Multistage electrotherapy delivered through chronically-implanted leads terminates atrial fibrillation with lower energy than a single biphasic shock

Abstract

Objectives: The goal of this study was to develop a low-energy, implantable device-based multistage electrotherapy (MSE) to terminate atrial fibrillation (AF).

Background: Previous attempts to perform cardioversion of AF by using an implantable device were limited by the pain caused by use of a high-energy single biphasic shock (BPS).

Methods: Transvenous leads were implanted into the right atrium (RA), coronary sinus, and left pulmonary artery of 14 dogs. Self-sustaining AF was induced by 6 ± 2 weeks of high-rate RA pacing. Atrial defibrillation thresholds of standard versus experimental electrotherapies were measured in vivo and studied by using optical imaging in vitro.

Results: The mean AF cycle length (CL) in vivo was 112 ± 21 ms (534 beats/min). The impedances of the RA-left pulmonary artery and RA-coronary sinus shock vectors were similar (121 ± 11 Ω vs. 126 ± 9 Ω; p = 0.27). BPS required 1.48 ± 0.91 J (165 ± 34 V) to terminate AF. In contrast, MSE terminated AF with significantly less energy (0.16 ± 0.16 J; p < 0.001) and significantly lower peak voltage (31.1 ± 19.3 V; p < 0.001). In vitro optical imaging studies found that AF was maintained by localized foci originating from pulmonary vein-left atrium interfaces. MSE Stage 1 shocks temporarily disrupted localized foci; MSE Stage 2 entrainment shocks continued to silence the localized foci driving AF; and MSE Stage 3 pacing stimuli enabled consistent RA-left atrium activation until sinus rhythm was restored.

Conclusions: Low-energy MSE significantly reduced the atrial defibrillation thresholds compared with BPS in a canine model of AF. MSE may enable painless, device-based AF therapy.

Keywords: ASET; BPS; CS; DFT; HRP; LA; LPA; MSE; OAP; PV; RA; RAA; VSET; atrial fibrillation; atrial shock excitation threshold; cardioversion; coronary sinus; defibrillation; defibrillation threshold; high-rate pacing; left atrium; left pulmonary artery; low energy; multistage electrotherapy; optical action potential; pulmonary vein; right atrial appendage; right atrium; single biphasic shock; ventricular shock excitation threshold.

Copyright © 2014 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Figures

Figure 1. Chronically Implanted Lead Positions and Experimental Timeline

(A) Fluoroscopic images of the anatomic positions of chronically-implanted transvenous leads and subcutaneous (SC) access ports from left lateral (left panel) and left anterior oblique (right panel) views. (B) Schematic depiction of lead positions. Shocks were delivered from the right atrium (RA) coil to the left pulmonary artery (LPA) coil or the RA coil to the coronary sinus (CS) coil. (C) Experimental timeline showing model development and approximate times of defibrillation (defib) studies. AF = atrial fibrillation; HRP = high rate pacing; LA = left atrium; LV = left ventricle; PT = pulmonary trunk; RV = right ventricle; SVC = superior vena cava; Wk = week.

Figure 2. In Vivo Cardioversion of AF by BPS Versus MSE

(A) Defibrillation therapies tested. The left panel shows a single truncated exponential single biphasic shock (BPS). The right panel shows the multistage electrotherapy (MSE). Therapy in red was delivered through defibrillation coils, whereas the blue stage was delivered through the right atrial appendage pacing lead. (B) Surface electrogram and defibrillation threshold (DFT) of the sample in vivo atrial fibrillation (AF) terminations by using BPS and MSE. (C and D) Summary of in vivo atrial DFTs (n = 8) for BPS versus MSE. The peak shock voltage represents the maximum leading-edge voltage required for cardioversion by BPS or BPS delivered in Stage 1 of MSE. The total energy represents the sum of the energy of all stages of each therapy. Values are mean ± SE in C and median + quartiles in D.

Figure 3. DF Analysis of AF In Vitro

(A) In vitro tissue preparation of the endocardial canine atrium used to record optical action potentials (OAPs). Field of view is shown by the white box. (B) Spatial map of the dominant frequency (DF) during the sample in vitro AF episode. Example OAP traces during AF are shown from the selected regions. (C) Spatial pattern of regularity index. A value close to 1 represents a highly stable region with a narrow power distribution around DF. Regions close to the pulmonary veins (PVs) show increased stability compared with the free atrial wall. LCA = left coronary artery; RCA = right coronary artery; other abbreviations as in Figure 1.

Figure 4. Optical Mapping of Successful Termination of AF by MSE

The white box in the top left panel shows the field of view. Activation maps during a representative successful application of MSE with a peak voltage of 7 V/cm. (A and B) AF (C) Stage 1 shocks. (D to H) Stage 2 shocks. (I to K) select Stage 3 pulses. (L) Restored sinus rhythm. Abbreviations as in Figure 2.

Figure 5. Phase Analysis of Successful and Unsuccessful Termination of AF by MSE

Spatial maps of phase immediately after each intervention of MSE in sample successful and unsuccessful terminations. (A) Successful termination with a peak shock strength of 7 V/cm displayed with representative optical trace from middle of the field of view (orange trace). The panels show the evolution of phase during therapy application, beginning with an AF example, then proceeding to Stage 1 shocks 1 and 2; Stage 2 shocks 2, 4, and 6; and first stimulus of Stage 3. The middle left panel in A shows a representative optical action potential with the definition of phase. (B) Unsuccessful termination with a peak shock strength of 5 V/cm displayed with representative optical trace from the middle of the field of view (blue trace). Panels show evolution of failed response to therapy, starting from an AF example, then progressing to Stage 1 shocks 1 and 2; Stage 2 shocks 2 and 4 through 6; and first stimulus of Stage 3. Abbreviations as in Figure 2.