# Mapping and Targeting Focal Sources Before and After Surgical Ablation of Atrial Fibrillation

> **NIH NIH R01** · CASE WESTERN RESERVE UNIVERSITY · 2020 · $362,250

## Abstract

Project Summary/Abstract
 Atrial fibrillation (AF) is the most common tachyarrhythmia, with the number of Americans diagnosed
estimated at more than six million. It is associated with an increased risk of stroke, heart failure, and all-cause
mortality. In patients with paroxysmal AF, which most often is initiated by triggers from the pulmonary veins
(PVs), pulmonary vein isolation (PVI) has been relatively effective in treating AF. However, in patients with
persistent and long-standing persistent (LSP) AF, ablation treatment of AF, which includes PVI, has been only
modestly effective because of the lack of patient-specific “mechanistic” targets to ablate. As a result, the
ablation procedure is largely an empiric “one size fits all” approach. To emphasize that fact, recent clinical trials
in patients with persistent and LSP AF involving endocardial catheter ablation or surgical ablation showed that
there was no significant difference in the rate of freedom from AF between patients who underwent PVI alone
and those who underwent PVI plus additional empiric ablation lesion sets. Furthermore, ablation lesions
beyond the PVI significantly increased the need for implantation of a permanent pacemaker. All this supports
the need for 1) identifying the mechanism(s) that maintain AF by activation pattern; 2) understanding the
effects of each ablation lesion set on atrial activation patterns responsible for maintaining AF so that we can
determine what changes in activation patterns created by the ablation lesion are critical for terminating AF and
preventing its recurrence. Thereby, ablation therapy of persistent and LSP AF could change from a largely
empiric approach to a patient-specific targeted approach. Our recent studies using simultaneous, biatrial, high
density (510 - 512 electrodes), epicardial contact mapping in patients with persistent and LSP AF undergoing
open heart surgery found that wave fronts emanating from focal sources and breakthrough sites maintained
AF. Also, our preliminary studies in patients with persistent and LSP AF showed that AF was still present
immediately after surgical ablation, and was associated with continued activation patterns described above.
The central hypothesis of this proposal is that persistent AF after surgical ablation is due to the continuation of
baseline focal sources maintaining AF, and that interrupting their activation will terminate AF. The hypothesis
to be tested has three specific aims: Aim 1 is to identify focal sources in patients with persistent and LSP AF.
Aim 2 is to test the hypothesis that a continuation of wave fronts emanating from focal sources after surgical
ablation (PVI ± additional linear ablation lines) maintains AF. We will investigate the effects of each ablation
lesion set on the activation behavior of baseline focal sources and breakthrough sites. Aim 3 is to test the
hypothesis that targeted ablation of focal sources will reliably terminate AF. We will develop an efficient
ablation ...

## Key facts

- **NIH application ID:** 9951105
- **Project number:** 5R01HL146463-02
- **Recipient organization:** CASE WESTERN RESERVE UNIVERSITY
- **Principal Investigator:** Seungyup Lee
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $362,250
- **Award type:** 5
- **Project period:** 2019-07-01 → 2024-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9951105

## Citation

> US National Institutes of Health, RePORTER application 9951105, Mapping and Targeting Focal Sources Before and After Surgical Ablation of Atrial Fibrillation (5R01HL146463-02). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/9951105. Licensed CC0.

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