Conduction System Pacing Optimized Therapy

Study Overview
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Brief Summary
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The purpose of the CSPOT study is to determine the best mode of cardiac resynchronization therapy (CRT) pacing for different populations of CRT patients, comparing traditional biventricular (BiV), conduction system pacing (CSP)-only, and conduction system pacing optimized therapy (CSPOT) also known as a combination of conduction system pacing (CSP) and left ventricular (LV) pacing. Additionally, safety of the system will be assessed.

Official Title
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Conduction System Pacing Optimized Therapy Study

Conditions
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Heart Failure

Intervention / Treatment
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* Device: Left ventricular coronary sinus configuration
* Device: Conduction system pacing-only configuration
* Device: Conduction System Pacing Optimized Therapy (CSPOT) configuration


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patient is willing and able to provide written informed consent Subject is at least 18 years of age Patient is willing and able to comply with the protocol, including follow-up visits The patient's medical records must be accessible by the enrolling site over the follow-up period Standard CRT-D or CRT-P indications, with a preference for IVCD and non-LBBB patients, where LBBB is defined according to Strauss criteria. De-novo CRT implant, including upgrade from pacemaker or ICD Exclusion Criteria: Subject has persistent or permanent AF (Atrial Fibrillation)/AFL (Atrial Flutter) Subject has 2nd or 3rd degree AV (Atrioventricular) Block Subject has RBBB with no additional conduction block Subject has intrinsic (non-paced) QRS width less than or equal to 120 ms Subject experienced MI within 40 days prior to enrollment Subject underwent valve surgery, within 90 days prior to enrollment Subject is post heart transplantation or is actively listed on the transplantation list Subject is implanted with a LV assist device Subject has severe renal disease Subject is on continuous or uninterrupted infusion (inotropic) therapy for heart failure Subject has severe aortic stenosis (with a valve area of <1.0 cm or significant valve disease expected to be operated within study period) Subject has severe aortic calcification or severe peripheral arterial disease Subject has complex and uncorrected congenital heart disease Subject has mechanical heart valve Pregnant or breastfeeding woman (pregnancy test required for woman of child-bearing potential and who are not on a reliable form of birth regulation method or abstinence) Subject is enrolled in another study that could confound the results of this study without documented pre-approval from Medtronic study manager

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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Single Arm<br>On the date of implant, subjects will undergo Conduction System Pacing Optimized Therapy (CSPOT) lead placement, then Conduction System Pacing Optimized Therapy (CSPOT) acute pacing protocol, and then device implant. During the acute pacing protocol, all subjects will undergo three types of pacing configurations (defined in the intervention descriptions), and will serve as their own control. The subject will then be implanted with the cardiac resynchronization therapy defibrillator (CRT-D) or cardiac resynchronization therapy pacemaker (CRT-P) device will be implanted. Each subject's device will be programmed to conduction system pacing optimized therapy (CSPOT) configuration. Subjects will be followed for 6 months. | Device: Left ventricular coronary sinus configuration<br>* For subjects with a pacemaker, pacing of the left ventricular coronary sinus only. For subjects with a defibrillator, biventricular pacing of the left ventricular coronary sinus and the right ventricle.<br>Device: Conduction system pacing-only configuration<br>* Conduction system pacing (CSP) of the left bundle branch.<br>Device: Conduction System Pacing Optimized Therapy (CSPOT) configuration<br>* A combination of left ventricle (LV) pacing and conduction system pacing (CSP) of the left bundle branch.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Electrical synchronization response | Standard Deviation of Activation Times (SDAT), a measurement of dyssynchrony, taken by the ECG belt, a diagnostic tool used to provide feedback and additional information on the CRT pacing at the time of the device implant or at a device follow up. | At implant | 
| Hemodynamic response | For each intervention (i.e. left ventricular coronary sinus, conduction system only, and conduction system pacing optimized therapy), the pacing will switch back and forth between the intervention's pacing configuration and an atrial-only pacing configuration for several repetitions. For each repetition, left ventricular (LV) dP/dt max, a measurement of the initial velocity of myocardial contraction, will be measured for both configurations, and the median value across repetitions will be found for each configuration. Finally, the percent change in LV dP/dt max will be calculated as the difference between the median value from the intervention's pacing configuration and the median value from atrial-only pacing, divided by the median value from atrial-only pacing. This percent change will be used as the measurement of hemodynamic response for the given intervention. | At implant | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Left ventricular ejection fraction (LVEF) | Left ventricular ejection fraction will be measured, based on echocardiography, at the baseline visit and again at the 6-month follow-up visit. Change will be calculated as the value observed at baseline subtracted from the value observed at 6 months. | Baseline and 6 months | 
| Left ventricular end systolic volume (LVESV) | Left ventricular end systolic volume will be measured, based on echocardiography, at the baseline visit and again at the 6-month follow-up visit. The change will be calculated as difference between the 6-month and baseline values, divided by the baseline value. | Baseline and 6 months | 
| Clinical Composite Score (CCS) | The Clinical Composite Score (CCS) is a validated 3-level categorical variable that can take the values - Improved, Unchanged, or Worsened - at each follow-up visit. It is based on mortality, HF events, termination of device function, NYHA score, and patient global assessment. Briefly, the scoring system is as follows: A patient is considered worsened if they die, demonstrate a worsened NYHA class, report at least moderately worsened heart-failure symptoms, or are hospitalized or permanently discontinue therapy because of or associated with worsening heart-failure A patient is considered improved if they have not worsened and either demonstrate improvement in NYHA class or report at least moderately improved heart-failure symptoms A patient is considered stabilized if they have not worsened or improved | 6 months |