Obstructive sleep apnea (OSA), central sleep apnea (CSA) and heart failure (HF) are states of metabolic demand and sympathetic nervous system (SNS) activation. In patients with sleep apnea and HF, continuous positive airway pressure (CPAP) initially may reduce left ventricular (LV)stroke volume (SV) but subsequently improves and 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 long-term adaptive servo-ventilation (ASV) favorably affects cardiac energetics. Any such benefit may also relate to reduced sympathetic nervous system (SNS) activation. However its effect on myocardial SNS function is also not well studied.
In a pilot study we demonstrated early (6 week) beneficial effects of CPAP in patients with OSA and HF. The current proposal (AMEND) is a unique substudy of the recently funded ADVENT-HF trial (Adaptive Servo Ventilation for Therapy of Sleep Apnea in HeartFailure) (NCT01128816; CIHR; D. Bradley, PI).
We propose to evaluate the long-term (6 month) effects of ASV on daytime 1) oxidative metabolism; 2) the work metabolic index (WMI) as an estimate of mechanical efficiency; 3) myocardial sympathetic nerve (SN) pre-synaptic function; and 4) heart rate (HR) variability in patients with HF and coexisting OSA or CSA. In conjunction with echocardiographic measures of LV stroke work, positron emission tomography (PET) derived \[11C\] acetate kinetics will be used as a measure of oxidative metabolism, to determine the WMI. \[11C\] hydroxyephedrine (HED) retention will be used to measure cardiac SN pre-synaptic function.
Primary Hypotheses: In patients with chronic stable HF and CSA or OSA without excessive daytime sleepiness (EDS), long-term (6-month) ASV therapy yields:
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.
Eligibility
Sex
ALL
Min age
18 Years
Max age
—
Healthy volunteers
No
This study (AMEND) is a single centre substudy of the ADVENT-HF trial (NCT01128816). ADVENT-HF is a RCT that will test the effects of ASV on morbidity and mortality in patients with HF and OSA or CSA.
The AMEND substudy is a clinical physiologic proposal designed to determine the effects of long-term (6 months) ASV on cardiac energetics and SN function in patients with chronic stable HF and sleep apnea extending our previous evaluation of short-term CPAP in patients with OSA and HF
Inclusion Criteria:
1. American Heart Association (AHA) Stages B, C and D heart failure due to ischemic, idiopathic or hypertensive causes with;
2. systolic dysfunction, ejection fraction (EF) ≤45% by echocardiography
3. optimal medical therapy conforming to the AHA guidelines (and for this proposal, stable therapy for \>4 weeks)
4. sleep apnea with an Apnea/hypopnea Index ≥15, which will be divided into OSA (\> 50% events obstructive), or CSA (\> 50% of events central in nature)for patients with OSA, an Epworth Sleepiness Scale score of \>10 and no or mild daytime sleepiness (by the International Classification of Sleep Disorders
5. age \>18 years;
6. willingness to receive ASV therapy
7. informed consent
Exclusion Criteria:
1. Myocardial infarction, cardiac surgery or angioplasty within 3 months prior to enrollment,
2. listed for heart transplantation,
3. HF due to primary valvular heart disease,
4. pregnancy
5. current use of ASV or CPAP.
6. awaiting revascularization;
7. previous cardiac transplant;
8. life expectancy less than 6 months due to other co-morbidity;
9. a large transmural scar defined on previous perfusion imaging (severe resting perfusion defect (\<50% uptake) occupying \>25% of the LV);
10. concomitant treatment or use of: tricyclic antidepressants, cocaine or drugs which may alter catecholamine uptake.
For heart rate variability (HRV) analysis additional exclusions will include: a) a permanent pacemaker; b) atrial fibrillation; c) significant ventricular arrhythmia or sinus node dysfunction; patients may be excluded from HRV analysis and still be eligible for the sub-study
Primary outcome measure(s)
ASV therapy yields a reduction in the rate of oxidative metabolism as measured by [11C]acetate kinetics using PET imaging in patients with HF, OSA and/or CSA — 6 months
ASV therapy yields an improvement in energy transduction from oxidative metabolism to stroke work as measured by an increase in the daytime work-metabolic index inpatients with HF, OSA and/or CSA. — 6 months
Trial sites (1)
Facility
City
Region
Status
University of Ottawa Heart Institute
Ottawa
Ontario
More Ottawa Heart Institute Research Corporation trials in Canada
This page summarises publicly available registry data for informational purposes — not medical advice. Eligibility is determined by each study team; patients should discuss participation with their clinician.
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