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Biphasic versus Monophasic Cardioversion in Shock-ResistantAtrial Fibrillation: A Randomized Clinical Trial

YAARIV KHAYKIN, M.D., DAVID NEWMAN, M.D., MARNIE KOWALEWSKI, R.N.,VICTORIA KORLEY, M.D., and PAUL DORIAN, M.D., M.SC.

From Terrence Donnelly Heart Center, Department of Medicine, St. Michael’s Hospital, Toronto, Ontario, Canada

Biphasic versus Monophasic Cardioversion. Introduction: Cardioversion of atrial fibrillation usingmonophasic transthoracic shocks occasionally is ineffective. Biphasic cardioversion requires less energythan monophasic cardioversion, but its efficacy in shock-resistant atrial fibrillation is unknown. Thus, wecompared the efficacy of cardioversion using biphasic versus monophasic waveform shocks in patients withatrial fibrillation previously refractory to monophasic cardioversion.

Methods and Results: Fifty-six patients with prior failed monophasic cardioversion were randomized toeither a 360-J monophasic damped sinusoidal shock or biphasic truncated exponential shocks at 150 J,followed by 200 J and then 360 J, if necessary. If either waveform failed, patients were crossed over to theother waveform. The primary endpoint was defined as the proportion of patients achieving sinus rhythmfollowing initial randomized therapy. Stepwise multivariate logistic regression examined independent pre-dictors of shock success, including patient age, sex, left atrial diameter, body mass index, drug therapy,and waveform. Twenty-eight patients were randomized to the biphasic shocks and 28 to the monophasicshocks. Sinus rhythm was restored in 61% of patients with biphasic versus 18% with monophasic shocks(P = 0.001). Seventy-eight percent success was achieved in patients who crossed over to the biphasic shockafter failing monophasic cardioversion, whereas only 33% were successfully cardioverted with a monopha-sic shock after crossover from biphasic shock (P = 0.02). Overall, 69% of patients who received a biphasicshock at any point in the protocol were cardioverted successfully, compared to 21% with the monopha-sic shock (P < 0.0001). The type of shock was the strongest predictor of shock success (P = 0.0001) inmultivariate logistic regression.

Conclusion: An ascending sequence of 150-, 200-, and 360-J transthoracic biphasic cardioversionshocks are successful more often than a single 360-J monophasic shock. Thus, biphasic shocks shouldbe the recommended configuration of choice for all cardioversions. (J Cardiovasc Electrophysiol, Vol. 14,pp. 868-872, August 2003)

atrial fibrillation, cardioversion, monophasic, biphasic, waveform

Introduction

Atrial fibrillation is the most common cardiac arrhythmia.1

It causes considerable disability, impairs quality of life, andis difficult to treat.2 It is common for physicians in clinicalpractice to prefer sinus rhythm to atrial fibrillation in manypatients, largely for symptom relief. Electrical cardioversionto restore sinus rhythm is a frequently and routinely used safeand effective procedure to restore sinus rhythm in patientswith persistent atrial fibrillation.

Up to 20% of patients will not be successfully cardiovertedusing “conventional” transthoracic cardioversion.3 “Conven-tional” waveforms use either a damped monophasic sinu-soidal or a truncated exponential capacitor discharge duringwhich current flow is stopped abruptly (“truncated”). Newerdevices deliver shocks with a biphasic waveform. With thiswaveform, current first flows in one direction for a specifiedduration, followed by a second phase during which the di-rection of current is reversed.4-8 Biphasic waveform shocks

Supported by a grant from St. Michael’s Hospital Health Sciences ResearchProgram, Toronto, Ontario, Canada, and Medtronic Physio-Control, Red-mond Washington.

Address for correspondence: Paul Dorian, M.D., Department of Medicine,St. Michael’s Hospital, 30 Bond Street, 7-050Q; Toronto, Ontario, Canada,M5B 1W8. Fax: 416-864-5283; E-mail: dorianp@smh.toronto.on.ca

Manuscript received 17 March 2003; Accepted for publication 7 May 2003.

have a higher efficacy than monophasic shocks for internaldefibrillation9 and transthoracic defibrillation in electrophys-iology laboratory studies10-12 and in out-of-hospital cardiacarrest.13,14 Recent studies have shown that biphasic wave-forms are effective for external cardioversion of atrial fib-rillation at lower energies than monophasic shocks15-19 andthat the lower energies required for cardioversion result in lesspostcardioversion skin injury and pain.20 Although biphasicwaveforms were more efficient than monophasic waveformsin these studies, the overall success of cardioversion was sim-ilar for the two waveforms. For the minority of patients inwhom monophasic shocks fail to restore sinus rhythm, it isnot known if biphasic shocks are likely to be successful. Wehypothesized that biphasic shocks would be more effectivethan maximum energy monophasic shocks in “difficult to car-diovert” patients. We conducted a randomized clinical trial ofcardioversion efficacy in patients with atrial fibrillation previ-ously refractory to a monophasic damped sinusoidal shocks at360 J, comparing monophasic waveform shocks and biphasictruncated exponential waveform shocks.

Methods

Patients

Patients with persistent atrial fibrillation of at least21 days’ duration, who were believed by their cardiologiststo require a cardioversion after failing at least one previous

Khaykin et al. Biphasic versus Monophasic Cardioversion 869

attempt at external cardioversion (for the current episode)using ≥1 attempt with 360-J monophasic damped sinusoidalshocks, were enrolled into the trial. All patients were in con-tinuous atrial fibrillation from the time of their failed car-dioversion until study entry. They were continuously an-ticoagulated for at least 3 weeks prior to the study andhad an international normalized ratio (INR) ≥2 on the dayof the procedure. The study protocol was approved by theSt. Michael’s Hospital Research Ethics Board, and each pa-tient provided written informed consent.

Cardioversion Protocol

Patients underwent standard cardioversion proceduresduring brief general anesthesia, standardized to contain pre-procedure lorazepam, fentanyl, and propofol. Pre-gelled, ad-hesive pads (EDGE System, Medtronic Physio-Control, Red-mond WA, USA) were placed in the left posterior position(over the left scapula) and the left parasternal area. Followingpad placement, the patients were randomly assigned in equalproportions to either a 360-J monophasic damped sinusoidalshock (delivered from a commercially available defibrillator,Lifepak12, Medtronic Physio-Control) or to biphasic trun-cated exponential shocks in incremental order of 150 J, fol-lowed by 200 J and then 360 J, if necessary (delivered froma commercially available defibrillator, Lifepak12, MedtronicPhysio-Control). The control waveform was a monophasicdamped sinusoidal waveform generated with 50-µF capaci-tance, 21-mH inductance, and internal resistance of 11 �. Thebiphasic waveform was a single-capacitor (196 µF) wave-form in which the initial voltage and the duration of the firstphase are adjusted to compensate for patient impedance.21

Initial voltage in this device is automatically increased for pa-tients with higher impedance to maintain relatively constantenergy delivery over the range of patient impedance. Suc-cessful cardioversion was defined as at least five consecutivebeats of atrial origin without evidence of fibrillatory activityduring diastole. If an organized atrial rhythm was restoredbut atrial fibrillation recurred, the protocol was consideredterminated. Patients who failed cardioversion following theinitial randomized treatment (waveform) were crossed overto the other treatment.

Analysis

The primary endpoint was defined as the proportion ofpatients achieving sinus rhythm following the initial (ran-domized) therapy, for each of the two waveforms. The pro-portion of patients achieving sinus rhythm in each group wascompared using Chi-square analysis. A multivariate logis-tic regression model was developed to examine independentpredictors of shock success, including patient age, sex, leftatrial diameter, body mass index, use of medical therapy,and waveform, using a stepwise regression procedure. Dif-ferences were considered significant when P < 0.05.

Results

Patient Characteristics

Overall, 56 patients were enrolled in the study betweenJanuary 2000 and August 2002 and randomized to receivemonophasic (n = 28) or biphasic (n = 28) shocks for elec-tive cardioversion of atrial fibrillation. All patients were con-firmed to have been in atrial fibrillation just before admin-

TABLE 1

Baseline Clinical Characteristics

Monophasic Biphasic

No. of patients 28 28Age (years) 59.7 ± 10.8 58.3 ± 14.6Males (%) 82 82Height (cm) 175.5 ± 8.1 176.4 ± 9.0Weight (kg) 96.9 ± 29.0 94.5 ± 27.4Body mass index 30.2 ± 11.9 30.3 ± 8.6Diagnosis

History of myocardial infarction 5 (18%) 6 (21%)Hypertension 17 (61%) 16 (57%)Stroke or transient ischemic attack 1 (4%) 0Diabetes 2 (7%) 3 (11%)

No. of previous cardioversions 1.4 ± 0.7 1.8 ± 2.1Duration of atrial fibrillation (weeks) 26 ± 19 24 ± 18Left ventricular function

Normal (%) 44 42Mild dysfunction (%) 36 35Moderate dysfunction (%) 20 15Severe dysfunction (%) 0 8

Left atrial dimension (mm) 44.0 ± 5.8 46.9 ± 5.4(n = 24) (n = 17)

Significant mitral valve disease (%) 14 19Medication

Amiodarone (%) 43 64Sotalol (%) 7 4Class IA/IC antiarrhythmic (%) 43 29Any antiarrhythmic (%) 71 79Beta-blocker (%) 46 43Calcium channel blocker (%) 15 14Digoxin (%) 36 14Any AV nodal blocker (%) 68 57

Values are given as mean ± SD.None of the comparisons were significant at the 0.05 significance level.

istration of cardioversion shocks. Clinical characteristics ofthe patients and the diagnoses are given in Table 1. None ofthe differences were statistically significant.

Cardioversion Results

Overall cardioversion results are given in Table 2. Com-pared to the monophasic waveform, the biphasic waveformresulted in significantly higher rates of cardioversion suc-cess both as initial therapy (61% success vs 18% success,P = 0.001) and as crossover therapy for those who failedtheir original waveform assignment and subsequently werecrossed over to the alternate waveform (78% biphasic vs 27%monophasic, P = 0.002). Overall, 69% of patients were suc-cessfully cardioverted with a biphasic shock versus 21% withmonophasic shock (P < 0.0001). Cumulative success rateswith biphasic shocks of 150, 200, and 360 J were 22%, 43%,and 69%, respectively (Fig. 1).

At equivalent energy, biphasic shocks are associated withsignificantly lower peak current than monophasic shocks. The360-J biphasic shocks had a peak current of 28.9 ± 6 A (range18.6–42.4) versus 43.5 ± 8.2 A (range 26.5–63.8) for the 360-J monophasic shocks (P < 0.0001). By comparison, the 200-Jbiphasic shock was associated with a peak current of 21.2 ±3.9 A, or less than 50% of the average peak current of a 360-Jmonophasic shock.

Postcardioversion Outcomes

Only 13 patients (23%) were not successfully cardiovertedin the main study. One patient was successfully cardioverted

870 Journal of Cardiovascular Electrophysiology Vol. 14, No. 8, August 2003

TABLE 2

Overall Cardioversion Results

Monophasic Biphasic

Initial Cross-over Total Initial Cross-over Total

n 28 11 39 28 23 51Successfully cardioverted 5 (18%) 3 (27%) 8 (21%) 17 (61%) 18 (78%) 35 (69%)

Monophasic cross-over includes only patients with initial failure of the biphasic waveform shock.Biphasic cross-over includes only patients with initial failure of the monophasic waveform shock.

with a 360-J biphasic shock but reverted to atrial fibrillationafter three sinus beats (and was defined per protocol as a “fail-ure”), and could not be cardioverted with a 360-J monophasicshock. Five patients were successfully cardioverted with a“double-paddle” monophasic 720-J shock. Two patients whofailed cardioversion on cross-over to the biphasic waveformfailed a second biphasic shock at 360 J and subsequently re-ceived a “double-paddle” monophasic 720-J shock deliveredfrom two defibrillators discharging simultaneously, whichthey also failed. Two patients crossed over to biphasic shockwere successfully cardioverted with a second biphasic shockat 360 J with manual pressure applied over the anterior de-fibrillator pad. Three patients received no further attempt atcardioversion.

In total, including postprotocol shocks, only six patientswere in atrial fibrillation at discharge from the procedureroom. No adverse events were documented in the study. Onepatient who failed monophasic waveform assignment but car-dioverted successfully with a biphasic waveform had earlyrecurrence of atrial fibrillation (within 30 min).

Univariate analyses using the primary endpoint of car-dioversion success at any energy level indicated that wave-form was the strongest significant predictor of shock suc-cess (Table 3), although patient weight (higher weight led toa lower probability of defibrillation) was of borderline sig-nificance (P = 0.05). In a multivariate model, only shockwaveform (odds ratio 9.50; 95% CI [confidence interval]3.40, 26.50]) and body weight (odds ratio 0.978/kg; 95%CI 0.959, 0.997) were significant predictors of successfulcardioversion.

Figure 1. Cumulative probability of cardioversion success with increasingbiphasic (bi) shock energies and with a single 360-J monophasic (mono)shock.

Discussion

Although previous studies demonstrated that biphasicshocks are more successful at lower energies and cause lesspostprocedural pain than monophasic shocks,15-20 they didnot show that biphasic shocks are significantly superior tomonophasic shocks with respect to overall success. In thesestudies, there have been slightly, but nonsignificantly, fewerfailures in patients assigned to the biphasic group. No ran-domized trial has compared biphasic to monophasic shocksin the subset of “shock-resistant” patients. To date, bipha-sic shock superiority in shock-resistant atrial fibrillation hasbeen shown in a single retrospective analysis of eight pa-tients.22 Another study demonstrated higher cardioversionsuccess rates on cross-over to the biphasic waveform aftera failed monophasic cardioversion in patients who were nota priori resistant to the monophasic shocks.17 Our study se-lected the 10% to 20% of patients who fail cardioversion withthe standard monophasic shocks despite up to 360 J of en-ergy.20 The biphasic device used in this study was impedancecompensated, adjusting initial voltage and pulse duration asa function of shock impedance. This results in substantiallyless total current required for cardioversion (e.g., 13.3 ±4.0 A for successful cardioversion with a biphasic shock vs40.5 ± 11.1 A for cardioversion with monophasic shock20).The current study indicates that many “hard to cardiovert” pa-tients who fail cardioversion despite monophasic shocks at360 J will be cardioverted successfully with biphasic shocks.

Cardioversion with monophasic shocks is generallystarted with lower energies of 200 J,23 with energies increasedup to 300 or 360 J if lower energies fail. Once normal rhythmis achieved, there is a reasonable chance that it can be main-tained, at least in the short term.24 Currently, most patientswho fail one or several attempts at the highest deliverable

TABLE 3

Univariate Analysis of Cumulative Success of Cardioversion of AtrialFibrillation

Univariate Odds Ratios

Covariate Odds Ratio 95% CI

Age (per year) 1.034 0.997, 1.073Sex (male vs female) 0.965 0.335, 2.778Left atrial dimension (per mm) 1.041 0.952, 1.138Body mass index (kg/m2) 0.980 0.942, 1.020Weight (per kg) 0.985 0.969, 1.000Atrial fibrillation duration (per week) 1.002 0.978, 1.027Antiarrhythmic therapy (yes vs no) 0.612 0.228, 1.640AV-nodal blocking drugs (yes vs no) 0.440 0.183, 1.056Waveform (biphasic vs monophasic) 8.476 3.192, 22.511

Khaykin et al. Biphasic versus Monophasic Cardioversion 871

energies from standard external defibrillators are allowed toremain in atrial fibrillation, and subsequent treatments areprimarily directed at controlling ventricular response. Somepatients are referred to specialized centers for intracardiaccardioversion. Although this can be a more successful ap-proach,25,26 it requires an invasive procedure, specializedequipment, and specialized facilities. Another more cum-bersome method that has undergone limited study is directcurrent cardioversion using simultaneous output from twoexternal defibrillators.27 Alternatively, certain antiarrhythmicdrugs may reduce atrial cardioversion threshold, albeit with arisk of proarrhythmia. A recent report showed 100% successrates of cardioversion following ibutilide pretreatment.28

Based on the results of this study, cardioversion withbiphasic energies should be attempted for all patients whofail monophasic shocks. In such patients, it seems reasonableto begin attempts at 200-J biphasic waveform (at least for thewaveform used in this study); 360-J stored energy may benecessary for the full potential benefit of biphasic waveformshocks to be realized. The high biphasic success rate thus sub-stantially reduces the potential need for drug-enhanced car-dioversion with ibutilide,28 internal cardioversion, or doubledefibrillator cardioversion in patients who fail cardioversionwith a conventional device.

Biphasic shocks may be effective due to better stimula-tion efficacy, achieving success with lower potential gradi-ents,29 recruiting more cells, and resulting in greater prolon-gation of the refractory period.29 Biphasic shocks may alsoresult in better myocardial resynchronization, with the firstphase hyperpolarizing most cells and activating Na+ chan-nels, and the second phase depolarizing the “critical mass”of myocardium.30,31 Finally, less “refibrillation” may followa biphasic shock as the slow decay of transmembrane poten-tial common after a monophasic shock is eliminated by thesecond phase of the shock (charge “burping”).20,32

Study Limitations

Patients randomized to biphasic shocks had the opportu-nity to receive several successive shocks if the first 150-Jbiphasic shock failed. It is possible that monophasic shockswould have been more successful if the shock sequences hadbeen balanced, that is, if three successive attempts at 360-Jmonophasic waveform had been tried in patients randomizedto initial attempts using the monophasic waveform. However,all patients had previously failed at least one 360-J monopha-sic shock, and biphasic shocks were significantly more effec-tive after cross-over than monophasic shocks, suggesting thatshock waveform itself, rather than merely the number of at-tempts, was responsible for the difference between the twostudy groups. Different biphasic waveforms are available, andthese results apply only to the specific biphasic waveformunder study. For the sake of consistency and to prevent bias,which could be introduced by differences in cardioversiontechnique, we used pre-gelled pads without manual pressure,although higher success rates may have been achieved hadmanual paddle pressure been applied.

Conclusion

Biphasic cardioversion, at energies of up to 360 J, results insuccessful cardioversion of the majority of patients with pre-viously failed monophasic cardioversion and is significantly

superior to a strategy of attempting another monophasic car-dioversion at 360 J. It seems reasonable to use a defibrillatordelivering biphasic waveforms for all patients requiring car-dioversion for atrial fibrillation and to attempt biphasic car-dioversion in all cases of monophasic shock-resistant atrialfibrillation before resorting to other riskier or more complexstrategies to restore sinus rhythm.

Acknowledgments: The authors are grateful to Suzan Cvitkovic, MartaBoszko, Paula Lank, and Fred Chapman for their assistance.

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