Comparison of biphasic and monophasic shocks for defibrillation using a nonthoracotomy system

Comparison of Biphasic and Monophasic Shocks for Defibrillation Using a Nonthoracotomy System D. George Wyse, MD, PhD, Katherine M. Kavanagh, MD, Anne M. Gillis, MD, L. Brent Mitchell, MD, Henry J. Duff, MD, Robert S. Sheldon, MD, PhD, Teresa M. Kieser, MD, Andrew Maitland, MD, Patricia Flanagan, BN, John Rothschild, MD, and Rahul Mehra, PhD

A compmison of defib~Glatii thresholds was madeusingbiphasicandmowphadcshocks delivered by a B lead system in 2 clinically distinct @oups of patients. l’ha first @oup were patienb receiving an implantable caMoverterdefibrillator who were studied befors SU~WiththGr-ClOS8d.7h8WCOWl

@WJP were patients undW#W -w =m bypass mng (CABG) who were studied before surgery with their chssts open but rea#woximated. Biphasic defibrillation threshokb (stored emergy) were isigniintly (p 4.001) less than mwophadc ones in sul#ects with the impkmtable cardioverteMefibrillator (12.3 + 5.3 vs 21.1 f 9.3 J) or CAB0 (14.6 f 7.1 vs 24.2 f 12.6 J). lhese values are lass than were previously reported with a similar nonthoracotomyleadColb iiguration.nletw were nosigniicwtdiinws betwesntha2@oupsinallmeasuremsnts dsrived from correspomlimi fack -VW a~impedancetandedtobs@eaterin patimts with CABG. However, subjects with CABG had #eater left ventricular ejection frx~ tions and did not have hi of potentially lethal ventricular mBythmias Despite these di+ ~thecanclusionthatbiphasicshodu3are more effective would have been made in a study ofeithar~palons.ltisconcludedthat patients with CABG who have not had preceding potentially lethal ventricular anllythmii may be a potential sourcs of sum subjects for b fibrillatii resear& such as epicafdiil mappin& which requires that the chest bs opsn. (Am J Cardiol1993;71:197-202)

From the Divisions of Cardiology and Cardiovascular Surgery, University of Calgary/Foothills Hospital, Calgary, Alberta, Canada, and Medtronic Inc., Minneapolis, Minnesota. This study was supported by the Heart and Stroke Foundation of Alberta, Calgary, Alberta, Canada, and by Medtronic Inc., Minneapolis, Minnesota, and was presented in abstract form at the Annual Meeting of the Royal College of Physicians and Surgeons of Canada, Toronto, Ontario, Canada. Manuscript received April 30, 1992, revised manuscript received and accepted August 17, 1992. Address for reprints: D. George Wyse, MD, PhD, Division of Cardiology, Foothills Hospital, 1403 29 Street NW, Calgary, Alberta T2N 2T9, Canada.

he traditional source of human subjects for defibrillation research is patients who are receiving an implantable cardioverter-defibrillator (ICD) after having a prior episode of potentially lethal ventricular tachyarrhythmia. The increasing use of nonthoracotomy lead systems limits research instrumentation that requires an open chest (i.e., epicardial mapping). Surrogate subjects for the latter type of defibrillation research may be useful. Patients undergoing electrosurgery for Wolff-Parkinson-White syndrome have been used as subjects for defibrillation research.‘v2 The use of this patient population has been questioned: and the use of surgery in such patients has diminished with the increased use of radiofrequency catheter ablation. Patients undergoing coronary artery bypass grafting (CABG) may be considered as surrogate subjects for defibrillation research. CABG is common, and 1 clinical trial is implanting ICDs in high-risk patients undergoing CABG who have not had a ventricular tachyarrhythmia.4 However, the comparability of results of defibrillation research performed in such patients and that performed in ICD candidates with spontaneous ventricular tachyarrhythmias has not been established. Accordingly, as part of an evaluation of the efficacy of transvenous monophasic and biphasic defibrillation shocks in humans, we also compared the results in closed-chest ICD patients and open-chest CABG patients.

T

METHODS Patient selection:

Patients undergoing ICD implantation without concomitant surgery constituted the lirst group, and those undergoing CABG without concomitant surgery constituted the second group. The latter patients were excluded from the study if they had left main coronary artery disease or unstable angina in the month before surgery. With the specific approval of each patient’s cardiologist, cardiac surgeon and anesthetist, all patients gave written, informed consent. This study and its consent form were approved by the local institutional review board. The cardiac surgeon and anesthetist had the option of withdrawing the patient from the study intraoperatively if they were concerned regarding the patient’s clinical status. DdWiiMOll tlulesho# B All patients were studied under general anesthesia, which generally included a short acting narcotic (fentanyl or sufentanil), a sedative (midazolam), a neuromuscular blocking agent (vecuronium, pancuronium or metocurine) and a volatile anesthetic (enflurane, halothane or isoflurane). There BIPHASIC AND MONOPHASIC DEFIBRILLATION

197

TABLE I Experimental Subjects DFT (J)

Age (yr) No.

& Sex

1 2 3 4 5 6 7 8 9 Mean

56M 68M 65M 54M 57M 69M 70F 69F 72M 64 2 7

Weight

(kg)

Clinical Diagnosis

LVEF CABG,

88.5

-

97.0 117.5 85.0 89.6 84.3 54.8 50.6 69.2 81.8 ? 20.9

Open-Chest CAD CAD CAD CAD, CAD CAD, CAD, CAD CAD.

0.72 0.48 0.75 0.69 0.48 0.72 0.72 0.65 + 0.12

Presenting Rhythm

45F 78M 6BM 60M 56M 73M 69M 47M 58M 18F 53M 66M 58 f 16

59.0 76.0 72.0 68.0 67.0 72.0 72.0 73.4 65.0 63.3 83.5 67.5 69.9 + 6.4

Diltlazem Diltiazem Diltiazem

-

MI

HCM CAD, CAD, CAD, CAD, CAD, CAD, CAD, IDCM ARVD IDCM CAD,

0.55 0.18 0.20 0.32 0.22 0.34 0.26 0.29 0.30 0.72 0.51 0.24 0.34 + 0.17*

Monophasic

Biphasic

Group

MI MI

-

MI

-

ICD, Closed-Chest 1 2 3 4 5 6 7 8 9 10 11 12

Medications

Nifedipine Diltiazem Nifedipine Propranolol

37.8 37.7 13.7 42.4 21.3 28.1 14.1 11.5 11.2 24.2 k 12.6

22.6 22.8 6.9 23.4 14.1 16.9 8.8 5.7 10.4t 14.6 + 7.11

12.4 10.1 26.9 23.2 18.6 10.5 37.7 22.5 8.4 26.5 26.9 30.4 21.2 k 9.3

7.9 5.1 13.4 18.3 11.1 2.6 15.8 14.2 8.8 16.4 13.7 19.8 12.3 k 5.31

Group VF VT VF VT VT VT VT VT VT VT

Ml MI Ml Ml Ml Ml Ml

Ml

Verapamil Amiodarone -

Propranolol -

VT

*p ~0.05: tp
were no differences in anesthetic use between the 2 groups of patients. A Medtronic model 10284 transvenous defibrillation catheter (electrode surface area 4.26 cm*) was positioned with its tip at the right ventricular apex through a femoral vein. This electrode was the cathode for the first pulse. A small R2 defibrillator skin patch (Critical Care Products Division, Darox Corporation; electrode surface area 50.24 cm*) was positioned high (top edge, level with manubrial angle) in the left axilla (center at midaxillaq line) and was the anode for the first pulse. All shocks were delivered from a Medtronic model 2394 defibrillator. Patients were randomly assigned to receive either a monophasic or biphasic

shock during the first episode of ventricular fibrillation. A crossover design assessedthe alternate waveform during the second episode of ventricular fibrillation. Patients were fibrillated using alternating current delivered through the endocardial electrode catheter, and shocks were administered 10 seconds after cessation of alternating current fibrillation. For both monophasic and biphasic shocks, the leading-edge voltage of the initial shock was 580 V (approximately 20 J). The nominal tilt of all pulses was 65% (approximate pulse duration 5 ms). The biphasic shock was supplied from a single capacitor and thus the leading-edge voltage of the second pulse was equal to the

START 20J (560(200)

4

Iu

30J

3fy

r

STOP

198

IU

(62?/230)

s 32.6J (740/260) I

STOP

u r-l

27.5J (660/240) I

STOP

n3Btbws of pulsefs cessful;

,Ff60’.1

,u(2+XI)s,

S 22.5J

17.5J (540/l

i6’oro)

STOP

90) I

STOP

BIo voltages 1 (monopharic

of leading edge and biphasic)

and2 (bipha8ic),respecuvely.8=suo

15J

25J

(760{270)

U

FlGUREl.-for--lItOf ddiblmtion tluesMd!%llkrmberr/rlpb

(4lAyt40)

12.5J (460/i

60) I

STOP

THE AMERICAN JOURNAL OF CARDIOLOGY VOLUME 71

7.5J (350/l

2.5J 20)

I

STOP

wv70) I

STOP

JANUARY15,1993

IJ

q

UrnI.

terminal voltage of the lirst pulse. The polarity of pulse 2 was the reverse of pulse 1. The nominal tilt of the second pulse remained 65%, and the 2 pulses (approximately 5 ms each) were separated by 0.2 ms. The sequence of shocks used to determine defibrillation threshold used a binary search method (Figure 1). Defibrillation threshold was defined as the lowest energy providing successful defibrillation (Figure 1). Both stored and delivered energies were calculated. Patients undergoing ICD implantation were tested with the chest closed before any surgery. Patients undergoing CABG were studied after median stemotomy and venous cannulation without cardiopulmonary bypass, but with the sternum reapproximated. Data acquisition and analysis: The defibrillator was connected to a Honeywell VR 16 oscillographic recorder and a Hewlett-Packard tape recorder by a Medtronic model 2394004 breakout module. These recorders were used to simultaneously obtain surface electrocardiographic leads I, aVF and Vi, an intracardiac electrogram from the electrode catheter, and a marker channel from the ICD. The voltage and current delivered to the patient were recorded and measured on a Nicloet 3091 oscilloscope connected through Medtronic model 2707 signal isolation units. One channel of the oscilloscope was used to record voltage and another to measure current. The voltage and current of the leading and trailing edges of each pulse were measured and from these values, tilt, impedance and stored and delivered energy were calculated. Continuous data are presented as mean f 1 SD. Comparisons were obtained by paired or unpaired t test, as appropriate. Proportional data were compared using Fisher’s exact test. Statistical significance was accepted at p ~0.05. Curve-fitting used linear regression. All calculations were performed using commercially available, computer programs (MRTOD, Seattle, Washington). RESULTS Patients: The clinical characteristics of the 2 groups of patients are presented in Table I. Four of 9 patients with CABG had a previous myocardial infarction. Eight of 12 patients in the ICD group had coronary artery disease, and all 12 had a previous myocardial infarction. The remaining 4 patients in the latter group had cardiomyopathy (2 idiopathic dilated, and 1 each hypertrophic and right ventricular arrhythmogenic). A major difference between the 2 groups was that no patient with CABG had had lethal ventricular arrhythmias compared with all but 1 ICD patient. The patient with arrhythmogenic right ventricular dysplasia was an l&year-old with a strong family history of sudden death and inducible, sustained ventricular tachycardia. The mean left ventricular ejection fraction was significantly less for ICD patients. Approximately 90% of ICD patients approached consented to participate, and 3 were excluded intraoperatively because ventricular fibrillation could not be induced through the endocardial catheter. Approximately 25% of patients with CABG approached consented to participate, and 3 were excluded intraoperatively (2 because of difficulty with uansvenous instrumentation, and BIPHASIC AND MONOPHASIC DEFIBRILLATION 199

1 because of withdrawal by the surgeon owing to STsegment depression during induction of anesthesia). Another 3 patients (2 ICD and 1 CABG) completed the protocol, but were excluded because electronic equipment malfunction resulted in no data. One patient with CABG developed a sternal wound infection after surgery; another developed small, inferior Q waves and a peak serum creatine kinase MB fraction of 126 units (3.84%; perioperative myocardial infarction) after an episode of ventricular fibrillation in the cardiac intensive care unit. The maximal, peak serum, creatine kinase MB fraction in the other 8 patients with CABG was 60 units (5.17%), and all but the patient with the sternal wound infection were discharged within 15 days without other significant problems. Neither 2 perioperative complications (1 sternal wound infection and 1 perioperative myocardial infarction) were thought to be related to the protocol. One ICD patient was thought to have a pulmonary embolus (pleuritic chest pain and hemoptysis) after surgery, and 1 had a cardiac arrest leading to hypotension and transient renal failure. Five ICD patients had transient atrial fibrillation after surgery, 2 had transient worsening of heart failure, and 1 had a hematoma at the device pocket site. No complication was thought to be due to the protocol. Defibrillatioa~ threshdds: The voltage and current recorded at defibrillation threshold for the leading and trailing edges of each pulse are presented in Table II. For each measurement, the mean values obtained for biphasic pulses were less (p ~0.03) than those obtained for monophasic pulses within each group of patients. For each waveform, there were no significant differences comparing these values in open-chest CABG patients with those in closed-chest ICD patients. Impedance was virtually identical for all pulses within each group of patients, but tended (not significant) to be greater when the chest was open. ICD 40

DISCUSSION The 2 main lindings of this study am that: (1) biphasic shocks for defibrillation using this particular nonthoracotomy system in humans result in a lower defibrillation threshold than do monophasic shocks, and this threshold was less than that previously reported with a similar lead contiguration; and (2) this same result was obtained in 2 groups of subjects that differed in their mean left ventricular ejection fraction, whether their chests were opened or closed, and whether they were to undergo CABG or to receive an ICD. Biphasic shocks were previously reported to be more effective than were monophasic ones in dogs5 and humans6,7 using epicardial patches. Furthermore, several nonthoracotomy systems in dogs8-10 and humans” have shown a similar advantage of biphasic shocks. This study reports lower defibrillation thresholds with bi-

CABG

I-

P - 0.001 I

I

P < 0.001 I

P = 0.001

I

I

I

1

P < 0.001

30

2 g 7

The defibrillation thresholds expressed as total stored and delivered energy for biphasic and monophasic shocks are depicted in Figure 2, and individual data are presented in Table I. Energy needed for biphasic defibrillation was signiticantly less than that for monophasic defibrillation within each patient group. However, there were no significant differences when comparing the same waveform in open-chest CABG patients with that in closed-chest ICD patients. The percentage of patients successfully defibrillated is plotted against the total stored energy for biphasic and monophasic shocks in Figure 3. Complete success (100%) using the combined data was achieved with 123.4 J for biphasic pulses, and 50% success needed 12.9 J; corresponding values for monophasic pulses were 42.4 and 22.0 J, respectively. Whereas biphasic shocks were more effective over the entire range of stored energies, the major advantage of biphasic shocks was observed for the tertile of patients with the highest defibrillation thresholds.

I

I

FWURE 2. Defikilbtion pmswdsrtotelstomdand&liiered ~forbiphsriCandmonophrrdc

20

shodcsin2~psofpathts. CABQ=eoronayaterybyplustiNfWG ICD = impbttabk cdiovwtedefibriliatar.

10

200

uuwhdde

u

Monophasic

Stored

q

Monopharic

Delivered

Energy Energy

n q

Biphasic

Stored

Biphasic

Delivered

THE AMERICAN JOURNAL OF CARDIOLOGY VOLUME 71

Energy Energy

JANUARY 15, 1993

ex-

phasic shocks than with monophasic ones, and in both types of shock, the values obtained were much lower than those previously found using this nonthoracotomy lead system in humans. We believe this difference is due to positioning of the skin patch high in the left axilla, thus facilitating defibrillation of the base of the heart. The reasons for the reduced defibrillation thresholds with biphasic shocks are unknown, but several possibilities have been suggested. 12,13Previous studies assessing biphasic cardiac stimulation14 suggested that the lirst pulse of a biphasic shock repolarizes some cells and depolarizes others. The repolarization of cells results in reactivation of sodium channels to their resting state. These repolarized cells are more readily depolarized by the second pulse. This hypothesis implies that a biphasic shock can depolarize a larger mass of myocardium than can a monophasic one using the same amount of energy. The 2 groups of experimental subjects in this study were distinctly different clinically. Therefore, it may be anticipated that the 2 groups would have different defibrillation thresholds. However, this was not the case. Counterbalancing factors affecting defibrillation threshold in the 2 groups may explain the unexpected similarities. Transthoracic impedance15J6 and left ventricular mass17 have been reported to have a role in defibrillation threshold. Having the chest open resulted in a slightly higher impedance that would have been expected to increase defibrillation threshold in patients with CABG. However, there was no difference in defibrillation threshold between CABG and ICD patients. This may imply that there is a counterbalancing factor increasing the defibrillation threshold in ICD patients. This factor may be a greater left ventricular mass in ICD patients. Cardiopulmonary bypass has been reported to have no effect on defibrillation threshold,18 and therefore, although our patients with CABG were not on bypass, the presence of the venous cannula probably had no effect. Other factors reported to affect defibrillation threshold that were probably neutralized by the present protocol include duration of fibrillation,19-21 implant time, catheter stability and adrenergic tone.22v23 Several antiarrhythmic drugs have been reported to affect defibrillation threshold.23-31 Two patients in this study were receiving propranolol, which may have increased defibrillation threshold,23 but 1 was in each of the 2 groups of patients. In addition, a patient in the ICD group was receiving amiodarone. However, chronic amiodarone treatment in humans has been reported to have no effects on defibrillation threshold.30 One patient in the ICD group was receiving verapamil, which has been reported to increase defibrillation threshold,31 and 4 in the CABG group were receiving diltiazem and 2 nifedipine. The effects of the latter 2 calcium antagonists on defibrillation threshold have not been reported. There was no difference in anesthetic use between the 2 groups. It is unlikely that antiarrhythmic drug therapy had any significant impact on the results of this study. Study implications: Defibrillation thresholds noted in this study using a nonthoracotomy lead system were much less than those previously reported. The results suggest a wider applicability of this lead configuration,

particularly in regard to the position of the skin patch. The difference between defibrillation thresholds for biphasic and monophasic shocks was noted in both groups of experimental subjects. Therefore, it is inferred that open-chest CAE3G patients who are not receiving an ICD may be a potential source of subjects for defibrillation research. However, further studies in larger groups are needed. This finding has important practical implications for research in humans on defibrillation using epicardial mapping. 13,32The chest must be open to do the mapping, and as more ICDs are implanted using nonthoracotomv aumoaches, such studies will not be possible in most ICD patients. The use of patients vAth l Biphasic 0 Monophasic

100

bQ

-

20

.

0

L

FIGI E3.Plotofpementsu~ldefikillatJonv6rsuste talstoredemrgyforbiplwmioandnronophslicrhodurop amlm&hikprmdr,i@antabkudiovuteM8RMllator (EDI ad coronaryartey~fmfw(cABQ)pati~ areshownsepately,andbottool,all~wecolrr bined.tlottom,c~~w8susedtocdcul8te5o% -ofl2.9Jforbiphasicrhodu(r=O.~)and22J far momphdc olles (c = 0.982). BIPHASIC AND MONOPHASIC DEFIBRILLATION 201

CABG may be a suitable surrogate for epicardial mapping research during defibrillation.

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72&727. 31. Jones DL, Klein of lidocaine

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JANUARY 15,1993