Effects of Multipoint Pacing CRT-D on Neurohormonal Activation.

Study Overview
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Brief Summary
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This study will examine the additional clinical benefit conferred by multipoint pacing (MPP) compared to standard CRT over a period of 3 months. Patients will be randomized to MPP ON vs. OFF and followed for a total of 6 months. This includes two crossover periods for each pacing modality (MPP on vs. off).

Detailed Description
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Cardiac resynchronization therapy (CRT) is limited by a high proportion of non-responders. Pacing activation from multiple separated left ventricular (LV) sites might improve the depolarization pattern, thereby promoting more physiological activation. To explore the effect of MPP on cardiac neuro-hormonal activity, the investigators will enroll approximately 30 patients who already underwent CRT-D implantation with a quadripolar LV lead connected to a device capable of MPP. This pilot study will have a randomized, double-blind, cross-over design. Patients will be randomized to receive either standard biventricular pacing (MPP-OFF) or MPP (MPP-ON) within 4-6 months following the implantation procedure. Each subject will crossover to the other study group after three months. The baseline evaluation should be acquired prior to the device being programmed to the randomized setting. Repeat evaluations will be performed at the end of each 3 month crossover period. Participation in this study will last approximately 6 months. Patients, as well as investigators other than the EP physicians, will be blinded to the pacing mode.

Official Title
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Randomized, Crossover Study of the Effects of MultiPoint Left Ventricular Pacing on Neurohormonal Activation.

Conditions
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Heart Failure

Intervention / Treatment
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* Device: Cardiac Resynchronization Therapy with MultiPoint Pacing


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients implanted with a St. Jude Medical CRT-D system with MPP capability Patients must be willing and able to sign an appropriate informed consent form and comply with study requirements NT pro-BNP levels equal to or greater than 500 pg/ml. Exclusion Criteria: History of stroke, PCI, myocardial infarction or unstable angina pectoris within the last 3 months. Atrial fibrillation with noncontrolled heart rate Need for intravenous inotropic support for CHF Classification of Status 1 for cardiac transplantation or consideration for transplantation over the next 12 months Undergone a cardiac transplantation Currently participating in any other clinical investigation Life expectancy < 12 months due to a disorder other than CHF Inability to comply with the follow-up procedures Patients who are or may potentially be pregnant

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 85 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: Crossover Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: MultiPoint Pacing On<br>Patients will be randomized to the MPP-ON Arm vs MPP-OFF in in crossover fashion with 3 months in each period. | Device: Cardiac Resynchronization Therapy with MultiPoint Pacing<br> <br> |
| Active Comparator: MultiPoint Pacing Off<br>Patients will be randomized to the MPP-OFF arm vs MPP-ON in crossover fashion with 3 months in each period. | Device: Cardiac Resynchronization Therapy with MultiPoint Pacing<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in blood concentrations of N-terminal pro-B type natriuretic peptide (NT pro-BNP) | Changes in plasma NT pro-BNP using the difference from baseline to three months as compared to the difference from three to six months within a patient. | Baseline. 3-Month. 6-Month. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in Neurohormonal Activation | Renin, Aldosteron, Norepinephrine, Endothelin-1. | Baseline. 3-Month. 6-Month. | 
| Heart Failure Hospitalizations |  | 3-Month. 6-Month. | 
| New York Heart Association (NYHA) Class changes |  | Baseline. 3-Month. 6-Month. | 
| Changes in Quality of Life (QOL), as assessed by the Minnesota Living With Heart Failure Questionnaire |  | Baseline. 3-Month. 6-Month. | 
| Echocardiographic changes | Left ventricular end diastolic volume. Left ventricular end systolic volume. Left ventricular ejection fraction. Mitral regurgitation severity. | Baseline. 3-Month. 6-Month. | 
| Appropriate device interventions (anti-tachycardia pacing or shock) |  | 3-Month. 6-Month. | 
| Phrenic Nerve Complication Free Rate |  | 3-Month. 6-Month. | 
| Occurrence of atrial and ventricular arrhythmias (amount and duration [h/day]). |  | 3-Month. 6-Month. | 
| Flow-mediated vasodilation | Differences in FMD between groups | Baseline. 3-month. 6-month | 
| Packer's clinical composite score | Distribution of improved, unchanged and worsened patients as defined per Packer's clinical composite score | Baseline. 3-month. 6-month. | 
| 6-Minute-Walking-Distance | The distance walked by subjects during a 6 minutes walking test | Baseline. 3 Month. 6 Month. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Cardiac Resynchronization Therapy, non responders, MultiPoint Pacing (MPP)