Use of Adenosine to Determine the Electrophysiological Mechanism of Premature Ventricular Contractions

Unblinded, controlled, non-randomized, mechanistic study to determine whether physiological mechanisms underlying PVC are sensitive to adenosine. One hundred subjects undergoing clinically-indicated, standard-of-care cardiac electrophysiology study (EPS) procedure for PVCs will receive adenosine and/or verapamil to learn if their arrhythmias are inducible similarly to sustained ventricular tachycardia.

Study Overview

• Status: Recruiting
• Conditions: Premature Ventricular Contraction (PVC)
• Intervention / Treatment: Drug: Adenosine

Detailed Description

The cellular mechanism of premature ventricular contractions (PVCs) is unknown. The investigators have previously observed that 5% of patients in the investigators electrophysiology laboratory with ventricular outflow tract PVCs have inducible sustained ventricular tachycardia (VT) that behaves in a manner similar to patients who present clinically with sustained ventricular tachycardia, i.e., sensitive to adenosine and triggered activity. This suggests that outflow arrhythmias may be a continuum of a single mechanism.

Adenosine is known to terminate ventricular arrhythmias that are due to triggered activity (ref Lerman). To study the effects of adenosine on PVC, the investigators will administer Verapamil to slow down the heart initially and adenosine after catheters are introduced to patients who are being treated for symptomatic PVC and have consented to treatment with an invasive electrophysiology study and catheter ablation. The investigators will observe if there is any effect of reduced PVC following adenosine administration.

The investigators hypothesize that PVC will be suppressed by exogenous adenosine and/or verapamil. The information from this study will elucidate the underlying cellular mechanism of this common arrhythmia. Such knowledge could potentially lead to developing therapeutic targets. Moreover, it will have potential clinical applications for inducing outflow tract PVCs/VT in patients whose arrhythmia is suppressed at the time of their invasive electrophysiology study.

Analysis of the Holter recording of premature ventricular contractions:

Analysis of the PVC coupling intervals can be helpful for delineating the mechanism of PVCs. Holter monitors are being obtained on these patients prior to ablation as part of standard of care. Holters monitors, if performed at our institution, will be analyzed in detail in a retrospective fashion. Holter reports from 1/1/2015 - 5/15/2019 will be reviewed.

Specifically, evaluating the time intervals between PVCs and normal heart beats may elucidate potential arrhythmia mechanism as triggered activity or modulated parasystole. Since a subject has approximately 100,000 heart beats in 24 hours, the Holter data have to be read by a converter file and outputted to an Excel file for our further analysis. The investigators do not have access to a converter file and it is not commercially available. The investigators will send the de-identified data to Dr. Mortara at UCSF. The investigators will then analyze the timing intervals among PVCs and normal heart beats. It should be noted that these Holters are obtained as part of a patient's normal evaluation and are not obtained for the purposes of this study.

• Study Type: Interventional
• Enrollment (Estimated): 100
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: James E Ip, M.D; Phone Number: 212 746 2158; Email: jei9008@med.cornell.edu
• Study Contact Backup: Name: Dolores T Reynolds, BSN; Phone Number: 212 746 4617; Email: dtr2001@med.cornell.edu

Study Locations

• United States
  • New York
    • New York, New York, United States, 10065
      • Recruiting
      • Weill Cornell Medicine
      • Contact: James E Ip, M.D; Phone Number: 212 746 2158; Email: jei9008@med.cornell.edu
      • Contact: Dolores T Reynolds, BSN; Phone Number: 212 746 4617; Email: dtr2001@med.cornell.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 66 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Diagnosis of premature ventricular contractions (PVCs)
• Scheduled to undergo an electrophysiology study with the intention of performing cardiac ablation for the treatment of PVCs
• Male or female between the ages of 18 and 70 years
• Capable of giving informed consent

Exclusion Criteria:

• Any structural heart disease
• Coronary artery disease (≥ 70% stenosis)
• Current treatment with anti-arrhythmic drugs
• Pregnant
• Asthma (if administering adenosine)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Other: Adenosine/ Verapamil Arm; Adenosine: 0.84 mg/kg IV (140 mcg/kg/minute IV for 6 minutes) Verapamil: 0.15 mg/kg IV Adenosine is known to terminate ventricular arrhythmias that are due to triggered activity (ref Lerman). To study the effects of adenosine on PVC, the investigators will administer Verapamil to slow down the heart initially and adenosine after catheters are introduced to patients who are being treated for symptomatic PVC and have consented to treatment with an invasive electrophysiology study and catheter ablation.

Drug: Adenosine; Adenosine: 0.84 mg/kg (140 mcg/kg/minute IV for 6 minutes) Verapamil 0.15 mg/kg; Other Names: Verapamil 0.15 mg/kg

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Effects of Adenosine on premature ventricular contractions (PVCs) as measured by EKG;	The metrics that will be collected will be: Baseline frequency of premature ventricular contractions (PVCs); Frequency of premature ventricular contractions (PVCs) during adenosine administration	baseline
Effects of verapamil on premature ventricular contractions (PVCs) as measured by EKGs.	The metrics that will be collected will be: Baseline frequency of premature ventricular contractions (PVCs); Frequency of premature ventricular contractions (PVCs) during verapamil administration	baseline

Collaborators and Investigators

• Sponsor: Weill Medical College of Cornell University
• Investigators: Principal Investigator: James E Ip, M.D, Weill Medical College of Cornell University

Study record dates

Study Major Dates

• Study Start (Actual): February 13, 2017
• Primary Completion (Estimated): December 31, 2025
• Study Completion (Estimated): December 31, 2025

Study Registration Dates

• First Submitted: June 29, 2017
• First Submitted That Met QC Criteria: July 13, 2017
• First Posted (Actual): July 14, 2017

Study Record Updates

• Last Update Posted (Actual): August 3, 2025
• Last Update Submitted That Met QC Criteria: July 30, 2025
• Last Verified: July 1, 2025

More Information

Terms related to this study

• Keywords: Subjects; diagnosed
• Additional Relevant MeSH Terms: Cardiac Conduction System Disease; Urogenital Diseases; Cardiovascular Diseases; Pathologic Processes; Female Urogenital Diseases and Pregnancy Complications; Heart Diseases; Obstetric Labor, Premature; Obstetric Labor Complications; Pregnancy Complications; Arrhythmias, Cardiac; Cardiac Complexes, Premature; Premature Birth; Ventricular Premature Complexes; Calcium-Regulating Hormones and Agents; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Sensory System Agents; Analgesics; Neurotransmitter Agents; Anti-Arrhythmia Agents; Membrane Transport Modulators; Purinergic Agents; Calcium Channel Blockers; Vasodilator Agents; Purinergic P1 Receptor Agonists; Purinergic Agonists; Verapamil; Adenosine
• Other Study ID Numbers: 1609017561

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes