Effects of Continuous Positive Airway Pressure Therapy on Myocardial Energetics and Sympathetic Nerve Function in Patients With Heart Failure and Obstructive Sleep Apnea.
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 67
- 试验地点
- 2
- 主要终点
- Measurements of oxidative metabolism (11C clearance rate constant 'k') and WMI
研究概览
简要总结
Heart failure affects approximately 5-6 million North Americans and is increasing in prevalence. Sleep-related disorders, such as obstructive sleep apnea (OSA) often coexist (11-37% incidence) with heart failure. OSA is the repeated temporary interruption of breathing during sleep and occurs when the air passages in the upper respiratory tract become blocked during sleep. OSA adversely affects the cardiovascular system resulting in hypoxia (decrease in oxygen supply), which decreases the oxygen supply to the heart. Patients with OSA are treated with continuous positive airway pressure (CPAP). It has also been shown that CPAP reduces angina during sleep, minimizes sympathetic nervous system (SNS) activation and improves left ventricular (LV) function, although the mechanism of action is not clear. Carbon-11 acetate PET imaging allows for the assessment of how the heart works and how efficiently the heart uses oxygen in certain circumstances. Carbon-11 hydroxyephedrine (HED) measures cardiac nervous system activity, which may have an effect on heart rate. The study will evaluate the term effects of continuous positive airway pressure (CPAP), a common treatment for patients with OSA, on the heart's efficiency or ability to work and its effect on the nervous system activity of the heart. Two patient groups will be evaluated 1.) patients with congestive heart failure and obstructive sleep apnea will be randomized to early or late CPAP to address the primary hypothesis of the study and 2.) patients with congestive heart failure only (matched control group). Both the primary randomized study group and secondary study group will be evaluated using [11C]acetate PET, [11C]HED PET and echocardiography. Measurements will be obtained at baseline, 1 week (where possible) and 6-8 weeks.
详细描述
OSA and heart failure (HF) are states of increased afterload, metabolic demand and sympathetic nervous system(SNS) activation. In patients with OSA and HF, CPAP initially may reduce LV stroke volume(SV) but subsequently improves LV function. This may relate to an early beneficial effect on myocardial energetics through early reduction in metabolic demand that subsequently leads to improved efficiency of LV contraction. However, it is not clear whether CPAP favourably affects cardiac energetics. Any such benefit may also relate to reduced SNS activation with CPAP therapy. However its effect on myocardial SN function is also not well studied. We propose to evaluate the temporal effect of CPAP on daytime 1) oxidative metabolism; 2) the WMI as an estimate of mechanical efficiency; 3) myocardial SN pre-synaptic function; and 4) HR variability in patients with OSA and HF. We will also determine whether these parameters are altered compared to a group of patients with HF without OSA. In conjunction with echocardiographic measures of LV stroke work, PET derived [11C]acetate kinetics will be used as a measure of oxidative metabolism, to determine the work metabolic index (WMI). [11C]HED retention will be used to measure cardiac SN pre-synaptic function.
HYPOTHESES
Primary Hypotheses:
In patients with chronic stable HF and OSA, 6-8 weeks' of CPAP demonstrates:
- beneficial effects on daytime myocardial metabolism leading to a reduction in the rate of oxidative metabolism as measured by [11C]acetate kinetics using PET imaging;
- improvement in energy transduction from oxidative metabolism to stroke work as measured by an increase in the daytime work-metabolic index.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Single (Investigator)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •systolic LV dysfunction (LVEF<40%; by echocardiography, radionuclide or contrast ventriculography)
- •symptoms of HF: NYHA Class II to III
- •stable condition with optimally tolerated medical therapy, unchanged for > 4 weeks
- •Obstructive sleep apnea (OSA) diagnosed on nocturnal polysomnogram with an apnea/hypopnea index (AHI) >15 events/hr and a predominantly obstructive pattern(more than 80% of events being obstructive in nature)OR
- •no OSA: defined as AHI<5 (control subjects) will be matched with the OSA group for gender, age + 5 years, ejection fraction (EF) +5%, drug therapy and etiology of HF (ischemic or non-ischemic)
- •willingness to receive CPAP therapy
- •informed consent
排除标准
- •unstable angina or recent myocardial infarction (MI) (<4 weeks prior)
- •severe valvular dysfunction
- •requirement for revascularization
- •a permanent pacemaker
- •atrial fibrillation
- •significant ventricular arrhythmia or sinus node dysfunction
- •life expectancy less than 1 year due to other co-morbidity
- •significant restrictive and obstructive lung disease
- •concomitant treatment or use of: tricyclic antidepressants, cocaine or drugs which may alter catecholamine uptake; or hypnotic, benzodiazepine, selective serotonin reuptake inhibitors(SSRI), neuroleptic, narcotic or other medications which may alter sleep or sleep-disordered breathing
- •central sleep apnea
- •other primary sleep disorder (i.e. periodic limb movement with arousal >5 events/hr, narcolepsy, rapid eye movement (REM) behaviour disorder)
- •requiring supplemental oxygen therapy at night
- •debilitating daytime somnolence (indicating clear-cut indication for CPAP therapy)
- •a previous cardiac transplant
- •a large transmural scar defined on previous perfusion imaging(severe resting perfusion defect (<50% uptake) occupying >25% of the LV)148-150
- •age < 18 years
- •pregnant or breast-feeding
研究组 & 干预措施
1
Heart Failure-OSA Group, randomized to early CPAP
干预措施: Positron Emission Tomography (Other)
2
Heart Failure-OSA Group, randomized to late CPAP
干预措施: Positron Emission Tomography (Other)
3
Heart Failure- no OSA, no CPAP therapy, observational group
干预措施: Positron Emission Tomography (Other)
结局指标
主要结局
Measurements of oxidative metabolism (11C clearance rate constant 'k') and WMI
时间窗: at 6-8 weeks
The differences in the measurements of oxidative metabolism (11C clearance rate constant 'k') and WMI will be analyzed using t-tests for the treatment groups
C-11 Hydroxyephedrine (HED) retention
时间窗: 6-8 weeks
C-11 HED retention will be a measure myocardial SN pre-synaptic function in treatment groups
次要结局
- Changes in other parameters including New York Heart Association (NYHA) class, HR, BP, LV volumes, stroke work-index, and QoL scores will also be analyzed. The subgroups of ischemic and non-ischemic etiology will be analyzed(at 6-8 weeks)
研究者
Rob Beanlands
Robert S Beanlands, MD, FRCPC, Chief of Cardiology
Ottawa Heart Institute Research Corporation