Specialized Pacing for Patients With Congenital Heart Disease
| Status: | Not yet recruiting |
|---|---|
| Conditions: | Peripheral Vascular Disease, Cardiology, Cardiology, Cardiology |
| Therapuetic Areas: | Cardiology / Vascular Diseases |
| Healthy: | No |
| Age Range: | 14 - 65 |
| Updated: | 5/18/2018 |
| Start Date: | January 1, 2019 |
| End Date: | August 1, 2023 |
| Contact: | Jeremy P Moore, MD, MS |
| Email: | jpmoore@mednet.ucla.edu |
| Phone: | 310-267-7600 |
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.
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.
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.
The Specific Aims of this protocol are:
Primary Aim: To determine the performance of CLS for CHD patients after both transvenous and
epicardial pacemaker implantation
Hypothesis: CLS after either pacemaker implantation strategy will result in equivalent
improvements in autonomic control of chronotropic response as compared to standard sensor
based rate modulation
Primary outcome: Objective change in autonomic modulation of heart rate while randomized to
CLS pacing with mental stress and ANSAR testing
Secondary outcomes: Increase in aerobic capacity, non-sedentary behavior, and quality of life
while randomized to CLS pacing
This will be a single-blind (blinded subjects) randomized cross-over study, in which each
patient will receive treatment A (CLS-on or CLS-off) for 3 months followed by treatment B
(CLS-off or CLS-on).
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%
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.
6.0 Study Procedures
All patients enrolled in the study will undergo the following baseline assessment and data
collection:
- Demographics (age, gender, race/ethnicity)
- Review of data confirming the presence of sinus node dysfunction with chronotropic
incompetence (prior exercise stress test and/or Holter monitor results)
- Review of clinical history, including age at diagnosis, congenital diagnosis, surgical
history, and cardiac device implant procedure
- Antiarrhythmic drugs prescribed and the respective dosages
- Prior ECG and echocardiography and advanced imaging reports
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. During the
testing period, subjects will be tracked with the implanted device accelerometer to quantify
physical activity. At 3 months, all subjects will undergo testing as noted below.
- 24 hour Holter monitoring with spectral analysis
- Cycle-ergometer stress with cardiopulmonary gas exchange analysis
- Free form activities with cardiopulmonary gas exchange analysis (staircase walking,
sweeping, suitcase lifting with right and left arms, etc.)
- ANSAR testing (hand grip, Valsalva, deep breathing, and orthostatic challenge)
- Mental stress test with continuous electrocardiographic recording
- Quality of life questionnaire (SF-36/Somerville index)
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 as described above. At the conclusion
of the study, patients will be asked which pacing mode is preferred.
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.
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.
The Specific Aims of this protocol are:
Primary Aim: To determine the performance of CLS for CHD patients after both transvenous and
epicardial pacemaker implantation
Hypothesis: CLS after either pacemaker implantation strategy will result in equivalent
improvements in autonomic control of chronotropic response as compared to standard sensor
based rate modulation
Primary outcome: Objective change in autonomic modulation of heart rate while randomized to
CLS pacing with mental stress and ANSAR testing
Secondary outcomes: Increase in aerobic capacity, non-sedentary behavior, and quality of life
while randomized to CLS pacing
This will be a single-blind (blinded subjects) randomized cross-over study, in which each
patient will receive treatment A (CLS-on or CLS-off) for 3 months followed by treatment B
(CLS-off or CLS-on).
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%
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.
6.0 Study Procedures
All patients enrolled in the study will undergo the following baseline assessment and data
collection:
- Demographics (age, gender, race/ethnicity)
- Review of data confirming the presence of sinus node dysfunction with chronotropic
incompetence (prior exercise stress test and/or Holter monitor results)
- Review of clinical history, including age at diagnosis, congenital diagnosis, surgical
history, and cardiac device implant procedure
- Antiarrhythmic drugs prescribed and the respective dosages
- Prior ECG and echocardiography and advanced imaging reports
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. During the
testing period, subjects will be tracked with the implanted device accelerometer to quantify
physical activity. At 3 months, all subjects will undergo testing as noted below.
- 24 hour Holter monitoring with spectral analysis
- Cycle-ergometer stress with cardiopulmonary gas exchange analysis
- Free form activities with cardiopulmonary gas exchange analysis (staircase walking,
sweeping, suitcase lifting with right and left arms, etc.)
- ANSAR testing (hand grip, Valsalva, deep breathing, and orthostatic challenge)
- Mental stress test with continuous electrocardiographic recording
- Quality of life questionnaire (SF-36/Somerville index)
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 as described above. At the conclusion
of the study, patients will be asked which pacing mode is preferred.
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.
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%
We found this trial at
1
site
Los Angeles, California 90095
310-825-4321
Phone: 310-267-7600
University of California at Los Angeles The University of California, Los Angeles (UCLA) is an...
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