Acute Mechanical Response to Anti-arrhythmic Drug Therapy

Study Overview
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Brief Summary
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The aim of this study is to determine if anti-arrhythmic drugs with a sodium channel-blocking mechanism exert a detrimental electromechanical effect on cardiac function in patients depending upon baseline intraventricular conduction and left ventricular function.

Detailed Description
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Amiodarone therapy is used frequently for control of ventricular arrhythmias in patients who receive painful shocks from an implantable cardioverter-defibrillator (ICD). Data in post-myocardial infarction (MI) patients and ICD patients suggest that amiodarone is mortality-neutral; it neither confers increased nor decreased mortality. However, these data are derived from patients largely with normal intraventricular conduction, manifesting as a QRS complex duration on the surface ECG <120 ms. Amiodarone, in addition to potassium-channel blocking effects, is a sodium channel-blocker. Because sodium channels mediate cardiac depolarization, and a QRS complex >120 ms is indicative of abnormal depolarization, amiodarone may not be benign in patients with such conduction defects. Patients with cardiac resynchronization therapy-defibrillators (CRT-D), who all have abnormal baseline intraventricular conduction, may therefore be adversely affected by amiodarone. Anecdotal clinical data suggest that this may be the case, but the question of amiodarone's cardiac safety profile in CRT patients has never been studied.

Official Title
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Acute Mechanical Response to Anti-arrhythmic Drug Therapy

Conditions
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Arrhythmias

Intervention / Treatment
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* Drug: Procainamide


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Implanted cardiac device requiring generator change and a new device Able to give informed consent Exclusion Criteria: Current membrane-active anti-arrhythmic Glomerular filtration rate (GRF)<30 milliliters (mL)/min MAP<60 mmHg Known intolerance to procainamide Pregnancy Age <18 or >85 years old Baseline QT interval >480 ms (500 ms if paced)

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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Accepts Healthy Volunteers

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: observational<br>All patients will undergo 12-lead ECG and transthoracic echocardiography on the day of the study. These studies will be performed on patients as their previously implanted device is reprogrammed to pace in different modes. Patients will then receive an infusion of procainamide (12 mg/kg up to a maximum of 1 g) at a rate of 20 mg/min. Repeat ECG and echocardiograms will then be performed. The patient's device will be programmed to a specific setting before and after the procainamide infusion. | Drug: Procainamide<br>* the procainamide will be infused at 12mcg/kg up to a max of 1 gram at a rate of 20mg/min which will take up to 1 hour to infuse<br>* Other names: procan;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in QRS duration | the QRS waveform measurements will be calculated on the EKG prior to and after the procainamide infusion | baseline and 1 hour post infusion | 
| changes in left ventricular volumes as measured via echocardiogram | the left ventricular volume will be calculated via echocardiogram pre and post procainamide infusion | baseline and 1 hour post infusion | 
| changes in ejection fraction as measured via echocardiogram | ejection fraction will be calculated via echocardiogram pre and post procainamide infusion. | baseline and 1hour post infusion | 
| changes in RV-LV electrical activation (in CRT patients) | The RV-LV electrical activation will be assessed during the device interrogation pre and post procainamide infusion. | baseline and 1 hour post infusion | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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anti-arrhythmic therapy