ASV Therapy for Heart Failure and Sleep Apnea

(AMEND Trial)

Overseen By Olga Walter

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Ottawa Heart Institute Research Corporation

Must not be taking: Tricyclics, Cocaine, others

Disqualifiers: Recent MI, Pregnancy, Heart transplant, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines how adaptive servo-ventilation (ASV) can assist individuals with both heart failure and sleep apnea, a disorder where breathing repeatedly stops and starts during sleep. Researchers aim to determine if using ASV for six months can enhance heart function and energy use during the day. The trial suits those with chronic heart failure and sleep apnea who do not experience excessive daytime sleepiness. Participants should already be on stable heart failure treatment and willing to try ASV therapy. As an unphased trial, this study provides a unique opportunity to explore a promising treatment option for improving quality of life.

Will I have to stop taking my current medications?

The trial requires participants to be on stable medical therapy for more than 4 weeks, according to AHA guidelines, so you should not stop your current medications if they meet these criteria.

What prior data suggests that adaptive servo-ventilation (ASV) is safe for patients with heart failure and sleep apnea?

Research shows that short-term use of a CPAP machine can enhance heart function by increasing a substance that indicates improved heart nerve function. However, it does not appear to affect the heart's overall energy use.

Studies have also confirmed that a special imaging test called a [11C] acetate PET scan is safe and provides useful information about heart energy use.

Overall, these findings suggest that using [11C] acetate and HED PET scans in trials is safe and offers valuable insights. Major negative side effects from these scans have not been reported. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about ASV therapy for heart failure and sleep apnea because it targets both conditions simultaneously, which is not something standard treatments typically do. Unlike conventional treatments that might focus solely on heart failure with medications like ACE inhibitors or beta-blockers, ASV therapy uses adaptive servo-ventilation to improve breathing patterns during sleep, directly addressing sleep apnea. This dual approach has the potential to improve cardiac function by enhancing sleep quality, thereby tackling a root cause of heart failure symptoms in these patients. This integrated treatment strategy is what sets ASV therapy apart and holds promise for better overall patient outcomes.

What evidence suggests that ASV therapy is effective for heart failure and sleep apnea?

Research suggests that adaptive servo-ventilation (ASV) might aid people with heart failure and sleep apnea by enhancing heart function. Early studies have shown that ASV can improve heart efficiency and reduce stress by regulating breathing patterns. Although short-term use of continuous positive airway pressure (CPAP) improved nerve function in the heart, it did not significantly affect overall heart energy use. This trial continues to investigate the long-term effects of ASV on heart function. Participants will undergo Carbon-11 acetate PET imaging to assess heart oxygen use, which may clarify the benefits of ASV. Overall, ASV appears promising for improving heart health in these patients. ^{1 5 6 7 8}

Who Is on the Research Team?

Rob S Beanlands, MD

Principal Investigator

Ottawa Heart Institute Research Corporation

Are You a Good Fit for This Trial?

This trial is for adults over 18 with heart failure due to ischemic, idiopathic or hypertensive causes and an ejection fraction ≤45%. Participants must have sleep apnea with an Apnea/hypopnea Index ≥15 and be on stable medical therapy. Exclusions include those listed for heart transplant, life expectancy under 6 months, pregnancy, current ASV or CPAP use, awaiting revascularization, recent cardiac events or certain drug uses.

Inclusion Criteria

My heart failure is due to blockage, unknown causes, or high blood pressure with an EF of 45% or less.

I am older than 18 years.

Informed consent

Exclusion Criteria

I have not had a heart attack or any heart surgery in the last 3 months.

My heart has a large scar affecting more than 25% of its left side.

You have another health problem that is likely to make you live for less than six months.

What Are the Treatments Tested in This Trial?

Interventions

• [C11]Acetate and HED PET

Trial Overview The study tests the long-term effects of adaptive servo-ventilation (ASV) on myocardial metabolism and sympathetic nerve function in patients with heart failure who also have obstructive (OSA) or central sleep apnea (CSA). It will measure changes in oxidative metabolism using PET imaging and work-metabolic index improvements after six months of ASV therapy.

How Is the Trial Designed?

Group I: [C11]Acetate HED PET Experimental Treatment 1 Intervention

AMEND is a single centre substudy of the ADVENT-HF trial. This 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. All subjects consenting to the ADVENT primary trial will be eligible to participate in the substudy. Substudy consenting patients will have \[11C\]acetate and \[11C\]HED PET imaging; HR variability; plasma norepinephrine (NE) levels, urine normetanephrine levels within 2 weeks of the sleep study. Baseline measurements will be repeated after 6 months in all patients.

Who Is Running the Clinical Trial?

Ottawa Heart Institute Research Corporation

Lead Sponsor

Trials

200

Recruited

95,800+

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/24993098/

Effects of Short-Term Continuous Positive Airway Pressure ... Short-term CPAP increased hydroxyephedrine retention, indicating improved myocardial sympathetic nerve function, but overall did not affect energetics.

2. clinicaltrials.gov clinicaltrials.gov/study/NCT02116140

Study Details | NCT02116140 | ASV Effects on Myocardial ... This 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 ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6660491/

Early therapeutic effects of adaptive servo-ventilation on ... Adaptive servo-ventilation (ASV), a novel respiratory support therapy for sleep disorders, may improve cardiac function in heart failure (HF).

4. patlynk.com patlynk.com/es/trial/NCT00756366

PET-OSA | CPAP Therapy in Patients With Heart Failure ... 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 ...

5. researchgate.net researchgate.net/publication/293047094_C-11-Meta-Hydroxyephedrine_A_Promising_PET_Radiopharmaceutical_for_Imaging_the_Sympathetic_Nervous_System

C-11-Meta-Hydroxyephedrine A Promising PET ... One of the recent studies suggested that 11 C-HED parameter can identify the beneficial impact of continuous positive airway pressure (CPAP) ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT03924102

Cardiac Perfusion and Metabolism With [11C] Acetate PET ... The purpose of this sub-study is to use positron emission tomography and computed tomography imaging (PET/CT) with an investigational drug called [11C] acetate ...

7. mdpi.com mdpi.com/1422-0067/25/10/5251

Sleep Apnea and Heart Failure—Current State-of-The-Art This review aims to comprehensively analyze the pathophysiological links and risk factors between sleep-disordered breathing and heart failure.

8. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7854759/

11C-acetate PET: a powerful tool to analyze metabolic and ... While metabolic analyses of heart failure are complex, they yield unique and useful data. 11C-acetate PET is a valuable and underutilized technique for ...