Low-energy multistage atrial defibrillation therapy terminates atrial fibrillation with less energy than a single shock

Abstract

Background: Implantable device therapy of atrial fibrillation (AF) is limited by pain from high-energy shocks. We developed a low-energy multistage defibrillation therapy and tested it in a canine model of AF.

Methods and results: AF was induced by burst pacing during vagus nerve stimulation. Our novel defibrillation therapy consisted of 3 stages: stage (ST) 1 (1-4 low-energy biphasic [BP] shocks), ST2 (6-10 ultralow-energy monophasic [MP] shocks), and ST3 (antitachycardia pacing). First, ST1 testing compared single or multiple MP and BP shocks. Second, several multistage therapies were tested: ST1 versus ST1+ST3 versus ST1+ST2+ST3. Third, 3 shock vectors were compared: superior vena cava to distal coronary sinus, proximal coronary sinus to left atrial appendage, and right atrial appendage to left atrial appendage. The atrial defibrillation threshold (DFT) of 1 BP shock was <1 MP shock (0.55 ± 0.1 versus 1.38 ± 0.31 J, P=0.003). Two to 3 BP shocks terminated AF with lower peak voltage than 1 BP or 1 MP shock and with lower atrial DFT than 4 BP shocks. Compared with ST1 therapy alone, ST1+ST3 lowered the atrial DFT moderately (0.51 ± 0.46 versus 0.95 ± 0.32 J, P=0.036), whereas 3-stage therapy (ST1+ST2+ST3) dramatically lowered the atrial DFT (0.19 ± 0.12 versus 0.95 ± 0.32 J for ST1 alone, P=0.0012). Finally, the 3-stage therapy was equally effective for all studied vectors.

Conclusions: Three-stage electrotherapy significantly reduces the AF DFT and opens the door to low-energy atrial defibrillation at or below the pain threshold.

Conflict of interest statement

Conflict of Interest Disclosures: Dr. Efimov is a chairman of the scientific advisory board, a member of the board of directors, and owns stock in CardiaLen, Inc.

Figures

Figure 1

Anatomic Positions of Defibrillation Electrodes. Schematic of a canine heart with locations of electrodes from which defibrillation therapies were delivered depicted. A: right anterior oblique (RAO) view showing superior vena cava and right atrial appendage disc electrodes. B: left anterior oblique (LAO) view showing left atrial appendage disc electrode. C: posteroanterior (PA) view showing distal and proximal coronary sinus coils. SVC, superior vena cava; RA, right atrium; PT, pulmonary trunk; RV, right ventricle; LV, left ventricle; CSp, proximal coronary sinus; CSd, distal coronary sinus.

Figure 2

Waveforms and Stages of Low Energy Defibrillation Therapy. A: Individual waveforms tested in Stage 1 (ST1) of the three-stage therapy. B: ST1+ST3 therapy. ST1 consists of 2 biphasic shocks delivered within 30-50% of the AF cycle length. ST3 consists of 8 bipolar atrial pacing stimuli delivered at 70-100% of the AF cycle length. C: ST1+ST2+ST3 therapy. ST1 consists of 2 biphasic shocks. ST2 consists of 8 lower voltage monophasic shocks, and ST3 consists of 8 atrial pacing stimuli. Each pulse in ST2 and ST3 is delivered at 70-100% of the AF cycle length. In both B and C, a delay of 100-400 ms separates each stage of therapy. MP, monophasic shock; BP, biphasic shock; AF, atrial fibrillation; CL, cycle length. ST1, stage 1; ST2, stage 2; ST3, stage 3.

Figure 3

Characteristics of Vagus Nerve Stimulation and Induced Arrhythmias. A: Mean frequency of vagal nerve stimulation (VNS) during induction of atrial fibrillation (AF) and atrial flutter (AFl). B: Mean dominant frequency of AF and AFl induced by burst pacing during VNS. C: Effect of VNS on atrial effective refractory period (ERP). All values are reported as mean ± standard deviation.

Figure 4

Determination of Atrial and Ventricular Shock Excitation Thresholds. An example of the surface electrocardiogram (EKG), atrial (AEG) and ventricular (VEG) electrograms, respectively, recorded during the measurement of atrial and ventricular shock excitation thresholds (SET) for shock vector RAA>LAA is shown. A: 0.5 V shock captured neither atrial nor ventricular tissue. B: 1 V shock captured atrial but not ventricular tissue. C: 6.5 V shock captured atrial and ventricular tissue. A, atrium; V, ventricle.

Figure 5

Shock Excitation Thresholds are Independent of Polarity and Electrode Position Mean atrial and ventricular shock excitation threshold (SET) is shown for different electrode sizes and individual vectors tested. A: Reversing polarity of the shock vector did not reduce SET significantly. Atrial (black bars) and ventricular (white bars) SETs from two vectors using 1.0 in diameter disc electrodes placed on the left and right atrial appendages (LAA and RAA, respectively) is depicted. For each vector, notation is anode > cathode. B: Atrial and ventricular SETs for the three vectors tested using 0.5 in diameter disc electrodes and a 4F CS lead with two 1 in coils. C: Impedances for each vector tested. Note that the RAA>LAA impedance using 0.5 inch electrodes (0.5″) was larger than for 1.0 inch electrodes (1″), resulting in increased ventricular SETs for the 0.5 inch electrodes.

Figure 6

Peak Voltage and Total Energy of Stage 1 therapies. For each therapy tested in Stage 1 (ST1), peak voltage (A) and total energy (B) is shown. MP, monophasic shock; BP, biphasic shock; the number preceding the shock type describes the number of shocks delivered, e.g., 1MP denotes a single MP shock while 4BP denotes four sequential BP shocks.

Figure 7

Representative Atrial Electrograms of AF Terminations. For each panel, peak voltage in Stage 1 (ST1) and total energy is denoted above the corresponding atrial electrogram. The time that each individual therapy was delivered is indicated with an arrow. A: ST1 therapy of two 100 V biphasic shocks (total energy 1.14 J) terminated AF. B: Stage 1 plus Stage 3 (ST1+ST3) lowered the peak voltage of ST1 to 70 V and the atrial defibrillation threshold (DFT) to 0.56 J. C: Three-stage therapy (ST1+ST2+ST3) dramatically reduced the total energy to 0.05 J and the peak voltage of ST1 to 20 V.

Figure 8

Atrial DFTs for each Shock Vector tested. Atrial DFTs of ST1, ST1+ST3 and ST1+ST2+ST3 are shown for each vector tested in total energy. A: Shock vector SVC>CSd. B: Shock vector CSp>LAA. C: Shock vector RAA>LAA. D: Atrial DFT of Three-Stage therapy (ST1+ST2+ST3) did not significantly differ with respect to shock vector tested. SVC, superior vena cava; CSd, distal coronary sinus; CSp, proximal coronary sinus; LAA, left atrial appendage; RAA, right atrial appendage.