High altitude pulmonary hypertension (HAPH), a chronic altitude related illness, is associated with hypoxemia, dyspnea and reduced exercise performance. We evaluated ECG and pulse wave-derived markers of cardiovascular risk in highlanders with HAPH (HAPH+) in comparison to healthy highlanders (HH) and lowlanders (LL) and the effects of hyperoxia. We studied 34 HAPH+ and 54 HH at Aksay (3250 m), and 34 LL at Bishkek (760 m), Kyrgyzstan. Mean pulmonary artery pressure by echocardiography was mean ± SD 34 ± 3, 22 ± 5, 16 ± 4 mmHg, respectively (p < 0.05 all comparisons). During quiet rest, breathing room air or oxygen in randomized order, we measured heart-rate adjusted QT interval (QTc), an ECG-derived marker of increased cardiovascular mortality, and arterial stiffness index (SI), a marker of cardiovascular disease derived from pulse oximetry plethysmograms. Pulse oximetry in HAPH+, HH and LL was, mean ± SD, 88 ± 4, 92 ± 2 and 95 ± 2%, respectively (p < 0.05 vs HAPH+, both comparisons). QTc in HAPH+, HH and LL was 422 ± 24, 405 ± 27, 400 ± 28 ms (p < 0.05 HAPH+ vs. others); corresponding SI was 10.5 ± 1.9, 8.4 ± 2.6, 8.5 ± 2.0 m/s, heart rate was 75 ± 8, 68 ± 8, 70 ± 10 bpm (p < 0.05, corresponding comparisons HAPH+ vs. others). In regression analysis, HAPH+ was an independent predictor of increased QTc and SI when controlled for several confounders. Oxygen breathing increased SI in HH but not in HAPH+, and reduced QTc in all groups. Our data suggest that HAPH+ but not HH may be at increased risk of cardiovascular mortality and morbidity compared to LL. The lack of a further increase of the elevated SI during hyperoxia in HAPH+ may indicate dysfunctional control of vascular tone and/or remodelling.
We investigated whether nocturnal oxygen therapy (NOT) mitigates the altitude-induced increase of pulmonary artery pressure in patients with chronic obstructive pulmonary disease (COPD) when staying overnight at moderate altitude. Patients with COPD living below 800m, underwent examinations at 490m and during 2 sojourns at 2048m (with a washout period of 2 weeks <800m between altitude sojourns). During nights at altitude patients received either NOT (3 l/min) or placebo (ambient air 3 l/min) via nasal cannula according to a randomized cross-over design. The main outcome was the difference of the tricuspid regurgitation pressure gradient (TRPG) measured by echocardiography on the 2nd day at altitude (performed under ambient air) between sojourns with NOT and placebo. Additional outcomes were other echocardiographic measures of the right and left heart function. Twenty-three COPD-patients (70% GOLD II / 30% GOLD III, mean±SD age 66±5years, FEV1 54±13% predicted) were included. TRPG significantly increased when patients travelled from 490m to 2048m (21.7±5.2mmHg; 2048m placebo 27.4±7.3mmHg; and 2048m NOT 27.8±8.3mmHg) without difference between interventions. The tricuspid annular plane systolic excursion was significantly higher after NOT vs. placebo (2.6±0.6 vs. 2.3±0.4cm, mean difference (95% confidence interval) 0.3(0.1 to 0.5)cm, p=0.005). NOT did not mitigate the acute effect of altitude on the TRPG in COPD lowlanders travelling to altitude compared to placebo. Whether NOT during prolonged altitude sojourns affects right heart function remains to be studied.
Introduction: Patients with cardiopulmonary disorders may be at risk of malignant arrhythmia due to long-QT syndrome. A large proportion of these patients undergo sleep studies including overnight ECG. The purpose of this study was to compare an automated algorithm versus manual scoring of QT-intervals in patients with COPD undergoing sleep studies. Methods: We collected 62 overnight ECG recordings in 28 patients with COPD. All one-minute QT-intervals corrected for heart rate (QTc) were quantified, both by the automated algorithm and by manual cursor-assisted measurements of a mean ECG curve computed for each 1-min epoch. Manual scoring was done blinded for the results from the algorithm. Agreement of the two methods was calculated using Bland-Altman statistics. To quantify the accuracy for clinically relevant QT prolongations, we used confusion matrixes for 3 thresholds (460, 480, and 500ms). Results: 32944 one-minute intervals were analysed. Mean difference between manual and algorithm-based QTc-intervals was -1.4ms, with limits of agreement of -18.3, 15.5ms. A total of 2587, 357 and 0 QTc-intervals exceeding the threshold 460, 480, and 500ms, respectively, were identified by manual scoring. Using the automated algorithm, diagnostic classification revealed an accuracy of 0.98 (95%CI 0.98/0.98), 1.00 (1.00/1.00), and 1.00 (1.00/1.00) for 460, 480, and 500ms, respectively. Conclusion: Clinically relevant QTc-prolongations were accurately identified by the automated algorithm. The implementation of this tool in hospital sleep laboratories may identify asymptomatic patients with long-QT at risk for malignant arrhythmia, allowing them to consult a cardiologist before an eventual cardiac event.
Right-to-left shunts (RLS) are prevalent in patients with chronic obstructive pulmonary disease (COPD) and might exaggerate oxygen desaturation, especially at altitude. The aim of this study was to describe the prevalence of RLS in patients with COPD traveling to altitude and the effect of preventive dexamethasone. Lowlanders with COPD [Global Initiative for Chronic Obstructive Lung Disease (GOLD) grades 1-2, oxygen saturation assessed by pulse oximetry (SpO2) >92%] were randomized to dexamethasone (4 mg bid) or placebo starting 24 h before ascent from 760 m and while staying at 3,100 m for 48 h. Saline-contrast echocardiography was performed at 760 m and after the first night at altitude. Of 87 patients (81 men, 6 women; mean ± SD age 57 ± 9 yr, forced expiratory volume in 1 s 89 ± 22% pred, SpO2 95 ± 2%), 39 were assigned to placebo and 48 to dexamethasone. In the placebo group, 19 patients (49%) had RLS, of which 13 were intracardiac. In the dexamethasone group 23 patients (48%) had RLS, of which 11 were intracardiac (P = 1.0 vs. dexamethasone). Eleven patients receiving placebo and 13 receiving dexamethasone developed new RLS at altitude (P = 0.011 for both changes, P = 0.411 between groups). RLS prevalence at 3,100 m was 30 (77%) in the placebo and 36 (75%) in the dexamethasone group (P = not significant). Development of RLS at altitude could be predicted at lowland by a higher resting pulmonary artery pressure, a lower arterial partial pressure of oxygen, and a greater oxygen desaturation during exercise but not by treatment allocation. Almost half of lowlanders with COPD revealed RLS near sea level, and this proportion significantly increased to about three-fourths when traveling to 3,100 m irrespective of dexamethasone prophylaxis.NEW & NOTEWORTHY The prevalence of intracardiac and intrapulmonary right-to-left shunts (RLS) at altitude in patients with chronic obstructive pulmonary disease (COPD) has not been studied so far. In a large cohort of patients with moderate COPD, our randomized trial showed that the prevalence of RLS increased from 48% at 760 m to 75% at 3,100 m in patients taking placebo. Preventive treatment with dexamethasone did not significantly reduce the altitude-induced recruitment of RLS. Development of RLS at 3,100 m could be predicted at 760 m by a higher resting pulmonary artery pressure and arterial partial pressure of oxygen and a more pronounced oxygen desaturation during exercise. Dexamethasone did not modify the RLS prevalence at 3,100 m.
Objectives: We evaluated whether nocturnal oxygen administration improves sleep and breathing disturbances in lowlanders with chronic obstructive pulmonary disease (COPD) staying for 2 nights at 2048m. Methods: 21 lowlanders with COPD, median age 68y, FEV1 55%predicted, travelled to a mountain village at 2048m (St. Moritz) twice for 2 days, separated by a 2 week washout period at <800m. During nights at 2048m, oxygen or ambient air (sham) was administered by nasal cannula at 3l/min according to a randomized, blinded, cross-over design. Co-primary outcomes were mean nocturnal oxygen saturation (SpO2) and apnea/hypopnea index (AHI) measured during polysomnography. Results: Oxygen supplementation decreased AHI and increased SpO2 compared to sham at 2048m (table). Conclusion: Lowlanders with COPD experience pronounced hypoxemia and restriction of sleep in the first night at 2048m that prevents by nocturnal oxygen supplementation. Our study provides novel data to counsel COPD patients travel to altitude
High-altitude pulmonary hypertension (HAPH) is an altitude-related illness associated with hypoxaemia that may promote sympathetic excitation and prolongation of the QT interval. The present case-control study tests whether QT intervals, markers of malignant cardiac arrhythmias, are prolonged in highlanders with HAPH (HAPH+) compared to healthy highlanders (HH) and healthy lowlanders (LL). The mean pulmonary artery pressure (mPAP) was measured by echocardiography in 18 HAPH+ (mPAP, 34 mmHg) and 18 HH (mPAP, 23 mmHg) at 3,250 m, and 18 LL (mPAP, 18 mmHg) at 760 m, Kyrgyzstan (p < .05 all mPAP comparisons). Groups were matched for age, sex and body mass index. Electrocardiography and pulse oximetry were continuously recorded during nocturnal polysomnography. The heart rate-adjusted QT interval, QTc, was averaged over consecutive 1-min periods. Overall, a total of 26,855 averaged 1-min beat-by-beat periods were semi-automatically analysed. In HAPH+, maximum nocturnal QTc was longer during sleep (median 456 ms) than wakefulness (432 ms, p < .05) and exceeded corresponding values in HH (437 and 419 ms) and LL (430 and 406 ms), p < .05, respectively. The duration of night-time QTc >440 ms was longer in HAPH+ (median 144 min) than HH and LL (46 and 14 min, p < .05, respectively). HAPH+ had higher night-time heart rate (median 78 beats/min) than HH and LL (66 and 65 beats/min, p < .05, respectively), lower mean nocturnal oxygen saturation than LL (88% versus 95%, p < .05) and more cyclic oxygen desaturations (median 24/hr) than HH and LL (13 and 3/hr, p < .05, respectively). In conclusion, HAPH was associated with higher night-time heart rate, hypoxaemia and longer QTc versus HH and LL, and may represent a substrate for increased risk of malignant cardiac arrhythmias.
During mountain travel, patients with chronic obstructive pulmonary disease (COPD) are at risk of experiencing severe hypoxemia, in particular, during sleep.
Objective
To evaluate whether preventive dexamethasone treatment improves nocturnal oxygenation in lowlanders with COPD at 3100 m.
Design, Setting, and Participants
A randomized, placebo-controlled, double-blind, parallel trial was performed from May 1 to August 31, 2015, in 118 patients with COPD (forced expiratory volume in the first second of expiration [FEV1] >50% predicted, pulse oximetry at 760 m ≥92%) who were living at altitudes below 800 m. The study was conducted at a university hospital (760 m) and high-altitude clinic (3100 m) in Tuja-Ashu, Kyrgyz Republic. Patients underwent baseline evaluation at 760 m, were taken by bus to the clinic at 3100 m, and remained at the clinic for 2 days and nights. Participants were randomized 1:1 to receive either dexamethasone, 4 mg, orally twice daily or placebo starting 24 hours before ascent and while staying at 3100 m. Data analysis was performed from September 1, 2015, to December 31, 2016.
Interventions
Dexamethasone, 4 mg, orally twice daily (dexamethasone total daily dose, 8 mg) or placebo starting 24 hours before ascent and while staying at 3100 m.
Main Outcomes and Measures
Difference in altitude-induced change in nocturnal mean oxygen saturation measured by pulse oximetry (Spo2) during night 1 at 3100 m between patients receiving dexamethasone and those receiving placebo was the primary outcome and was analyzed according to the intention-to-treat principle. Other outcomes were apnea/hypopnea index (AHI) (mean number of apneas/hypopneas per hour of time in bed), subjective sleep quality measured by a visual analog scale (range, 0 [extremely bad] to 100 [excellent]), and clinical evaluations.
Results
Among the 118 patients included, 18 (15.3%) were women; the median (interquartile range [IQR]) age was 58 (52-63) years; and FEV1was 91% predicted (IQR, 73%-103%). In 58 patients receiving placebo, median nocturnal Spo2at 760 m was 92% (IQR, 91%-93%) and AHI was 20.5 events/h (IQR, 12.3-48.1); during night 1 at 3100 m, Spo2was 84% (IQR, 83%-85%) and AHI was 39.4 events/h (IQR, 19.3-66.2) (P < .001 both comparisons vs 760 m). In 60 patients receiving dexamethasone, Spo2at 760 m was 92% (IQR, 91%-93%) and AHI was 25.9 events/h (IQR, 16.3-37.1); during night 1 at 3100 m, Spo2was 86% (IQR, 84%-88%) (P < .001 vs 760 m) and AHI was 24.7 events/h (IQR, 13.2-33.7) (P = .99 vs 760 m). Altitude-induced decreases in Spo2during night 1 were mitigated by dexamethasone vs placebo by a mean of 3% (95% CI, 2%-3%), and increases in AHI were reduced by 18.7 events/h (95% CI, 12.0-25.3). Similar effects were observed during night 2. Subjective sleep quality was improved with dexamethasone during night 2 by 12% (95% CI, 0%-23%). Sixteen (27.6%) patients using dexamethasone had asymptomatic hyperglycemia.
Conclusions and Relevance
In lowlanders in Central Asia with COPD traveling to a high altitude, preventive dexamethasone treatment improved nocturnal oxygen saturation, sleep apnea, and subjective sleep quality.
Objective: To evaluate the effects of acute exposure to high altitude and preventive dexamethasone treatment on postural control in patients with chronic obstructive pulmonary disease (COPD). Methods: In this randomized, double-blind parallel-group trial, 104 lowlanders with COPD GOLD 1-2 age 20-75 years, living near Bishkek (760 m), were randomized to receive either dexamethasone (2 × 4 mg/day p.o.) or placebo on the day before ascent and during a 2-day sojourn at Tuja-Ashu high altitude clinic (3100 m), Kyrgyzstan. Postural control was assessed with a Wii Balance BoardTM at 760 m and 1 day after arrival at 3100 m. Patients were instructed to stand immobile on both legs with eyes open during five tests of 30 s each, while the center of pressure path length (PL) was measured. Results: With ascent from 760 to 3100 m the PL increased in the placebo group from median (quartiles) 29.2 (25.8; 38.2) to 31.5 (27.3; 39.3) cm (P < 0.05); in the dexamethasone group the corresponding increase from 28.8 (22.8; 34.5) to 29.9 (25.2; 37.0) cm was not significant (P = 0.10). The mean difference (95% CI) between dexamethasone and placebo groups in altitude-induced changes (treatment effect) was -0.3 (-3.2 to 2.5) cm, (P = 0.41). Multivariable regression analysis confirmed a significant increase in PL with higher altitude (coefficient 1.6, 95% CI 0.2 to 3.1, P = 0.031) but no effect of dexamethasone was shown (coefficient -0.2, 95% CI -0.4 to 3.6, P = 0.925), even when controlled for several potential confounders. PL changes were related more to antero-posterior than lateral sway. Twenty-two of 104 patients had an altitude-related increase in the antero-posterior sway velocity of >25%, what has been associated with an increased risk of falls in previous studies. Conclusion: Lowlanders with COPD travelling from 760 to 3100 m revealed postural instability 24 h after arriving at high altitude, and this was not prevented by dexamethasone. Trial Registration: clinicaltrials.gov Identifier: NCT02450968.
