Improvement in Endothelial Dysfunction After Initiation of Anti-arrhythmic Therapy in Atrial Fibrillation Patients

This is a prospective, observational study that will examine endothelial dysfunction in atrial fibrillation before and after treatment with anti-arrhythmic agents and the extent to which baseline endothelial dysfunction improves after treatment.

Study Overview

• Status: Completed
• Conditions: Atrial Fibrillation
• Intervention / Treatment: Drug: Sotalol; Drug: Dofetilide

Detailed Description

This will be a prospective, observational study and roughly 60 patients will be recruited based on strict inclusion/exclusion criteria. Goal population includes adult patients with a diagnosis of paroxysmal or persistent atrial fibrillation seen in the electrophysiology clinic and admitted to the UPMC Presbyterian electrophysiology service for initiation of anti-arrhythmic medications.

The primary goal of the study will be to evaluate the degree of endothelial function recovery seen after initiating anti-arrhythmic medical therapy. We will assess genetic markers, arterial stiffness and vasodilation in response to acetylcholine iontophoresis, nitroprusside iontophoresis, local thermal hyperemia and reactive hyperemia. Laser speckle contrast imaging will be employed to evaluate the microvasculature. SphygmoCor (arterial tonometry) will be used to assess macrovasculature. Testing will be performed at baseline prior to the 1st dose of anti- arrhythmic therapy and repeated again 1-3 months later at outpatient follow-up visit. Additionally, follow-up phone calls or office visits will take place at 6 and 12 months after the initial data collection visit to document recurrence rate of atrial fibrillation.

• Study Type: Observational
• Enrollment (Actual): 12

Contacts and Locations

Study Locations

• United States
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15201
      • University of Pittsburgh Medical Center - Presbyterian University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: N/A
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

Adult patients with known or new diagnosis of either paroxysmal or persistent atrial fibrillation seen at the electrophysiology outpatient clinic and admitted to the electrophysiology service for initiation of anti-arrhythmic medications.

Description

Inclusion Criteria:

• Adult patients (18-75 years of age) with paroxysmal or persistent atrial fibrillation
• Patients who recovered from prior tachycardia induced cardiomyopathy will be allowed to enroll in the study.

Exclusion Criteria:

Exclusion criteria will include:

• age >75 years
• history of cardiomyopathy
• history of severe cardiac valvular disease
• history of coronary artery disease
• pulmonary artery hypertension
• congenital heart disease
• history of stroke
• chronic hypoxia
• recent worsening or flare up of obstructive or restrictive lung disease
• liver cirrhosis
• stage three or worse chronic kidney disease
• any major trauma or surgery within the preceding 3 months
• uncontrolled hyperthyroidism
• uncontrolled hypertension
• uncontrolled diabetes mellitus
• active malignancy
• poorly controlled connective tissue disease
• any acute or chronic inflammatory or infectious disease
• Patients who are already on class I or class III antiarrhythmic agents will be excluded from the study
• Patients on non-dihydropyridine calcium channel blockers and beta blockers will not be excluded from the study, as these agents are not considered anti-arrhythmics and are not hypothesized to affect endothelial function.

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort

Intervention / Treatment

Atrial Fibrillation Cohort; Adult patients with known or new diagnosis of either paroxysmal or persistent atrial fibrillation seen at the electrophysiology outpatient clinic and admitted to the electrophysiology service for initiation of anti-arrhythmic medications (dofetilide or sotalol).

Drug: Sotalol; The primary goal of the study will be to evaluate the change in endothelial function seen after initiating anti-arrhythmic medical therapy. Testing will be performed at baseline prior to the 1st dose of anti-arrhythmic therapy and again 1-3 months later at outpatient follow-up visit. We will record the resting flow (RF), biological zero (BZ) and peak flow (PF) as perfusion units (PU). Specifically, we will assess arterial stiffness and vasodilation in response to acetylcholine iontophoresis, nitroprusside iontophoresis, local thermal hyperemia and reactive hyperemia. Laser speckle contrast imaging will be employed to evaluate the microvasculature. SphygmoCor (arterial tonometry) will be used to assess macrovasculature.; Drug: Dofetilide; Same as described above with sotalol.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in microvascular endothelium dependent dilation following anti-arrhythmic therapy as measured in perfusion units	Change in microvascular endothelium dependent dilation (in response to acetylcholine) assessed with laser speckle contrast imaging after initiating antiarrhythmic medical therapy.	1 year

Secondary Outcome Measures

Outcome Measure	Time Frame
Correlation between microvascular endothelial dysfunction measured at baseline and atrial fibrillation recurrence.	1 year
Correlation between microvascular endothelial function improvement with antiarrhythmic medications and atrial fibrillation recurrence.	1 year
Correlation between microvascular endothelial function and atrial fibrillation severity represented by left atrial size and type of Afib (paroxysmal vs persistent).	1 year
Change in other vasodilation dysfunction indices measured after initiating antiarrhythmic medical therapy.	1 year
Correlation between vasodilation dysfunction indices measured at baseline and atrial fibrillation recurrence.	1 year
Whether missense mutation in Cyb5R3 T117S can predict atrial fibrillation recurrence.	1 year
Whether missense mutation in Cyb5R3 T117S is correlated with atrial fibrillation severity.	1 year

Collaborators and Investigators

• Sponsor: Samir Saba
• Investigators: Principal Investigator: Samir Saba, MD, Chief, Division of Cardiology, University of Pittsburgh Medical Center

Study record dates

Study Major Dates

• Study Start (Actual): May 1, 2019
• Primary Completion (Actual): December 31, 2020
• Study Completion (Actual): December 31, 2020

Study Registration Dates

• First Submitted: October 14, 2019
• First Submitted That Met QC Criteria: October 14, 2019
• First Posted (Actual): October 16, 2019

Study Record Updates

• Last Update Posted (Actual): January 14, 2021
• Last Update Submitted That Met QC Criteria: January 11, 2021
• Last Verified: January 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Heart Diseases; Cardiovascular Diseases; Arrhythmias, Cardiac; Atrial Fibrillation; Physiological Effects of Drugs; Adrenergic beta-Antagonists; Adrenergic Antagonists; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Anti-Arrhythmia Agents; Autonomic Agents; Peripheral Nervous System Agents; Membrane Transport Modulators; Sympatholytics; Potassium Channel Blockers; Sotalol; Dofetilide
• Other Study ID Numbers: STUDY18090003

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