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SyncAV Study: Investigation of the Efficacy of the SyncAV Fusion Pacing Algorithm on Exercise

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03768804
Recruitment Status : Enrolling by invitation
First Posted : December 7, 2018
Last Update Posted : April 2, 2020
Sponsor:
Information provided by (Responsible Party):
University of Oxford

Tracking Information
First Submitted Date  ICMJE December 3, 2018
First Posted Date  ICMJE December 7, 2018
Last Update Posted Date April 2, 2020
Actual Study Start Date  ICMJE May 31, 2019
Estimated Primary Completion Date December 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: April 16, 2019)
  • Exercise capacity [ Time Frame: 1 Year ]
    Exercise capacity as measured by cardiopulmonary exercise testing ("CPET") including blood sampling
  • BORG-RPE rating [ Time Frame: 1 Year ]
    Borg rating of perceived exertion ("Borg-RPE") during CPET
Original Primary Outcome Measures  ICMJE
 (submitted: December 6, 2018)
  • Exercise capacity [ Time Frame: 1 Year ]
    Exercise capacity as measured by cardiopulmonary exercise testing (CPET) including blood sampling
  • BORG-RPE rating [ Time Frame: 1 Year ]
    Borg rating of perceived exertion (Borg-RPE) during CPET
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: April 16, 2019)
  • QRS duration [ Time Frame: 1 Year ]
    QRS duration during exercise, compared to at rest
  • Exercise duration [ Time Frame: 1 Year ]
    Exercise duration as measured by cardiopulmonary exercise testing ("CPET")
  • PR duration [ Time Frame: 1 Year ]
    Intrinsic PR duration during exercise when fusion pacing is on
Original Secondary Outcome Measures  ICMJE
 (submitted: December 6, 2018)
  • QRS duration [ Time Frame: 1 Year ]
    QRS duration during exercise, compared to at rest
  • Exercise duration [ Time Frame: 1 Year ]
    Exercise duration as measured by CPET
  • PR duration [ Time Frame: 1 Year ]
    Intrinsic PR duration during exercise when fusion pacing is on
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE SyncAV Study: Investigation of the Efficacy of the SyncAV Fusion Pacing Algorithm on Exercise
Official Title  ICMJE Assessing the Effect of the SyncAV Algorithm in Cardiac Resynchronization Therapy on Exercise Capacity and QRS Duration on Exercise
Brief Summary

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.

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  ICMJE Interventional
Study Phase  ICMJE Not Applicable
Study Design  ICMJE Allocation: Randomized
Intervention Model: Crossover Assignment
Intervention Model Description:
Double blind, randomised crossover study
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Heart Failure, Systolic
Intervention  ICMJE
  • Other: SyncAV algorithm on
    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
    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
Study Arms  ICMJE
  • 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
    Intervention: Other: SyncAV algorithm on
  • 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
    Intervention: Other: SyncAV algorithm off
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Enrolling by invitation
Estimated Enrollment  ICMJE
 (submitted: December 6, 2018)
22
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE December 2020
Estimated Primary Completion Date December 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United Kingdom
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03768804
Other Study ID Numbers  ICMJE 13808
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Plan Description: No IPD to be shared
Responsible Party University of Oxford
Study Sponsor  ICMJE University of Oxford
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Neil Herring, BMBCh MRCP University of Oxford
PRS Account University of Oxford
Verification Date April 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP