Efficacy and Impact of Monophasic Versus BiphasicCountershocks for Transthoracic Cardioversion of

Persistent Atrial Fibrillation

Matej Marinsek, MD, Gregory Luke Larkin, MD, MSPH, Petra Zohar, MD,Mojca Bervar, MD, Mojca Pekolj-Bicanic, MD, Franciska Skrabl Mocnik, MD,

Marko Noc, MD, PhD, and Matej Podbregar, MD, PhD*

This report compares the cumulative efficacy of car-dioversion and skeletal muscle injury after eitherdamped sine wave monophasic or truncated expo-nential biphasic transthoracic cardioversion of persis-tent atrial fibrillation. The trial sought to refute the nullhypothesis of therapeutic equivalence betweenmonophasic and biphasic waveforms. Results of thestudy reveal similar cumulative efficacy of waveformsand greater levels of skeletal muscle damage whenpatients are younger and male, and when monopha-sic waveforms are used. �2003 by Excerpta Med-ica, Inc.

(Am J Cardiol 2003;92:988–991)

The use of human subjects for this study was ap-proved by the Celje General Hospital Ethics Com-

mittee, Celje, Slovenia. The study included 83 con-secutive patients with atrial fibrillation (AF) lasting�48 hours who were referred to the cardiology ser-vice for cardioversion either by general cardiologistsor general practitioners between January 2001 andJanuary 2002. Patients were excluded if AF was �48hours duration or if they underwent concomitant phar-machologic attempts at cardioversion. They were alsoexcluded if they were pregnant, �18 years of age,unable to provide written informed consent, unable tobe followed for �1 month, or if they had an acutecoronary syndrome or another serious antecedent ill-ness within the previous 3 weeks that precluded studyparticipation. Patients were eligible for inclusion ifthey underwent either appropriate anticoagulation forat least 3 weeks or transesophageal echocardiographyto exclude the presence of atrial thrombi before en-rollment. Enrolled subjects underwent additional an-ticoagulation for at least 4 weeks after the procedureand transthoracic echocardiography within 3 monthsafter the cardioversion attempt.

• • •After providing written informed consent, patients

were randomly assigned to either damped sine wavemonophasic or truncated exponential biphasic shocks.Computer based 1:1 randomization was done at thepatients’ bedside by personnel not included in thedirect care or evaluation of the patient. Wet polymergel pads (M3502A; Agilent Technologies, Andover,Massachusetts) were applied in the standard antero-lateral position by noninvestigators, also blinded tothe study hypothesis. Midazolam was given for pro-cedural sedation. Subjects randomized to themonophasic protocol received sequential shocks of100, 200, 300, and 360 J as needed (Code MasterXL�; Hewlett- Packard, Palo Alto, California). If thefourth shock failed, a 200-J biphasic shock was deliv-ered. Patients randomized to the biphasic protocolreceived sequential shocks of 70, 100, 150, and 200 J(Heartstream XL, Agilent Technologies). If the fourthshock failed, a 360-J monophasic shock was deliv-ered. All shocks were delivered during exhalation.Cardioversion was considered successful if an atrial Pwave was unmistakably identified �30 seconds afterthe shock. In all patients a 12-lead electrocardiogramwas recorded at 24 hours and at 1-month follow-up.

Blood samples were obtained for cardiospecifictroponin T, myoglobin, and creatine kinase (CK) im-mediately before and at 6 and 24 hours after proce-dure. Skeletal muscle injury was defined as an in-crease in either myoglobin or CK above referencelimits of 72 ng/ml and 125 U/L, respectively (RocheDiagnostics Corp., Indianapolis, Indiana). A sample of40 patients in each group provided a 90% power todetect a difference in outcome of 18% betweengroups, using � � 0.05.

Continuous variables are expressed as mean � SD.Comparison of dichotomous and continuous variablesbetween the groups was performed by chi-square andStudent’s t tests, respectively. To determine the vari-ables independently associated with successful cardio-version and post-shock skeletal muscle injury, multi-variate logistic and linear regressions were performed,respectively. A 2-tailed p value �0.05 was consideredsignificant.

During the study period, 87 consecutive eligiblepatients were identified. Four patients (1 in the bipha-sic and 3 in the monophasic arm) underwent success-ful cardioversion but were unable to be analyzed dueto protocol violations and a combination of human,computer, and laboratory failure. All of the remaining83 patients agreed to participate. Forty-three wererandomized to the biphasic protocol and 40 were

From Departments of Cardiology and Intensive Internal Medicine,Celje General Hospital, Celje, Slovenia; Division of Emergency Med-icine, University of Texas Southwestern Medical School, Dallas, Texas;and Center for Intensive Internal Medicine, University Medical Center,Ljubljana, Slovenia. Dr. Marinsek’s address is: Department of Cardi-ology, General Hospital Celje, Oblakova 5, Celje 3000, Slovenia.E-mail: mmarinsek@hotmail.com. Manuscript received March 5,2003; revised manuscript received and accepted June 18, 2003.

*The authors have no pertinent involvement in any organization with adirect financial interest in the subject of this report.

988 ©2003 by Excerpta Medica, Inc. All rights reserved. 0002-9149/03/$–see front matterThe American Journal of Cardiology Vol. 92 October 15, 2003 doi:10.1016/S0002-9149(03)00986-X

randomized to the monophasic protocol. Clinical char-acteristics of the patients studied are listed in Table 1.The mean number of shocks in patients who achievedconversion to sinus rhythm did not differ betweenbiphasic and monophasic groups (2.6 � 1.1 vs 2.4 �1.3; p � 0.72). The proportion of patients with car-dioversion progressively increased with the number ofshocks in both the monophasic and biphasic groups(after the fourth shock 90% vs 88.3%, p � 0.92;Figure 1). Alternative waveform crossover shock wasunsuccessful in 4 nonconverters in the monophasicgroup and 5 nonconverters in the biphasic group.Although the sample is small, there was no significantdifference in persistence of sinus rhythm betweenmonophasic and biphasic groups 24 hours (82.5% vs68%; p � 0.14) and 1 month (40% vs 26%; p � 0.13)after cardioversion.

Table 2 lists univariate predictors of successfulcardioversion. Multivariate stepwise logistic regres-

sion analysis revealed that patients weighing �90 kg,those who received �2 shocks, and those who re-ceived more than the median peak current of 55.5 Awere more likely to achieve cardioversion. Only theshorter duration of AF (�6 months) is a significantmultivariate predictor of remaining in sinus rhythm at24 hours (odds ratio [OR] 5.0, 95% confidence inter-val [CI] 1.3 to 18.7; p � 0.01). The only univariatepredictor of having sinus rhythm at 1 month wasreceiving �2 shocks. Similarly, a multivariate step-wise forward logistic regression model, testing as can-didates those variables with univariate p values �0.20(waveform, amiodarone, duration, and number ofshocks) revealed that such patients undergoing �2shocks were significantly less likely to be in sinusrhythm at 1 month (22% vs 46%, OR 0.25, 95% CI0.09 to 0.73; p � 0.01).

Peak current (17.5 � 4.4 vs 36.0 � 8.0 A; p�0.0001), cumulative energy (243 � 164 vs 507 �298 J; p �0.0001), and cumulative current (33.7 �19.0 vs 72.0 � 30.9 A; p �0.0001) were all lower inthe biphasic group. Troponin T remained within nor-mal limits in all patients. Elevations in CK (93 � 234vs 509 � 708 U/L; p �0.001) and myoglobin (87 �115 vs 446 � 526 ng/ml; p �0.0001) were signifi-cantly less in the biphasic group. The relation betweencumulative current, type of shock waveform, andmaximal myoglobin is depicted in Figure 2. To betterdelineate the candidate predictors of significant mus-cle damage, we performed multivariate linear regres-sion (Table 3), followed by univariate and multivari-ate logistic regression analyses on enzyme values�125 U/L for CK and �72 ng/ml for myoglobin. Inaddition to peak current (p �0.001) and monophasicwaveforms (p � 0.005), the other expected univariatepredictors in all cases were �2 shocks delivered (p�0.001). Increases in CK and myoglobin were alsopredicted by age �65 years for CK and male genderfor myoglobin (OR 3.7, 95% CI 1.4 to 10.1 [p �0.008] and OR 3.3, 95% CI 1.3, 8.3 [p � 0.01],respectively. In the multivariate logistic regressionmodel, the monophasic waveform emerges as thestrongest overall predictor of an elevated CK level(OR 13.2, 95% CI 3.9 to 45.5). For myoglobin eleva-tion, the multivariate logistic model revealed bothmale gender (OR 3.5, 95% CI 1.25 to 9.6) andmonophasic waveforms (OR 4.35, 95% CI 1.5 to 12.2)to be significant predictors.

• • •The present investigation demonstrates that cardio-

version rates of AF lasting �48 hours are similar toeither truncated exponential biphasic or damped sinewave monophasic shocks. The study also providesfurther support that both waveforms are safe to themyocardium.1–3 Decreased current requirements andthereby lower degree of skeletal muscle injury sug-gests that truncated exponential biphasic shocks maybe the preferred method for the transthoracic cardio-version of persistent AF.

Comparable cumulative success rates between bothwaveforms is in concordance with the work of Page etal.4 Previous studies, however, included patients with

TABLE 1 Baseline Characteristics

Shock Waveform

Biphasic(n � 43)

Monophasic(n � 40)

Age (yrs) 69 � 6 67 � 8Women 18 (42%) 17 (43%)Weight (kg) 79 � 14 84 � 18Duration of AF

�48 h–7 d 2 (5%) 2 (5%)�7 d–�6 mo 16 (37%) 15 (37%)6–�12 mo 7 (17%) 8 (20%)�12 mo 18 (41%) 15 (37%)

Underlying heart diseaseSystemic hypertension 29 (67%) 29 (72%)Coronary heart disease 6 (14%) 3 (8%)Valvular heart disease 5 (12%) 3 (8%)None 3 (7%) 5 (12%)

MedicationsAmiodarone 16 (37%) 11 (28%)� blocker 14 (33%) 14 (35%)

Left atrial size (mm) 45 � 6 44 � 6Left ventricular ejection fraction (%) 56 � 11 57 � 11Initial transthoracic impedance (�) 86 � 16 82 � 20

Numerical data are listed as mean value � SD.p � NS for all comparisons between biphasic and monophasic shock

groups.

FIGURE 1. Cumulative cardioversion efficacy of monophasic (M)and biphasic (B) shocks.

BRIEF REPORTS 989

acute as well as chronic AF.4,5 Thisstudy included only patients withchronic AF, and a greater proportionof patients with a long (�6 months)duration of AF (58% vs 25% in thestudy of Page et al4 and 58% vs 13%in the study of Mittal et al5). Resultsfurther support the comparable4-shock efficacy between both wave-forms, regardless of the duration ofAF. Conversion rates in themonophasic arm of our study wereslightly higher than previously re-ported.4 This may be explained, atleast in part, by differences in theposition of the pads, body habitus,and phase of ventilation duringwhich cardioversion was attempted.Although previous reports are con-flicting, the standard anterolateralposition of the pads may be moreeffective than the standard antero-posterior position.6 All shocks in ourstudy were applied during exhala-tion, which is likely to increase thesuccess rate.7 Traditional dampedsine waveforms assume a patient im-pedance of 50 �, but the averageimpedance of adult humans is �70�.8,9 The monophasic defibrillator

used in our study adjusted the preselected energy,thereby maintaining the peak current when impedanceexceeds 50 �. The lower success rates at 1 month areconsistent with previously published results showing ahigh relapse rate after successful cardioversion in pa-tients with chronic AF.10

In summary, this comparative randomized trial re-vealed similar rates of successful cardioversion be-tween biphasic and monophasic waveforms; however,patients with chronic AF who were younger, male,and exposed to monophasic waveforms were signifi-cantly more likely to incur greater levels of skeletal

TABLE 2 Cardioversion Outcomes (univariate predictors of success)

Predictor Variables Immediate SR p Value SR at 24 Hours p Value SR at 30 Days p Value

Men 0.49 (0.09–2.7) 0.40 1.9 (0.64–5.3) 0.25 0.82 (0.32–2.1) 0.67Weight �90 kg 0.23 (0.05–1.1) 0.05* 1.3 (0.38–4.6) 0.66 1.02 (0.35–3.0) 0.96Age �65 yrs 0.58 (0.12–2.8) 0.49 2.8 (0.72–10.6) 0.13 0.92 (0.33–2.5) 0.87Duration �6 mo 03.7 (0.41–33) 0.22 4.1 (1.1–15.7) 0.03* 1.96 (0.73–5.2) 0.18Systemic hypertension 0.99 (0.18–5.5) 0.99 0.42 (0.11–1.6) 0.20 0.99 (0.36–2.8) 0.98Amiodarone 0.65 (0.14–3.2) 0.59 1.4 (0.45–4.5) 0.54 1.9 (0.73–5.1) 0.18� blocker 1.3 (0.24–7.2) 0.75 1.02 (0.34–3.2) 0.96 1.0 (0.37–2.7) 1.0Ejection fraction �53% 1.2 (0.24–5.5) 0.87 0.69 (0.23–2.1) 0.51 1.02 (0.40–2.6) 0.97Left atrium �3.8 cm 2.8 (0.5–16.9) 0.23 0.74 (0.14–3.8) 0.71 0.63 (0.15–2.5) 0.51Impedance �80 � 0.11 (0.01–0.9) 0.02* 0.5 (0.18–1.4) 0.21 1.03 (0.40–2.6) 0.96�2 Shocks 1.2 (1.1–1.5) 0.002* 0.16 (0.05–0.54) 0.001* 0.32 (0.12–0.86) 0.02*Biphasic waveform 0.77 (0.16–3.7) 0.74 0.44 (0.14–1.3) 0.14 0.49 (0.19–1.2) 0.13Median peak current �55.5 A 1.2 (1.1–1.4) 0.006* 0.30 (0.09–0.93) 0.032* 0.79 (0.31–2.0) 0.62

*2-tailed Fisher’s exact test, p �0.05.Values are expressed as odds ratios (95% confidence interval).SR � sinus rhythm.

FIGURE 2. Relation between cumulative current, type of shock waveform, and maxi-mal post-shock myoglobin. Abbreviations as in Figure 1.

TABLE 3 Increased Creatine Kinase (CK) and Myoglobin(multivariate linear regression)

� Coefficient(95% CI)

Significance(p value)

CKMale gender 3.72 (0.334, 7.96) 0.032Peak current 0.133 (0.088, 0.18) 0.000Current waveform interaction 0.065 (0.01, 0.12) 0.022

MyoglobinMale gender 143 (14.1, 272.2) 0.03Peak current 9.8 (7.26, 12.4) 0.000Current waveform interaction 8.57 (4.63, 12.5) 0.000Monophasic waveform 350.8 (85.8, 615.7) 0.001

990 THE AMERICAN JOURNAL OF CARDIOLOGY� VOL. 92 OCTOBER 15, 2003

muscle damage. The clinical relevance of these find-ings awaits further study.

1. Neumayr G, Hagn C, Ganzer H, Friedrich G, Pechlaner C, Joanidis M,Schratzberger P, Wiedermann CJ. Plasma levels of troponin T after electricalcardioversion of atrial fibrillation and flutter. Am J Cardiol 1997;80:1367–1369.2. Joglar JA, Hamdan MH, Ramaswamy K, Zagrodzky JD, Sheehan CJ, NelsonLL, Andrews TC, Page RL. Initial energy for elective external cardioversion ofpersistent atrial fibrillation. Am J Cardiol 2000;86:348–350.3. Ricard P, Levy S, Boccara G, Lakhal E, Bardy G. External cardioversion ofatrial fibrillation: comparison of biphasic vs monophasic waveform shocks.Europace 2001;3:96–99.4. Page RL, Kerber RE, Russell JK, Trouton T, Waktare J, Gallik D, Olgin JE,Ricard P, Dalzell GW, Reddy R, et al, for the BiCard Investigators. Biphasicversus monophasic shock waveform for conversion of atrial fibrillation: theresults of an international randomized, double-blind multicenter trial. J Am CollCardiol 2002;39:1956–1963.5. Mittal S, Ayati S, Stein KM, Schwartzman D, Cavlovich D, Tchou PJ,

Markowitz SM, Slotwiner DJ, Scheiner MA, Lerman BB. Transthoracic cardio-version of atrial fibrillation: comparison of rectilinear biphasic versus dampedsine wave monophasic shocks. Circulation 2000;101:1282–1287.6. Alp NJ, Rahman S, Bell JA, Shahi M. Randomised comparison of antero-lateral versus antero-posterior paddle positions for DC cardioversion of persistentatrial fibrillation. Int J Cardiol 2000;75:211–216.7. Ewy GA, Hellman DA, McClung S, Taren D. Influence of ventilation phase ontransthoracic impedance and defibrillation effectiveness. Crit Care Med 1980;8:164–166.8. Kerber RE, Grayzel J, Hoyt R, Marcus M, Kennedy J. Transthoracic resistancein human defibrillation. Influence of body weight, chest size, serial shocks, paddlesize and paddle contact pressure. Circulation 1981;63:676–682.9. Kerber RE, Martins JB, Kienzle MG, Constantin L, Olshansky B, Hopson R,Charbonnier F. Energy, current and success in defibrillation and cardioversion:clinical studies using an automated impedance-based method of energy adjust-ment. Circulation 1988;77:1038–1046.10. Van Gelder IC, Crijns HJ, Tieleman RG, Brugemann J, De Kam P, GosselinkAT, Verheugt FW, Lie KI. Chronic atrial fibrillation. Success of serial cardio-version therapy and safety of oral anticoagulation. Arch Intern Med 1996;156:2585–2592.

Bidirectional Ventricular Tachycardiaand Channelopathy

Preecha Laohakunakorn, MD, D. Woodrow Benson, MD, PhD, Ping Yang, PhD,Tao Yang, MD, Dan M. Roden, MD, and John D. Kugler, MD

Based on similarity of electrocardiographic features,bidirectional ventricular tachycardia has been consid-ered a variant of long QT syndrome. Genes causinglong QT syndrome were used as candidate genes in 4patients with bidirectional ventricular tachycardia. In2 patients, we identified a common low penetranceHERG allele (R1047L) with an intermediate biophysi-cal phenotype. �2003 by Excerpta Medica, Inc.

(Am J Cardiol 2003;92:991–995)

B idirectional ventricular tachycardia (BVT) is aterm used to describe a beat-to-beat alternating

QRS axis and morphology during VT.1–5 As such, it isa form of polymorphic VT; the duration is usuallynonsustained with a slower rate than Torsades dePointes. BVT was first reported in association withdigitalis toxicity,6 but has also been associated withhypokalemic periodic paralysis, aconite poisoning,and exercise.1–5 The familial nature of BVT has beendemonstrated, and both autosomal dominant and re-cessive forms of inheritance have been reported.7,8

Recent reports of mutations in the cardiac ryanodinereceptor 2 gene (hRyR2), calsequestrin 2 gene

(CASQ2), and an inward-rectifying potassium chan-nel gene (KCNJ2) have established the genetic heter-ogeneity of BVT.9–14 Based on the similarity of elec-trocardiographic features, BVT has been considered avariant of long QT syndrome.2 To evaluate this pos-sibility, we used the sodium and potassium channelgenes previously identified as causes of long QT syn-drome as candidate genes in 4 patients with BVT.12,15

• • •Informed consent was obtained from all partici-

pants in accordance with the Medical University ofSouth Carolina Institutional Review Board for HumanResearch. A complete family and past medical history,detailed clinical examination, and cardiovascular eval-uation including standard electrocardiography, Holtermonitoring, and echocardiography were performed ineach patient. Additional testing was performed, butbecause clinical information was obtained by retro-spective review, the type of testing varied. Some fam-ily members also underwent standard electrocardiog-raphy, Holter monitor recording, and exercise testing.The QT intervals were measured on lead II and cor-rected for heart rate using Bazett’s formula.

There were 3 male patients and 1 female patient;clinical history and family history are listed in Table1. The physical examination was normal for all pa-tients. In particular, no patient or family member hadevidence of small mandible, hypertelorism, clinodac-tyly, or syndactyly, and none gave a history of peri-odic paralysis or episodic muscle weakness. Asymp-tomatic BVT was demonstrated in each subject(Figures 1 and 2). Cardiac catheterization and cardiacmagnetic resonance imaging, performed in patientsBVT1, BVT3, and BVT4, were normal. Electrophysi-ologic testing, performed in BVT1, BVT3, and BVT4,induced no arrhythmias.

From the Bumgrad Hospital, Bangkok, Thailand; Division of PediatricCardiology, Medical University of South Carolina, Charleston, SouthCarolina; Division of Pharmacology, Vanderbilt University MedicalCenter, Nashville, Tennessee; and University of Nebraska/CreightonUniversity Joint Division of Pediatric Cardiology, Children’s Hospital,Omaha, Nebraska. This study was supported in part by grantHL49989 to Dr. Roden and grant HL69712 to Dr. Benson from theNational Institutes of Health, Bethesda, Maryland. Dr. Benson’s ad-dress is: Cardiovascular Genetics ML 7042, Children’s Hospital Med-ical Center, 3333 Burnet Avenue, Cincinnati, Ohio 45229-3039.E-mail: woody.benson@cchmc.org. Manuscript received April 30,2003; revised manuscript received and accepted June 17, 2003.

991©2003 by Excerpta Medica, Inc. All rights reserved. 0002-9149/03/$–see front matterThe American Journal of Cardiology Vol. 92 October 15, 2003 doi:10.1016/S0002-9149(03)00987-1