Evaluating Myocardial Injury for Defibrillation Threshold Testing Methods for ICD Implantation

Study Overview
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Brief Summary
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The objective of this study is to evaluate myocardial injury, if any, as quantified by cardiac markers (Troponin-T) in defibrillation threshold (DFT) testing during implantation of implantable cardioverter defibrillators (ICDs) using the upper limit of vulnerability (ULV) method vs. standard defibrillation threshold method.

Detailed Description
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This is a prospective, randomized (1:1 DFT vs ULV testing), controlled clinical research trial. Patients undergoing ICD implant or device change out will be candidates for this study. Medical records for these patients will be screened prior to enrollment to ensure eligibility for the study. Each patient who is a candidate and who agrees to participate in the study will undergo the standard of care pre-procedure evaluation including a complete medical history evaluation, a complete physical examination and routine laboratory testing including chemistry panel, hematology panel, coagulation panel, a 12-lead electrocardiogram, and a urine pregnancy test (all females of child-bearing age). A candidate patient will be randomly assigned to either the standard DFT testing method group or the ULV testing method group. For the standard DFT testing group, per routine standard of care, the patient will be admitted to the hospital. The study requires a pre-procedure blood test of 3 ml for Troponin-T (TnT) which will be drawn prior to any DFT testing. The blood sample will be sent to the University of California, San Diego (UCSD) central laboratory for processing. The patient will then undergo the scheduled ICD implant procedure in a standard fashion. The standard defibrillation threshold testing will be performed using a low energy shock delivered on T-wave to induce ventricular fibrillation (VF). If VF is induced, the first shock is 25 Joules (J). If success, we will wait 5 minutes and repeat the process. If the 2nd shock yields success, the DFT testing is complete and a 10J safety margin achieved (device shock energy is set at 35J or as clinically indicated determined by treating Cardiac Electrophysiologist). A back-up external defibrillator will always be immediately available in case transvenous shocks fail. Blood pressure will be monitored before and immediately after each shock. After 4 hours, 8 hours and 16 hours post DFT testing, blood samples (3 ml for Troponin-T) will be drawn and sent to the UCSD central laboratory for processing. For the ULV testing group, per routine standard of care, the patient will be admitted to the hospital. The study requires a pre-procedure blood test (3 ml for Troponin-T.) which will be drawn prior to any ULV testing. The blood sample will be sent to the UCSD central laboratory for processing. The patient will then undergo the scheduled ICD implant procedure as is standard clinical care. The ULV testing is performed as follows: for single coil device, a 18J shock will be delivered at 0msec, +20 msec, -20msec and -40msec measured from the peak of the T-wave; for dual coil device, a 18J shock will be delivered at 0msec, -20msec, +20msec, and +40msec measured from the peak of the T-wave. If VF is not induced with any of the above mentioned shocks, the ULV will be considered as 18J and the ICD will be implanted with the first shock strength set at 30 joules or as clinically indicated determined by treating Cardiac Electrophysiologist. If VF is induced, a 25J rescue shock will be delivered as is standard and if successful, the device will be programmed to the maximum output of 35 joules or as clinically indicated determined by treating Cardiac Electrophysiologist. Blood pressure will be monitored before and immediately after each shock. After 4 hours, 8 hours and 16 hours post ULV testing, blood samples (3 ml for Troponin-T) will be drawn and sent to the UCSD central laboratory for processing. Other than the blood tests for Troponin-T, there is no change in routine post-operative management. Patients will be followed every three months, as is standard management for patients with ICDs. The TnT blood draws at 4-hour, 8-hour and 16-hour post implantation will not require longer hospital stay than is standard for patients undergoing ICD implantation. The results of Troponin-T measurement for the study patients will be reviewed by the cardiac electrophysiology (EP) research staff. If myocardial injury is noted (any TnT value >0.1 as per current assay at the UCSD laboratory), the patient will be monitored as is deemed clinically necessary by treating Cardiac Electrophysiologist, including possible repeat TnT measurements for evaluation of myocardial infarction. We will follow standard of care for management of myocardial injury as recommended by the American Heart Association and the American College of Cardiology. Elevated TnT measurements may delay hospitalization, if determined to be clinically necessary. If the repeat TnT measurement is <0.1, then myocardial injury is most unlikely and the positive TnT value is likely due to DFT shocks.

Official Title
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Evaluating Myocardial Injury During ICD Implantation Using the Upper Limit of Vulnerability (ULV) Method vs. Standard Defibrillation Threshold Testing

Conditions
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Cardiomyopathy, Heart Failure, Cardiac Arrhythmia

Intervention / Treatment
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* Device: Standard Defibrillation Testing
* Device: Upper Limit of Vulnerability Testing


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients eligible to receive an ICD implant or change out. Patients with a single or dual coil right ventricle (RV) defibrillation lead located in the RV apex. Patients greater than 18 years of age. Patients willing and able to give informed consent. Patients who have insurance which may cover additional hospital stay if myocardial injury resulted from testing Exclusion Criteria: Patients with medical conditions that would limit study participation. Patients that are pregnant

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Standard Defibrillation Testing<br>Standard Defibrillation Threshold Testing is a procedure in which a low energy shock will be delivered to the heart to induce ventricular fibrillation (VF) followed by a rescue shock to restore sinus rhythm. Process is repeated after 5 minutes. | Device: Standard Defibrillation Testing<br>* Once the ICD is implanted, Standard Defibrillation Threshold (DFT) testing will begin. A low energy shock will be delivered to the heart at the peak of the T wave to induce ventricular fibrillation (VF). Once VF is induced, a rescue shock of 25J will be delivered to restore sinus rhythm. This process will be repeated once more after 5 minutes.<br>* Other names: ICD implantation;|
| Active Comparator: Upper Limit of VulnerabilityTesting<br>Upper Limit of Vulnerability Testing is a procedure in which four 18J shocks will be delivered at specified intervals. If VF is induced, then a 25 J rescue shock will be delivered. | Device: Upper Limit of Vulnerability Testing<br>* Once the ICD is implanted, Upper Limit of Vulnerability (ULV) testing will commence. An 18 J shock will be delivered will at different points from the t-wave. If VF is not induced with any of these shocks, then the ULV will be considered to be 18J. If VF is induced, then a 25 J rescue shock will be delivered.<br>* Other names: ICD implantation;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Myocardial Damage | Myocardial damage will be evaluated by cardiac troponin (cTNT) lab collection before and then after ULV or DFT testing at 4 hours, 8 hours, and 20 hours. | 20 hours (hr) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Defibrillation Testings (DFT) vs. Upper Limit of Vulnerability (ULV) (VF Induced) | the DFT group cardiac troponin (cTNT) values were compared to the subjects within the ULV group that required VF induction. | 20 hours (hr) | 
| Defibrillation Testing (DFT) Versus Upper Limit of Vulnerability (ULV) (Non-induced) | The DFT group was compared to the ULV subgroup that did not require ventricular fibrillation (VF) induction. Cardiac troponin (cTNT) levels were analyzed. | 20 hours (hr) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Defibrillation testing, Upper Limit of Vulnerability, ULV, DFT, ICD, implantable cardioverter defibrillator, cardiomyopathy, cardiac arrhythmia, cardiac device testing