynamics at baseline, treatment, days of follow-up, and events (death, transplantation, pulmonary endarterectomy, or loss to follow-up) at last visit were analyzed. Patients were stratified into four time periods according to their date of diagnosis. Survival was analyzed overall and separately for PAH/CTEPH and time periods. 1427 PH patients were included (thereof 560 PAH, 383 CTEPH). Over the years, age at baseline (mean ± SD) significantly increased from 59 ± 14 years in 2001-2005 to 66 ± 14 years in 2016-2019 (p < 0.001) while the gender distribution tended toward equality. Mean pulmonary artery pressure and pulmonary vascular resistance significantly decreased over time (from 46 ± 15 to 41 ± 11 mmHg, respectively, 9 ± 5 to 7 ± 4 WU, p < 0.001). Three-year survival substantially increased over consecutive periods from 69% to 91% (for PAH 63%-95%, for CTEPH 86%-93%) and was poorer in PAH than CTEPH independently of time period (p < 0.001). Most patients were treated with mono- or combination therapy and an increasing number of CTEPH underwent pulmonary endarterectomy (40% 2016-2019 vs. 15% 2001-2005). This long-term PH registry reveals that over two decades of observation, newly diagnosed patients are older, less predominantly female, have less impaired hemodynamics and a better survival.

Exercise Performance in Central Asian Highlanders: A Cross-Sectional Study.

Forrer, Aglaia, Philipp M. Scheiwiller, Maamed Mademilov, Mona Lichtblau, Ulan Sheraliev, Nuriddin H. Marazhapov, Stéphanie Saxer, Patrick Bader, Paula Appenzeller, Shoira Aydaralieva, Aybermet Muratbekova, Talant M. Sooronbaev, Silvia Ulrich, Konrad E. Bloch, and Michael Furian. Exercise performance in central Asian highlanders: A cross-sectional study. High Alt Med Biol. 22:386-394, 2021. Introduction: Life-long exposure to hypobaric hypoxia induces physiologic adaptations in highlanders that may modify exercise performance; however, reference data for altitude populations are scant. Methods: Life-long residents of the Tien Shan mountain range, 2,500 - 3,500 m, Kyrgyzstan, free of cardiopulmonary disease, underwent cardiopulmonary cycle exercise tests with a progressive ramp protocol to exhaustion at 3,250 m. ECG, breath-by-breath pulmonary gas exchange, and oxygen saturation by pulse oximetry (SpO2) were measured. Results: Among 81 highlanders, age (mean ± SD) 48 ± 10 years, 46% women, SpO2 at rest was 88% ± 2%, peak oxygen uptake (V'O2peak) was 21.6 ± 5.9 mL/kg/min (76% ± 15% predicted for a low-altitude reference population); peak work rate (Wpeak) was 117 ± 37 W (77% ± 17% predicted), SpO2 at peak was 84% ± 5%, heart rate reserve (220 - age - maximal heart rate) was 28 ± 17/min, ventilatory reserve (maximal voluntary ventilation - maximal minute ventilation) was 68 ± 32 l/min, and respiratory exchange ratio was 1.03 ± 0.09. Peak BORG-CR10 dyspnea and leg fatigue scores were 5.1 ± 2.0 and 6.3 ± 2.1. In multivariable linear regression analyses, age and sex were robust determinants of Wpeak, V'O2peak, and metabolic equivalent (MET) at peak, whereas body mass index, resting systolic blood pressure, and mean pulmonary artery pressure were not. Conclusions: The current study shows that V'O2peak and Wpeak of highlanders studied at 3,250 m, near their altitude of residence, were reduced by about one quarter compared with mean predicted values for lowlanders. The provided prediction models for V'O2peak, Wpeak, and METs in central Asian highlanders might be valuable for comparisons with other high altitude populations.

Pulmonary haemodynamic response to exercise in highlanders versus lowlanders.

The aim of the study was to investigate the pulmonary haemodynamic response to exercise in Central Asian high- and lowlanders. This was a cross-sectional study in Central Asian highlanders (living >2500 m) compared with lowlanders (living <800 m), assessing cardiac function, including tricuspid regurgitation pressure gradient (TRPG), cardiac index and tricuspid annular plane systolic excursion (TAPSE) by echocardiography combined with heart rate and oxygen saturation measured by pulse oximetry (S pO2 ) during submaximal stepwise cycle exercise (10 W increase per 3 min) at their altitude of residence (at 760 m or 3250 m, respectively). 52 highlanders (26 females; aged 47.9±10.7 years; body mass index (BMI) 26.7±4.6 kg·m-2; heart rate 75±11 beats·min-1; S pO2 91±5%;) and 22 lowlanders (eight females; age 42.3±8.0 years; BMI 26.9±4.1 kg·m-2; heart rate 68±7 beats·min-1; S pO2 96±1%) were studied. Highlanders had a lower resting S pO2 compared to lowlanders but change during exercise was similar between groups (highlanders versus lowlanders -1.4±2.9% versus -0.4±1.1%, respectively, p=0.133). Highlanders had a significantly elevated TRPG and exercise-induced increase was significantly higher (13.6±10.5 mmHg versus 6.1±4.8 mmHg, difference 7.5 (2.8 to 12.2) mmHg; p=0.002), whereas cardiac index increase was slightly lower in highlanders (2.02±0.89 L·min-1 versus 1.78±0.61 L·min-1, difference 0.24 (-0.13 to 0.61) L·min-1; p=0.206) resulting in a significantly steeper pressure-flow ratio (ΔTRPG/Δcardiac index) in highlanders 9.4±11.4 WU and lowlanders 3.0±2.4 WU (difference 6.4 (1.4 to 11.3) WU; p=0.012). Right ventricular-arterial coupling (TAPSE/TRPG) was significantly lower in highlanders but no significant difference in change with exercise in between groups was detected (-0.01 (-0.20 to 0.18); p=0.901). In highlanders, chronic exposure to hypoxia leads to higher pulmonary artery pressure and a steeper pressure-flow relation during exercise.

Asthma rehabilitation at high vs. low altitude and its impact on exhaled nitric oxide and sensitization patterns: Randomized parallel-group trial.

BACKGROUND: Allergens and pollution are reduced at high altitude. We investigated the effect of asthma rehabilitation at high altitude (HA, 3100 m) compared to low altitude (LA, 760 m) on exhaled nitric oxide (FeNO) and on specific IgE levels for house dust mites (HDM,d1) and common pollen (sx1). METHODS: For this randomized controlled trial adult asthmatics living <1000 m were randomly assigned to a 3-week in-hospital-rehabilitation (education, physical- and breathing-exercises) at either LA or HA. Changes in FeNO, d1 and sx1 from baseline to end-rehabilitation were measured. RESULTS: 50 asthmatics (34 females) were randomized [mean ± standard deviation LA: n = 25, 44 ± 11 years, total IgE 267 ± 365kU/l; HA: n = 25, 43 ± 13 years, total IgE 350 ± 445kU/l]. FeNO significantly improved at HA from 69 ± 56 ppb at baseline to the first day at altitude 23 ± 19 ppb and remained decreased until end-rehabilitation with 37 ± 23 ppb, mean difference 95%CI -31(-50 to -13, p = 0.001) whereas at LA FeNO did not change. A significant decrease in d1 and sx1 at end-rehabilitation was observed in the LA-group [mean difference 95%CI -10.2 kUA/l (-18.9 to -1.4) for d1 and -4.95 kUA/l(-9.69 to -0.21) for sx1] but not in the HA-group. No significant difference between groups [d1 5.9 kUA/l(-4.2 to 16.2) and sx1 4.4 kUA/l(-3.5 to 12.4)] was found. CONCLUSION: Rehabilitation at HA led to significant FeNO reduction starting from the first day until end-rehabilitation despite unchanged levels of specific IgE. The significant decrease in d1 and sx1 at end-rehabilitation in the LA group might be explained by less HDM in the hospital and/or reduced seasonal pollen, as this decrease was not observed at HA.

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.

Risk Factor Profiles Achieved with Medical Therapy in Prevalent Patients with Pulmonary Arterial and Distal Chronic Thromboembolic Pulmonary Hypertension.

BACKGROUND: The latest pulmonary hypertension (PH) guidelines define therapeutic goals in terms of symptoms, exercise capacity, and haemodynamics for patients with pulmonary arterial hypertension (PAH) and recommend advanced combined medical therapy. For inoperable or post-surgical residual distal chronic thromboembolic PH (CTEPH) medical treatment is similarly advised. OBJECTIVES: We analysed whether risk factor goals are achieved and combination therapy is used in prevalent patients with PAH or distal CTEPH. METHODS: PAH or distal CTEPH patients who were seen at the University Hospital Zurich during the last year were analysed in terms of demography, clinical data, medication, and therapeutic goals. Achievement of therapeutic goals was defined as New York Heart Association (NYHA) class ≤II, N-terminal pro-brain natriuretic peptide (NTpro-BNP) < 300 ng/L, and 6-min walking distance (6MWD) > 440 m. RESULTS: A total of 108 PAH patients (age 59 ± 18 years, 62% female, 64% idiopathic, 36% associated) and 38 distal CTEPH patients (age 69 ± 14 years, 55% female) were included. They had been diagnosed on average 66 ± 48 months (±SD) previously. The percentage of PAH/CTEPH patients with NYHA ≤II was 52/53, respectfully, the percentage of those with NTproBNP < 300 ng/L was 61/52, and with 6MWD > 440 m 63/50. Overall, 33/31% fulfilled 3 and 29/35% fulfilled 2 of these goals. Regarding therapy, 43% of PAH patients were on double and 10% on triple combination therapy, whereas 16% of distal CTEPH patients were on double and 3% on triple combination therapy. CONCLUSIONS: In this real-life cohort of prevalent patients with PAH or distal CTEPH, targeted drug therapy resulted in an achievement of ≥2/3 predefined therapeutic goals in 2/3 of patients. Patients with PAH were more likely to receive combination therapy compared to CTEPH patients.