Specialized Pacing for Patients With Congenital Heart Disease

December 22, 2022 updated by: Jeremy P. Moore, MD, University of California, Los Angeles

A Randomized Trial of Closed Loop Stimulation After Epicardial Pacemaker Implantation for Congenital Heart Disease

The closed-loop stimulation (CLS) algorithm is a novel sensor-based technology that relies on the change in myocardial systolic impedance for modulation of the heart rate during physical and emotional stress.3 The pacing algorithm has been shown to be highly effective for a wide range of clinical scenarios. Despite the fact that congenital heart disease (CHD) patients are likely to derive significant benefit in terms of functional ability and aerobic capacity using this novel technology, the CLS system has not been adequately studied in this population. As many CHD patients also undergo epicardial placement of pacing systems at the time of concomitant cardiac surgery, CLS has been less often utilized in this population given almost no data in the setting of surgical electrode placement. The present study intends to examine the benefits of the CLS algorithm in the CHD population, employing the use of epicardial pacemaker systems in the study protocol.

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

Detailed Description

Sinus node dysfunction is highly prevalent among patients with congenital heart disease, manifesting as resting bradycardia or chronotropic incompetence. As children and adults with congenital heart disease are now expected to have increasing life-expectancy; with well over 1 million adult patients currently living in North America,1 issues such as mental health, acquired comorbidities and their impact on overall cardiovascular health have assumed increased scrutiny.

It is now understood that objective measures of aerobic capacity, such as peak VO2, peak VE/VCO2, and heart rate reserve predict all-cause mortality for adult patients with congenital heart disease. As the chronotropic response during exercise is a key determinant of aerobic capacity, improvement in sensor-based technology for heart rate support is expected to have a significant impact on functional capacity and longevity in this population. Some forms of congenital heart disease, such as single ventricle physiology after the Fontan population are especially likely to benefit, as cardiac output is determined almost exclusively by heart rate during exertion due to limited ability to augment cardiac stroke volume.2

It is also becoming increasingly clear that sedentary behaviors are highly relevant to overall cardiovascular health in the general adult population. Adult patients with congenital heart disease are at especially high risk for sedentary behavior as a result of 1) chronic restriction for physical activities based on ill-founded medical advice, 2) chronotropic incompetence resulting from prior surgical palliations and hemodynamic stressors, and 3) overestimation of physical activity.

5.0 Enrollment/Randomization

Patient Enrollment: The treating physician will identify potential subjects with a previously implanted pacemaker and present a brief overview of the study; if the subject is interested, the study will be described in detail. Informed consent will be obtained by the investigator after discussing the study, including the voluntary nature of participation and notification the subject can withdraw at any time. Ample time for questions and answers will be allowed. The investigator will give the subject and his/her legal guardian the opportunity to take the consent home to think about it more, with the option to call or meet with the investigator to ask additional questions. If the subject and/or his/her parent/legal guardian agree to participate, the investigator will ask them to sign a written, informed consent and assent. A copy of the assent and consent will be given to the subject and/or his/her parent/legal guardian.

Randomization Procedure: This will be a single-blind placebo-controlled randomized crossover study with 2 treatments: CLS-on versus CLS-off (accelerometer only). Each enrolled patient will receive both treatments for 3 months. The order of treatments will be randomized 1:1.

Randomization

There will be a 50:50 randomization, with half the subjects randomized to CLS-on then CLS-off, and half randomized to CLS-off then CLS-on.

Subjects previously receiving rate-responsive pacing with CLS that are randomly selected to CLS-on will continue with the identical programmed parameters. For subjects not previously receiving rate-responsive pacing with CLS that are randomly selected to CLS-on nominal programming will be utilized with a base rate of 60 beats per minute.

Subjects will then initiate treatment A (CLS-on or CLS-off) in a blinded fashion. At 3 months, subjects will undergo testing.

After 3 months of treatment A, subjects will be reprogrammed to treatment B. Tracking of physical activity with the device accelerometer will continue during this period. After 3 months of treatment B, repeat testing will be repeated.

Patients will be followed during both treatment phases per usual clinical routine. Patients who experience significant symptoms (extreme fatigue, debilitating palpitations, or other clinically relevant symptoms) will be evaluated by their treating physician. Subjects that have any adverse events during treatment A will discontinue treatment A and immediately crossover to treatment B. Subjects with events during treatment B will be removed from the study and unblinded. Further treatment will be determined by the treating physician.

Study Type

Interventional

Enrollment (Actual)

4

Phase

  • Phase 2
  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • California
      • Los Angeles, California, United States, 90095
        • University of California at Los Angeles

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

14 years to 65 years (Child, Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Congenital heart disease

    • Simple, moderate, or complex congenital heart disease

  • Adolescent or adult age group (age >14 and <65 years)

  • Significant sinus node dysfunction

    • Atrial pacing percentage >70%11
    • Intrinsic dysfunction resulting from congenital lesion or cardiac surgery
    • Secondary sinus node dysfunction due to antiarrhythmic drug therapy
  • Existing, fully functional pacemaker or ICD with CLS capability
  • Epicardial or transvenous route of pacemaker implantation

Exclusion Criteria:

  • Unable to complete cardiopulmonary exercise testing (CPET)
  • Contraindication to CPET
  • Decreased mental capacity or known psychiatric disorder
  • Congestive heart failure, NYHA cass IV
  • Total atrial tachyarrhythmia burden >20%

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Crossover Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: CLS-On
Subjects in this arm will be programmed to CLS-on to received closed loop stimulation-based pacing for 3 months, followed by a standard rate response for 3 months.
Device: Closed loop stimulation
Closed loop stimulation is a physiologic, rate-adaptive pacing algorithm.
Device: Standard rate response
Standard rate response is an algorithm to increase heartrate based on movement
Active Comparator: CLS-Off
Subjects in this arm, will be placed in a standard rate response for 3 months, followed by CLS-on to received closed loop stimulation-based pacing for 3 months.
Device: Closed loop stimulation
Closed loop stimulation is a physiologic, rate-adaptive pacing algorithm.
Device: Standard rate response
Standard rate response is an algorithm to increase heartrate based on movement

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of Participants With Blunted or Unchanged Effect of Mental Stress on Heart Rate
Time Frame: 3 months after the start of each intervention, a total of 6 months
Heart rate in response to mental stress during each intervention; a math test was performed during autonomic testing
3 months after the start of each intervention, a total of 6 months
Heart Rate Response During a 48-hour Assessment Period
Time Frame: 3 months after the start of each intervention, a total of 6 months
Average heart rate as measured by Holter monitor for 48 hours during each intervention
3 months after the start of each intervention, a total of 6 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Average Oxygen Consumption During Each Intervention
Time Frame: 3 months after the start of each intervention, a total of 6 months

Oxygen uptake as determined by cardiopulmonary gas exchange during a stress test under 4 conditions:

Sitting/standing 60 seconds Kettlebell walking 110 seconds Stairs 176 seconds Sweeping 62 seconds
3 months after the start of each intervention, a total of 6 months
Quality of Life as Assessed by SF-36
Time Frame: 3 months after the start of each intervention, a total of 6 months
Quality of life as assessed by SF-36 questionnaire following each period of intervetion. SF- 36 investigates the standard of quality of life through a general health assessment and not specific to a particular disease, age or treatment group. It is a 36-item questionnaire measuring 8 domains [physical functioning, role limitations due to physical health (role physical), bodily pain, general health, energy, social functioning, role limitations due to emotional health (role emotional), and emotional wellbeing]. Each domain score ranges from 0 (worst) to 100 (best), with higher scores reflecting better health-related functional status.
3 months after the start of each intervention, a total of 6 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of California, Los Angeles

Collaborators

Biotronik, Inc.

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

May 9, 2021

Primary Completion (Actual)

November 3, 2021

Study Completion (Actual)

November 3, 2021

Study Registration Dates

First Submitted

November 28, 2017

First Submitted That Met QC Criteria

November 28, 2017

First Posted (Actual)

December 4, 2017

Study Record Updates

Last Update Posted (Actual)

January 20, 2023

Last Update Submitted That Met QC Criteria

December 22, 2022

Last Verified

December 1, 2022

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 17-000932

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

Yes

product manufactured in and exported from the U.S.

No

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.

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