Strategic Management to Optimize Response To Cardiac Resynchronization Therapy

Study Overview
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Brief Summary
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The primary objective is to evaluate the benefit of the SmartDelay™ algorithm in patients with a prolonged RV-LV interval.

Detailed Description
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The primary hypothesis of SMART CRT is that among cardiac resynchronization therapy defibrillator (CRT-D) patients with prolonged inrerventricular delay between the RV and LV leads, CRT with atrioventricular optimization (AVO) will result in greater reverse LV remodeling compared with CRT programmed at nominal settings (120 ms).

Official Title
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Strategic Management to Optimize Response To Cardiac Resynchronization Therapy

Conditions
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Heart Failure

Intervention / Treatment
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* Device: CRT-D


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subject must be indicated to receive a de novo quadripolar Boston Scientific Cardiac Resynchronization Therapy Defibrillator (CRT-D) in conjunction with an ACUITY X4 LV lead. This includes subjects who are indicated to receive an upgrade to a BSC X4 CRT-D from a previously implanted device. In order to achieve a homogenous population for the study, qualifying subjects are those with heart failure who meet BSC US indications for use defined as those subjects who receive stable optimal pharmacologic therapy (OPT) for heart failure and who meet any one of the following classifications: Moderate to severe heart failure (NYHA Class III-IV) with EF ≤ 35% and QRS duration ≥ 120 ms Left bundle branch block (LBBB) with QRS duration ≥ 130 ms, EF ≤ 30%, and mild (NYHA Class II) ischemic or nonischemic heart failure or asymptomatic (NYHA Class I) ischemic heart failure Subject is age 18 or above, or of legal age to give informed consent specific to each country and national laws Subject is willing and capable of providing informed consent Subject is willing and capable of complying with visits and procedures as defined by this protocol Exclusion Criteria: Subjects with documented permanent complete AV block Subjects with permanent or chronic atrial fibrillation (AF) or in AF at the time of enrollment Subjects who have previously received cardiac resynchronization therapy with pacing in the left ventricle Subjects on the active heart transplant list or who has or is to receive ventricular assist device (VAD) Life expectancy shorter than 12 months due to any medical condition (e.g., cancer, uremia, liver failure, etc…) Subject with a known or suspected sensitivity to dexamethasone acetate (DXA) Subject is enrolled in any other concurrent clinical study, with the exception of local mandatory governmental registries and observational studies/registries, without the written approval from Boston Scientific Women of childbearing potential who are or plan to become pregnant during the course of the trial Subjects currently requiring dialysis

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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Accepts Healthy Volunteers

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 |
| --- | --- |
| Other: SmartDelay™ algorithm<br>Subjects programmed with AV Delay and pacing chamber determined by SmartDelay | Device: CRT-D<br>* Commercially approved quadripolar Boston Scientific Cardiac Resynchronization Therapy Defibrillator (CRT-D) devices and future generations of BSC X4 CRT-D devices approved by the appropriate regulatory bodies will be included in the trial. All devices utilized in the study will include SmartDelay™ and must be capable of providing SmartDelay recommendations for both biventricular pacing (BiV) and Left Ventricular (LV) only pacing. All enrolled subjects with implanted BSC X4 CRT-D system and identified with an RV-LV delay of ≥70ms were 1:1 randomized. Randomization occurred in the electronic data capturing system.<br>|
| Other: Fixed AV Delay with BiV pacing<br>Subjects programmed with a Fixed AV Delay of 120ms with BiV pacing | Device: CRT-D<br>* Commercially approved quadripolar Boston Scientific Cardiac Resynchronization Therapy Defibrillator (CRT-D) devices and future generations of BSC X4 CRT-D devices approved by the appropriate regulatory bodies will be included in the trial. All devices utilized in the study will include SmartDelay™ and must be capable of providing SmartDelay recommendations for both biventricular pacing (BiV) and Left Ventricular (LV) only pacing. All enrolled subjects with implanted BSC X4 CRT-D system and identified with an RV-LV delay of ≥70ms were 1:1 randomized. Randomization occurred in the electronic data capturing system.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| CRT Response | Comparing cardiac resynchronization therapy (CRT) response rates between AV Delay programming schemes defined by SmartDelay or a Fixed AV Delay of 120ms. A negative change in LVESV is considered an improvement; CRT response is defined by a change in Left Ventricular End Systolic Volume (LVESV) < -15% at 6 months compared to pre-implant baseline. | Pre-Implant baseline to 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Left Ventricular End Systolic Volume (Absolute Change) | Comparing absolute changes in Left Ventricular End Systolic Volume from Implant to 6 Months between AV Delay programming schemes defined by SmartDelay or a Fixed AV Delay of 120ms. Change is defined as 6-Month measurement - Implant measurement, in milliliters. A negative change in LVESV is considered an improvement. | Implant to 6 Months | 
| Change in Left Ventricular End Systolic Volume (Relative Change) | Comparing relative changes in Left Ventricular End Systolic Volume from Implant to 6 Months between AV Delay programming schemes defined by SmartDelay or a Fixed AV Delay of 120ms. Change is defined as 100*(6-Month measurement - Implant measurement)/(Implant Measurement), in %. A negative change in LVESV is considered an improvement. | Implant to 6 Months | 
| Change in Left Ventricular Ejection Fraction (Absolute Change) | Comparing absolute changes in Left Ventricular Ejection Fraction from Implant to 6 Months between AV Delay programming schemes defined by SmartDelay or a Fixed AV Delay of 120ms. Change is defined as 6-Month measurement - Implant measurement, in % of blood ejected during LV contraction. A positive change in LVEF is considered an improvement. | Implant to 6 Months | 
| Change in Left Ventricular Ejection Fraction (Relative Change) | Comparing relative changes in Left Ventricular Ejection Fraction from Implant to 6 Months between AV Delay programming schemes defined by SmartDelay or a Fixed AV Delay of 120ms. Change is defined as 100*(6-Month measurement - Implant measurement)/(Implant Measurement), in %. A positive change in LVEF is considered an improvement. | Implant to 6 Months | 
| Clinical Composite Score (CCS) | Th CCS combines four metrics: all-cause mortality, heart failure hospitalization (HFH), New York Heart Association (NYHA) Class, and quality of life as measured with the patient global assessment (GA) instrument. The CCS categorizes each subject into one of three groups: Improved, Unchanged or Worsened. Improved: Subjects that survived without a HFH through the 6-month visit window and had either an improvement in NYHA class or responded to GA with much better or very much better. Unchanged: All patients that reached the end of 6-month visit window that were not categorized as either Improved or Worsened. Worsened: Subjects that died or had HFH within 6-month visit window or had either a worsening in NYHA class or responded to GA with much worse or very much worse. | Implant to 6 Months | 
| Change in Kansas City Cardiomyopathy Questionnaire (KCCQ) Overall Summary Score | The KCCQ is a disease-specific instrument for monitoring the health status and quality of life of subjects with congestive heart failure. It includes a total of 23 items that assess quality of life in the following domains: physical function, symptom frequency and severity, symptom stability, self-efficacy and knowledge, social function, and overall quality of life. These domains can be combined into a functional status summary score (derived from the physical function and symptom scales) and an overall summary score which combines the physical function, symptom, social function and quality of life domains. KCCQ scores have a minimum of 0 and a maximum of 100. Higher score indicates better quality of life. | Implant to 6 Months |