This Article Abstract Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Cooper, R. A. S. Articles by Ideker, R. E. Search for Related Content PubMed PubMed Citation Articles by Cooper, R. A. S. Articles by Ideker, R. E. Pubmed/NCBI databases Medline Plus Health Information Atrial Fibrillation

(Circulation. 1997;96:2693-2700.)
© 1997 American Heart Association, Inc.

Articles

Internal Cardioversion of Atrial Fibrillation

Marked Reduction in Defibrillation Threshold With Dual Current Pathways

Randolph A. S. Cooper, MD; William M. Smith, PhD; ; Raymond E. Ideker, MD, PhD

From the Department of Medicine, Division of Cardiovascular Diseases, The University of Alabama at Birmingham Medical Center.

	Abstract

Top Abstract Introduction Methods Results Discussion References

 
Background The ultimate acceptance of a fully automatic atrial defibrillator will depend on the reduction of pain to acceptable levels, requiring a marked decrease in defibrillation thresholds. The purpose of this study was to determine whether atrial defibrillation thresholds can be reduced by sequential shocks delivered through two current pathways.

Methods and Results Sustained atrial fibrillation was induced with rapid atrial pacing in 12 adult sheep. Defibrillation electrodes were positioned in the right atrial appendage (RAap), distal coronary sinus (DCS), proximal coronary sinus (CSos), main/left pulmonary artery junction (PA), and right ventricular apex (RV). Single-capacitor biphasic waveforms (3/1 ms) were delivered through combinations of these electrodes. Probability-of-success curves were determined for single shocks with a single current pathway and sequential shocks with either single- or dual current pathways. The ED₅₀ for delivered energy for the dual current pathway RAap to DCS then CSos to PA was 0.36±0.13 J, which was significantly lower than the ED₅₀ of the standard single current pathway RAap to DCS (1.31±0.3 J) and was significantly lower than all other configurations tested.

Conclusions Internal atrial defibrillation thresholds can be markedly reduced with two sequential biphasic shocks delivered over two current pathways compared with the standard single shock delivered over a single current pathway or with sequential shocks delivered over a single current pathway.

Key Words: atrium • fibrillation • defribillation

	Introduction

Top Abstract Introduction Methods Results Discussion References

 
Atrial fibrillation remains one of the most common arrhythmias encountered in clinical medicine and often requires pharmacological and/or electrical therapy to restore sinus rhythm.^{1 2 3} Recently, biphasic-waveform shocks delivered via transvenous defibrillation electrodes have been shown to be an effective and feasible technique in animals⁴ and humans^{5 6 7 8 9} for the termination of atrial fibrillation. Clinical evaluation of an implantable atrial defibrillator is currently in progress.⁹ This clinical system consists of a biphasic waveform delivered through a single current pathway with electrodes in the lateral CS and right atrium.¹⁰ However, the present energy requirements for successful atrial defibrillation with this system remain sufficiently high that they are usually painful to the patient.^{7 11 12 13 14} Some clinical studies have demonstrated that the pain associated with internal atrial defibrillation shocks is related to the intensity of the shock.^{7 11 12 14} Current research efforts are focusing on methods to lower the defibrillation threshold in hopes of lowering the shock intensity and decreasing the pain associated with internal atrial defibrillation.

In both human^{15 16 17 18 19 20 21} and animal^{22 23 24 25 26 27} studies, sequential shocks delivered over dual current pathways have been shown to reduce the ventricular defibrillation threshold. The effect of dual current defibrillation pathways with sequential shocks on ADFTs is unknown.

Animal studies using multichannel mapping systems have demonstrated that the site of earliest atrial activations after unsuccessful single current pathway internal atrial defibrillation shocks is dependent on electrode locations.²⁸ After unsuccessful internal shocks, earliest atrial activations were located in areas in which the potential gradient field created by the shock was predicted to be low. This information was used in the design of the present study, which investigates the efficacy of a second shock delivered through a second current pathway. The second current pathway for the second shock was designed to encompass the parts of the atria that would be predicted to be in the low potential gradient area produced by the first current pathway and shock. The purpose of this study was to investigate the effect of sequential shocks delivered through single- and dual current pathways on internal ADFTs in a sheep model of short-term atrial fibrillation.

	Methods

Top Abstract Introduction Methods Results Discussion References

 
This study involving experimental animals was approved by the Institutional Animal Care and Use Committee at the University of Alabama at Birmingham Medical Center. It complies with Section 6 of the Animal Welfare Act, 1989, and adheres to the guiding principles outlined in the Guide for the Care and Use of Animals, National Institutes of Health publication No. 85-23.

Animal Preparation
A total of 18 adult sheep of both sexes (weight, 60 to 75 kg) were studied. Sustained atrial fibrillation, lasting at least 5 minutes, could be induced in 12 sheep. This study was performed in two parts, and 6 animals were used in each part for data analysis. After initial sedation of the sheep with a 1-to-1 mixture of tiletamine and zolazepam (Telazol, Elkins-Sinn, Inc) 3 mg/kg IM, a peripheral intravenous line was established in a hind leg. Induction for intubation was achieved by pentobarbital as a 20- to 30-mg/kg slow IV bolus. Once adequate anesthesia was induced, the animal was endotracheally intubated and placed on a volume-cycled ventilator with a set tidal volume of 8 to 12 mL/kg with a 4% isoflurane/oxygen mixture at a rate of 8 to 12 breaths per minute. After initial anesthesia induction with 4% isoflurane, the concentration was decreased to 2% to 3.5% to maintain a surgical plane of anesthesia as determined by monitoring of sympathetic stimulation level, blood pressure, and heart rate. The animals were placed on their backs on a fluoroscopy table. A 6F sheath was placed in a femoral artery by the Seldinger technique for continuous blood pressure monitoring, frequent arterial blood gas sampling, and frequent arterial electrolyte sampling. Surface ECG lead II and femoral artery blood pressure were continually displayed on a physiological monitor (78534C, Hewlett-Packard Ltd). Maintenance intravenous fluids were continuously infused. Electrolytes, oxygen delivery, and ventilator settings were adjusted to maintain normal physiological levels as indicated by blood sampling every 30 to 60 minutes. Neuromuscular blockade was achieved with succinylcholine 1 mg/kg IV followed by supplemental doses of 0.5 mg/kg as needed, depending on muscular tone. At the end of each study, euthanasia was induced with an intravenous bolus of potassium chloride. The location of each internal electrode was verified, and then the heart was surgically removed. The great vessels were trimmed to the point of insertion into each cardiac chamber, and the pericardium was removed. The heart was weighed and then preserved in formalin.

Electrode Placement
Two 8F sheaths (Daig Corp) were placed in the right external jugular vein by the Seldinger technique. A 12F sheath was placed in the left external jugular and right femoral veins by the Seldinger technique. Catheters were positioned with fluoroscopy in the following positions (Fig 1). Via an external jugular sheath, a 6F 10-electrode catheter with 5-mm rings separated by 2 mm (Electro-Catheter Corp) was placed in the PA so that the electrodes were positioned near the superoposterior aspect of the left atrium. This electrode was labeled PA (Fig 1). Via another external jugular sheath, a 7F 30-electrode catheter with 5-mm rings separated by 2 mm (Electro-Catheter Corp) was placed in the CS so that the distal 8 electrodes were as lateral as possible in the DCS and were labeled DCS (Fig 1), and the next 8 electrodes were labeled CSos (Fig 1), positioned at the proximal CS at the level of the CS ostium. A modified quadripolar catheter (Mansfield EP-Boston Scientific Corp) with a 2-in stainless steel wire coil wrapped around the distal part of the catheter and soldered to the proximal two electrodes was positioned in the RV. The proximal coil electrode was labeled RV (Fig 1), and the distal two electrodes were used to record a ventricular bipolar electrogram for synchronization of the shocks. Via the right femoral venous sheath, a modified quadripolar catheter (EP Technologies) with a 2-in stainless steel wire coil wrapped around the distal part of the catheter and soldered to the proximal two electrodes was positioned in the right atrium. The distal tip of the catheter was positioned in the appendage, and the body of the catheter with the defibrillation coil was positioned to lie along the anterolateral portion of the right atrial free wall. The proximal coil electrode was labeled RAap (Fig 1). The distal two electrodes were used to record an atrial bipolar electrogram and to burst pace the atria.

View larger version (100K): [in this window] [in a new window]   Figure 1. Defibrillation electrode locations. A, Right anterior oblique (RAO) fluoroscopic view of defibrillation electrode locations. B, Left anterior oblique (LAO) fluoroscopic view of defibrillation electrode locations.

Defibrillation Waveforms
Shocks were delivered sequentially to a single current pathway or to two current pathways from a single programmable defibrillator (model HVS-02, Ventritex Inc) with a capacitance of 150 µF. The output of the defibrillator was controlled by a Macintosh Computer (Apple Computer Corp) equipped with a digital output board (NB-reverse MIO-16, National Instruments Corp). The digital outputs were connected to two pairs of high-voltage cross-point switches that could either pass current straight through or invert it. Also, the pulse width, the polarity, and the current pathway for each phase generated by the cross-point switches were programmable with custom software. Because the shock was produced from one defibrillator, all phases of the two biphasic waveforms demonstrated decaying voltages from a single capacitor in which the trailing edge of each preceding phase was equal to the leading-edge voltage of the succeeding phase. Each biphasic waveform had a first-phase duration of 3 ms and a second-phase duration of 1 ms (Fig 2). For a single-capacitor, single current pathway configuration, the second cross-point output was turned off. For sequential biphasic and dual current pathway configurations, both cross-point outputs were used, and both of the sequential biphasic waveforms together emulated the output from a single capacitor. The first biphasic waveform was delivered through the first current pathway, and the second biphasic waveform was delivered through the second current pathway (Fig 2). The shocks to the right ventricular bipolar electrogram were synchronized by an endocardial custom-made R-wave detector that was able to trigger the Ventritex defibrillator and cross-point switches via custom software on the Macintosh Computer.

View larger version (18K): [in this window] [in a new window]   Figure 2. Defibrillation waveform. Biphasic waveforms for single current pathway, single current sequential pathways, and dual current pathway configurations for parts 1 and 2. For single current pathway configurations, a biphasic waveform with first phase 3 ms long and second phase 1 ms long was delivered through first current pathway. Single current pathway biphasic waveform emulated a single-capacitor discharge in that trailing-edge voltage of phase 1 (V1T) was equal to leading-edge voltage of phase 2 (V2L). For single current sequential and dual current pathway configurations, a biphasic waveform with first phase 3 ms long and second phase 1 ms long was delivered through first current pathway, and a second biphasic waveform with first phase 3 ms long and the second phase 1 ms long was delivered through same current pathway as first shock for single current sequential configurations and through a second current pathway for dual current pathway configurations. Single current sequential and dual current pathway configurations emulated a single-capacitor discharge in that V1T was equal to V2L, trailing-edge voltage of phase 2 (V2T) was equal to leading-edge voltage of phase 3 (V3L), and trailing-edge voltage of phase 3 (V3T) was equal to leading-edge voltage of phase 4 (V4L). Time separation between each phase of biphasic waveforms and between two biphasic waveforms was < 0.2 ms.

Atrial Fibrillation Induction and Definitions
Atrial fibrillation was induced by rapid atrial pacing with a 2-ms, 10-V pulse at a cycle length of 30 to 90 ms delivered from the distal pair of electrodes on the RAap catheter or a pair of the 5-mm ring electrodes on the CS catheter. Atrial fibrillation was defined as irregular atrial activity seen on atrial electrograms with an approximate cycle length of <150 ms and with an irregularly irregular ventricular response. Atrial fibrillation was defined as sustained if it lasted for 5 minutes after the rapid pacing was discontinued. Atrial flutter was defined as regular atrial activity seen on atrial electrograms with an approximate cycle length of 250 ms. Atrial flutter episodes were not shocked. Episodes of flutter were allowed to either degenerate spontaneously into atrial fibrillation or convert back to sinus rhythm. If sustained atrial fibrillation was inducible, then shocks were given approximately every 1 to 2 minutes until cardioversion was successful. Successful cardioversion was defined as the return of normal sinus rhythm within 1 to 2 seconds after a shock or the return of normal sinus rhythm after any postshock conduction problem, such as sinus arrest or atrioventricular block, resolved. After successful cardioversion shocks, atrial fibrillation was induced again with rapid atrial pacing and was allowed to continue for 2 to 3 minutes after discontinuation of the pacing before further test shocks were delivered.

Lead Systems and Data Acquisition and Defibrillation Protocol
In part 1 of the study, 7 single current and 7 dual current pathway configurations were compared (Table 1). In part 2, 5 single current pathways with a single shock, 1 dual current pathway with sequential shocks, and 5 single current pathways with sequential shocks were compared (Table 2). The actual current and voltage waveforms delivered to each pair of electrodes were initially isolated and recorded across a 0.25- resistor in series with the electrodes and a 200:1, 100-M resistor divider in parallel with the electrodes. These data were recorded on a waveform analyzer (DATA6100, Data Precision), and the impedance between the electrodes and the total delivered energy of each phase of the two biphasic waveforms were computed.

View this table: [in this window] [in a new window]   Table 1. Part 1: Electrode Configurations and 50% Probability of Successful Defibrillation Data

View this table: [in this window] [in a new window]   Table 2. Part 2: Electrode Configurations and 50% Probability of Successful Defibrillation Data

The ADFT was determined first for each waveform/lead combination in each animal. The ADFT was determined by a modified Purdue method with an initial starting voltage of 50 V. If the initial shock failed, then the next and subsequent shock voltages were increased by 20 V until a shock succeeded. Then the voltage was decreased by 10 V and another shock was given. If the initial shock succeeded, then the next and subsequent shock voltages were decreased by 20 V until a shock failed. The next shock after the failure was increased by 10 V and tested. The ADFT was defined as the lowest voltage that achieved defibrillation. The order in which each ADFT was determined was randomized for each animal by drawing chits.

After all ADFTs were determined, probability-of-success curves were determined for each waveform/lead system combination in each animal. Starting with the previously measured ADFT value, a total of 10 shocks were given with an up-down technique with 20-V steps for each waveform/lead system combination. After each shock, the success or failure was noted. If a shock succeeded, the next shock was decreased by 20 V, and if a shock failed, the next shock was increased by 20 V. Randomization was achieved by drawing chits for each waveform/lead system combination and giving 5 shocks for the particular waveform/lead system chosen. Once all chits were drawn and all combinations had been tested, the chits were replaced and selected again. Thus, a total of 10 shocks was given for each waveform/lead system combination.

Statistical Analysis
Results are expressed as mean±SD unless otherwise specified. For all statistical tests performed, a value of P<.05 was considered significant. The data obtained for each waveform/lead system combination were fit to a probit curve by nonlinear least-squares analysis. The 50% success points in terms of leading-edge voltage and total energy were derived from these curves for each animal. Student's t test was used to compare the 50% success points between waveform configurations. Individual pathway differences were tested, with control for multiple comparisons, with the Student-Newman-Keuls test. The overall effect of current pathway was tested by repeated-measures ANOVA.

	Results

Top Abstract Introduction Methods Results Discussion References

 
A total of 18 sheep were studied, and sustained atrial fibrillation could be induced in 12. The mean heart weights for the animals with sustainable and nonsustainable atrial fibrillation were 392±35 and 268±29 g, respectively.

Table 1 shows the means and SDs for the 50% success points for defibrillation in terms of leading-edge voltage and total delivered energy for each waveform/lead system combination for part 1. With paired t test analysis, the dual current electrode pathway RAap to DCS followed by CSos to PA had significantly lower voltage and energy requirements than all other electrode systems tested. With the more conservative Student-Newman-Keuls test, the dual current electrode pathway RAap to DCS followed by CSos to PA had significantly lower 50% successful leading-edge voltage requirements than all other electrode systems tested except for two dual current electrode configurations (RAap to RV, then CSos to PA and RAap to DCS, then RV to PA). Fig 3 shows the mean, median, and 5th, 25th, 75th, and 95th percentile values for the 50% successful total energies for each electrode configuration. The dual current electrode pathway RAap to DCS followed by CSos to PA had significantly lower 50% successful energy requirements than all other electrode systems except for one dual current electrode configuration (RAap to DCS, then RV to PA) by both paired t test and Student-Newman-Keuls test analysis.

View larger version (22K): [in this window] [in a new window]   Figure 3. A 50% probability of successful defibrillation total energy. Mean, median, and 5th, 25th, 75th, and 95th percentile values for 50% successful total energies for each electrode configuration for part 1. Configuration number (abscissa) corresponds to configuration number in Table 1. Dual current pathway RAap to DCS, then CSos to PA configuration had significantly lower defibrillation energy requirements than all other configurations tested by paired t test analysis (*P<.05). Same dual current pathway configuration had significantly lower defibrillation energy requirements (P<.05) than all other configurations tested except for RAap to DCS, then RV to PA configuration () by Student-Newman-Keuls test.

Table 2 shows the means and SDs for the 50% success points for defibrillation in terms of leading-edge voltage and total delivered energy for each waveform/lead system combination for part 2. With the Student-Newman-Keuls test, the dual current electrode pathway RAap to DCS followed by CSos to PA had significantly lower 50% successful leading-edge voltage requirements than all other electrode systems tested. Fig 4 shows the mean, median, and 5th, 25th, 75th, and 95th percentile values for the 50% successful total energies for each electrode configuration. The dual current electrode pathway RAap to DCS followed by CSos to PA had significantly lower 50% successful energy requirements than all other electrode systems by Student-Newman-Keuls test analysis.

View larger version (21K): [in this window] [in a new window]   Figure 4. 50% probability of successful defibrillation total energy. Mean, median, and 5th, 25th, 75th, and 95th percentile values for 50% successful total energies for each electrode configuration for part 2. Configuration number (abscissa) corresponds to configuration number in Table 2. Dual current pathway RAap to DCS, then CSos to PA configuration had significantly lower defibrillation energy requirements (*P<.05) than all other configurations tested by Student-Newman-Keuls test.

Both the RA to DCS single current pathway and the RA to DCS, then CSos to PA dual current pathways were tested in both sets of animals; the combined 50% successful defibrillation energies for all 12 animals were 1.31±0.3 J (RA to DCS) and 0.36±0.13 J (RA to DCS, then CSos to PA). With paired t test analysis, the dual current electrode pathway RAap to DCS followed by CSos to PA had significantly lower energy requirements than the RA to DCS single current pathway.

More than 2000 total shocks in 12 animals were delivered, and no ventricular arrhythmias were noted with appropriately synchronized defibrillation shocks.

	Discussion

Top Abstract Introduction Methods Results Discussion References

 
Background
In this study, we compared the cardioversion efficacies of multiple single-shock single current defibrillation pathways, multiple sequential-shock single current electrode systems, and multiple sequential-shock dual current electrode systems in a sheep model of atrial fibrillation with the hope that an electrode and waveform configuration could be found that halted atrial fibrillation with shock strengths of low voltage and current. We chose to study these configurations for several reasons. First, internal ADFTs with a single current pathway in humans have been shown to be in the 1- to 5-J range for patients with a history of paroxysmal atrial fibrillation^{5 6 7 8} ; however, these shock strengths are still in a range that is associated with significant discomfort.^{7 13 29} Second, studies in animals with ventricular fibrillation have shown a significant decrease in defibrillation threshold requirements with dual current pathways with sequential shocks compared with single current pathways with single shocks,^{22 23 24 25 26 27} suggesting that sequential shocks over dual current defibrillation pathways might reduce the atrial defibrillation shock requirements. Third, studies in animals with atrial fibrillation have shown that the earliest sites after unsuccessful single internal atrial defibrillation shocks are dependent on shocking electrode configurations.²⁸ We hypothesized that by strategically placing additional electrodes for a second shock and current pathway, we could affect these early sites that occur after a first current pathway shock and thus lower the ADFT. With this knowledge, better clinical systems might be developed to minimize the pain associated with internal atrial defibrillation shocks.

Comparison With Previous Basic Atrial Defibrillation Studies
We previously demonstrated in this same sheep model of atrial fibrillation that certain biphasic waveforms were superior to monophasic waveforms with a single defibrillation current pathway.⁴ Also, we have shown that the optimal single current pathway used electrodes that surrounded both atria (right atrial appendage and DCS).⁴ The mean defibrillation threshold for the best biphasic waveform in that study, which had equal first- and second-phase durations of 3 ms each, was 0.8 to 1.2 J. In the present study, the use of a dual current defibrillation pathway and sequential biphasic shocks with the first shock delivered between the RAap and the DCS and the second shock delivered between the CSos and the PA demonstrated a >70% reduction in energy requirements compared with the optimum single current pathway (0.36±0.13 versus 1.31±0.3 J for 50% successful defibrillation).

Mechanisms and Comparisons With Ventricular Defibrillation
Animal studies have demonstrated a close relationship between the extracellular potential gradient distribution produced throughout the ventricles by a shock and whether or not the shock will successfully terminate ventricular fibrillation.^{30 31 32 33 34 35} For defibrillation to occur, it is thought that a minimal potential gradient must be generated by the shock throughout most or all of the ventricular myocardium.^{33 34 35} The distribution of potential gradients in the heart after a shock is very uneven for electrodes located on or in the heart. There are high gradient areas near the electrodes and low gradient areas farthest away from the electrodes.^{33 35 36} These areas of low gradient are the regions in which earliest activation originates after unsuccessful defibrillation shocks.^{33 35} Furthermore, high potential gradients can have detrimental effects on the heart, including postshock arrhythmias,³⁷ conduction disturbances,^{38 39} myocardial dysfunction,⁴⁰ and myocardial necrosis.⁴¹ The potential gradient distribution created by a shock in the heart depends on several factors, including the electrode size and location.⁴² The optimal electrode system for ventricular defibrillation minimizes the high-gradient areas near the electrodes and raises the critical amount of ventricular tissue above the minimum gradient to achieve defibrillation.

It has been argued that the electrodes for ventricular defibrillation should encompass as much of the fibrillating tissue as possible so that the current pathway for the shock traverses both ventricles as well as the intraventricular septum.⁴² These findings and theories have been used to develop more efficient lead systems for implantable ventricular defibrillators.⁴³ One way to reach the minimal gradient to achieve defibrillation throughout the heart and minimize the gradient near the electrodes is by giving two smaller shocks separated spatially and temporally instead of one large shock. Guse et al²⁵ demonstrated in dogs with electrically induced ventricular fibrillation the improved efficacy of a dual current electrode pathway configuration using transvenous, subcutaneous patch electrodes and sequential biphasic shocks. The design of the dual current pathways used in that study was guided by mapping studies demonstrating the location of the earliest activations and regions of low potential gradients after unsuccessful ventricular defibrillation shocks.⁴⁴ Using a second shock and current pathway that encompassed the area of low potential gradient produced by the first shock, they were able to demonstrate a 57% reduction in threshold energy requirements with sequential biphasic shocks with dual current pathways compared with a single shock delivered through a single current pathway or sequential biphasic shocks delivered through a single current pathway. Thus, they demonstrated not only that sequential shocks were important but also that the delivery of the two shocks over two separate current pathways was important to minimize the ventricular defibrillation threshold. Johnson and coworkers²⁶ demonstrated that the timing of two sequentially delivered biphasic shocks over dual current pathways also was important for minimizing threshold energy requirements. They found that in dogs with electrically induced ventricular fibrillation, the optimal time separation between two biphasic shocks given through two current pathways was 0.2 ms.

These findings in animal models of ventricular fibrillation with dual current pathway sequential shocks are very similar to our findings. In this study, the selection of the electrode configurations was guided by a mapping study in sheep with acutely induced atrial fibrillation.²⁸ That mapping study demonstrated that the earliest sites of atrial activation after unsuccessful single current pathway shocks were dependent on electrode configuration and appeared to occur in regions in which the potential gradient field produced by the shock would be predicted to be low. The dual-electrode configurations used in the present study were designed to employ a second shock and current pathway that encompassed the areas in which the previous mapping study had shown the earliest activations to occur. We were able to demonstrate that a dual current defibrillation pathway (RAap to DCS, then CSos to PA) with sequential biphasic shocks separated by 0.2 ms had a 72% reduction in energy requirements for internal atrial defibrillation compared with the best single current pathway (RAap to DCS) with a single biphasic shock. Also, this dual current pathway (RAap to DCS, then CSos to PA) with sequential shocks had a 39% reduction in energy requirements compared with the best single current pathway with sequential shocks (RAap to DCS, then RAap to DCS). This suggests that sequential shocks and the delivery of these shocks through dual current pathways are both important for lowering atrial defibrillation shock strength. These results also suggest that the mechanism of improved efficacy of dual current pathways and sequential shocks in atrial fibrillation are similar to those proposed for ventricular fibrillation. Furthermore, the fact that not all dual current pathways show the same amount of improvement of defibrillation requirements suggests that this improved efficacy depends on the current pathways used.

When the electrodes were tied together to make a single anode and cathode (part 2, configurations 6 through 11), the delivery of sequential shocks through these electrode configurations actually increased the ADFT despite a decrease in mean impedance. Two reasons for this might be that (1) current shunting occurs between the adjacent anode and cathode electrodes without current passing through the main mass of the atria and (2) low potential gradient regions are created between the two anodes and between the two cathodes because these electrodes are equipotential.⁴²

Safety
The safety of internal atrial defibrillation has been addressed in several previous animal and human studies.^{4 5 6 7 8} All of these studies demonstrated that as long as the shocks were synchronized to the ventricular activation, almost no ventricular arrhythmias were seen. This study further supports these findings. All shocks were appropriately synchronized, and no ventricular arrhythmias were observed in more than 750 single and more than 1250 dual current pathway shocks.

Tolerability and Clinical Implications
Johnson et al⁴⁵ compared the internal cardioversion efficacy of a biphasic waveform with each phase 3 ms in duration with that of a 6-ms monophasic waveform in 18 patients by use of a RAap to CS current vector. They found that the biphasic waveform had a significantly lower threshold than the monophasic waveform, but the average threshold energy was still 2.3±1.1 J for the biphasic waveform. Cooper et al⁸ compared multiple biphasic and monophasic waveforms with a single current pathway RAap to CS vector in 13 patients. The optimal biphasic waveform (5/5 ms) had a mean ADFT of 1.2±0.6 J.

Murgatroyd and coworkers,⁷ using a RAap to CS single current vector and a 3/3-ms biphasic waveform, evaluated the tolerability of transvenous atrial defibrillation shocks in 19 patients. A pain scale was used to assess the discomfort in nonsedated patients, starting with low-energy shocks. After each shock, the patients were asked to score the shock in terms of discomfort and whether they wanted sedation. If the patient desired sedation, intravenous midazolam was given. Shock strengths were increased until defibrillation was achieved, and shocks that required sedation were scored as causing severe discomfort. They found that the range of tolerable shock strengths not requiring sedation was 0.1 to 1.2 J; however, the mean defibrillation threshold was 2.16±1.02 J (range, 0.7 to 4.4 J). Thus, the majority of the patients required sedation to achieve successful atrial defibrillation, with only 2 of the 19 patients successfully defibrillated without sedation. Another study evaluated the discomfort of internal single current pathway biphasic shocks for atrial defibrillation in 11 nonsedated patients with a history of paroxysmal or chronic atrial fibrillation.²⁹ Shocks were delivered in 0.5-J increments between right atrial and CS electrodes. The majority of the patients (73%) indicated that shock strengths <1 J were painful, and all patients required sedation for shock strengths >2 J. The mean ADFT was 9.6±6.6 J (range, 0.5 to 20 J). From these studies, it appears that discomfort caused by the shock is related to the strength of the shock and that even with optimization of electrode and waveform configurations, the mean ADFTs determined in previous clinical studies were still >1 J, which has been shown to cause severe discomfort in most patients.^{7 11 12 13 14}

This study did not measure discomfort of the shocks because general anesthesia was used to avoid pain to the animals. The defibrillation thresholds for dual current defibrillation pathways determined in sheep with acutely induced atrial fibrillation are probably lower than in patients with spontaneous atrial fibrillation. However, with these findings in sheep, it may be possible to guide and focus clinical studies to minimize the shock strengths and discomfort required for successful defibrillation of the atria. From these animal and human studies using a single current pathway, the mean ADFT energy in sheep with acutely induced atrial fibrillation was approximately one half that of the ADFT energies determined in patients with a history of paroxysmal atrial fibrillation. If this relationship also holds true for dual current pathways, the mean ADFT in humans may be slightly less than 1 J. It remains to be seen whether such a reduction in fact occurs in patients. It also remains to be determined whether this reduction in defibrillation voltage and energy decreases discomfort sufficiently to justify the added complexity of two additional electrodes, one of which, in this study, is in the PA. With sequential shocks, one would hope that the mean defibrillation threshold could be reduced to <1 J without requiring use of an electrode in the pulmonary artery. However, further basic and clinical research is needed to see whether this can be accomplished.

	Selected Abbreviations and Acronyms

 

ADFT = atrial defibrillation threshold CS = coronary sinus CSos = proximal coronary sinus DCS = distal coronary sinus PA = main/left pulmonary artery junction RAap = right atrial appendage RV = right ventricular apex

	Acknowledgments

 
This study was supported in part by National Institutes of Health research grants HL-42760, HL-28429, and HL-33637 and National Science Foundation Engineering Research Center grant CDR-8622201.

	Footnotes

 
Reprint requests to Randolph A.S. Cooper, MD, Room B140 Volker Hall, 1670 University Blvd, The University of Alabama at Birmingham, Birmingham, AL 35294-0019.

Received March 13, 1997; revision received May 8, 1997; accepted May 15, 1997.

	References

Top Abstract Introduction Methods Results Discussion References

 
1. Kannel WB, Abbott RD, Savage DD, McNamara PM. Epidemiologic features of chronic atrial fibrillation. N Engl J Med. 1982;306:1018-1022.[Abstract]

2. Wolf PA, Dawber TR, Thomas E Jr, Kannel WB. Epidemiologic assessment of chronic atrial fibrillation and risk of stroke: the Framingham study. Neurology. 1978;28:973-977.[Abstract/Free Full Text]

3. Pai S, Torres V. Atrial fibrillation: new management strategies. Curr Prob Cardiol. 1993;18:233-300.

4. Cooper RAS, Alferness CA, Smith WM, Ideker RE. Internal cardioversion of atrial fibrillation in sheep. Circulation. 1993;87:1673-1686.[Abstract/Free Full Text]

5. Johnson EE, Yarger MD, Wharton JM. Monophasic and biphasic waveforms for low energy internal cardioversion of atrial fibrillation in humans. Circulation. 1993;88(suppl I):I-592. Abstract.

6. Murgatroyd FD, Johnson EE, Cooper RA, Lau C, Alt E, Kappenburger LJ, Smith JM, Camm AJ, Wharton JM. Safety of low energy transvenous atrial defibrillation: world experience. Circulation. 1994;90(suppl I):I-14. Abstract.

7. Murgatroyd FD, Slade AKB, Sopher SM, Rowland E, Ward DE, Camm AJ. Efficacy and tolerability of transvenous low energy cardioversion of paroxysmal atrial fibrillation in humans. J Am Coll Cardiol. 1995;25:1347-1353.[Abstract]

8. Cooper RAS, Johnson EE, Wharton JM. Internal atrial defibrillation in humans: the improved efficacy of biphasic waveforms and the importance of phase duration. Circulation. 1997;95:1487-1496.[Abstract/Free Full Text]

9. Levy S, Ricard P, Lau C, Lok N, Camm AJ, Murgatroyd F, Kappenberger LJ, Jordaens LJ, Brugada P. Multicenter Low Energy Transvenous Atrial Defibrillation (XAD) Trial. Circulation. 1995;92(suppl I):I-472. Abstract.

10. Lau CP, Tse HF, Lee K, Lok MB, Ho DSW, Soffer MB, Camm AJ. Initial clinical experience of a human implantable atrial defibrillator. Pacing Clin Electrophysiol. 1996;19:625. Abstract.

11. Nathan AW, Bexton RS, Spurrell RAJ, Camm AJ. Internal transvenous low energy cardioversion for the treatment of cardiac arrhythmias. Br Heart J. 1984;52:377-384.[Abstract/Free Full Text]

12. Jung W, Tebbenjohanns J, Wopert C, Luderitz B. Safety, efficacy, and pain perception of internal atrial defibrillation in humans. Circulation. 1995;92(suppl I):I-472. Abstract.

13. Steinhaus DM, Cardinal D, Mongeon L, Mattson L, Waters M, Foley L, Corrigan S. Atrial defibrillation: are low energy shocks acceptable to patients? Pacing Clin Electrophysiol. 1996;19:625. Abstract.

14. Lok NS, Lau CP, Lai-Fun-Lee K, Tse HF, Ayers G. Effect of different right atrial lead locations on the efficacy and tolerability of low energy transvenous atrial defibrillation with an implantable lead system. Pacing Clin Electrophysiol. 1996;19:633. Abstract.

15. Bardy GH, Ivey TD, Allen MD, Johnson G, Greene HL. Prospective comparison of sequential pulse and single pulse defibrillation with use of two different clinically available systems. J Am Coll Cardiol. 1989;14:165-171.[Abstract]

16. Yee R, Jones DL, Klein GJ, Sharma AD, Kallok MJ. Sequential pulse countershock between two transvenous catheters: feasibility, safety, and efficacy. Pacing Clin Electrophysiol. 1989;12:1869-1877.[Medline] [Order article via Infotrieve]

17. Yee R, Klein GJ, Leitch JW, Jones DL, Leather RA, Kim YH. Improved defibrillation efficacy by combined biphasic and sequential shock delivery. Circulation. 1991;84(suppl II):II-649. Abstract.

18. Jones DL, Klein GJ, Guiraudon GM, Sharma AD, Kallok MJ, Bourland JD, Tacker WA Jr. Internal cardiac defibrillation in man: pronounced improvement with sequential pulse delivery to two different lead orientations. Circulation. 1986;73:484-491.[Abstract/Free Full Text]

19. Jones DL, Klein GJ, Guiraudon GM, Sharma AD, Kallok MJ, Tacker WA Jr, Bourland JD. Sequential pulse defibrillation in man: comparison of thresholds in normal subjects and those with cardiac disease. Med Instrum. 1987;21:166-169.[Medline] [Order article via Infotrieve]

20. Jones DL, Klein GJ, Guiraudon GM, Sharma AD. Sequential pulse defibrillation in humans: orthogonal sequential pulse defibrillation with epicardial electrodes. J Am Coll Cardiol. 1988;11:590-596.[Abstract]

21. Jones DL, Klein GJ, Rattes MF, Sohla A, Sharma AD. Internal cardiac defibrillation: single and sequential pulses and a variety of lead orientations. Pacing Clin Electrophysiol. 1988;11:583-591.[Medline] [Order article via Infotrieve]

22. Jones DL, Klein GJ, Kallok MJ. Improved internal defibrillation with twin pulse sequential energy delivery to different lead orientations in pigs. Am J Cardiol. 1985;55:821-825.[Medline] [Order article via Infotrieve]

23. Kallok MJ, Bourland JD, Tacker WA Jr, Jones DL, Klein GJ, Wessale JL. Optimization of epicardial electrode size and implant site for reduced sequential pulse defibrillation thresholds. Med Instrum. 1986;20:36-39.[Medline] [Order article via Infotrieve]

24. Jones DL, Natale A, Kim YH, Klein GJ, Wood GK, Robarts JP. New waveforms and defibrillation in pigs: biphasic, sequential and biphasic-sequential. Proc Med Instrum. 1990;25:46. Abstract.

25. Guse PA, Walcott GP, Rollins DL, Smith WM, Ideker RE. Defibrillation electrode configurations developed from cardiac mapping that combine biphasic shocks with sequential timing. Am Heart J. 1992;124:1491-1500.[Medline] [Order article via Infotrieve]

26. Johnson EE, Alferness CA, Wolf PD, Smith WM, Ideker RE. Effect of pulse separation between two successive biphasic shocks given over different lead configurations on ventricular defibrillation efficacy. Circulation. 1992;85:2267-2274.[Abstract/Free Full Text]

27. Guse PA, Rollins DR, Krassowska W, Wolf PD, Smith WM, Ideker RE. Effective defibrillation in pigs using interleaved and common phase sequential biphasic shocks. Pacing Clin Electrophysiol. 1993;16:1719-1734.[Medline] [Order article via Infotrieve]

28. Cooper RAS, Smith WM, Ideker RE. Early activation sites after unsuccessful internal atrial defibrillation shocks: the effect of electrode configuration. Pacing Clin Electrophysiol. 1996;19:706. Abstract.

29. Jung W, Pfeiffer D, Wolpert C, Pizzulli L, Fehske W, Schumacher B, Lewalter T, Omran H, Korte T, Luderitz B. Which patients do benefit from an implantable atrial defibrillator? J Am Coll Cardiol. 1996;27:301. Abstract.

30. Krassowska W, Frazier DW, Pilkington TC, Ideker RE. Potential distribution in three-dimensional periodic myocardium, II: application to extracellular stimulation. IEEE Trans Biomed Eng. 1990;37:267-284.[Medline] [Order article via Infotrieve]

31. Lepeschkin E, Jones JL, Rush S, Jones RE. Local potential gradients as a unifying measure for thresholds of stimulation, standstill, tachyarrhythmia and fibrillation appearing after strong capacitor discharges. Adv Cardiol. 1978;21:268-278.[Medline] [Order article via Infotrieve]

32. Frazier DW, Krassowska W, Chen P, Wolf PD, Dixon EG, Smith WM, Ideker RE. Extracellular field required for excitation in three-dimensional anisotropic canine myocardium. Circ Res. 1988;63:147-164.[Abstract/Free Full Text]

33. Chen P, Wolf PD, Claydon FJ III, Dixon EG, Vidaillet HJ Jr, Danieley ND, Pilkington TC, Ideker RE. The potential gradient field created by epicardial defibrillation electrodes in dogs. Circulation. 1986;74:626-636.[Abstract/Free Full Text]

34. Witkowski FX, Penkoske PA, Plonsey R. Mechanism of cardiac defibrillation in open-chest dogs with unipolar DC-coupled simultaneous activation and shock potential recordings. Circulation. 1990;82:244-260.[Abstract/Free Full Text]

35. Wharton JM, Wolf PD, Smith WM, Chen P, Frazier DW, Yabe S, Danieley N, Ideker RE. Cardiac potential and potential gradient fields generated by single, combined, and sequential shocks during ventricular defibrillation. Circulation. 1992;85:1510-1523.[Abstract/Free Full Text]

36. Tang ASL, Wolf PD, Claydon FJ III, Smith WM, Pilkington TC, Ideker RE. Measurement of defibrillation shock potential distributions and activation sequences of the heart in three-dimensions. IEEE Trans Biomed Eng. 1988;76:1176-1186.

37. Lesigne C, Levy B, Saumont R, Birkui P, Bardou A, Rubin B. An energy-time analysis of ventricular fibrillation and defibrillation thresholds with internal electrodes. Med Biol Eng. 1976;14:617-622.[Medline] [Order article via Infotrieve]

38. Yabe S, Smith WM, Daubert JP, Wolf PD, Rollins DL, Ideker RE. Conduction disturbances caused by high current density electric fields. Circ Res. 1990;66:1190-1203.[Abstract/Free Full Text]

39. Jones JL, Lepeschkin E, Jones RE, Rush S. Response of cultured myocardial cells to countershock-type electric field stimulation. Am J Physiol. 1978;235:H214-H222.

40. Pansegrau DG, Abboud FM. Hemodynamic effects of ventricular defibrillation. J Clin Invest. 1970;49:282-297.

41. Dahl CF, Ewy GA, Warner ED, Thomas ED. Myocardial necrosis from direct current countershock: effect of paddle size and time interval between discharge. Circulation. 1974;50:956-961.[Abstract/Free Full Text]

42. Ideker RE, Wolf PD, Alferness CA, Krassowska W, Smith WM. Current concepts for selecting the location, size, and shape of defibrillation electrodes. Pacing Clin Electrophysiol. 1991;14:227-240.[Medline] [Order article via Infotrieve]

43. Dixon EG, Tang ASL, Wolf PD, Meador JT, Fine MJ, Calfee RV, Ideker RE. Improved defibrillation thresholds with large contoured epicardial electrodes and biphasic waveforms. Circulation. 1987;76:1176-1184.[Abstract/Free Full Text]

44. Kavanagh KM, Tang ASL, Simpson E, Melnick SB, Smith WM, Ideker RE. Fibrillation recurrence sites following failed nonthoracotomy defibrillation. Circulation. 1990;82(suppl III):III-182. Abstract.

45. Johnson E, Smith W, Yarger M, Cooper R, Broughton A, Wharton JM. Clinical predictors of low energy defibrillation thresholds in patients undergoing internal cardioversion of atrial fibrillation. Pacing Clin Electrophysiol. 1994;17:742. Abstract.

This article has been cited by other articles:

				S. J. Walsh, G. Manoharan, O. J. Escalona, J. Santos, N. Evans, J. McC. Anderson, M. Stevenson, J. D. Allen, and A.A. J. Adgey Novel rectangular biphasic and monophasic waveforms delivered by a radiofrequency-powered defibrillator compared with conventional capacitor-based waveforms in transvenous cardioversion of atrial fibrillation. Europace, October 1, 2006; 8(10): 873 - 880. [Abstract] [Full Text] [PDF]

				C. M. Dollery and P. Libby Atherosclerosis and proteinase activation Cardiovasc Res, February 15, 2006; 69(3): 625 - 635. [Abstract] [Full Text] [PDF]

				G. Q. Villani, M. F. Piepoli, and A. Capucci Reproducibility of internal atrial defibrillation threshold in paroxysmal and persistent atrial fibrillation Europace, January 1, 2004; 6(4): 267 - 272. [Abstract] [Full Text] [PDF]

				J.C. Geller, S. Reek, C. Timmermans, T. Kayser, H.-F. Tse, C. Wolpert, W. Jung, A.J. Camm, C.-P. Lau, H. J.J. Wellens, et al. Treatment of atrial fibrillation with an implantable atrial defibrillator -- long term results Eur. Heart J., December 1, 2003; 24(23): 2083 - 2089. [Abstract] [Full Text] [PDF]

				X. Zheng, M. E. Benser, G. P. Walcott, and R. E. Ideker Right Atrial Septal Electrode for Reducing the Atrial Defibrillation Threshold Circulation, August 28, 2001; 104(9): 1066 - 1070. [Abstract] [Full Text] [PDF]

				G. Gasparini, A. Bonso, S. Themistoclakis, F. Giada, and A. Raviele Low-energy internal cardioversion in patients with long-lasting atrial fibrillation refractory to external electrical cardioversion: results and long-term follow-up Europace, January 1, 2001; 3(2): 90 - 95. [Abstract] [PDF]

				X. Zheng, M. E. Benser, G. P. Walcott, S. D. Girouard, D. L. Rollins, W. M. Smith, and R. E. Ideker Reduction of Atrial Defibrillation Threshold With an Interatrial Septal Electrode Circulation, November 21, 2000; 102(21): 2659 - 2664. [Abstract] [Full Text] [PDF]

				D. Pfeiffer and B. Luderitz The right atrial/transoesophagael approach for conversion of atrial fibrillation: a hybrid method for compromise? Eur. Heart J., May 2, 2000; 21(10): 785 - 787. [PDF]

				R. A. S. Cooper, V. J. Plumb, A. E. Epstein, G. N. Kay, and R. E. Ideker Marked Reduction in Internal Atrial Defibrillation Thresholds With Dual-Current Pathways and Sequential Shocks in Humans Circulation, June 30, 1998; 97(25): 2527 - 2535. [Abstract] [Full Text] [PDF]

This Article Abstract Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Cooper, R. A. S. Articles by Ideker, R. E. Search for Related Content PubMed PubMed Citation Articles by Cooper, R. A. S. Articles by Ideker, R. E. Pubmed/NCBI databases Medline Plus Health Information Atrial Fibrillation