CPAP Therapy in Patients With Heart Failure and Obstructive Sleep Apnea. (PET-OSA)

This study has been completed.
Sponsor:
Collaborator:
Heart and Stroke Foundation of Ontario
Information provided by (Responsible Party):
Rob Beanlands, University of Ottawa Heart Institute
ClinicalTrials.gov Identifier:
NCT00756366
First received: September 18, 2008
Last updated: August 28, 2013
Last verified: August 2013
  Purpose

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.


Condition Intervention Phase
Heart Failure
Obstructive Sleep Apnea
Other: Positron Emission Tomography
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single Blind (Investigator)
Primary Purpose: Treatment
Official Title: Effects of Continuous Positive Airway Pressure Therapy on Myocardial Energetics and Sympathetic Nerve Function in Patients With Heart Failure and Obstructive Sleep Apnea.

Resource links provided by NLM:


Further study details as provided by University of Ottawa Heart Institute:

Primary Outcome Measures:
  • Measurements of oxidative metabolism (11C clearance rate constant 'k') and WMI [ Time Frame: at 6-8 weeks ] [ Designated as safety issue: No ]
    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 [ Time Frame: 6-8 weeks ] [ Designated as safety issue: No ]
    C-11 HED retention will be a measure myocardial SN pre-synaptic function in treatment groups


Secondary Outcome Measures:
  • 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 [ Time Frame: at 6-8 weeks ] [ Designated as safety issue: No ]

Enrollment: 67
Study Start Date: July 2005
Study Completion Date: December 2011
Primary Completion Date: June 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: 1
Heart Failure-OSA Group, randomized to early CPAP
Other: Positron Emission Tomography
PET imaging at baseline, 1 week and 6-8 weeks. CPAP begins after baseline PET scan.
Other Name: PET
Active Comparator: 2
Heart Failure-OSA Group, randomized to late CPAP
Other: Positron Emission Tomography
PET imaging at Baseline, 1 week and 6-8 weeks. CPAP begins after 6-8 week PET scan.
Other Name: PET
3
Heart Failure- no OSA, no CPAP therapy, observational group
Other: Positron Emission Tomography
PET scan at baseline and 6-8 weeks, no CPAP therapy
Other Name: PET

Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00756366

Locations
Canada, Ontario
University of Ottawa Heart Institute
Ottawa, Ontario, Canada, K1Y 4W7
Sponsors and Collaborators
University of Ottawa Heart Institute
Heart and Stroke Foundation of Ontario
Investigators
Principal Investigator: Rob S Beanlands, MD, FRCP C University of Ottawa Heart Institute
  More Information

No publications provided

Responsible Party: Rob Beanlands, Robert S Beanlands, MD, FRCPC, Chief of Cardiology, University of Ottawa Heart Institute
ClinicalTrials.gov Identifier: NCT00756366     History of Changes
Other Study ID Numbers: 2005982-01H, HSFO #NA5665, HSFO #T6426
Study First Received: September 18, 2008
Last Updated: August 28, 2013
Health Authority: Canada: Health Canada

Keywords provided by University of Ottawa Heart Institute:
positron emission tomography
myocardial energetics
sympathetic nerve function

Additional relevant MeSH terms:
Apnea
Heart Failure
Sleep Apnea Syndromes
Sleep Apnea, Obstructive
Respiration Disorders
Respiratory Tract Diseases
Signs and Symptoms, Respiratory
Signs and Symptoms
Heart Diseases
Cardiovascular Diseases
Sleep Disorders, Intrinsic
Dyssomnias
Sleep Disorders
Nervous System Diseases

ClinicalTrials.gov processed this record on September 14, 2014