PET-OSAEffects of Continuous Positive Airway Pressure Therapy on Myocardial Energetics and Sympathetic Nerve Function in Patients With Heart Failure and Obstructive Sleep Apnea.
Positron Emission Tomography
Apnea+10
+ Cardiovascular Diseases
+ Heart Diseases
Treatment Study
Summary
Study start date: July 1, 2005
Actual date on which the first participant was enrolled.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: 1. 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; 2. improvement in energy transduction from oxidative metabolism to stroke work as measured by an increase in the daytime work-metabolic index. Secondary Hypotheses: In patients with chronic stable heart failure and OSA, 1. CPAP leads to an early (1 week'') reduction in daytime oxidative metabolism that precedes the improvement in work-metabolic index, indicating an early energy sparing effect; 2. CPAP leads to i) an increase in daytime myocardial SN pre-synaptic function as measured by increased \[11C\]HED retention on PET imaging, and ii) a parallel decrease in sympathetic and increase in vagal modulation of sino-atrial discharge (i.e. heart rate (HR) variability) 3. there is impaired daytime myocardial oxidative metabolism, work-metabolic index, and myocardial sympathetic nerve function compared to patients with heart failure without OSA. 'original protocol indicated 1 month follow up but was changed to 6-8 weeks in order to accommodate patient logistics and imaging centre scheduling. ''Logistics did not permit all patients to complete 1 week scan.
Protocol
This section provides details of the study plan, including how the study is designed and what the study is measuring.67 patients to be enrolled
Total number of participants that the clinical trial aims to recruit.Treatment Study
Eligibility
Researchers look for people who fit a certain description, called eligibility criteria: person's general health condition or prior treatments.Any sex
Biological sex of participants that are eligible to enroll.Over 18 Years
Range of ages for which participants are eligible to join.Healthy volunteers not allowed
If individuals who are healthy and do not have the condition being studied can participate.Conditions
Pathology
Criteria
Inclusion Criteria: * 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 Exclusion Criteria: * 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
Study Plan
Find out more about all the medication administered in this study, their detailed description and what they involve.3 intervention groups are designated in this study
This study does not include a placebo group
Treatment Groups
Group I
Active ComparatorGroup II
Active ComparatorGroup III
Study Objectives
Primary Objectives
Secondary Objectives
Study Centers
These are the hospitals, clinics, or research facilities where the trial is being conducted. You can find the location closest to you and its status.This study has 1 location