Original Contribution

Optimization of initial energy for cardioversion of atrial tachyarrhythmias with biphasic shocks^?

Johann Reisinger MD?, Christine Gstrein MD, Thomas Winter MD,

Eduard Zeindlhofer MD, Kurt Hollinger MD, Michael Mori MD, Alexandra Schiller MD, Andreas Winter MD, Helmut Geiger MD, Peter Siostrzonek MD

Department of Internal Medicine/Cardiology, Krankenhaus Barmherzige Schwestern, Seilerstatte 4, 4010 Linz, Austria

Received 12 September 2008; accepted 17 October 2008

Abstract

Objective: Recommendations for optimal first-shock energies with biphasic waveforms are conflicting. We evaluated prospectively the relation between type and duration of atrial tachyarrhythmias and the probability of successful cardioversion with a specific biphasic shock waveform to develop recommendations for the initial energy setting aiming at the lowest total cumulative energy with 2 or less consecutive shocks.

Methods: We analyzed 453 consecutive patients undergoing their first transthoracic electrical cardioversion, including 358 attempts for Atrial fibrillation and 95 attempts for atrial flutter (AFL) or atrial tachycardia (AT). A step-up protocol with a truncated exponential biphasic waveform starting at 50 J was used. Total cumulative energies were estimated under the assumption of a 2-tiered escalating shock protocol with different initial energy settings and a “rescue shock” of 250 J for AFL/AT or 360 J for AF. The initial energy setting leading to the lowest total cumulative energy was regarded as the optimal first-shock level.

Results: Cardioversion was successful in 448 patients (cumulative efficacy, 99 %). In patients with AFL/AT, the lowest total cumulative energy was attained with an initial energy setting of 50 J. In patients with AF, lowest values were achieved with an initial energy of 100 J for arrhythmia durations of 2 days or less and an initial energy of 150 J for arrhythmia durations of more than 2 days.

Conclusion: We recommend an initial energy setting of 50 J in patients with AFL/AT, of 100 J in patients with AF 2 days or less, and of 150 J with AF more than 2 days.

(C) 2010

Introduction

^? This study was supported by the Medizinische Gesellschaft fur Oberosterreich, Linz, Austria.

* Corresponding author. Tel.: +43 732 7677 7202; fax: +43 732 7677

7414.

E-mail address: [email protected] (J. Reisinger).

For many years, monophasic shocks have been used for transthoracic electrical cardioversion of atrial tachyarrhyth- mias. Currently, devices delivering biphasic shocks are increasingly available [1]. To minimize the duration of this procedure, knowledge about the initial shock energy required for a reasonable high success rate with the first applied shock

0735-6757/$ - see front matter (C) 2010 doi:10.1016/j.ajem.2008.10.028

would be helpful, particularly if certain known character- istics of the arrhythmia could be incorporated into a simple clinical prediction rule. Numerous investigations have already examined the efficacy of biphasic shocks for cardioversion of atrial tachyarrhythmias [2]. However, data on the success rate of different shock energies stratified by type and duration of the arrhythmia are limited. To our knowledge, only one relatively small study [3] among numerous investigations concerning the truncated exponen- tial biphasic shock waveform (as incorporated in Medtronic Physio-Control devices) [4-11] specifically addressed this topic. Moreover, recommendations for initial shock energies are still conflicting. Although several clinical studies have consistently shown that biphasic shocks do not induce significant elevations of cardiac troponin levels [4,12,13], certain mechanisms of possible myocardial injury including electroporation, formation of oxygen-derived free radicals, and conformational damage to ionic pumps or channels by high peak or cumulative shock energies are still under discussion [14,15]. Consequently, it seems prudent to avoid the initial use of high-energy shocks for elective cardiover- sion procedures.

Therefore, the purpose of this prospective observational study was to evaluate the relation between type and duration of atrial tachyarrhythmias and the probability of successful cardioversion using the truncated exponential biphasic waveform in a series of consecutive patients. Specifically, we tried to optimize recommendations for the initial energy setting aiming at the lowest possible total cumulative energy with the application of 2 or less consecutive shocks to shorten the cardioversion procedure as much as possible without unnecessarily exposing all patients to the maximal energy output of the device.

Methods

Study population

We examined prospectively all consecutive patients 18 years and older who underwent transthoracic electrical cardioversion for Atrial fibrillation , atrial flutter (AFL), or atrial tachycardia (AT) at the intensive care unit of our hospital. The recruitment period extended from April 2000 to July 2007. In patients with multiple procedures during this period, only the first cardioversion was included in our analysis. Patients with an arrhythmia duration of more than 48 hours were treated with phenprocoumon (Marcoumar, Roche, Vienna, Austria) for a minimum of 3 weeks at an international normalized ratio of more than 2.0 or underwent a transeso- phageal echocardiogram that showed the absence of Left atrial thrombus while receiving therapeutic heparin immediately before cardioversion. In case of a preceding attempt of pharmacological cardioversion, a time delay of 2 hours was left between intravenous administration of an antiarrhythmic

drug and the electrical cardioversion procedure. Arrhythmia duration was determined by combination of the patient’s history and electrocardiograms (if available). In patients with AF, 4 different time intervals of arrhythmia duration were specified in advance for the analysis of cardioversion rates (with cutoff values at 2, 30, and 90 days, respectively).

Cardioversion procedure

Electrical cardioversion was performed with the patient in the postabsorptive state and under short general anesthesia with 1% propofol (Diprivan, AstraZeneca, Vienna, Austria, or Propofol-Lipuro, Braun, Melsungen, Germany). In all patients, a biphasic truncated exponential waveform device (Medtronic Physio-Control Lifepak 12 or 20; Medtronic Inc, Redmond, Wash) was used with sequential shocks of 50, 100, 150, 200, 250, 300, and 360 J (if necessary). This device automatically measures transthoracic impedance during the first few milliseconds and prolongs the duration of the shock to compensate for increased impedance [16]. All shocks were synchronized to the QRS complex. The time interval between subsequent shocks in our protocol was at least 1 minute. An anterior-lateral electrode position (right infraclavicular area and left mid-axillary area lateral to the ventricular apex) was used in all patients except those with a right-sided pectorally implanted pacemaker in whom an anterior-posterior electrode position was chosen. For the anterior-lateral electrode position, hand-held steel paddles covered by disposable polymer gel pads (Defib-Pads 2345N, 3M Health Care, St Paul, Minn) were applied, whereas for the anterior-posterior electrode position, self-adhesive defibrillation patches (Quik- Combo, Medtronic Inc) were used. If necessary, the skin was shaved immediately before applying the electrodes [17]. Successful cardioversion was defined as the presence of sinus rhythm (or a captured atrial paced rhythm) with at least 1 clearly identified P wave visible within 30 seconds after delivery of a shock. Immediate recurrence was defined as reappearance of the atrial tachyarrhythmia within 10 minutes. Echocardiographic data obtained within 1 month of cardio- version were used for assessment of left ventricular systolic function and left atrial size.

The study was performed in accordance with the Declaration of Helsinki and written informed consent was obtained prior to the procedure from each patient. As the protocol of the procedure complied fully with the established clinical routine for electrical cardioversion at our hospital and the aims of this study were purely observational, approval by the local ethics committee was not required. This study was completely independent of the manufacturer of the specific device used, and no industrial support was provided.

Statistical analysis

Data with normal distribution are described by mean value and SD. Differences between groups involving

proportions were assessed by Fisher exact test (2-tailed), as appropriate. Based on our data, we derived a calculation model for the optimization of the first-shock energy level. Total cumulative energies for specific patient groups with various types and durations of atrial tachyarrhythmias were estimated under the assumption of a 2-tiered escalating shock protocol with different initial energy settings and (if unsuccessful) a “rescue shock” of 250 J for AFL/AT or of 360 J for AF to achieve the highest possible probability of successful cardioversion for each patient. The initial energy setting leading to the lowest total cumulative energy in a specific patient group was regarded as the optimal first-shock energy level for these individuals. Moreover, exploratory multivariable logistic regression analysis was performed separately for patients with AFL/AT and those with AF to detect effects of various variables on the success of cardioversion at lower energy (defined as 50 J for AFL/AT and <=100 J for AF) and on the immediate recurrence of the arrhythmia. The following independent variables were forced simultaneously into the statistical model: age, sex, weight of the patient, duration of the arrhythmia, preceding use of an antiarrhythmic drug of class I-C or class III (each in contrast to neither of the two), and presence of underlying disease. Results are presented as adjusted odds ratios (OR) and 95% confidence intervals (CI). A 2-sided P value less than .05 was considered statistically significant. The Hosmer-Lemeshow test was used to check the goodness of fit of the model. All calculations were performed with SPSS statistical software (Version 13.0, SPSS Inc, Chicago, Ill).

Results

General characteristics

The study population comprised 453 consecutive patients (289 men, 164 women; mean age, 68 +- 11 years; range, 20 to 90 years) who underwent a total of 675 attempts for transthoracic electrical cardioversion of AF (n = 548) or AFL/AT (n = 127). In patients undergoing multiple procedures, only the first cardioversion during the recruit- ment period was included in the study, leaving 358 attempts for AF and 95 for AFL/AT for analysis. Baseline patient data are presented in Table 1, including the distribution of underlying disease that was deemed to be primarily associated with the arrhythmia in an individual patient. Echocardiograms within 1 month of cardioversion were available in 355 patients (78%). However, data for numerical quantification of left atrial size were adequate in only 165 patients (36%).

Before electrical cardioversion, class I-C Antiarrhythmic drugs (flecainide, propafenone) were administered in 70 patients (16%), and class III antiarrhythmic drugs (amiodar- one, sotalol, ibutilide), in 178 patients (39%). At the discretion of the attending physician, class I-C drugs and

ibutilide were given intravenously to attempt immediate pharmacological cardioversion, whereas amiodarone and sotalol represented chronic oral antiarrhythmic therapy. A total of 9 patients originally presenting with AF showed transformation into AFL after administration of flecainide or propafenone and were counted as belonging to the AFL/AT group. No treatment with antiarrhythmic drugs of class I-C or III before electrical cardioversion was used in 205 patients (45%). Rate limiting therapy with a ?-blocker or a nondihydropyridine Calcium-channel blocker was optional. An anterior-lateral electrode position was used in 443 patients (98%), whereas in 10 patients (2%) with a right- sided pectorally implanted pacemaker, an anterior-posterior electrode position was applied. The mean dose of propofol was 132 +- 52 mg per procedure.

Shock efficacy

Successful electrical cardioversion was achieved in 448 patients (cumulative efficacy, 99%), whereas in 5 patients (1%), application of energy levels up to 360 J was without effect (in 2 patients with AF <=2 days and in 3 patients with

Table 1 Baseline patient data

AF AFL/AT (n = 358) (n = 95)

Age (y) 68 +- 11 69 +- 11 Men/women 231/127 58/37 Body weight (kg) 84 +- 17 81 +- 20 Duration of arrhythmia <=2 days (n [%]) 126 (35) 22 (23) N2 to <=30 days (n [%]) 75 (21) 43 (45) N30 to <=90 days (n [%]) 86 (24) 23 (24) N90 days (n [%]) 71 (20) 7 (7) Underlying disease None (n [%]) 48 (13) 7 (7) Hypertension (n [%]) 146 (41) 30 (32) Coronary artery disease (n [%]) 67 (19) 23 (24) nonischemic cardiomyopathy (n [%]) 28 (8) 5 (5) Valvular heart disease (n [%]) 37 (10) 12 (13) Other (n [%]) 32 (9) 18 (19) Preceding antiarrhythmic therapy Flecainide (n [%]) 57 (16) 8 (8) Propafenone (n [%]) 4 (1) 1 (1) Amiodarone (n [%]) 51 (14) 21 (22) Sotalol (n [%]) 38 (11) 3 (3) Ibutilide (n [%]) 31 (9) 34 (36) Left atrial anteroposterior 46 +- 8 50 +- 9 size (mm) Left ventricular systolic function Normal/reduced (n/n [%/%]) 160/117 40/38 (58/42) (51/49)

Values are expressed as mean +- SD or number (%) of patients. Echo- cardiographic data on left ventricular function were available in 277 patients with AF and in 78 patients with AFL/AT, whereas data on left atrial size were available in 133 and 32 patients, respectively.

Fig. 1 Probability of conversion to sinus rhythm at different energy levels according to type and duration of atrial tachyarrhythmias.

AF N90 days). The probability of conversion to sinus rhythm at the different levels of energy, stratified by type and duration of the atrial tachyarrhythmia, is shown in Fig. 1.

Total cumulative shock energies under the assumption of a 2-tiered escalating shock protocol are depicted in Fig. 2 for AFL/AT and in Fig. 3 for AF. In patients with AFL/AT, the lowest value was attained with an initial energy setting of 50

J. In patients with AF, lowest values were achieved with an initial energy setting of 100 J for arrhythmia durations of 2 days or less and an initial energy setting of 150 J for arrhythmia durations of more than 2 days.

Fig. 2 Total cumulative shock energies under the assumption of a 2-tiered escalating shock protocol for patients with AFL/AT. The arrow lines below the bar graph indicate that, in this calculation model, all unsuccessful shocks at the initial energy setting are followed by a rescue shock of 250 J.

Fig. 3 Total cumulative shock energies under the assumption of a 2-tiered escalating shock protocol for patients with AF of various durations. The arrow lines below the bar graphs indicate that, in this calculation model, all unsuccessful shocks at the initial energy setting are followed by a rescue shock of 360 J.

Variable Unit Adjusted OR P (95% CI)

Body weight 1 kg (increase) 0.94 (0.92-0.96) b.001 Arrhythmia duration <=30 vs N30 d 2.55 (1.43-4.56) .002 Sex Female vs male 2.24 (1.11-4.50) .024 Age 1 y (increase) 0.99 (0.96-1.02) .395 Underlying disease Yes vs no 1.04 (0.44-2.42) .934 Class I-C drug Yes vs neither a 0.65 (0.34-1.23) .184 Class III drug Yes vs neither a 0.82 (0.35-1.94) .657

a Denotes receiving neither class I-C nor class III drugs.

Multivariable analysis revealed that lower patient weight, female sex, and shorter duration of the arrhythmia were significantly associated with the success of electrical cardioversion at lower energy (ie, <=100 J) in patients with AF (Table 2). This statistical model had a predictive accuracy of 79% and an acceptable fit (Hosmer-Lemeshow ?2 = 4.442, df = 8, P = .815). In patients with AFL/AT, multivariable analysis did not detect any significant associa- tion regarding the prediction of success with low-energy shocks (ie, at 50 J).

Table 2 Predictors of successful cardioversion with low- energy shocks (defined as <=100 J) in patients with AF (multivariable logistic regression analysis)

Immediate arrhythmia recurrence

An immediate recurrence of atrial tachyarrhythmias within 10 minutes after successful electrical cardioversion was observed in 41 patients (11%) with AF and in 4 patients (4%) with AFL/AT (P = .052). Multivariable analysis did not reveal a significant association between any of the examined independent variables and immediate arrhythmia recurrence in patients with AF. There was only a trend for fewer immediate recurrences in patients on class I-C drugs (adjusted OR, 0.53; 95% CI, 0.26-1.11; P = .092)

and in those without underlying disease (adjusted OR, 0.33; 95% CI, 0.08-1.47, P = .147). The small number of events in patients with AFL/AT precluded any meaningful statistical analysis.

Discussion

We evaluated prospectively the relation between type and duration of atrial tachyarrhythmias and the probability of successful electrical cardioversion using a specific truncated exponential biphasic waveform in a large cohort of consecutive patients. The diagram presented in Fig. 1 allows the selection of appropriate initial shock energies satisfying different preferences for a desirable first-shock success rate. Aiming at the lowest possible total cumulative energy with the application of 2 or less consecutive shocks, we recommend an initial energy setting of 50 J in patients

with AFL/AT, of 100 J in patients with AF of 2 days or less duration, and of 150 J with AF of more than 2 days in duration. If the initial shock fails to restore sinus rhythm, a rescue shock of 250 J for AFL/AT or of 360 J for AF should be applied to secure the highest possible probability of successful cardioversion for each patient. Multivariable analysis revealed that lower patient weight, female sex, and shorter arrhythmia duration were significantly associated with the success of electrical cardioversion at lower energy (ie, <=100 J) in patients with AF, whereas no independent predictors could be found in patients with AFL/AT. The immediate recurrence rate within 10 minutes was 11% in patients with AF and 4% in those with AFL/AT.

There are 2 different approaches to energy selection for electrical cardioversion [2]. Some physicians favor the initial use of a high energy setting or even the highest possible energy of the device to maximize the chance of first-shock success, thereby shortening the procedure and sparing Sedative agents [18]. Others prefer to follow an escalating energy protocol, which allows cardioversion at the lowest energy for each individual patient and may minimize postshock arrhythmia, skin burns, skeletal muscle injury, and the remote possibility of myocardial damage or device failure in patients with implanted pacemaker or cardioverter- defibrillator systems [19,20]. We tried to develop recom- mendations for the initial energy setting stratified by the 2 most easily known characteristics of the arrhythmia (ie, type and duration) aiming at the lowest possible total cumulative energy with 2 or less consecutive shocks while preserving the highest possible likelihood of successful cardioversion by a “rescue shock.” This 2-tiered escalating protocol with an optimized initial energy setting seems to be a clinically reasonable compromise to shorten the procedure as much as possible without unnecessarily exposing all patients to the maximal energy output of the device. The results of our multivariable analysis suggest that incorporation of more variables into the prediction rule (e.g., weight and sex of the patient) could make the recommendations even more accurate. However, prediction rules are much more likely to be used by busy clinicians if they include only a small number of variables.

The effect of arrhythmia duration and body habitus on the success of electrical cardioversion is well documented for other shock waveforms [21-26]. However, only a single study [3] evaluated the influence of these variables on energy requirements in 94 patients with AF undergoing cardioversion with the truncated exponential biphasic waveform (as incorporated in Medtronic Physio-Control devices), predicting successful cardioversion with low- energy shocks (ie, <=100 J) for an AF duration of <=25 days with a sensitivity of 74%. Our results extend these findings to a much larger patient population and provide detailed information regarding selection of appropriate first-shock energies. Moreover, knowledge about the influence of sex seems to be rather limited but may be indeed of interest. The effect of female sex on energy requirements is

probably multifactorial. A higher percentage of body fat should exert an unfavorable influence by increasing transthoracic impedance [27,28]. However, the smaller thoracic cages of women compared to men appear to determine the overall beneficial effect of Female gender on the success of electrical cardioversion at lower energy as shown in our study.

Multivariable analysis revealed no significant impact of the preceding use of antiarrhythmic drugs on energy requirements of electrical cardioversion using a truncated exponential biphasic waveform. Neither the administration of class I-C drugs nor the prior use of class III drugs seemed to have a detrimental or beneficial effect. These findings are in contrast to the results of studies involving monophasic shocks [29-33], suggesting that biphasic shocks may be less sensitive to the administration of antiarrhythmic drugs before cardioversion. Of note, we never administered ibutilide with the purpose to facilitate electrical cardioversion [31] but always with the intention of pharmacological cardioversion, and a time delay of 2 hours was left between intravenous administration of ibutilide and the electrical cardioversion procedure.

However, a nonsignificant beneficial trend for the preceding use of class I-C drugs regarding immediate arrhythmia recurrence could be observed in patients with AF. This trend is in accordance with the results of previous investigations [32] promoting certain antiarrhythmic drugs as an adjunct to electrical cardioversion at least in case of immediate reinitiation of AF after delivery of a shock.

Several limitations potentially influence the applicability of our findings. Our results refer to the specific truncated exponential biphasic waveform tested but may not be valid for other biphasic shock waveforms. In a step-up protocol with escalating energies, the success rates of subsequent shocks may not be completely independent of its predecessors. Two counteracting factors may be operative in this context. First, the probability of success for higher- energy shocks in a sequential protocol is negatively influenced by the failure to convert with lower-energy shocks. Second, lowering transthoracic impedance by the preceding shock could facilitate successful cardioversion with the following shock, and even the use of an impedance-compensating biphasic waveform may not fully eliminate this phenomenon. Therefore, our optimized initial energy settings may be slightly over- or under- estimated, but this possible limitation could only be ascertained by a prospective validation of our prediction rule with randomized allocation of different initial shock energies. Moreover, our recommendations regarding initial energy selection apply only to patient populations where the distribution of different antiarrhythmic drugs before electrical cardioversion approximates the frequency in our patient cohort. Echocardiographic data were not incorpo- rated into the multivariable analysis due to missing numerical values in a considerable fraction of patients. Data on body mass index could not be used because patient height was not documented.

Conclusions

Aiming at the lowest possible total cumulative energy with <=2 consecutive shocks using the specific truncated exponential biphasic waveform incorporated in Medtronic Physio-Control devices, we recommend an initial energy setting of 50 J in patients with AFL/AT, of 100 J in patients with AF of 2 or less days in duration, and of 150 J with AF of more than 2 days in duration. Although impedance- compensating biphasic shocks should be less sensitive to transthoracic impedance, the influence of weight and sex on the success rate at lower energy remains substantial in patients with AF.

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