Response of Cardiac Resynchronization Therapy Optimization With Ventricle to Ventricle Timing in Heart Failure Patients

Study Overview
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Brief Summary
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The purpose of the study is to evaluate the benefit of interventricular (V-V) delay optimization in reducing the non-responder rate in patients with cardiac resynchronization defibrillator (CRT-D) devices. The primary endpoint of this study is CRT responder rate. For patients enrolled with new CRT-D systems, patients are considered non-responders if BOTH of the following requirements are fulfilled: < 10% improvement in 6-minute hall walk, and no class improvement or worsening in New York Heart Association (NYHA) scale. For those receiving CRT-D devices as replacements of older CRT-D systems, patients are considered non-responders if BOTH of the following requirements are fulfilled: > 1 heart failure (HF) related hospitalization, and no class improvement or worsening in NYHA scale.

Detailed Description
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Study Methods This is a prospective, randomized (simultaneous biventricular (BiV) pacing vs. sequential BiV pacing) study. Any patient that receives an FDA approved St. Jude Medical (SJM) CRT-D with V-V timing is eligible for enrollment. At 3 months post enrollment (or at implant for CRT-D replacements), patients screened as non-responders are randomized to either simultaneous or sequential BiV pacing. Patients requiring a replacement CRT-D device that are identified as non-responders to CRT are enrolled at the screening/randomization visit. Patients are followed for a period of 6 months post randomization: Enrollment (1 week pre CRT-D implant to < 2 weeks post CRT-D implant) Screening/Randomization Visit (3 months post enrollment) Follow-up Visit (6 months post randomization) Total # of centers - 80 centers Sample size - 800 patients screened for CRT non-responders

Official Title
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RESPONSE HF - Response of Cardiac Resynchronization Therapy Optimization With Interventricular (VV) Timing in Heart Failure Patients

Conditions
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Heart Failure

Intervention / Treatment
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* Device: Simultaneous VV Pacing
* Device: Sequential VV Pacing


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patient has a standard indication for a CRT-D. Patient has the ability to complete a 6-minute hall walk with the only limiting factor to be fatigue or shortness of breath. Patient is geographically stable and willing to comply with the required follow-up schedule. Prior to 1 month of randomization, patient's HF medications are maintained stable and remain stable throughout the study. Patients requiring a CRT-D replacement must comply with BOTH of the following: > 1 HF related hospitalization No class improvement or worsening in NYHA scale Exclusion Criteria: Patient's life expectancy is less than 12 months. Patient has had cardiac surgery within 6 months of enrollment. Patient has an epicardial ventricular lead system. Patient is less than 18 years old. Patient is 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: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Simultaneous VV Pacing<br>Programmed to simultaneous biventricular pacing | Device: Simultaneous VV Pacing<br>* Right ventricular and left ventricular pacing delivered simultaneously.<br>|
| Active Comparator: Sequential VV Pacing<br>Programmed to sequential biventricular pacing | Device: Sequential VV Pacing<br>* Right ventricular and left ventricular pacing delivered sequentially.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| CRT Responder Rate | Patients underwent baseline NYHA class and 6-minute hall walk distance (6-MHWD) assessment. After device implantation AV delays were optimized and all patients were programmed to simultaneous biventricular (BiV) pacing. At the 3-month follow-up, the NYHA class and 6-MHWD were reassessed. Non-responders were randomized 1:1 to either sequential BiV pacing with VV optimization or simultaneous BiV pacing. The responder rate at 6 months post randomization was compared between the two groups. Which is why the numbers are broken further down in the Outcome Measure table. | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| NYHA Class Progression | New York Heart Association (NYHA) functional classification provides a way of classifying the extent of heart failure. It places patients in one of four categories based on how much they are limited during physical activity; the limitations/symptoms are in regard to normal breathing and varying degrees in shortness of breath and/or angina pain. | 6 months | 
| 6 Minute Hall Walk Distance Test (6-MHWD) | Patients were considered non-responders if the 6-MHWD had not improved by greater than or equal to 10% compared to baseline. This statement is accurate and appropriate. | 6 months | 
| Left Ventricular Ejection Fraction (LVEF) | Ejection fraction is a measurement of the percentage of blood leaving your heart each time it contracts. The left ventricle is the heart's main pumping chamber, so ejection fraction is usually measured only in the left ventricle (LV). | Randomization and 9 months |