氧和乙酰唑胺对毛细血管前肺动脉高压伴睡眠呼吸紊乱患者夜间心脏传导、复极和心律失常的影响。

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

机构信息

From the Pulmonary Clinic, Department of Cardiovascular and Thoracic Medicine, University Hospital Zurich, Zurich, Switzerland.

出版信息

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

DOI:10.1378/chest.14-0495

PMID:24991933

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.

摘要

背景

睡眠呼吸障碍（SDB）在毛细血管前肺动脉高压（PH）患者中很常见。夜间氧疗（NOT）和乙酰唑胺可改善 PH 患者的 SDB，NOT 可改善运动能力。我们研究了 NOT 和乙酰唑胺对 PH 和 SDB 患者夜间心脏传导、复极和心律失常的影响。

方法

在一项随机、安慰剂对照、双盲、交叉试验中，23 名动脉性（n=16）或慢性血栓栓塞性 PH（n=7）和 SDB 患者（定义为平均夜间氧饱和度<90%或夜间氧饱和度下降>3%>10/h，白天 PaO2≥7.3 kPa）接受了 NOT（3 L/min）、乙酰唑胺片（2×250 mg）和 sham-NOT/安慰剂治疗，每种治疗持续 1 周，治疗之间间隔 1 周洗脱期。在每个治疗期末，通过整夜多导睡眠图记录 3 导联心电图。在深夜和清晨，平均三个心动周期的复极指数，并计算夜间心律失常。

结果

与安慰剂相比，NOT 可使夜间（68±10 次/分比 72±9 次/分，P=0.010）和清晨的心率降低。在深夜，与安慰剂相比，乙酰唑胺治疗时校正后的 PQ 时间延长（平均差异 10 毫秒；95%CI，0-20 毫秒；P=0.042）。在 NOT 治疗的清晨，与安慰剂相比，校正后的 QT（QTc）间期缩短（平均差异，-25 毫秒；95%CI，-45 至-6 毫秒；P=0.007），心电图上 T 波峰至终点之间的间隔缩短（平均差异，-11 毫秒；95%CI，-21 至-1 毫秒；P=0.028）。心律失常少见且与所有治疗相似。