Effect of oxygen and acetazolamide on nocturnal cardiac conduction, repolarization, and arrhythmias in precapillary pulmonary hypertension and sleep-disturbed breathing

Chest. 2014 Nov;146(5):1226-1236. doi: 10.1378/chest.14-0495.

Abstract

Background: Sleep-disturbed breathing (SDB) is common in patients with precapillary pulmonary hypertension (PH). Nocturnal oxygen therapy (NOT) and acetazolamide improve SDB in patients with PH, and NOT improves exercise capacity. We investigated the effect of NOT and acetazolamide on nocturnal cardiac conduction, repolarization, and arrhythmias in patients with PH and SDB.

Methods: In a randomized, placebo-controlled, double-blind, crossover trial, 23 patients with arterial (n = 16) or chronic thromboembolic PH (n = 7) and SDB defined as a mean nocturnal oxygen saturation < 90% or dips (> 3%) > 10/h with daytime Pao2 ≥ 7.3 kPa were studied. Participants received NOT (3 L/min), acetazolamide tablets (2 × 250 mg), and sham-NOT/placebo each during 1 week separated by a 1-week washout period. Three-lead ECG was recorded during overnight polysomnography at the end of each treatment period. Repolarization indices were averaged over three cardiac cycles at late evening and at early morning, and nocturnal arrhythmias were counted.

Results: NOT was associated with a lower overnight (68 ± 10 beats/min vs 72 ± 9 beats/min, P = .010) and early morning heart rate compared with placebo. At late evening, the heart rate-adjusted PQ time was increased under acetazolamide compared with placebo (mean difference, 10 milliseconds; 95% CI, 0-20 milliseconds; P = .042). In the morning under NOT, the heart rate-adjusted QT (QTc) interval was decreased compared with placebo (mean difference, -25 milliseconds; 95% CI, -45 to -6 milliseconds; P = .007), and the interval between the peak and the end of the T wave on the ECG was shorter compared with acetazolamide (mean difference, -11 milliseconds; 95% CI, -21 to -1 milliseconds; P = .028). Arrhythmias were rare and similar with all treatments.

Conclusions: In patients with PH with SDB, NOT reduces nocturnal heart rate and QTc in the morning, thus, favorably modifying prognostic markers.

Trial registry: ClinicalTrials.gov; No.: NTC-01427192; URL: www.clinicaltrials.gov.

Trial registration: ClinicalTrials.gov NCT01427192.

Publication types

  • Comparative Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetazolamide / administration & dosage*
  • Administration, Oral
  • Aged
  • Arrhythmias, Cardiac / complications
  • Arrhythmias, Cardiac / drug therapy*
  • Arrhythmias, Cardiac / physiopathology
  • Carbonic Anhydrase Inhibitors / administration & dosage
  • Cross-Over Studies
  • Dose-Response Relationship, Drug
  • Double-Blind Method
  • Electrocardiography
  • Female
  • Follow-Up Studies
  • Heart Conduction System / drug effects*
  • Heart Conduction System / physiopathology
  • Heart Rate / drug effects
  • Humans
  • Hypertension, Pulmonary / complications
  • Hypertension, Pulmonary / drug therapy*
  • Hypertension, Pulmonary / physiopathology
  • Male
  • Middle Aged
  • Oxygen / administration & dosage*
  • Oxygen Inhalation Therapy / methods*
  • Polysomnography
  • Retrospective Studies
  • Sleep Wake Disorders / complications
  • Sleep Wake Disorders / drug therapy*
  • Sleep Wake Disorders / physiopathology
  • Treatment Outcome

Substances

  • Carbonic Anhydrase Inhibitors
  • Acetazolamide
  • Oxygen

Associated data

  • ClinicalTrials.gov/NCT01427192