Atropine vs Isoprenaline in the Invasive Diagnosis of Arrhythmias

Comparison of the Clinical Utility of Atropine and Isoprenaline in the Invasive Diagnosis of Arrhythmias

During electrophysiological study (EPS) multiple drugs are used to reveal arrhythmias and/or conductive system disorders. Two most often used agents are atropine and isoprenaline. Due to their distinct pharmacological properties, they are affecting myocardium in different manner. Those dissimilarities can affect the EPS course and long-term prognosis. The aim of presented study is to evaluate the optimal protocol of pharmacotherapy during EPS.

Study Overview

• Status: Not yet recruiting
• Conditions: Cardiac Arrhythmia; Supraventricular Arrhythmia
• Intervention / Treatment: Drug: Comparison of atropine and isoprenaline

Detailed Description

Electrophysiological study (EPS) is essential tool for heart rhythm disorders diagnostic. Inducibility of arrhythmia before ablation to confirm the diagnosis and inability to do so after the procedure is crucial for long-term success. Multiple drugs are used to reveal arrhythmias and/or conductive system disorders. Two most often used are atropine and isoprenaline. Atropine is a natural, selective antagonist of cholinergic receptors M1 and M2. It reverses the inhibitory effect of vagal nerve on myocardium. This improves sinus node automatism and conduction in atrioventricular node. Isoprenaline is a preferential agonist of beta-1-adrenergic receptors. It has bathmotropic and chronotropic effect. During daily clinical practice those two drugs are often used interchangeably. However, differences in pharmacokinetics and pharmacodynamics may affect the results. There are lack of data directly comparing those two agents. There are isolated evidences that arrhythmia inducibility rate after the ablation differs between those two drugs. This may lead to the misconception of ablation as successful. The aim of presented study is to evaluate the optimal protocol of pharmacotherapy during EPS.

• Study Type: Interventional
• Enrollment (Estimated): 200
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Krzysztof Kaczmarek, MD, PhD; Phone Number: +48 42 201 43 60; Email: krzysztof.kaczmarek@umed.lodz.pl

Study Locations

• Poland
  • Lodz, Poland, 93-216
    • Department of Electrocardiology Medical University of Lodz

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Patients with indication for electrophysiological study according to present guidelines of European Society of Cardiology

Exclusion Criteria:

• Not willing or incapable to give written informed consent.
• Previous diagnosed ventricle tachycardia or fibrillation
• Previous diagnosed atrial fibrillation or flutter
• Glaucoma (contraindication for atropine)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Atropine; Patients in whom during electrophysiological study atropine will be used. I.v. bolus of 0.01 mg/kg b.w. will be administered to reach the increase of heart rate of 25% or up to 130/min. If necessary, dose will be increased every 5 minutes until mention above parameters are achieved. Maximum dose will be 0.4 mg/kg b.w.	Drug: Comparison of atropine and isoprenaline; Comparison of heart conductive system and arrhythmia inducibility after using atropine or isoprenaline
Active Comparator: Isoprenaline; Patients in whom during electrophysiological study isoprenaline will be used. Continuous i.v. infusion of 0.01 mcg/kg b.w./min will be administered to reach the increase of heart rate of 25% or up to 130/min. If necessary, dose will be doubled every 5 minutes until mention above parameters are achieved. Maximum dose will be 20 mcg/min.	Drug: Comparison of atropine and isoprenaline; Comparison of heart conductive system and arrhythmia inducibility after using atropine or isoprenaline

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Evaluation of sino-atrial conduction time	Sino-atrial conduction time (ms) during programed atrial stimulation will be assessed to examine the function of sinus node.	During the procedure
Evaluation of sinus node recovery time	Sinus node recovery time (ms) during programed atrial stimulation will be assessed to examine the function of sinus node.	During the procedure
Evaluation of anterograde atrioventricular conduction	Anterograde Wenkebach point (ms) and effective refractory period of atrioventricular node (ms) during programed atrial stimulation will be assessed.	During the procedure
Evaluation of retrograde atrioventricular conduction	Retrograde Wenkebach point (ms) and effective refractory period of atrioventricular node (ms) during programed ventricular stimulation will be assessed.	During the procedure
Arrhythmia inducibility	Inducibility of anticipated arrythmia before and after drug administration and after eventual ablation.	During the procedure
Long-term success rate	Recurrence of clinical arrhythmia during 12 months of observation	12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of adverse events during the electrophysiological study.	Analysis of adverse events during the electrophysiological study according to used drug. Adverse events includes: death, stroke, cardiogenic shock, anaphylaxis, myocardial infarction, electric storm.	During the procedure
Incidence of adverse events during the 12-month follow up.	Analysis of adverse events during the 12-month follow up according to used drug. Adverse events includes: death, stroke, cardiogenic shock, anaphylaxis, myocardial infarction, electric storm.	12 months
Length of the procedure	Analysis of the whole procedure time according to used drug.	During the procedure
Procedure time form drug administration till the end.	Analysis of the procedure time form atropine/isoprenaline administration till the end.	During the procedure

Collaborators and Investigators

• Sponsor: Medical University of Lodz

Publications and helpful links

General Publications

• Stellbrink C, Diem B, Schauerte P, Brehmer K, Schuett H, Hanrath P. Differential effects of atropine and isoproterenol on inducibility of atrioventricular nodal reentrant tachycardia. J Interv Card Electrophysiol. 2001 Dec;5(4):463-9. doi: 10.1023/a:1013258331023.
• Toda I, Kawahara T, Murakawa Y, Nozaki A, Kawakubo K, Inoue H, Sugimoto T. Electrophysiological study of young patients with exercise related paroxysms of palpitation: role of atropine and isoprenaline for initiation of supraventricular tachycardia. Br Heart J. 1989 Mar;61(3):268-73. doi: 10.1136/hrt.61.3.268.
• Hatzinikolaou H, Rodriguez LM, Smeets JL, Timmermans C, Vrouchos G, Grecas G, Wellens HJ. Isoprenaline and inducibility of atrioventricular nodal re-entrant tachycardia. Heart. 1998 Feb;79(2):165-8. doi: 10.1136/hrt.79.2.165.

Study record dates

Study Major Dates

• Study Start (Estimated): November 9, 2023
• Primary Completion (Estimated): September 1, 2025
• Study Completion (Estimated): December 1, 2025

Study Registration Dates

• First Submitted: January 12, 2022
• First Submitted That Met QC Criteria: October 9, 2023
• First Posted (Actual): October 13, 2023

Study Record Updates

• Last Update Posted (Actual): October 13, 2023
• Last Update Submitted That Met QC Criteria: October 9, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Keywords: Ablation; Atropine; Electrophysiological study; Isoprenaline; Supraventricular arrhythmia
• Additional Relevant MeSH Terms: Pathologic Processes; Heart Diseases; Cardiovascular Diseases; Arrhythmias, Cardiac; Physiological Effects of Drugs; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Anti-Arrhythmia Agents; Parasympatholytics; Autonomic Agents; Peripheral Nervous System Agents; Muscarinic Antagonists; Cholinergic Antagonists; Cholinergic Agents; Protective Agents; Adrenergic Agonists; Cardiotonic Agents; Adjuvants, Anesthesia; Bronchodilator Agents; Anti-Asthmatic Agents; Respiratory System Agents; Adrenergic beta-Agonists; Sympathomimetics; Mydriatics; Atropine; Isoproterenol
• Other Study ID Numbers: RNN/327/20/KE

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No