Comparison of the Efficacy and Safety ofTwo Biphasic Defibrillator Waveformsfor the Conversion of Atrial Fibrillation

to Sinus RhythmSusan Neal, RN, Tachapong Ngarmukos, MD, Darleen Lessard, MS, and

Lawrence Rosenthal, MD, PhD

The overall efficacy of transthoracic biphasic shocks de-livered for conversion of atrial fibrillation (AF) has beendemonstrated. We compared 2 different energy wave-forms, either the biphasic rectilinear (BRL) waveform orthe biphasic truncated exponential (BTE) waveform, inthe conversion of AF to sinus rhythm. The relation be-tween energy required for the conversion of AF, the typeof biphasic waveform, and patient characteristics wereexamined. Serum levels of cardiac troponin I were mea-sured before and after cardioversion, as well as post-procedural skin erythema and discomfort. In this pro-spective trial, 101 patients (mean age 61 � 15 years, 72men [71%]) referred for elective electrical cardioversionof AF were randomized to either a BTE or a BRL device.Shocks were delivered in a step-up fashion beginningwith 50 J (then 100 J, 200 J, repeat 200 J, and thencrossover to 360 J). One hundred patients were suc-

cessfully converted to sinus rhythm (99% success rate).There was no difference in efficacy at any energy levelused, regardless of the duration of the arrhythmia. Inaddition, there was no difference in cumulative success.Troponin I did not significantly increase after cardiover-sion, regardless of the total energy used. A positivecorrelation between skin erythema and skin discomfortafter shock (24 to 48 hours) was seen with increasingcumulative energies. There was also a positive trendtoward increasing energy requirements as chest circum-ference and body mass index increased. Thus, biphasicwaveforms are safe and effective at converting AF tosinus rhythm. In this study population, there was noclinical difference between the BRL and the BTEwaveforms. �2003 by Excerpta Medica, Inc.

(Am J Cardiol 2003;92:810–814)

A lthough biphasic waveform devices appear to bemore effective than monophasic waveform de-

vices, there have been no human studies directly com-paring different biphasic waveforms with each other.Therefore, it is unknown whether one biphasic wave-form morphology is superior in terms of efficacy andoverall safety. The primary purpose of this study wasto compare the safety and overall efficacy of 2 differ-ent transthoracic biphasic waveforms for conversionof atrial fibrillation (AF) to sinus rhythm. Secondarygoals included examination of the relation betweenenergy required to convert AF, the type of biphasicwaveform, and patient characteristics.

METHODSDefibrillators and waveform morphology: Two dif-

ferent transthoracic biphasic defibrillation deviceswere used in this study: the biphasic rectilinear (BRL)waveform device (Zoll M-series biphasic; Zoll Med-ical Corp., Burlington, Massachusetts) and the bipha-sic truncated exponential (BTE) waveform device

(Physiocontrol Lifepak-12; Physio-Control, Red-mond, Washington). The 2 devices deliver a biphasicwaveform shock; however, the waveforms differ inthe morphology and duration of the first phase of theshock. Both devices reverse polarity and deliver atruncated exponential waveform as the second phaseof the shock. The devices also differ in the manner inwhich they respond to patient-specific transthoracicimpedance. The BRL device changes the defibrilla-tor’s internal impedance to compensate for differencesin transthoracic impedance, allowing the delivery of aconstant current, fixed-duration shock.1 The BTEwaveform device prolongs the duration of the shock tocompensate for increased transthoracic impedance2

(Figure 1).Protocol and study design: This prospective, ran-

domized, single-center clinical trial compared BRLwith BTE waveform for efficacy of conversion of AF.The UMass Memorial Institutional Review Commit-tee approved the study. Between July 2001 and May2002, all eligible patients were randomized to 1 of 2treatment arms. Group I patients underwent cardiover-sion with the BTE waveform and Group II patientsunderwent cardioversion with the BRL waveform. Tobe considered for randomization, patients were re-quired to be appropriately anticoagulated to safelyundergo electrical cardioversion, as determined by theattending physician. Inclusion criteria included refer-ral for elective, transthoracic electrical cardioversion

From the Section of Cardiac Electrophysiology and Pacing, Division ofCardiovascular Medicine, Department of Medicine, UMass MemorialMedical Center, Worcester, Massachusetts. Manuscript receivedMarch 7, 2003; revised manuscript received and accepted June 6,2003.

Address for reprints: Lawrence S Rosenthal, MD, PhD, Section ofCardiac Pacing and Electrophysiology, UMass Memorial MedicalCenter, 55 Lake Avenue North, Worcester, Massachusetts 01655.E-mail: rosenthl@ummhc.org.

810 ©2003 by Excerpta Medica, Inc. All rights reserved. 0002-9149/03/$–see front matterThe American Journal of Cardiology Vol. 92 October 1, 2003 doi:10.1016/S0002-9149(03)00888-9

of AF, age �18 years, body weight �45 kg, and theability to give informed consent. Exclusion criteriaincluded cardiac rhythm other than AF documented atthe time of the procedure, hemodynamic instability orinability to tolerate sedation and cardioversion proto-col, cardioversion done in conjunction with other elec-trophysiologic procedures (except transesophagealechocardiogram), age �18 years, body weight �45kg, pregnancy, or incarceration.

After obtaining informed consent and electrocar-diographic documentation of AF, baseline demo-graphic data and serum cardiac troponin I were col-lected. Identical self-adhesive cardioversion patches(model PAD2518EPS; TZ Medical Inc., Portland, Or-egon) were used on all subjects and positioned in theanterior right parasternal (anode) and posterior leftinfrascapular (cathode) locations. Patients were se-dated according to institutional conscious sedationguidelines. Once sedated, the patient was randomizedto 1 of the 2 treatment arms. Shocks were delivered instep-up fashion (50, 100, 200, and 200 J) using thesame waveform until successful conversion of AF orcompletion of the protocol. If the second 200-J shockfailed, the patient was given a 360-J synchronizedshock using the BTE waveform device. Four hoursafter cardioversion, blood was collected for determi-nation of serum cardiac troponin I, and the patient wasdischarged from the study. At our institution, a serumcardiac troponin I level �0.5 ng/ml is consideredclinically significant. Successful conversion was de-fined as the presence of P waves, a captured atrialpaced rhythm, or junction rhythm for 3 consecutivebeats. In case of unsuccessful conversion after com-pletion of protocol shocks or early recurrences of AF,

further shocks were given at the discretion of theattending physician. All shocks and cumulative en-ergy were recorded and included in analysis of skincondition and serum cardiac troponin I (includingthose after the completion of the step-up protocol ordelivered for early recurrences of AF). Only shocksdelivered within the step-up protocol were included inthe analysis of efficacy. A follow-up phone interviewwas performed to assess skin condition and patientskin comfort 24 to 48 hours after the procedure. Pa-tients were asked to rate their comfort level (no dis-comfort, mild discomfort, moderate discomfort, se-vere discomfort) and the redness of their skin (noredness, mild redness, or severe redness).

Statistical analysis: Differences in the distributionof clinical characteristics between groups were exam-ined using the chi-square test of statistical significancefor discrete variables and Student’s t test for continu-ous variables. All tests of statistical significance were2 tailed. Pearson’s correlation coefficients were usedto test for correlation between variables. A p value of0.05 was considered significant. The power of thisstudy was 90% with an � of 0.05 to detect differencesof �20% between groups.

RESULTSSample: Of 102 consecutive patients who were

eligible for enrollment in the study, 101 were random-ized (mean age 61 � 15 years, 72 men [71%]). Forty-eight subjects were randomized to Group I (BRL) and53 were randomized to Group II (BTE). Baseline

FIGURE 1. The difference in waveform morphology between BTE(PhysioControl) and BRL (Zoll) at low and high impedance levels.These biphasic waveforms differ in the morphology and durationof the first phase of the shock. The devices also differ in themanner that they respond to transthoracic impedance. The BRLdevice changes the defibrillator’s internal impedance to compen-sate for patient-specific differences in transthoracic impedance,allowing the delivery of a constant current, fixed-duration shock.The BTE waveform device prolongs the duration of the shock tocompensate for increased transthoracic impedance. Both wave-forms reverse polarity and deliver a truncated exponential wave-form as the second phase of the shock.

TABLE 1 Patient Characteristics and Clinical DemographicData

BTE Group(n � 48)

BRL Group(n � 53)

CharacteristicAge (yrs) 60.0 � 16.0 63.0 � 16.0Men 33 � 69% 39 � 74%Body height (cm) 175.8 � 11.4 177.7 � 11.5Body weight (kg) 96.3 � 28.3 93.9 � 25.4Body mass index (kg/m2) 30.9 � 7.9 29.6 � 7.1Body surface area (m2) 2.1 � 0.3 2.1 � 0.3Chest circumference (cm) 116.2 � 16.4 112.7 � 14.5

Heart diseaseCoronary artery disease 19 (40%) 16 (30%)Hypertension 25 (53%) 29 (55%)Valvular disease 26 (55%) 24 (45%)Cardiothoracic surgery(within 6 mo)

4 (8%) 3 (5%)

Hyper/hypothyroidism 4 (9%) 5 (9%)Medication usage

� blockers 21 (44%) 22 (42%)Calcium antagonist 13 (27%) 10 (19%)Digoxin 10 (21%) 6 (11%)Antiarrhythmic agent 31 (65%) 40 (75%)

Sotolol 18 (38%) 25 (47%)Amiodarone 4 (8%) 7 (13%)Dofedolide 9 (19%) 8 (15%)

Duration of AF1–48 h 15 (31%) 14 (26%)48 h–1 mo 16 (33%) 23 (43%)�1 mo 17 (35%) 17 (32%)

Values expressed as mean � SD or number of patients (%).

ARRHYTHMIAS AND CONDUCTION DISTURBANCES/BIPHASIC DEFIBRILLATOR WAVEFORMS FOR THE CONVERSION OF AF 811

characteristics were similar between groups (Table 1).The number of patients enrolled with postoperativeAF, defined as AF within 6 months of cardiothoracicsurgery, was low in both groups.

One patient was excluded from analysis of skincondition and comfort because she received shocksfrom both waveforms (after completion of the step-upprotocol). This patient received a total of 9 shocks(1,710 J) and was eventually converted with tandem200-J biphasic shocks (1 from each waveform). Thepatient reported moderate pain, severe itch, and severeskin redness. All shocks given to this patient, until thecompletion of step-up protocol, were included in theanalysis of efficacy.

Energy and shocks: Independent of efficacy, cumu-lative energy was significantly higher for the BTEgroup (161 � 162 J) than the BRL group (120 � 117J; p � 0.026). Early recurrence of AF was similarbetween groups (6 BTE vs 5 BRL). However, the BTEgroup received higher-energy (postprotocol) shocksfor early recurrence of AF. Therefore, the number ofshocks was similar between the 2 groups (1.9 � 0.9 in

the BTE group vs 1.6 � 0.8 in theBRL group; p � 0.14).

Troponin: Of the first 62 patients,55 had serum cardiac troponin I lev-els measured at baseline and aftercardioversion. Of these 55 patients(age 61 � 15 yrs, 40 men [73%]), 36(66%) had heart disease and/or hy-pertension; no patient had elevatedtroponin I at baseline (0.03 � 0.05ng/ml). No patient had elevated tro-ponin I (�0.5 ng/ml) at 4.18 � 1.07hours after shock. Troponin I aftershock was 0.03 � 0.04 ng/ml andwas similar between the 2 groups(0.03 � 0.03 ng/ml BTE vs 0.04 �0.04 ng/ml BRL; p � 0.62).

Skin appearance and comfort:Postshock comfort was similar be-tween groups: 59% (n � 27) of theBTE group versus 61% (n � 31) ofthe BRL group reported no pain;17% (n � 8) of the BTE group ver-sus 23% (n � 12) of the BRL groupreported mild itching; 20% (n � 9)of the BTE group versus 14% (n �7) of the BRL group reported mildpain and moderate itch; and 4% (n �2) of the BTE group versus 2% (n �1) of the BRL group reported mod-erate pain and severe itch (p � 0.70).Skin appearance was also similar be-tween groups: 57% (n � 26) of theBTE group versus 55% (n � 28) ofthe BRL group reported no redness;43% (n � 20) of the BTE groupversus 43% (n � 22) of the BRLgroup reported mild redness; and nopatients in the BTE group versus 1(2%) in the BRL group reported se-

vere redness (p � 0.63). Independent of group, therewas a positive correlation between skin appearanceand total energy delivered (r � 0.35, p � 0.0004),between skin appearance and number of shocks (r �0.46, p �0.0001; Figure 2), between comfort and totalenergy (r � 0.29, p � 0.003), and between comfortand number of shocks (r � 0.35, p � 0.004; Figure 3).

Efficacy: Overall efficacy in restoration of sinusrhythm independent of waveform was 99% and didnot differ significantly between groups, with 97.9% (n� 47) of the BTE group versus 100% (n � 53) of theBRL group in sinus rhythm at the completion of theprotocol (p � 0.29). Effective energy was also similarbetween groups. At completion of the 50-J step, 52%(n � 25) of the BTE group and 62% (n � 34) of theBRL group were in sinus rhythm (p � 0.26). Atcompletion of the 100-J step, 83% (n � 40) of theBTE group and 94% (n � 50) of the BRL group werein sinus rhythm (p � 0.12). At completion of the first200-J step, 96% (n � 46) of the BTE group and 100%(n � 53) of the BRL group were in sinus rhythm (p �0.28). At completion of the second 200-J step as well

FIGURE 2. The correlation between skin appearance and cumulative energy, indepen-dent of group (r � 0.35, p � 0.0004) and the correlation between skin appearanceand number of shocks (r � 0.46, p <0.0001). Skin erythema increases with cumula-tive energy and number of shocks.

FIGURE 3. The correlation between comfort and total delivered energy, independentof group (r � 0.29, p � 0.003), and between comfort and number of shocks (r �0.35, p � 0.004). Postshock discomfort increases with cumulative energy and num-ber of shocks.

812 THE AMERICAN JOURNAL OF CARDIOLOGY� VOL. 92 OCTOBER 1, 2003

as the 360-J step, 97.9% (n � 47) of the BTE groupand 100% (n � 53) of the BRL group were in sinusrhythm (p � 0.28; Figure 4). Independent of wave-form, there was a modest correlation between success-ful energy and body habitus (Table 2).

DISCUSSIONThis study was the first human study that directly

compared the efficacy of different biphasic waveformswith each other. The 2 biphasic waveforms provedhighly successful for the conversion of AF. Successfulenergy and overall efficacy did not differ significantlybetween waveform groups. No patient in the BRLgroup required �200 J for successful conversion.Only 1 patient in the BTE group was not successfullyconverted with 200 J. This patient also failed to con-vert with either 360-J BTE or 200-J BRL shocks.Independent of waveform, the high success rate (99%)of the biphasic waveforms in this study was consistentwith the findings of other studies that compared bi-phasic waveforms with monophasic waveforms forcardioversion of AF.3–5 These results also parallelprevious studies demonstrating that both biphasicwaveforms (BTE and BRL) require less energy forsuccessful conversion of AF than monophasic wave-forms.3–5 Additionally, biphasic waveform deviceshave demonstrated improved defibrillation efficacy in

patients with high transthoracic im-pedance (�70 ohm) compared withmonophasic waveforms.1

The energy required for success-ful cardioversion with monophasicwaveforms has been shown to be re-lated to many factors, includingtransthoracic impedance, duration ofAF, the presence of untreated hyper-thyroidism, underlying mitral steno-sis, congestive heart failure, andbody habitus through its influence ontransthoracic impedance.4–9 In thisstudy, most patients (83% of theBTE group and 94% of the BRLgroup) were successfully convertedto sinus rhythm with a 100-J biphasicshock. No difference was noted inthe duration of AF, presence of struc-tural heart disease, use of antiar-rhythmic agents (including agentsthought to increase defibrillationthreshold), or the energy required forsuccessful cardioversion. Based onthe findings of this study, a 100-Jbiphasic shock is a reasonable start-ing energy for the conversion of AFregardless of the biphasic waveformused. We did not measure transtho-racic impedance. Instead, we mea-sured body mass index, body surfacearea, and chest circumference toidentify patients believed to havehigh transthoracic impedance. Inde-

pendent of waveform, there was a modest, yet signif-icant, correlation (about 30% to 37%) between suc-cessful energy and body size. This finding isconsistent with those of other studies using monopha-sic waveforms7 and would support the common prac-tice of using higher first-shock energy for larger pa-tients.

Although there is substantial evidence to supportthe safety of transthoracic cardioversion usingmonophasic waveforms,9–19 no such evidence existswith regard to the safety of delivering transthoracicbiphasic waveform shocks. Studies measuring tropo-nin I10–13 and troponin T10,14,15 after defibrillation andcardioversion with monophasic shocks have not dem-onstrated an increase in these cardiac-specific pro-teins. In this study, troponin I did not increase signif-icantly in any patient in either group after biphasiccardioversion shocks. However, the sensitivity of tro-ponin I at 4 hours after cardioversion (potential injury)is not known. Additionally, some studies have sug-gested that using less energy with lower peak currentsmay decrease the amount of postprocedural discom-fort experienced by the patient.5 Again, this hypothe-sis has not been rigorously tested using biphasic en-ergy shocks. In this study there was no difference inpostprocedural comfort or skin appearance betweenwaveforms. Nonetheless, independent of waveform,there were modest correlations between postproce-

FIGURE 4. Percentage of subjects in each group in sinus rhythm at the completion ofeach step of the protocol. At completion of the 50-J step, 52% (n � 25) of the BTEgroup and 62% (n � 34) of the BRL group were in sinus rhythm (p � 0.26). At com-pletion of the 100-J step, 83% (n � 40) of the BTE group and 94% (n � 50) of theBRL group were in sinus rhythm (p � 0.12). At completion of the 200-J step, 96% (n� 46) of the BTE group and 100% (n � 53) of the BRL group were in sinus rhythm (p� 0.28). At completion of the second 200-J step as well as the 360-J step, 97.9% (n� 47) of the BTE group and 100% (n � 53) of the BRL group were in sinus rhythm (p� 0.28).

TABLE 2 Correlation Between Body Habitus and Successful Energy

Energy

r Value p Value50 J 100 J 200 J

Body mass index (kg/m2) 28.2 � 5.3 32.3 � 8.6 35.3 � 11.0 0.31 0.001Body surface area (m2) 2.00 � 0.3 2.23 � 0.25 2.32 � 0.32 0.37 0.0001Chest circumference (cm) 110 � 15 118 � 13 128 � 16 0.37 0.0001

ARRHYTHMIAS AND CONDUCTION DISTURBANCES/BIPHASIC DEFIBRILLATOR WAVEFORMS FOR THE CONVERSION OF AF 813

dural skin appearance and total energy delivered,comfort and energy, skin appearance and number ofshocks, and comfort and number of shocks.

1. Mittal S, Ayati S, Stein KM, Knight BP, Morady F, Schwartzman D, Cavlov-ich D, Platia EV, Calkin H, Tchou PJ, et al. Comparison of a novel rectilinearbiphasic waveform with a damped sine wave monophasic waveform for trans-thoracic ventricular defibrillation. Zoll Investigators. J Am Coll Cardiol 1999;34:1595–1601.2. Geddes LA, Havel W. Evolution of the optimum bidirectional (�/� Biphasic)wave for defibrillation. Biomed Instrum Technol 2000;34:39–54.3. Keane D, Boyd E, Anderson D, Robles A, Deverall P, Morris R, Jackson G,Sowton E. Comparison of biphasic and monophasic waveforms in epicardialatrial defibrillation. J Am Coll Cardiol 1994;24:171–176.4. Mittal S, Ayati S, Stein KM, Schwartzman D, Cavlovich D, Tchou PJ,Markowitz SM, Slotwiner DJ, Scheiner MC, Lerman BB. Transthoracic cardio-version of atrial fibrillation: comparison of rectilinear biphasic versus dampedsine wave monophasic shocks. Circulation 2000;101:1282–1287.5. Dorian, P, Koster, RW, Chapman FW, Schmitt PW, O’Grady SG. A prospec-tive, randomized comparison of monophasic and biphasic shocks for externalconversion of atrial fibrillation: shock efficacy and post-procedure pain (abstr).Eur Heart J 2001;22(suppl):89.6. Trohman, RG, Parrillo, JE. Direct current cardioversion: indications, tech-niques, and recent advances. Crit Care Med 2000;28(suppl):N170–N173.7. Rashba EJ, Bouhouch R, Koshy S, MacMurdy K, Shorofsky SR, Peters RW,Gold MR. A new algorithm for transthoracic cardioversion of atrial fibrillationbased on body weight. Am J Cardiol 2001;88:1043–1045.8. Ricard P, Levy S, Trigano J, Paganelli F, Daoud E, Man KC, Strickberger SA,Morady F. Prospective assessment of minimum energy needed for externalelectrical cardioversion of atrial fibrillation. Am J Cardiol 1997;79:815–816.

9. 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;86:348–350.10. Lund M, French JK, Johnson RN, Williams BF, White HD. Serum troponinT and I after elective cardioversion. Eur Heart J 2000;21:245–253.11. Vikenes K, Omvik P, Farstad M, Nordrehaug JE. Cardiac biochemicalmarkers after cardioversion of atrial fibrillation or atrial flutter. Am Heart J2000;140:690–696.12. Allan JJ, Feld RD, Russell AA, Ladenson JH, Rogers MA, Kerber RE, JaffeAS. Cardiac troponin I levels are normal or minimally elevated after transthoraciccardioversion. J Am Coll Cardiol 1997;30:1052–1056.13. Bonnefoy E, Chevalier P, Kirkorian G, Guidolet J, Marchand A, Touboul P.Cardiac troponin I does not increase after cardioversion. Chest 1997;111:15–18.14. Greaves K, Crake T. Cardiac troponin T does not increase after electricalcardioversion for atrial fibrillation or atrial flutter. Heart 1998;80:226–228.15. Grubb NR, Cuthbert D, Cawood P, Flapan AD, Fox KA. Effect of DC shockon serum levels of total creatine kinase, MB-creatine kinase mass and troponin T.Resuscitation 1998;36:193–199.16. Sparks PB, Kulkarni R, Vohra JK, Mond HG, Jayaprakash S, Yapanis AG,Grigg LE, Kalman JM. Effect of direct current shocks on left atrial mechanicalfunction in patients with structural heart disease. J Am Coll Cardiol 1998;31:1395–1399.17. Mazzone C, Pandullo C, Scardi S, Salvi R, Miccio M, Cattarini G, MorgeraT. Left atrial and appendage mechanical function after pharmacological orelectrical cardioversion in patients with chronic atrial fibrillation: a multicenter,randomized study. Ital Heart J 2000;1:128–136.18. Harjai K, Mobarek S, Abi-Samra F, Gilliland Y, Davison N, Drake K, RevallS, Cheirif J. Mechanical dysfunction of the left atrium and the left atrial append-age following cardioversion of atrial fibrillation and its relation to total electricalenergy used for cardioversion. Am J Cardiol 1998;81:1125–1129.19. Welch PJ, Afridi I, Joglar JA, Sheehan CJ, Zagrodzky JD, Abraham TP, PageRL, Hamdan MH. Effect of radiofrequency ablation on atrial mechanical functionin patients with atrial flutter. Am J Cardiol 1999;84:420–425.

814 THE AMERICAN JOURNAL OF CARDIOLOGY� VOL. 92 OCTOBER 1, 2003