Multi-lead ECG to Effectively Optimize Resynchronization Devices: New CRT Recipients

Study Overview
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Brief Summary
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Cardiac resynchronization therapy (CRT), or atrial-synchronized biventricular (BiV) pacing, is an FDA-approved device therapy option for heart failure (HF) patients with reduced left ventricular ejection fraction and electrical dyssynchrony. A traditional CRT device has pacing leads implanted within the right atrium (RA), the right ventricle (RV), and within a coronary vein overlying the lateral or posterior left ventricle (LV). Within the past decade, various multi-center randomized controlled trials have reported improved quality of life, aerobic exercise capacity, LV systolic function and structure, as well as decreased hospitalization rates and mortality among patients with HF. Despite improvements in CRT technology with multipoint pacing, quadripolar leads, and adaptive pacing algorithms, approximately 30% of patients do not clinically benefit and are considered non-responders. This study looks to optimize new CRT device recipients using information obtained from standard ECG machines.

Detailed Description
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This is a prospective, randomized study designed to evaluate if CRT device optimization, guided by electrocardiography, improves echocardiographic and clinical outcomes among HF patients with a CRT device implanted for standard indications. All patients will have measurement of electrocardiograms at a range of device settings. Patients will be randomized in a 1:1 ratio to either the active comparator arm (standard CRT programming), or the experimental arm (CRT device programmed by the information obtained by ECGs). Standard CRT programming used in this study is simultaneous biventricular (BiV) pacing with a fixed atrioventricular delay. At 6 months, control patients who were initially randomized to standard programming will have programming changed based on the ECG optimization information. Patients will be blinded to randomization. Change of LV size and function will be performed prior to randomization, and again  6 and  12 months following CRT implant in both subgroups.

Official Title
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Multi-lead ECG to Effectively Optimize Resynchronization Devices: New CRT Recipients

Conditions
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Heart Failure, Systolic

Intervention / Treatment
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* Device: Reprogramming of CRT Device Settings to Optimal Electrical Synchrony


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients (or their legal guardian) must be willing to provide informed consent and sign a data privacy authorization (HIPAA) form Age greater than or equal 18 years Pre-CRT EF less than or equal 40% Patients will be receiving or have received a first-time CRT device for standard clinical indications within  2 months of study enrollment Adequate echocardiographic images for LV EF and LV ESV determination On optimal medical therapy Exclusion Criteria: Patients who are pregnant or may become pregnant Patient has a history of severe allergic reactions from ECG gel/ electrode adhesives Patient has a His Bundle pacing lead Patient has right bundle branch block (RBBB) Patient is enrolled in concurrent research study that would potentially confound the results of this study Premature ventricular contraction (PVC) burden greater than or equal to 10%

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 100 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: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: 1:1 randomization - active comparator and experimental arm (note: at 6 months the control arm will crossover)
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Standard CRT Programming, then ECG CRT Optimization<br>The control arm patients will have standard CRT programming for the first 6 months, and then will be reprogrammed based on the ECG CRT optimization information for the following 6 months | Device: Reprogramming of CRT Device Settings to Optimal Electrical Synchrony<br>* Reprogramming of CRT device to maximize the benefit based on the ECG CRT optimization information.<br>|
| Experimental: ECG CRT Optimization<br>The experimental arm patients will have CRT device reprogrammed based on the ECG CRT optimization information for 12 months. | Device: Reprogramming of CRT Device Settings to Optimal Electrical Synchrony<br>* Reprogramming of CRT device to maximize the benefit based on the ECG CRT optimization information.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in left ventricular size | Change in left ventricular end-systolic volume (LVESV), measured by echocardiogram, in patients in the experimental arm vs active comparator arm | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in left ventricular function | Change left ventricular ejection fraction (EF), measured by echocardiogram, in patients in the experimental arm vs active comparator arm | 6 months | 
| Change in left ventricular size | Change in LVESV, measured by echocardiogram, in the subset of patients with left bundle branch block (LBBB) or intraventricular conduction delay (IVCD) in the experimental arm vs the active comparator arm | 6 months | 
| Change in left ventricular size | Change in LVESV, measured by echocardiogram, in the subset of patients with complete heart block (CHB) or persistent atrial fibrillation (AF) in the experimental arm vs the active comparator arm | 6 months | 
| Change in left ventricular size | Change in LVESV, measured by echocardiogram, in patients in the active comparator arm (crossed-over to optimization device settings at 6 months) at 12 months vs 6 months | 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Cardiac Resynchronization Therapy, Pacing, Echocardiography, Electrocardiography, Optimization, Heart Failure