ASV Effects on Myocardial Energetics and Sympathetic Nerve Function in Heart Failure and Sleep Apnea.

DEFINITIONS Obstructive sleep apnea (OSA) is characterized by: episodes of partial or complete pharyngeal collapse leading to obstructive hypopnea and apnea during sleep. OSA often coexists with HF.

Central sleep apnea (CSA) is characterized by: reductions in central respiratory drive during sleep that leads to episodes of partial or complete cessation of airflow. CSA often co-exists with HF.

Continuous positive airway pressure(CPAP) delivers air through a nasal or oral interface to preserve upper airway patency. It is a treatment for symptomatic OSA or some patients with CSA.

Adaptive Servoventilation (ASV) is effective in alleviating OSA and CSA. It provides expiratory positive pressure to alleviate OSA, and inspiratory positive airway pressure to eliminate CSA.

Oxidative metabolism: utilization of substrates via the tricarboxylic acid cycle for Adenosine triphosphate (ATP) production; it is linked to myocardial oxygen consumption and can be measured with [11C]acetate PET.

The work-metabolic index (WMI) is the external work (minute-work) of the left ventricle corrected for the rate of oxidative metabolism and is an estimate of mechanical efficiency.

Myocardial sympathetic neuron (SN) presynaptic function is the measure of uptake and storage of neuronal catecholamines in the heart measured by [11C]hydroxyephedrine (HED) PET.

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

• American Heart Association (AHA) Stages B, C and D heart failure due to ischemic, idiopathic or hypertensive causes with;
• systolic dysfunction, ejection fraction (EF) ≤45% by echocardiography
• optimal medical therapy conforming to the AHA guidelines (and for this proposal, stable therapy for >4 weeks)
• 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
• age >18 years;
• willingness to receive ASV therapy
• informed consent

Exclusion criteria

• Myocardial infarction, cardiac surgery or angioplasty within 3 months prior to enrollment,
• listed for heart transplantation,
• HF due to primary valvular heart disease,
• pregnancy
• current use of ASV or CPAP.
• awaiting revascularization;
• previous cardiac transplant;
• life expectancy less than 6 months due to other co-morbidity;
• a large transmural scar defined on previous perfusion imaging (severe resting perfusion defect (<50% uptake) occupying >25% of the LV);
• 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