A model of atrial fibrillation in dogs with chronic heart failure

Document Type

Conference Proceeding

Publication Date

7-26-2024

Publication Title

Eur J Heart Fail

Abstract

Background: Atrial fibrillation (AF) is the most common rhythm disorder in humans, affecting an estimated 38 million people Worldwide and is particularly common in patients with heart failure (HF) where it contributes to early mortality. Various large animal models of lone AF exist but a robust model of AF in the setting of chronic HF is lacking. We evaluated the ease of induction, duration, and reproducibility of AF in a well-established coronary microembolization model of HF with reduced ejection fraction (EF) as a potential pre-clinical tool for assessing the safety and efficacy of novel therapies targeting AF in HF patients. Methods: 17 anesthetized HF dogs (LV EF <35%) weighing between 21.0 and 28.2 kg were studied. A Josephson quadripolar electrophysiology catheter positioned in the high right atrium (RA) was used. The RA was stimulated for 60 sec at increments of 100 beats/min, starting from a rate of 400 beats/min up to a rate of 600 beats/min. If sustained AF induction was not seen, an atrial extra-stimuli technique (up to 5 extra-stimuli) was used at a drive train of 600 msec (30 cycles). After AF was induced, the duration of AF was assessed for up to 600 seconds; if AF did not terminate spontaneously within 600 seconds, AF was terminated by Direct Current cardioversion at 100J. A second AF induction was performed consecutively for confirmation and an average of both AF inductions was used for all parameters. This process was repeated 2 additional times at 2 hour intervals to assess reproducibility. AF induction threshold and duration were each assigned a score of 1 to 8 such that a combined score of 16 would indicate low AF induction threshold and long AF sustainability whereas a score of 2 would indicate high threshold for AF induction and low AF sustainability. Results: Data are shown in the Table. On average, the induction threshold was approximately 500 beats/min and typical AF duration was 300 to 400 seconds, indicating relatively low AF threshold and substantial duration. The pacing threshold for AF induction, AF duration, and combined score were relatively stable across all 3 timepoints (baseline, 2 hours, and 4 hours) with no statistically significant differences. Conclusions: These results point to a robust model of AF induction in dogs with chronic HF characterized by low AF induction threshold and high sustained AF duration that are easily quantifiable and relatively stable. This model may represent a useful pre-clinical tool for evaluating the efficacy of therapies targeting AF in the setting of HF.

Volume

26

First Page

45972

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