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

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.

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