- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03768804
SyncAV Study: Investigation of the Efficacy of the SyncAV Fusion Pacing Algorithm on Exercise
Assessing the Effect of the SyncAV Algorithm in Cardiac Resynchronization Therapy on Exercise Capacity and QRS Duration on Exercise
In patients with weak pumping function of the heart, uncoordinated contraction of the chambers can be corrected using a cardiac resynchronization therapy ("CRT") pacemaker. These devices make patients live longer by improving how the heart pumps and reducing symptoms such as breathlessness. However, not all patients benefit from CRT and programming devices optimally can greatly influence success. Predicting the correct timings of contraction between the atria (top chambers of the heart) and the ventricles (bottom chambers), as well as between the left and right ventricles, especially when heart rate increases during exercises, is challenging.
A new approach to optimizing CRT programming has been proposed known as 'fusion-pacing'. This allows the electrical wave from the heart's own conduction system to merge or fuse with the impulse from the pacemaker in the left ventricle. The timing of the pacemaker's impulse is continuously adjusted to measurements the device makes of the hearts natural conduction. What is not clear is how effective 'fusion-pacing' is during exercise when the hearts natural conduction changes rapidly and unpredictably. We plan to investigate this by monitoring the electrocardiogram ("ECG") whilst accurately measuring exercise performance and ability during a cardiopulmonary exercise test ("CPET") on an exercise bike. We will also ask participants to rate their perceived exercise intensity to see whether fusion pacing improves ECG resynchronization, exercise performance, and patients' symptoms compared to standard programming.
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
Heart failure represents a significant health problem, with the last national heart failure audit demonstrating prevalence in the United Kingdom of 900,000 patients, accounting for 5% of all acute hospital admissions. This is expected to increase with an ageing population. Despite improvements in medical therapy, prognosis remains poor, with an in- hospital mortality of 9.6%, and an estimated mortality of 30-40% at 1 year after diagnosis.
Multiple randomised controlled trials have demonstrated that cardiac resynchronization therapy pacemaker devices ("CRT") are an effective therapy for patients with poor pumping function and altered electrical conduction of the heart (left bundle branch block, "LBBB"), improving both morbidity and mortality. However, only 60-70% of patients notice a symptomatic improvement with CRT and even in patients who do respond, response can often be improved further by optimising how the device is programmed.
CRT devices improve coordination of heart pumping by pacing both ventricles of the heart. A key function of this is to coordinate the timing of contraction of the the atria and the ventricles (atrio-ventricular, or "AV", optimisation). This allows maximal filling of the left ventricle with blood. More recently, it has become important not only in standard bi-ventricular ("BiV") pacing, but to allow left ventricular pacing to be timed with intrinsic conduction to the right ventricle to provide CRT (so called 'fusion' pacing).
Multiple methods have been described to assess AV optimisation, including echocardiographic measurements. However, echo based methods are labour intensive, and their value is uncertain. Device algorithms utilising analysis of the intra-cardiac electrogram ("IEGM") have become an attractive alternative due to their rapid and automated nature, although evidence suggests that they may not have clinical benefit over using fixed AV delays. In addition, intrinsic AV conduction is known to alter with exercise, normally becoming shorter. Optimisation of AV delays in CRT on exercise has been shown to improve cardiac output. Device algorithms can therefore allow dynamic adjustment of AV delays as they change with exercise and heart rate (rate-adaptive AV delay or "RAAVD"). Indeed, use of individually tailored RAAVD in CRT patients has demonstrated an increase in exercise capacity.
Patients with heart failure and LBBB often have normal intrinsic right ventricular activation through the right bundle. Utilization of timed left ventricular ("LV") pacing to merge (or fuse) with this intrinsic conduction may confer benefits over standard BiV pacing, but requires relatively normal intrinsic AV conduction as well as correct timing of LV pacing to right ventricular ("RV") activation. Algorithms now exist which allow dynamic reassessment of intrinsic conduction and so adjustment of the optimal AV delay. They can therefore compensate for changes in the intrinsic AV delay on exercising, and so maintain adequate fusion pacing and CRT optimisation. One such software algorithm is SyncAV, developed by Abbott (Abbott Vascular, 3200 Lakeside Drive, Santa Clara, California 95054-2807). SyncAVTM assesses intrinsic AV conduction every 256 beats. It then sets a shorter programmed AV delay by subtracting a set period (known as the "delta" - adjustable but nominally set to 50ms) from the intrinsic time.
There is some evidence that fusion pacing gives benefit in terms of both acute pumping function of the heart and long term response to CRT. However, what remains unclear is whether the effect of dynamic AV optimisation and fusion pacing is maintained on exercise. Firstly, the re-analysis and adjustment intervals may be insufficient to allow effective fusion throughout exercise. It is therefore possible that with rapidly changing heart rates this coordinated timing is lost, leading to inefficient conduction of electricity through the heart. This could result in large periods of time on exercising without effective CRT and so poor exercise tolerance. Secondly, there is evidence that in patients with heart failure AV intervals do not alter with change in heart rate in a similar way to healthy controls. One study found that the degree of change is greater on exercise, whilst one demonstrated that in a CRT population only a third of patients had shorter optimal AV delay intervals on exercise, with a third being unchanged and a third longer. The use of a fixed "delta" in SyncAVTM may therefore result in incorrect adjustment of AV intervals as intrinsic conduction changes, with the effectiveness of SyncAV therefore depending on how the intrinsic interval changes.
We will use a prospective single-centre randomized single-blind crossover study to investigate the effectiveness of SyncAV on exercise, by randomising participants to either use of SyncAV or fixed AV delays, and then carrying out cardiopulmonary exercise testing ("CPET").
Study Type
Enrollment (Anticipated)
Phase
- Not Applicable
Contacts and Locations
Study Locations
-
-
Oxfordshire
-
Oxford, Oxfordshire, United Kingdom, OX1 3PT
- Department of Physiology, Anatomy and Genetics, University of Oxford
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Age ≥18 and able to give informed consent.
- Patients with existing cardiac resynchronization therapy ("CRT") devices able to utilise the SyncAV algorithm, implanted ≥6 months and under follow up at Oxford University Hospitals National Health Service ("NHS") Foundation Trust.
- Evidence of response to CRT, defined as functional improvement or left ventricular ("LV") remodelling on imaging.
- Sinus rhythm and PR interval <250ms.
- Able to exercise to perform cardiopulmonary exercise testing ("CPET").
Exclusion Criteria:
- Pregnancy or breast feeding.
- Atrial fibrillation or atrial tachycardia.
- Underlying 2nd or 3rd degree heart block.
- PR interval ≥250ms.
- Chronotropic incompetence, defined as use of rate-response algorithm or ≥80% atrial pacing.
- Any concurrent condition contraindicating use of CPET.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Crossover Assignment
- Masking: Triple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Other: SyncAV algorithm on
Device randomised to have SyncAV on, with delta programmed to the value which gives the narrowest QRS duration at rest and pseudo left ventricular ("LV") only pacing
|
Cardiac Resynchronisation Device will be set to have the SyncAV algorithm on for the duration of the cardiopulmonary exercise test ("CPET"), before being reset to pre-existing settings
|
Other: SyncAV algorithm off
Device randomised to have SyncAV off, with a fixed sensed atrioventricular ("AV") delay of 120ms or shorter if necessary to prevent fusion, and biventricular ("BiV") pacing
|
ardiac Resynchronisation Device will be set to have the SyncAV algorithm off and a fixed AV delay, for the duration of the CPET, before being reset to pre-existing settings
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Exercise capacity
Time Frame: 1 Year
|
Exercise capacity as measured by cardiopulmonary exercise testing ("CPET") including blood sampling
|
1 Year
|
BORG-RPE rating
Time Frame: 1 Year
|
Borg rating of perceived exertion ("Borg-RPE") during CPET
|
1 Year
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
QRS duration
Time Frame: 1 Year
|
QRS duration during exercise, compared to at rest
|
1 Year
|
Exercise duration
Time Frame: 1 Year
|
Exercise duration as measured by cardiopulmonary exercise testing ("CPET")
|
1 Year
|
PR duration
Time Frame: 1 Year
|
Intrinsic PR duration during exercise when fusion pacing is on
|
1 Year
|
Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Neil Herring, BMBCh MRCP, University of Oxford
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Anticipated)
Study Completion (Anticipated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- 13808
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
IPD Plan Description
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
product manufactured in and exported from the U.S.
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Heart Failure, Systolic
-
Central Hospital, Nancy, FranceUnknown
-
Zensun Sci. & Tech. Co., Ltd.Active, not recruitingChronic Systolic Heart FailureChina
-
Zensun Sci. & Tech. Co., Ltd.TerminatedChronic Systolic Heart FailureChina
-
Hospital Moinhos de VentoTakedaUnknownHeart Failure, Systolic | Systolic Heart Failure | Cardiac FailureBrazil
-
Jiangsu HengRui Medicine Co., Ltd.UnknownChronic Systolic Heart FailureChina
-
Merck KGaA, Darmstadt, GermanyMerck Ltd.Completed
-
University of NebraskaEli Lilly and Company; Daiichi Sankyo, Inc.Completed
-
Abbott Medical DevicesCompletedSystolic Heart FailureAustralia, Hong Kong, Japan
-
University of CincinnatiCompletedSystolic Heart FailureUnited States
-
GlaxoSmithKlineCompletedHeart Failure, CongestiveKorea, Republic of
Clinical Trials on SyncAV algorithm on
-
Antonio RapacciuoloNot yet recruiting
-
Abbott Medical DevicesActive, not recruitingCongestive Heart FailureSpain, United States, Canada, Belgium, China, Korea, Republic of, Taiwan, Sweden, Japan, France, United Kingdom, Saudi Arabia, Germany, India, Portugal, Austria, Italy, Finland, Hong Kong, Netherlands, Poland, Puerto Rico, Russian Federation and more
-
Kıvanç AkçaHacettepe UniversityCompleted
-
Abbott Medical DevicesAbbottCompletedHeart Failure | Left Bundle-Branch BlockUnited Kingdom, France, Italy, Canada
-
Keimyung University Dongsan Medical CenterBiotronik SE & Co. KGCompletedHeart Failure | Sick Sinus Syndrome | PacemakerKorea, Republic of
-
Medtronic Bakken Research CenterMedtronicTerminatedHeart Failure | Atrial Fibrillation | Sudden Cardiac DeathGermany
-
Sun Yat-sen UniversityActive, not recruiting
-
Seoul National University HospitalNot yet recruitingLeft Ventricular Systolic Dysfunction
-
Stanford UniversityUniversity of Colorado, DenverCompletedType 1 Diabetes MellitusUnited States
-
University of ArizonaUnknown