Patients with Obstructive Sleep Apnea Have Cardiac Repolarization Disturbances when Travelling to Altitude: Randomized, Placebo-Controlled Trial of Acetazolamide.
Obstructive sleep apnea (OSA) promotes myocardial electrical instability and may predispose to nocturnal sudden cardiac death. We evaluated whether hypobaric hypoxia during altitude travel further impairs cardiac repolarization in patients with OSA, and whether this is prevented by acetazolamide, a drug known to improve oxygenation and central sleep apnea at altitude.



Thirty-nine OSA patients living < 600 m, discontinued continuous positive airway pressure therapy during studies at 490 m and during two sojourns of 3 days at altitude (2 days at 1860 m, 1 day at 2590 m). During one altitude sojourn, patients took acetazolamide, during the other placebo, or vice versa, according to a randomized, double-blind crossover design. Twelve-lead electrocardiography and pulse oximetry (SpO2) were recorded during nocturnal polysomnography. Heart rate corrected mean QT intervals during the entire night (meanQTc) and during 1 min of the night with the longest meanQTc (maxQTc) were determined.



At 490 m the median nocturnal SpO2 was 93%, medians of meanQTc and maxQTc were 420 ms and 478 ms. At 2590 m, on placebo, SpO2 was lower (85%), and meanQTc and maxQTc were prolonged to 430 ms and 510 ms (P < 0.02 vs. 490 m, all corresponding comparisons). At 2590 m on acetazolamide, median SpO2 was increased to 88% (P < 0.05 vs. placebo), meanQTc was reduced to 427 ms (P < 0.05 vs. placebo), whereas maxQTc remained increased at 502 ms (P = ns vs. placebo).



At 2590 m OSA patients experienced cardiac repolarization disturbances in association with hypoxemia. Prolongation of meanQTc at altitude was prevented and hypoxemia was improved by acetazolamide, whereas maxQTc remained increased suggesting imperfect protection from repolarization disturbances.



ClinicalTrials.gov ID: NTC-00714740. URL: www.clinicaltrials.gov.
Sleep Disorders Center and Pulmonary Division, University Hospital of Zurich, Zurich, Switzerland.
Tsogyal Daniela
TD
Latshang
Sleep Disorders Center and Pulmonary Division, University Hospital of Zurich, Zurich, Switzerland.
Barbara
B
Kaufmann
Sleep Disorders Center and Pulmonary Division, University Hospital of Zurich, Zurich, Switzerland.
Yvonne
Y
Nussbaumer-Ochsner
Sleep Disorders Center and Pulmonary Division, University Hospital of Zurich, Zurich, Switzerland.
Silvia
S
Ulrich
Sleep Disorders Center and Pulmonary Division, University Hospital of Zurich, Zurich, Switzerland.
Michael
M
Furian
Sleep Disorders Center and Pulmonary Division, University Hospital of Zurich, Zurich, Switzerland.|Center for Integrative Human Physiology, University of Zurich, Zurich, Switzerland.
Malcolm
M
Kohler
Pulmonary Division, Cantonal Hospital Muensterlingen, Muensterlingen, Switzerland.
Robert
R
Thurnheer
Department of Cardiology, University Heart Center Zurich, Zurich, Switzerland.
Ardan Muammer
AM
Saguner
Department of Cardiology, University Heart Center Zurich, Zurich, Switzerland.|Center for Integrative Human Physiology, University of Zurich, Zurich, Switzerland.
Firat
F
Duru
Sleep Disorders Center and Pulmonary Division, University Hospital of Zurich, Zurich, Switzerland.|Center for Integrative Human Physiology, University of Zurich, Zurich, Switzerland.
Konrad Ernst
KE
Bloch
D000086:Acetazolamide / Q000627:therapeutic use*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000531:Altitude; D001145:Arrhythmias, Cardiac / Q000209:etiology / Q000517:prevention & control*; D002257:Carbonic Anhydrase Inhibitors / Q000627:therapeutic use*; D018592:Cross-Over Studies; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D000860:Hypoxia / Q000209:etiology / Q000503:physiopathology*; D008297:Male; D008875:Middle Aged; D010092:Oximetry; D017286:Polysomnography; D020181:Sleep Apnea, Obstructive / Q000150:complications / Q000503:physiopathology*
D002257:Carbonic Anhydrase Inhibitors; D000086:Acetazolamide
altitude; cardiac arrhythmias; cardiac repolarization; sleep apnea; sudden cardiac death