Comparative efficacy of monophasic and biphasic waveforms for transthoracic cardioversion of atrial fibrillation and atrial flutter

Comparative efficacy of monophasic and biphasic waveforms for transthoracic cardioversion of atrial fibrillation and atrial flutter Osnat T. Gurevitz, MD,a Naser M. Ammash, MD,a Joseph F. Malouf, MD,a Krishnaswamy Chandrasekaran, MD,a Ana Gabriela Rosales, MS,b Karla V. Ballman, PhD,b Stephen C. Hammill, MD,a Roger D. White, MD,c Bernard J. Gersh, MB, ChB,a and Paul A. Friedman, MDa Rochester, Minn

Background Transthoracic cardioversion fails to restore sinus rhythm in 6% to 33% of patients with atrial fibrillation. This study sought to determine the relative efficacy of biphasic waveforms compared with monophasic waveforms in the treatment of atrial arrhythmias. Methods

A total of 912 patients underwent 1022 transthoracic cardioversions between May 2000 and December 2001. A monophasic damped sine waveform was used in the first 304 cases, and a rectilinear biphasic defibrillator was used in the next 718 cases.

Results Use of a biphasic waveform was associated with 94% success in conversion to sinus rhythm compared with 84% with a monophasic waveform ( P b .001). The cumulative energy required to restore sinus rhythm was lower with biphasic shocks in both atrial fibrillation and atrial flutter groups (554 F 413 J for monophasic vs 199 F 216 J for biphasic shocks in the atrial fibrillation group, P b .001; 251 F 302 J vs 108 F 184 J, respectively, in the atrial flutter group, P b .001). In a multivariate analysis, use of a biphasic shock was associated with a 3.9-fold increase in success of cardioversion. Conclusion When used to cardiovert atrial arrhythmias, the rectilinear biphasic waveform was associated with higher success rates and lower cumulative energies than the monophasic damped sine waveform. (Am Heart J 2005;149:316 - 21.)

Atrial fibrillation is the most common sustained arrhythmia encountered in clinical practice and frequently necessitates direct-current cardioversion.1 The failure rate of restoring sinus rhythm with standard (monophasic waveform) transthoracic cardioversion is 6% to 33%.2 To increase cardioversion success rates, new techniques have been introduced, including internal cardioversion,3 dual simultaneous external defibrillation,4 pretreatment with class III antiarrhythmic drugs such as ibutilide,2 and use of biphasic waveforms. Biphasic waveforms decrease the internal5-10 and external11-13 ventricular defibrillation thresholds and the internal14 and epicardial15 atrial defibrillation thresholds. Small randomized studies

From the aDivision of Cardiovascular Diseases, bDivision of Biostatistics, and cDepartment of Anesthesiology, Mayo Clinic, Rochester, Minn. This study received no grant support. The authors have no conflict of interest with this manuscript. Submitted January 20, 2004; accepted July 4, 2004. Correspondence: Paul A. Friedman, MD, Division of Cardiovascular Diseases, Mayo Clinic, 200 First Street SW, Rochester, MN 55905. 0002-8703/$ - see front matter n 2005, Elsevier Inc. All rights reserved. doi:10.1016/j.ahj.2004.07.007

have also demonstrated the clinical efficacy of biphasic waveforms for transthoracic cardioversion of atrial fibrillation.16,17 This study compared results with biphasic versus monophasic waveforms in a large series of consecutive patients with atrial fibrillation or atrial flutter. Our prospective cardioversion protocol used ibutilide in the event of cardioversion failure; in addition, we sought to determine the drug’s utility after biphasic waveforms were adopted.

Methods Mayo Clinic cardioversion unit The cardioversion unit at Saint Marys Hospital, Mayo Clinic, Rochester, Minn, was established in May 2000 to optimize care for patients undergoing elective cardioversion. Standardized, evidence-based clinical protocols have been established and are used prospectively to guide anticoagulation and cardioversion. When a patient enters the unit, all relevant clinical data are recorded into a computerized database; transesophageal echocardiography, if indicated, is performed on site, and echocardiographic parameters are recorded. Rhythm is confirmed via 12-lead electrocardiography immediately before cardioversion.

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Figure 1

Precardioversion anticoagulation protocol. AF indicates atrial fibrillation; AFL, atrial flutter; INR, international normalized ratio; IV, intravenous; SQ, subcutaneous; and TEE, transesophageal echocardiography.

Between May 2000 and December 2001, 912 consecutive patients underwent 1022 transthoracic cardioversions of atrial fibrillation (n = 762) or atrial flutter (n = 260) in the cardioversion unit. A monophasic damped sine waveform external defibrillator (Zoll M series; Zoll Medical Corporation, Burlington, Mass) was used for the first 304 consecutive cardioversions; a rectilinear biphasic defibrillator (Zoll) was used for the next 718 cases. The cardioversion unit computerized database was used to obtain information about the clinical characteristics of patients, success rates of the 2 waveforms, cumulative energy, use of ibutilide, and the occurrence of cardioversion-related complications. The absence or presence of skin burns was determined through clinical assessment by a specialized nurse practitioner.

Equipment and waveforms The defibrillators delivered either an escalating high-energy monophasic damped sine waveform or an escalating lowenergy rectilinear biphasic waveform consisting of a 6millisecond first phase followed by a 4-millisecond truncated exponential second phase of opposite polarity (200-J maximum selected energy). The amplitude of the first and second phases varied on the basis of the selected energy level. The waveform has an integrated patient impedance measurement sensing pulse. The shape of the first phase is controlled by software that compensates for transthoracic impedance to maintain a relatively constant current. The positive and negative phases are separated by 100 microseconds. Defibril-

lation patches (Pro-padz, Zoll) were positioned in the anteriorposterior configuration.

Anticoagulation and defibrillation protocols All cardioversions were done with the patient in the postabsorptive state and under general anesthesia with thiopental sodium. The primary physician prescribed antiarrhythmic medications. Figure 1 illustrates the anticoagulation protocol used in the cardioversion unit. Shocks were synchronized to the R wave and delivered in a step-up protocol until either sinus rhythm was restored or maximal energy was delivered. For patients with atrial fibrillation, monophasic shocks of 200, 300, and 360 J were used; once available, biphasic shocks of 50, 75, 100, 120, 150, and 200 J were used. For patients with typical atrial flutter, monophasic shocks were delivered at 50, 100, 200, 300, and 360 J, and biphasic shocks at 20, 30, 50, 100, and 200 J. In the event that the maximal energy shock failed to restore sinus rhythm, 1 mg of ibutilide (Corvert; Pharmacia & Upjohn, Kalamazoo, Mich) was infused for 10 minutes, unless the patient met exclusion criteria for use of the drug. These included a QTc of z480 milliseconds, left ventricular ejection fraction of V 0.30, pregnancy, or physician preference. Patients in whom atrial fibrillation or atrial flutter recurred less than 5 minutes after a successful shock were given an additional shock at the energy level that was successful initially. Patients with recurrence of the arrhythmia more than 5 minutes after achievement of sinus rhythm but while still in the unit were considered for ibutilide

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Table I. Clinical characteristics of patients with atrial fibrillation undergoing monophasic or biphasic cardioversion

Characteristic Age (y) Male Body mass index (kg/m2) Left atrium area (cm2) LVEF Previous TIA or CVA Previous MI Hypertension Diabetes History of AF or AFL Amiodarone Sotalol Propafenone

Monophasic shocks (n = 229)

Biphasic shocks (n = 444)

69 F 13 65 30 F 8 5.0 F 2.3 0.53 F 0.16 7 10 43 9 49 18 5 18

70 F 12 66 30 F 7 4.5 F 2.0 0.53 F 0.14 12 16 57 15 56 19 5 17

P .349 .884 .768 .107 .430 .054 .051 b.001 .048 .072 .911 .928 .890

Continuous variables are expressed as mean F SD; other values are percentages of patients. LVEF, left ventricular ejection fraction; TIA, transient ischemic attack; CVA, cerebrovascular accident; MI, myocardial infarction; AF, atrial fibrillation; AFL, atrial flutter.

treatment and an additional shock. All patients who received ibutilide were monitored for 4 hours, at the end of which an electrocardiogram was obtained. If the QTc was either b 440 milliseconds or N 440 milliseconds but no longer than the baseline QTc, patients were dismissed from the unit. A QTc either N 480 milliseconds or N 440 milliseconds and longer than the baseline QTc required overnight observation. Successful cardioversion was defined as being achieved when the patient left the unit in sinus rhythm. The last administered shock that resulted in sinus rhythm was considered the beffectiveQ energy. All administered shocks were counted toward the cumulative energy. This study was approved by the Mayo Foundation Institutional Review Board. No industry funding was received in support of this study.

Table II. Clinical characteristics of patients with atrial flutter undergoing cardioversion

Characteristic

Monophasic shocks (n = 70)

Biphasic shocks (n = 169)

P

67 F 15 74 29 F 5 4.7 F 2.0 0.48 F 0.17 9 11 46 14 36 13 6 21

68 F 14 77 30 F 7 4.6 F 2.4 0.49 F 0.16 9 18 50 17 43 17 4 21

.606 .663 .417 .678 .636 .986 .222 .519 .661 .281 .470 .484 .918

Age (y) Male Body mass index (kg/m2) Left atrium area (cm2) LVEF Previous TIA or CVA Previous MI Hypertension Diabetes History of AF or AFL Amiodarone Sotalol Propafenone

Continuous variables are expressed as mean F SD; other values are percentages of patients.

Table III. Success rates of cardioversion from atrial fibrillation and atrial flutter at lower energy levels Monophasic shocks Energy level (J) (monophasic vs biphasic) Atrial fibrillation 200 vs 50 300 vs 75 360 vs 100 Atrial flutter 50 vs 20 100 vs 30 200 vs 50

Biphasic shocks

No.

%

No.

%

90/200 42/110 55/68

45 38 81

173/447 124/274 79/150

39 45 53

33/48 5/15 8/10

69 33 80

76/116 27/40 13/13

66 68 100

All tests were 2-sided, and statistical significance was accepted as P b .05.

Statistical analysis Analyses were performed separately for 2 distinct groups. Group 1 was composed of 673 patients who presented initially with atrial fibrillation, and group 2 was composed of 239 patients who presented initially with atrial flutter. Within each group, results were analyzed by the type of waveform used. Comparisons of continuous variables were conducted with use of a 2-sample t test when the variable distributions were symmetric and the Wilcoxon rank sum test otherwise. Categorical variables were compared between the 2 groups with a m2 or Fisher exact test, as appropriate. Alternating logistic regression models were used to determine the patient and clinical characteristics that were associated independently with cardioversion success. The alternating logistic regression method, an outgrowth of the generalized estimating equations, was used to account for patients who underwent more than 1 cardioversion episode. Stepwise, backward, and forward elimination techniques were used in the multivariate alternating logistic regression models.

Results Patient characteristics A total of 912 patients underwent 1022 transthoracic cardioversions between May 2000 and December 2001. Atrial fibrillation was treated in 762 cardioversions (232 monophasic, 530 biphasic), and atrial flutter in 260 (72 monophasic, 188 biphasic). Patient clinical characteristics are summarized in Tables I and II. In patients with atrial fibrillation, the biphasic group had a higher incidence of hypertension and diabetes than the monophasic group ( P b .001 and P = .048, respectively). In patients with atrial flutter, no difference in any clinical characteristics was evident between the monophasic and biphasic groups. Antiarrhythmic drug use was similar in patients undergoing monophasic or biphasic cardioversion.

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Table IV. Success rates of cardioversion from atrial fibrillation and atrial flutter before and after ibutilide administration Atrial fibrillation All cases (n = 762)

Monophasic shocks (n = 232)

Atrial flutter

Biphasic shocks (n = 530)

All cases (n = 260)

Monophasic shocks (n = 72)

Biphasic shocks (n = 188)

Intervention

No.

%

No.

%

No.

%

P*

No.

%

No.

%

No.

%

Successful after shock Successful after shock and ibutilide Successful after shock, ibutilide, and subsequent shock

679 687 708

89 90 93

187 193 206

81 83 89

492 494 502

93 93 95

.007 .004 .005

252 254 255

97 98 98

69 70 70

96 97 97

183 184 185

97 98 98

P* .18 .34 .54

*P value comparing success rates of monophasic versus biphasic shocks.

Efficacy in restoring sinus rhythm Successful conversion to sinus rhythm was achieved in 675 episodes (94%) with biphasic waveforms, but in only 256 episodes (84%) with monophasic shocks ( P b .001). On analysis of the atrial fibrillation and atrial flutter groups separately, biphasic waveforms increased success rates significantly only in patients with atrial fibrillation (from 81% to 93%, P = .007). No additional benefit in successful restoration of sinus rhythm was obtained by using biphasic waveforms in patients with atrial flutter (96% success with monophasic vs 97% with biphasic shocks, P = .176). The cumulative energy required to restore sinus rhythm was significantly lower with biphasic shocks in both atrial fibrillation and atrial flutter groups (554 F 413 J for monophasic shocks vs 199 F 216 J for biphasic shocks in the atrial fibrillation group, P b .001; 251 F 302 J for monophasic shocks vs 108 F 184 J for biphasic shocks in the atrial flutter group, P b .001). The success rates for monophasic shocks at lower energy levels are listed in Table III. Patients for whom the exact shock protocol sequence was not followed (n = 211; 21%) were excluded from this subanalysis. Exclusion of these patients did not affect the overall results. After adjustment for age and sex, biphasic shocks were associated with a 3.9-fold (95% CI 1.93-7.85, P b .001) increase in success compared with monophasic shocks. Adverse effects of cardioversion Skin burns were more frequent in patients with atrial fibrillation undergoing monophasic than biphasic cardioversion (11% vs 1%, P b .001). No statistically significant difference was found between the 2 waveforms in the occurrence of postcardioversion bradyarrhythmia (1% for monophasic vs 2% for biphasic shocks), the need for pacing (0% vs 1%), or the occurrence of postcardioversion thromboembolic events (0% for both monophasic and biphasic shocks).

Role of ibutilide Of the 84 patients in whom cardioversion failed, 42 received ibutilide. Of these 42 patients, 8 had return of normal sinus rhythm after ibutilide alone, and 21 after additional shocks. Overall, the addition of ibutilide, with or without a subsequent shock, resulted in successful conversion to sinus rhythm in 32 patients (76%) with initially failed cardioversion. Ibutilide, when given alone, did not significantly increase the success rates of cardioversion in any group; however, the administration of ibutilide followed by subsequent shock increased the rate of cardioversion from 81% to 89% in patients with atrial fibrillation treated with monophasic shocks. The addition of ibutilide did not improve the rate of cardioversion in patients with atrial fibrillation or atrial flutter who received biphasic shocks or in patients with atrial flutter irrespective of waveform used (Table IV) because of the already high rate of cardioversion in these groups. However, of the 16 patients in whom biphasic shocks failed and who subsequently received ibutilide, 12 had successful cardioversion. One patient, an 81-year-old woman with an ejection fraction of 0.40 and precardioversion heart rate of 54 beats/min, developed torsades de pointes after ibutilide, which required defibrillation. She had received a monophasic shock. She was observed in the intensive care unit overnight with no further complications. Subsequently, all patients who received ibutilide also received 1 g of magnesium sulfate intravenously on resumption of sinus rhythm. No further ibutilide-induced arrhythmias or complications have occurred.

Discussion External cardioversion of atrial fibrillation has not changed considerably during the past 4 decades.18 Although it is safe and simple to perform, success rates obtained with standard monophasic defibrillators are far from satisfactory.2 This has led to the implementation of internal cardioversion,3 use of dual external

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defibrillators delivering up to 720 J,4 and adjunct drug therapy.2 Although increasing success rates, these methods add complexity and risks to the procedure. Internal cardioversion carries the risks of any invasive approach and requires complex special equipment and specialized personnel. Dual external defibrillators delivering energy levels as high as 720 J increase the risk of skin burns and myocardial damage. The use of class III agents adds the risk of proarrhythmia, is contraindicated in some patient subgroups, and may require longer inhospital monitoring after sinus rhythm is restored.2,19,20 A growing body of evidence has shown the added benefit of biphasic waveforms.5-17 A recent study by Page et al21 showed that biphasic shocks were more effective than a monophasic waveform for cardioversion of atrial fibrillation. In the current report, we describe our experience with both waveforms, using a systematic, prospective, evidenced-based, noninvasive approach. This approach allows the assessment of new cardioversion techniques as they become available.

Efficacy and safety of biphasic waveforms Rectilinear biphasic waveform shocks in this study proved to be significantly more effective than monophasic waveforms in restoring sinus rhythm, achieving a 94% success rate compared with 84% ( P b .001). This result has confirmed results from previous smaller studies. Ricard et al17 described a 93% success rate in converting atrial fibrillation in 30 patients treated with biphasic truncated exponential waveform cardioversion compared with 88% in 27 patients treated with monophasic damped sine waveform cardioversion. Similarly, Mittal et al16 found a 94% success rate in 88 patients with atrial fibrillation treated with rectilinear biphasic shocks compared with 79% in 77 patients who received monophasic damped sine waveform cardioversion. To our knowledge, this study is the first to investigate the efficacy of the rectilinear biphasic waveform in cardioversion of atrial flutter. This biphasic waveform did not improve the success rates of cardioversion for patients with atrial flutter, probably because atrial flutter conversion with monophasic waveforms has a high success rate (96%). However, the cumulative energy required for restoration of sinus rhythm was significantly lower for biphasic than monophasic shocks for both atrial fibrillation (199 vs 554 J, P b .001) and atrial flutter (108 vs 251 J, P b .001). Because the adverse effects of cardioversion such as myocardial damage, proarrhythmia, and skin burns are related to use of higher energy levels,22 use of lowenergy biphasic waveforms is warranted whenever feasible for cardioversion of atrial flutter and atrial fibrillation. Indeed, in this study, skin burns were much more common after monophasic than after biphasic shocks. Previous studies have shown that

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biphasic shocks result in less postshock myocardial dysfunction than do monophasic shocks.12,23-27 This clinical aspect was not assessed in the current study. We found no difference in the occurrence of postshock arrhythmias, the need for temporary pacing, or the occurrence of thromboembolic events between waveforms. However, the absence of observed postshock arrhythmias and events can be attributed theoretically to the relative rarity of these events in our study population.

Role of ibutilide in improving success rates of cardioversion Ibutilide is a class III antiarrhythmic agent that when administered alone achieves conversion of atrial fibrillation to sinus rhythm in 20% to 47% of patients.2,20 Pretreatment with 1 mg of ibutilide increased the success rate of monophasic cardioversion for atrial fibrillation from 72% to 100%.2 To our knowledge, the current study is the first to investigate the role of ibutilide administration to patients undergoing biphasic cardioversion of atrial fibrillation or atrial flutter. The use of ibutilide followed by a shock can greatly improve the success rates of monophasic cardioversion of atrial fibrillation. Given its high success rate, the biphasic waveform limited the need for ibutilide facilitation. However, in patients with an ejection fraction N 0.30 and QTc b480 milliseconds in whom biphasic shocks failed, ibutilide facilitation was successful in 76%. Limitations Patients included in this study were not randomly assigned to receive monophasic or biphasic shocks. Rather, the first 299 patients were treated with monophasic shocks, whereas the subsequent 613 patients received biphasic shocks. However, comparison of clinical characteristics of these patients did not reveal statistically significant differences in age, sex, body mass index, size of the left atrium, ejection fraction, or the use of antiarrhythmic medications between patients assigned to monophasic versus biphasic shocks. Moreover, because patients studied represent a consecutive series over a short period, selection bias is eliminated. Only 1 biphasic waveform was tested in this study. Our results cannot be extrapolated to other types of biphasic waveforms. Conclusions A low-energy rectilinear biphasic waveform with impedance compensation significantly improved success rates of atrial fibrillation external cardioversion compared with a standard high-energy damped sine wave monophasic waveform. The use of ibutilide in patients with atrial fibrillation who were treated with this monophasic waveform increased success rates to a level obtained with biphasic cardioversion without added risk.

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Ibutilide use is not required frequently with this biphasic waveform but can lead safely to successful cardioversion in those patients in whom monophasic cardioversion fails, with appropriate patient selection and monitoring. Cardioversion success rates of atrial flutter are relatively high with monophasic cardioversion and generally are not improved further by either the biphasic waveform or the addition of ibutilide. However, the lower cumulative energy needed to cardiovert atrial fibrillation or atrial flutter when the biphasic waveform is used does reduce the risk of skin burns and is therefore recommended, even for patients with atrial flutter.

References 1. Fuster V, Ryden LE, Asinger RW, et al. ACC/AHA/ESC guidelines for the management of patients with atrial fibrillation: executive summary. A report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the European Society of Cardiology Committee for Practice Guidelines and Policy Conferences (Committee to Develop Guidelines for the Management of Patients With Atrial Fibrillation) developed in collaboration with the North American Society of Pacing and Electrophysiology. Circulation 2001;104: 2118 - 50. 2. Oral H, Souza JJ, Michaud GF, et al. Facilitating transthoracic cardioversion of atrial fibrillation with ibutilide pretreatment. N Engl J Med 1999;340:1849 - 54. 3. Boriani G, Biffi M, Camanini C, et al. Transvenous low energy internal cardioversion for atrial fibrillation: a review of clinical applications and future developments. Pacing Clin Electrophysiol 2001;24:99 - 107. 4. Bjerregaard P, El-Schafei A, Janosik DL, et al. Double external direct-current shocks for refractory atrial fibrillation. Am J Cardiol 1999;83: 972-4, A910. 5. Fain ES, Sweeney MB, Franz MR. Improved internal defibrillation efficacy with a biphasic waveform. Am Heart J 1989;117:358 - 64. 6. Winkle RA, Mead RH, Ruder MA, et al. Improved low energy defibrillation efficacy in man with the use of a biphasic truncated exponential waveform. Am Heart J 1989;117:122 - 7. 7. Chapman PD, Vetter JW, Souza JJ, et al. Comparative efficacy of monophasic and biphasic truncated exponential shocks for nonthoracotomy internal defibrillation in dogs. J Am Coll Cardiol 1988;12:739 - 45. 8. Bardy GH, Ivey TD, Allen MD, et al. A prospective randomized evaluation of biphasic versus monophasic waveform pulses on defibrillation efficacy in humans. J Am Coll Cardiol 1989;14: 728 - 33. 9. Kavanagh KM, Tang AS, Rollins DL, et al. Comparison of the internal defibrillation thresholds for monophasic and double and single capacitor biphasic waveforms. J Am Coll Cardiol 1989;14:1343 - 9. 10. Wyse DG, Kavanagh KM, Gillis AM, et al. Comparison of biphasic and monophasic shocks for defibrillation using a nonthoracotomy system. Am J Cardiol 1993;71:197 - 202.

Gurevitz et al 321

11. Bardy GH, Gliner BE, Kudenchuk PJ, et al. Truncated biphasic pulses for transthoracic defibrillation. Circulation 1995;91:1768 - 74. 12. Bardy GH, Marchlinski FE, Sharma AD, et al. Multicenter comparison of truncated biphasic shocks and standard damped sine wave monophasic shocks for transthoracic ventricular defibrillation: Transthoracic Investigators. Circulation 1996;94: 2507 - 2514. 13. Mittal S, Ayati S, Stein KM, et al. Comparison of a novel rectilinear biphasic waveform with a damped sine wave monophasic waveform for transthoracic ventricular defibrillation: ZOLL Investigators. J Am Coll Cardiol 1999;34:1595 - 601. 14. Cooper RA, Johnson EE, Wharton JM. Internal atrial defibrillation in humans: improved efficacy of biphasic waveforms and the importance of phase duration. Circulation 1997;95:1487 - 96. 15. Keane D, Boyd E, Anderson D, et al. Comparison of biphasic and monophasic waveforms in epicardial atrial defibrillation. J Am Coll Cardiol 1994;24:171 - 6. 16. Mittal S, Ayati S, Stein KM, et al, for the BiCard Investigators. Transthoracic cardioversion of atrial fibrillation: comparison of rectilinear biphasic versus damped sine wave monophasic shocks. Circulation 2000;101:1282 - 7. 17. Ricard P, Levy S, Boccara G, et al. External cardioversion of atrial fibrillation: comparison of biphasic vs monophasic waveform shocks. Europace 2001;3:96 - 9. 18. Lown B, Perlroth MG, Kaidbey S, et al. bCardioversionQ of atrial fibrillation: a report on the treatment of 65 episodes in 50 patients. N Engl J Med 1963;269:325 - 31. 19. Ellenbogen KA, Stambler BS, Wood MA, et al. Efficacy of intravenous ibutilide for rapid termination of atrial fibrillation and atrial flutter: a dose-response study. J Am Coll Cardiol 1996;28: 130 - 6. 20. Stambler BS, Wood MA, Ellenbogen KA, et al. Efficacy and safety of repeated intravenous doses of ibutilide for rapid conversion of atrial flutter or fibrillation: Ibutilide Repeat Dose Study Investigators. Circulation 1996;94:1613 - 21. 21. Page RL, Kerber RE, Russell JK, et al, for the BiCard Investigators. Biphasic versus monophasic shock waveform for conversion of atrial fibrillation: the results of an international randomized, double-blind multicenter trial. J Am Coll Cardiol 2002;39:1956 - 63. 22. Xie J, Weil MH, Sun S, et al. High-energy defibrillation increases the severity of postresuscitation myocardial dysfunction. Circulation 1997;96:683 - 8. 23. Jones JL, Jones RE. Decreased defibrillator-induced dysfunction with biphasic rectangular waveforms. Am J Physiol 1984;247: H792-6. 24. Tung L. Detrimental effects of electrical fields on cardiac muscle. Proc IEEE 1996;84:366 - 78. 25. Tang W, Weil MH, Sun S, et al. The effects of biphasic and conventional monophasic defibrillation on postresuscitation myocardial function. J Am Coll Cardiol 1999;34:815 - 22. 26. Cooper RA, Alferness CA, Smith WM, et al. Internal cardioversion of atrial fibrillation in sheep. Circulation 1993;87:1673 - 86. 27. Kavanagh KM, Duff HJ, Clark R, et al. Monophasic versus biphasic cardiac stimulation: mechanism of decreased energy requirements. Pacing Clin Electrophysiol 1990;13:1268 - 76.