Impact of Anxiety on Cardiac Substrate Modification in Women With Atrial Fibrillation Undergoing Catheter Ablation (AWARE)

This pilot study aims to assess the impact of anxiety on the cardiac substrate remodeling in female patients with paroxysmal and persistent atrial fibrillation (AF).

Study Overview

• Status: Unknown
• Conditions: Atrial Fibrillation
• Intervention / Treatment: Procedure: Catheter ablation

Detailed Description

Hypothesis: High level of anxiety promotes remodeling of cardiac substrate via persistent inflammation, resulting in an increase in the prevalence of left atrial scar and non-pulmonary vein (non-PV) triggers in women with AF.

Rationale: Anxiety is generally defined as a psycho-biological emotional state or reaction that consists of unpleasant feelings of tension, apprehension, nervousness, and worry, and activation of the autonomic nervous system. This disorder is typically more common in women than men. There is considerable evidence to suggest close interactions between anxiety and inflammation and inflammation and AF.

Earlier studies have documented strong association between anxiety and inflammation as shown by high levels of inflammatory biomarkers such as C-reactive protein (CRP), total white blood cell (TWBC) count, fibrinogen and interleukin-6 in patients with anxiety. Chronic inflammation results in structural remodeling of the atrial architecture such as fibrotic changes that supports genesis and perpetuation of AF. In cardiac fibrosis, myocytes coupled with fibroblasts can undergo early depolarization resulting in increased ectopic beats and repetitive firing leading to the origin of non-pulmonary vein (non-PV) drivers. Left atrial scar is another known consequence of cardiac fibrosis. Therefore, it is prudent to hypothesize that high level of anxiety for prolonged period results in structural remodeling of cardiac substrates evidenced by increased prevalence of left atrial scar and non-PV triggers in female patients with paroxysmal and persistent AF.

Scar and non-PV triggers are known independent predictors of arrhythmia recurrence in AF patients undergoing catheter ablation. Recurrences of AF, despite complete PV disconnection, strongly suggest an important possible role of these foci in serving as a source for the persistence of this arrhythmia. Altered conduction and barriers resulting from the atrial scar form the critical circuits for intra-atrial re-entry that promotes AF persistence.

Recent progress in technology and knowledge have provided better understanding and allowed the electrophysiologists to improve on the ablation procedure in order to make it more safe and effective. However, there are still scores of unanswered questions in this relatively young research domain, one of which is if anxiety impacts cardiac substrate remodeling that potentially influences ablation-outcome. Also, of note, anxiety affects how patients perceive their illness, particularly for women, and influence healthcare utilization and economic burden. Therefore, if the role of anxiety would be ascertained, timely intervention of the same would lead to improvement in the success rate of the ablation therapy in females that highly dominate this subset of AF population.

Study Design: This pilot study will prospectively enroll 152 consenting female patients undergoing catheter ablation for AF. Eligible patients will be enrolled after signing informed consent, approved by Institutional Review Board of the participating institution.

• Study Type: Interventional
• Enrollment (Anticipated): 152
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Texas
    • Austin, Texas, United States, 78705
      • Recruiting
      • Texas Cardiac Arrhythmia Institute, St. David's Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

1. Age: ≥ 18 years
2. Sex: female
3. Undergoing catheter ablation for paroxysmal or persistent AF
4. Able and willing to provide written informed consent

Exclusion Criteria:

1. Receiving behavioral therapy or medications for the anxiety disorder
2. On hormonal supplement
3. On long-term steroid or anti-inflammatory drugs

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Group 1: with baseline anxiety+catheter ablation; Baseline anxiety will be defined as; Cardiac Anxiety Questionnaire (CAQ) score >2.14 Hospital Anxiety and Depression Questionnaire (HAD) >7 State-Trait Anxiety Inventory (STAI): State-anxiety score >40	Procedure: Catheter ablation; Pulmonary vein antrum isolation (PVAI) plus entire posterior wall plus coronary sinus plus left part of the septum. This intervention will be received by all as standard of care; Other Names: RFCA
Active Comparator: Group 2: Without baseline anxiety + catheter ablation; Cardiac Anxiety Questionnaire (CAQ) score <2.14 Hospital Anxiety and Depression Questionnaire (HAD) <7 State-Trait Anxiety Inventory (STAI): State-anxiety score <40	Procedure: Catheter ablation; Pulmonary vein antrum isolation (PVAI) plus entire posterior wall plus coronary sinus plus left part of the septum. This intervention will be received by all as standard of care; Other Names: RFCA

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Correlation between baseline anxiety score and prevalence of left atrial scar and non-pulmonary vein triggers	intraoperative

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Correlation of baseline anxiety score with scar severity		intraoperative
Correlation of baseline TWBC and CRP level with the anxiety score		baseline
Change in CAQ score		12 months
Recurrence status	Recurrence of AF/ AFlutter/ atrial tachycardia off or on anti-arrhythmic drugs	1 year
Change in HAD score		12 months
Change in State-anxiety		12 months

Collaborators and Investigators

• Sponsor: Texas Cardiac Arrhythmia Research Foundation
• Investigators: Principal Investigator: Mitra Mohanty, MD MS FHRS, Texas Cardiac Arrhythmia Research Foundation

Study record dates

Study Major Dates

• Study Start: September 1, 2015
• Primary Completion (Anticipated): July 1, 2020
• Study Completion (Anticipated): July 1, 2022

Study Registration Dates

• First Submitted: September 3, 2015
• First Submitted That Met QC Criteria: September 9, 2015
• First Posted (Estimate): September 11, 2015

Study Record Updates

• Last Update Posted (Actual): September 10, 2019
• Last Update Submitted That Met QC Criteria: September 9, 2019
• Last Verified: September 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Heart Diseases; Cardiovascular Diseases; Arrhythmias, Cardiac; Atrial Fibrillation
• Other Study ID Numbers: TCAI_AWARE

Plan for Individual participant data (IPD)

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