HIS-Purkinje Conduction System Pacing Optimized Trial of Cardiac Resynchronization Therapy

Study Overview
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Brief Summary
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This is a randomized, prospective, single-blinded trial to determine the overall rate of successful His-Purkinje conduction system pacing Optimized Trial of Cardiac Resynchronization Therapy (HOT-CRT) versus biventricular pacing using coronary sinus lead (BVP) to compare acute and mid-term outcomes. Acute outcomes include change in QRS duration pre-and post-pacing (degree of QRS narrowing) and incidence of major periprocedural complications (pericardial tamponade, need for lead revision, etc.). Mid-term outcomes include echocardiographic response at 6 months along with a composite clinical outcome of heart failure hospitalization, ventricular arrhythmias, crossover, and all-cause mortality.

Detailed Description
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This is a single-blinded study of 100 patients randomized to a strategy of His-Purkinje conduction system pacing Optimized Trial of Cardiac Resynchronization Therapy (HOT-CRT) versus biventricular pacing using coronary sinus (CS) lead (BVP). Both treatment options use standard-of-care, FDA-approved devices. The distinction is only in the allocation toward HOT-CRT and BVP. Treating physicians will be aware of assignment in order to facilitate routine device follow-up. Echocardiographic and electrocardiographic evaluation will also be performed in a blinded manner. Cross-over is permitted between treatment group allocation if: CS lead cannot be placed due to difficult cannulation of the CS, limited branches at the posterolateral or lateral wall, or phrenic nerve capture. These subjects may then cross-over to HOT-CRT. HOT-CRT subjects may cross-over if His or left bundle pacing lead cannot be positioned with adequate stability and reasonable pacing output, or if optimal QRS narrowing cannot be achieved. Implant procedure will be per routine percutaneous access, as is standard for pacemaker and Implantable Cardioverter Defibrillators (ICDs). . All subjects will receive an FDA-approved cardiac resynchronization therapy pacemaker or defibrillator device, as per standard of care outlined for the subject. Follow-up will be performed at 2 weeks post-implant for incision check and device interrogation as is standard of care. In addition, routine device and clinical follow-up will be scheduled at 3 and 6 months. Electrocardiography (ECG) will be performed pre-implant, prior to hospital discharge, at 3 months, and 6 months. Echocardiography will be performed pre-implant and 6 months to evaluate for change in Left Ventricular Ejection Fraction (LVEF), chamber dimensions, volumes, and change in Left Ventricular (LV) end systolic volume index as is standard of care in the treatment of patients with advanced heart failure. New York Heart Association (NYHA) functional class and quality of life (utilizing the Kansas City Cardiomyopathy Questionnaire (KCCQ) and EQ 5D) will be assessed pre-implant and at 6 months.

Official Title
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HIS-Purkinje Conduction System Pacing Optimized Trial of Cardiac Resynchronization Therapy

Conditions
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Heart Failure，Congestive, Cardiomyopathies, Left Ventricular Dysfunction

Intervention / Treatment
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* Device: HOT-CRT
* Device: Biventricular Pacing


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients at least 18 years of age Diagnosis is NYHA Class II, III, and ambulatory Class IV heart failure with either ischemic or nonischemic cardiomyopathy and patients with NYHA Class I symptoms and ischemic cardiomyopathy, with at least one of the following: LV systolic dysfunction with LVEF ≤ 35% and Evidence of bundle branch block with QRS duration > 120 msec LV systolic dysfunction with LVEF ≤ 50% and with need for >40% Right Ventricular (RV) pacing Exclusion Criteria: Existing CRT device Inability of patient capacity to provide consent for themselves either due to medical or psychiatric comorbidity Pregnancy Participation in other device trials Inability to complete study requirements

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
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: HOT-CRT<br>Subjects randomized to HOT-CRT will undergo CRT as described below. His bundle pacing lead will be placed initially to achieve CRT. If complete resynchronization is achieved (BBB normalization) but capture thresholds are high (1.5-2V), the lead may be placed in the distal conduction system (left bundle branch area). If only partial QRS narrowing is achieved, a coronary sinus lead may be placed and LV timing may be optimized to achieve maximal resynchronization. This will be at the discretion of the implanting physician. Only FDA approved leads and devices will be used. | Device: HOT-CRT<br>* Subjects enrolled in the study will receive a permanent cardiac implantable electronic device (CIED) (CRT-pacemaker or CRT-defibrillator) as clinically indicated. Subjects randomized to HOT-CRT will have His bundle pacing lead placed initially to achieve CRT. If complete resynchronization is achieved (BBB normalization) but capture thresholds are high (1.5-2V), the lead may be placed in the distal conduction system (left bundle branch area). If only partial QRS narrowing is achieved, a coronary sinus lead may be placed and left ventricular timing may be optimized to achieve maximal resynchronization.<br>|
| Active Comparator: Biventricular Pacing<br>Subjects randomized to biventricular pacing will undergo left ventricular lead placement in the coronary sinus venous branches.Only FDA approved leads and devices will be used. | Device: Biventricular Pacing<br>* Subjects enrolled in the study will receive a permanent CIED (CRT-pacemaker or CRT-defibrillator) as clinically indicated. Subjects randomized to Biventricular pacing will undergo left ventricular lead placement in the coronary sinus venous branches.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Improvement in left ventricular ejection fraction | change in LVEF measured by 2D echo at 6 months compared to baseline | 6 months | 
| Freedom from major complications or need for CRT lead revision | complication such as lead dislodgment, pericardial tamponade, pneumothorax, systemic embolism, phrenic nerve stimulation not correctable by programming | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Heart failure hospitalization (HFH) | Heart failure hospitalization is defined as an unplanned outpatient or emergency department visit or inpatient hospitalization in which the patient presented with signs and symptoms consistent with heart failure and required intravenous therapy. | 6 months | 
| Ventricular tachycardia or ventricular fibrillation requiring ICD therapy | ventricular tachycardia or ventricular fibrillation that required ICD therapy such as anti-tachycardia pacing or shock | 6 months | 
| Crossover of treatment from HOT-CRT to BVP or BVP to HOT-CRT | Failure to implant His bundle or left bundle pacing lead requiring cross over to coronary sinus lead; failure to implant coronary sinus lead necessitating cross-over to His bundle or left bundle pacing lead | 6 months | 
| Change in NYHA functional class | Functional class change at 6 months compared to baseline. | 6 months | 
| Change in QRS duration | QRS duration at final programmed configuration between the 2 groups will be compared at implant and at 6 month follow-up | 6 months | 
| Change in LV end-systolic volume index | 15% or more increase in LV end-systolic volume index at 6 months compared to baseline. | 6 months | 
| Composite endpoint of death, HFH, ventricular arrhythmias or crossover | Time to combined endpoint of death, HFH, VA or crossover. | 6 months | 
| Change in quality of life (QOL)scores | Change in QOL measured by the Kansas City Cardiomyopathy Questionnaire at 6 months compared to baseline. Scores are transformed to a range of 0-100, in which higher scores reflect better health status. | 6 months | 
| Change in quality of life (QOL)scores | Change in QOL measured by EuroQol-5D at 6 months compared to baseline. Scores on each of 5 patient reported dimensions are converted to a single utility index using country specific value sets. Additionally, a visual analog scale from 0-100, in which higher score reflects better health status. | 6 months | 

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