Role of Cardiac Biomarkers in Prediction of Outcome in Atrial Fibrillation Patients Undergoing Catheter Ablation (IMPACTII)

Association of Cardiac Biomarkers With AF Ablation

The purpose of this study is to assess if pre-ablation levels of inflammatory biomarkers serve as independent predictors of procedure outcome To evaluate the inflammatory activation following catheter ablation by measuring serum-biomarker levels 24-hours after the procedure and examine the predictive role in procedure success To study the association of certain biomarkers with specific types of AF (paroxysmal or persistent or long standing persistent)

Study Overview

• Status: Completed
• Conditions: Atrial Fibrillation
• Intervention / Treatment: Procedure: Radio-frequency catheter ablation

Detailed Description

Specific Aim: The purpose of this prospective study is to evaluate the role of inflammatory biomarkers in predicting procedure-outcome in AF patients undergoing catheter ablation.

Background: AF is the most common arrhythmia in clinical practice, affecting > 2.3 million people in US. It increases dramatically with age and is seen in as many as 9% of individuals by the age of 80 (1). A major cause of stroke, AF is also associated with a 2-fold increase in mortality (1).

Symptomatic AF has been demonstrated to be consistently associated with elevated inflammatory activity in the atrial tissue as evidenced by the facts that AF occurs in 40% of patients following cardiac bypass surgery and 50% of patients undergoing valvular surgery (2). Recent studies have also demonstrated that elevated CRP level can increase the risk of AF up to 31% (2). Oxidative damage experienced during AF leads to myocardial necrosis which in turn induces low-grade inflammation resulting in eventual fibrosis of the atrial myocardium. Thus, inflammation can be responsible for adverse structural and electrical remodeling of the cardiac tissue which can further perpetuate the existence, maintenance, and recurrence of this arrhythmia.

Radiofrequency catheter ablation (RFCA) has evolved as a promising curative therapy for drug-refractory AF. However, the recurrence of AF after RFCA is a common clinical problem, occurring in 25-50% of patients in the follow-up period (3) and some patients undergo multiple ablation procedures before being cured of the arrhythmia. Published retrospective studies have demonstrated that systemic inflammation generated during AF ablation is associated with fewer early arrhythmia recurrences (4). Therefore, measurement of inflammatory markers within 24 hours of RFCA could be helpful in further exploration of any association between the degree of inflammatory activation and procedure outcome.

Myriad Rules-Based Medicine, Inc (Myriad RBM) in Austin, TX 78759 has developed biomarker panels that have been validated to detect early signs of inflammation. Myriad RBM will process the blood samples on a preliminary panel of 77 biomarkers, identified to be possible predictors of procedural outcome in RFCA in AF patients.

Study design:

This study will assess a panel of 77 biomarkers in human serum samples that have been identified by the pilot study results as the potential predictors of procedural outcome in catheter ablation for AF. The study population will consist of 150 volunteering patients with AF undergoing RFCA. Blood samples will be collected at two time points from each patient; one at baseline and the other in the morning after the procedure.

Study Procedure:

For each patient, one 8.5 ml tube of whole blood will be collected via venipuncture before and the morning after the ablation procedure.

Ablation Procedure:

Standard radiofrequency catheter ablation procedure will occur in accordance with the physician's discretion.

Blood sample collection:

The whole blood sample will be collected in a Serum Separator Tube (SST) using BD venipuncture procedure, and labeled with an anonymous patient identifier. Only clinical research staff will be able to identify study participants.

Following collection, the samples will be centrifuged for 15 minutes at 900Xg at room temperature, within two hours of collection. Plasma, located as a clear straw-color fluid at the top of the specimen, would be transferred to another sterile tube and stored at -200 C. Samples will be picked up weekly by the RBM team to be stored at -800 C until the end of the study, when all samples will be simultaneously analyzed.

Limited information will also be recorded such as age, gender, height, weight, caffeine intake and information about medications, smoking history, family history of atrial fibrillation (if known), and information about the outcome of the procedure. Researchers at RBM will be blinded to the patient history and demographic data.

After this study is complete the researchers at RBM will store any leftover blood. The researchers may use the leftover samples in future unspecified research studies, which may or may not be related to the AF procedure. Even if the blood sample is used for other studies, the researchers will not have a way to identify the patient.

Follow-Up:

At the 6 and 12 month time points, information will be collected from the medical record regarding recurrence of AF.

Risk Analysis:

Minor risks associated with a venous blood draw may include fainting or bruising, pain or discomfort and a 1/1000 risk of infection at the site where blood is drawn.

• Study Type: Observational
• Enrollment (Actual): 155

Contacts and Locations

Study Locations

• United States
  • Texas
    • Austin, Texas, United States, 78727
      • Texas Cardiac Arrhythmia Institute, St. david's Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

Patients undergoing catheter ablation for atrial fibrillation

Description

Inclusion Criteria:

Age: 50-70 years

• Patients undergoing catheter ablation of atrial fibrillation
• Able and willing to give written consent

Exclusion Criteria:

• Reversible causes of AF such as pericarditis and hyperthyroidism

  • Associated chronic inflammatory diseases such as chronic gingivitis or peri-odontitis, rheumatoid Arthritis, IBD including Ulcerative Colitis and Crohn's disease, Lupus, Ankylosing Spondylitis, COPD, psoriasis, vasculitis
  • Any other co-morbid conditions except Diabetes and hypertension
  • Patients taking long-term anti-inflammatory, steroid medication, or immune suppression medication.

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Arrhythmia recurrence	Patients will be monitored for arrhythmia recurrence for 1 year after the ablation procedure. At the end of the study, biomarker data will be analyzed to see any predictive association with AFib recurrence	1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Left atrial scar	if atrial scar is detected during the first ablation procedure, we will assess the association of scar with any of the 77 biomarkers, specifically those indicating fibrosis	During ablation procedure

Collaborators and Investigators

• Sponsor: Texas Cardiac Arrhythmia Research Foundation

Study record dates

Study Major Dates

• Study Start: July 1, 2014
• Primary Completion (Actual): April 1, 2015
• Study Completion (Actual): May 1, 2016

Study Registration Dates

• First Submitted: July 31, 2014
• First Submitted That Met QC Criteria: August 1, 2014
• First Posted (Estimate): August 4, 2014

Study Record Updates

• Last Update Posted (Actual): October 19, 2017
• Last Update Submitted That Met QC Criteria: October 17, 2017
• Last Verified: October 1, 2017

More Information

Terms related to this study

• Keywords: atrial fibrillation, catheter ablation, blood-biomarkers
• Additional Relevant MeSH Terms: Pathologic Processes; Heart Diseases; Cardiovascular Diseases; Arrhythmias, Cardiac; Atrial Fibrillation
• Other Study ID Numbers: TCAI_IMPACT II