Left Ventricular MultiSpot Pacing for CRT (iSPOT)

Study Overview
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Brief Summary
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The purpose of the iSPOT Study is to evaluate the contractility using positive left ventricular (LV) dP/dt max across LV pacing site(s) in patients indicated for cardiac resynchronization therapy (CRT).

Official Title
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Left Ventricular MultiSpot Pacing for CRT (iSPOT)

Conditions
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Heart Failure

Intervention / Treatment
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* Procedure: Electrophysiological Study


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subject is indicated for cardiac CRT or CRT-D device according to current applicable European Society of Cardiology (ESC)/American Heart Association (AHA) guidelines Subject has a left bundle branch block (LBBB) conduction pattern Subject is in stable sinus rhythm at the time of implant (no atrial arrhythmias lasting > 30 seconds during the last 2 weeks prior to inclusion and no documented atrial fibrillation (AF) episodes allowed during the last 2 weeks prior to inclusion) Subject receives optimal heart failure oral medical therapy (ACE inhibitor and/or angiotensin receptor blockers (ARB) and Beta Blockers), and is on a stable medication scheme for at least 1 month prior to enrollment Subject (or the legal guardian) is willing to sign informed consent form Subject is 18 years or older or as specified minimal age per local law/regulation Exclusion Criteria: Subject has permanent atrial fibrillation/ flutter or tachycardia Subject experienced recent myocardial infarction (MI), within 40 days prior to enrollment Subject underwent coronary artery bypass graft (CABG) or 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 left ventricular assist device (LVAD) Subject is on chronic renal dialysis Subject has severe renal disease (defined as estimated Glomerular Filtration Rate (equation provided by Modification of Diet in Renal Disease study): (eGFR) < 30 mL/min/1.73m2) Subject is on continuous or uninterrupted infusion (inotropic) therapy for heart failure (≥ 2 stable infusions per week) Subject has severe aortic stenosis (with a valve area of <1.0 cm2 or significant valve disease expected to be operated within study period) Subject has complex and uncorrected congenital heart disease Subject has a mechanical heart valve Pregnant or breastfeeding women, or women of child bearing potential and who are not on a reliable form of birth control Subject is enrolled in one or more concurrent studies that would confound the results of this study Subject is already implanted with a device

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: Electrophysiological Study<br>Subjects will receive pacing from one right ventricular lead and one left ventricular catheter/lead with multiple LV pacing spots during electrophysiological study procedure | Procedure: Electrophysiological Study<br>* Subjects will receive pacing from one right ventricular lead and one left ventricular catheter/lead with multiple LV pacing spots<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage Change in Positive Left Ventricular (LV) dP/dt Max (mm HG/Sec) of Multispot LV Pacing Configuration Compared to Normal Biventricular Pacing | Measure the percentage change in positive left ventricular (LV) dP/dt max (mm HG/sec) of multispot LV pacing configuration compared to normal biventricular pacing in patients undergoing a research study, an electrophysiological exploratory procedure or cardiac resynchronization therapy (CRT) implant. The percentage changes correspond to a percentage change between a pacing configuration (pacing on, e.g., Multispot pacing) and baseline (LV pacing off). There are several repetitions of pacing off and on for each pacing configuration. For one repetition, the percentage change is determined as ([median dP/dt max during pacing On] - (median baseline dP/dt max during pacing Off])/[median dP/dt max during pacing Off]. From all percentage changes for a given pacing configuration and subject, a regression analysis is performed to determine the regression predicted highest percentage change. The presented percentage change is the average over all subjects. | Participants will be followed for the time of the EP procedure, which has an average duration of 2 to 3 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage Change in Positive Left Ventricular (LV) dP/dt Max (mm HG/Sec) of Multi-vein LV Pacing Configuration Compared to Normal Biventricular Pacing | Measure the percentage change in positive left ventricular (LV) dP/dt max (mm HG/sec) of multi-vein LV pacing configuration compared to normal biventricular pacing in patients undergoing a research study, an electrophysiological exploratory procedure or CRT-implant. The percentage changes correspond to a percentage change between a pacing configuration (pacing on, e.g., Multispot pacing) and baseline (LV pacing off). There are several repetitions of pacing off and on for each pacing configuration. For one repetition, the percentage change is determined as ([median dP/dt max during pacing On] - (median baseline dP/dt max during pacing Off])/[median dP/dt max during pacing Off]. From all percentage changes for a given pacing configuration and subject, a regression analysis is performed to determine the regression predicted highest percentage change. The presented percentage change is the average over all subjects. | Participants will be followed for the time of the EP procedure, which has an average duration of 2 to 3 hours | 
| Percentage Change in Positive Left Ventricular (LV) dP/dt Max (mm HG/Sec) of Multi-vein LV Pacing Configuration Compared to Multispot LV Pacing Configuration | Measure the percentage change in positive left ventricular (LV) dP/dt max (mm HG/sec) of multi-vein LV pacing configuration compared to multispot LV pacing in patients undergoing a research study, an electrophysiological exploratory procedure or CRT-implant. The percentage changes correspond to a percentage change between a pacing configuration (pacing on, e.g., Multispot pacing) and baseline (LV pacing off). There are several repetitions of pacing off and on for each pacing configuration. For one repetition, the percentage change is determined as ([median dP/dt max during pacing On] - (median baseline dP/dt max during pacing Off])/[median dP/dt max during pacing Off]. From all percentage changes for a given pacing configuration and subject, a regression analysis is performed to determine the regression predicted highest percentage change. The presented percentage change is the average over all subjects. | Participants will be followed for the time of the EP procedure, which has an average duration of 2 to 3 hours | 
| Correlation of Blood Pressure, Electrograms (EGMs) and Electrocardiographic Mapping Measurements With the Positive LV dP/dt Max Values | Correlate blood pressure, EGMs and electrocardiographic mapping measurements with the percentage change LV dP/dt max values obtained during each of the three pacing configurations BiV (BiV distal, BiV mid, BiV proximal, BiV anterior, BiV posterior), MultiVein and MultiSpot. Correlation will be summarized over all pacing configurations and time points since the interest is in the overall correlation between LV dP/dt max and other measurements, not in the correlation per pacing configuration or per time point. A linear mixed effects models as described in Roy, Biometrical Journal 48 (2006) 2, 286- 301 was used for the diastolic and systolic blood pressures. Due to the convergence problems for the linear mixed for Q-LV and QRS, the general linear model as described in Blank & Altman, Biometrical Journal 310 (1995), p 446, was used for Q-LV and QRS. | Participants will be followed for the time of the EP procedure, which has an average duration of 2 to 3 hours | 
| Use of Non-invasive Measurements to Identify Pacing Configuration With Highest Positive LV dP/dt Max | Evaluate whether the non-invasive measurements (Nexfin blood pressures) that are also collected during the study can identify the pacing configuration with the highest percentage change LV dP/dt max. For each patient and all time points of data collection, a regression analysis was applied to determine the highest predicted percentage change LV dP/dtmax or percentage change Nexfin pressure per configuration. The Kappa statistic was then determined based on a 7x7 contingency table where the rows and columns corresponded to the pacing configurations. There is no interest in determining the agreement statistics Kappa per time point or per configuration since the interest of this analysis is in the overall agreement between LV dP/dt max and non-invasive measurements. | Participants will be followed for the time of the EP procedure, which has an average duration of 2 to 3 hours | 
| Within Patient Variability in Positive LV dP/dt Max | Evaluate the within patient variability in positive LV dP/dt max measurements. The standard deviation of the percentage change LV dP/dt max between pacing configurations will be evaluated to obtain information for future sample size calculations for the primary outcome.The standard deviation is summarized over all available subjects and could be used as an estimate of within patient variability for future sample size calculations for the primary outcome. | Participants will be followed for the time of the EP procedure, which has an average duration of 2 to 3 hours |