Resynchronization for Ambulatory Heart Failure Trial - LV Endocardial

Study Overview
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Brief Summary
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This trial will compare two strategies for patients with Heart Failure, Left Ventricular systolic dysfunction, and intermediate QRS durations. The control group is conventional CRT. The experimental group is LVendo CRT

Detailed Description
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Patients randomized to the Conventional CRT will receive a CRT device with or without ICD. Device implantation will be performed within 10 working days of randomization. Patients randomized to LV endocardial CRT will receive a CRT device with or without ICD, placed in the same time frame and will have RA and RV leads implanted as the conventional CRT group. The device will be implanted in a facility that has the capacity to perform trans-atrial septal puncture with ultrasound guidance. The LV lead will be placed using a trans-atrial septal approach using a specially designed puncture tools and LVendo delivery tool kits specifically designed for this study

Official Title
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Resynchronization for Ambulatory Heart Failure Trial - LV Endocardial

Conditions
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Heart Failure, Left Ventricular Dysfunction

Intervention / Treatment
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* Device: Conventional CRT
* Device: LV endocardial CRT


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with NYHA Class II or III or ambulatory IV HF symptoms Optimal HF Medical Therapy of at least 3 months (2009 ACCF/AHA, ESC 2012) LVEF less than or equal to 35% Sinus rhythm (can have paroxysmal atrial fibrillation) QRS morphology is non-RBBB QRS durations more than or equal to 120 ms, but less than 150 ms Patients are able to receive chronic oral anticoagulation Patients with pacemaker or ICD that meet the above criteria may be upgraded to CRT-D or CRT-P Exclusion Criteria: Planned Atrial Fibrillation Ablation within 12 months Patients with mitral or tricuspid prosthetic valve that precludes the placement of an LV lead transvenously or trans-septally Patients with RBBB Patients with LV thrombus Patients with permanent atrial fibrillation Patients with contraindications to oral anti-coagulation In-hospital patients with acute cardiac or non-cardiac illness that requires intensive care Acute coronary syndrome (including MI) < 4 weeks Coronary revascularization (CABG or PCI) < 3 months Uncorrected or uncorrectable primary valvular disease Restrictive, hypertrophic or reversible form of cardiomyopathy Severe primary pulmonary disease such as cor pulmonale Expected to undergo cardiac transplantation within one year (status I) Patients with a life expectancy of less than one year from non-cardiac cause. Patients included in other clinical trials that will affect the objectives of this study Those unable or unwilling to provide informed consent Those with a history of noncompliance to medical therapy

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: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: This trial will compare two management strategies for patients with Heart Failure, left ventricular systolic dysfunction, and intermediate prolonged QRS duration (120-149ms). The control group is conventional Cardiac Resynchronization Therapy (CRT). The experimental group is LV endocardial CRT.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Conventional CRT<br>Patients randomized to the Conventional CRT will receive a CRT device with or without ICD. Device implantation will be performed within 10 working days of randomization. Conscious sedation or general anesthesia can be used for the implant procedure. The device will be implanted in a facility that has the capacity to perform coronary sinus venography at the time of implantation. The RA lead will be placed in the RA appendage or high RA. The RV lead should be placed at the RV apex or distal RV septum (R wave > 7 mV, pacing threshold < 1.5 V at a pulse-width of 0.5 ms). The LV lead should be positioned through the CS to an LV branch. The lead should be placed at one of the left ventricular venous branches, avoiding the LV apex and scar region identified by pre-implant imaging | Device: Conventional CRT<br>* Patients randomized to the Conventional CRT will receive a CRT device with or without ICD. Device implantation will be performed within 10 working days of randomization. Conscious sedation or general anesthesia can be used for the implant procedure. The device will be implanted in a facility that has the capacity to perform coronary sinus venography at the time of implantation. The RA lead will be placed in the RA appendage or high RA. The RV lead should be placed at the RV apex or distal RV septum (R wave > 7 mV, pacing threshold < 1.5 V at a pulse-width of 0.5 ms). The LV lead should be positioned through the CS to an LV branch. The lead should be placed at one of the left ventricular venous branches, avoiding the LV apex and scar region identified by pre-implant imaging.<br>|
| Experimental: LV endocardial CRT<br>Patients randomized to LV endocardial CRT will receive a CRT device with or without ICD, placed in the same time frame, and will have RA and RV leads implanted as the conventional CRT group. The device will be implanted in a facility that has the capacity to perform trans-atrial septal puncture with ultrasound guidance (TEE or ICE) at the time of implantation. The LV lead will be placed using a trans-atrial septal approach, using a specially designed puncture tools and LVendo delivery tool kits specifically designed for this study. Special care will be taken to avoid the LV apex and transmural scar identified by pre-implant imaging. | Device: LV endocardial CRT<br>* Patients randomized to LV endocardial CRT will receive a CRT device with or without ICD, placed in the same time frame, and will have RA and RV leads implanted as the conventional CRT group. The device will be implanted in a facility that has the capacity to perform trans-atrial septal puncture with ultrasound guidance (TEE or ICE) at the time of implantation. The LV lead will be placed using a trans-atrial septal approach, using a specially designed puncture tools and LVendo delivery tool kits specifically designed for this study. Special care will be taken to avoid the LV apex and transmural scar identified by pre-implant imaging.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Assessment of LVESVi | LV reverse remodeling as measured by the difference of LVESVi on echocardiography (echo) | Baseline to 6 months & 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Ventricular arrhythmia burden determined by the device capture of arrhythmias and adjudication by a device review committee blinded to patient's treatment allocation. |  | Baseline to 6 months & 12 months | 
| NT-proBNP measurement |  | Baseline to 6 months & 12 months | 
| 6 Minute Hall Walk Distance |  | Baseline to 6 months & 12 months | 
| Quality of Life Measure | EQ5D-5L & Minnesota Living with HF | Baseline to 6 months & 12 months | 
| Mortality |  | Baseline to 6 months & 12 months | 
| Heart Failure Admissions |  | Baseline to 6 months & 12 months | 
| Reduction of LVEF |  | Baseline to 6 months & 12 months |