Ignite Creation Date:
2024-05-06 @ 2:43 AM
Last Modification Date:
2024-10-26 @ 11:22 AM
Study NCT ID:
NCT02116140
Status:
ACTIVE_NOT_RECRUITING
Last Update Posted:
2023-11-29
First Post:
2014-04-14
Brief Title:
ASV Effects on Myocardial Energetics and Sympathetic Nerve Function in Heart Failure and Sleep Apnea
Sponsor:
Ottawa Heart Institute Research Corporation
Organization:
Ottawa Heart Institute Research Corporation
Study Overview
Official Title:
Effects of Long Term Adaptive Servo Ventilation Therapy on Myocardial Energetics and Sympathetic Nerve Function in Heart Failure and Sleep Apnea The AMEND Sub-study
Status:
ACTIVE_NOT_RECRUITING
Status Verified Date:
2023-11
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
AMEND
Brief Summary:
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 LVstroke 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 11Cacetate 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
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 11Cacetate 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
Detailed Description:
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 pressureCPAP 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 11Cacetate 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 11Chydroxyephedrine HED PET
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 pressureCPAP 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 11Cacetate 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 11Chydroxyephedrine HED PET
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| NA7158 | OTHER_GRANT | Heart Stroke Foundation | None |