JACC “01 SEplFmbEl

20. NO I ,991 707-I I

707

EXPERIMENTAL

STUDIES

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Low Energy Conversion of Atria1 Fibrillation in the Sheep AmE C. JOHN

POWELL,

T. FALLON,

JEREMY

N. RUSKIN,

MB. 6s. PHD, HASAN GARAN. MD,

PHD. SUBRAMANIAM

MD,

ivlo. FA~c.

C. KRISHNAN.

BRIAN A. MCGOVERN,

MD,

MD,

FACC

oajediw. In this study, the feasibility. rnieary and safetyol tow enrr~ internal atrkt cardioversion were invrrtigated in B sheepmodel. The relation belwnn the level of energy used for alrial defibrillation and the probability of successfulcardioversian WBJexamined. Eockgrwtd. Atria, fibrillation k a c~tttm~n clinical arrhytbndP that frsquenlly IecYrs after termination with hilh energy external cnrdioversion.In smnepatknts with drug-re6xtory and poorly tokrated atrial fibrillation, an automatic implantttbk cardioverter may prove useful by pmvidbtg rapid retoraticm of sinus rhythm. Mel/t& In I6 pentobsrbitab8natbettzed sheep,a right atrial spring ekctrcxk wasimplsnted prcutaweusly and a kft thwack c~taneow patch atwtmde WIS ptnrd en the thorax. Sustained rtrkl fibrillation wa induced by rapid ntrial pacing mtd termi. wed by biphesit whodal 4hwzbssynchronized TVtk R ww of therurfnce *kxtrocardicgrsm wx,.

Atria! fibrillation occurs in 0.4% of the adult population and in 2% to 4% of persons ‘560 years of age il). After direct current cardioversion. the arrhythmia recws within 6 to I2 months in the majority of patienls who do not receive antiarrhythmic drug therapy (2-5). Even with drug therapy, including the use of newer agents such as propafenone and sotalol, recurrence of the arrhythmia is common. and langterm therapy with antiarrhyrhmic drugs is often paurly tolerated (6-l I). Furthemmre. in some patents the onset of atrial fibrillation may result in major hemodynamic deterioratioa and prompt restoration of sinus rhytbr.: may be critical. Alternative therapy with transcatheter or surgical ablation of the altioventricular node is reserved for only the most refractory cases because it results in pacemaker dependence and may cause a s&optimal hemodynamic state and carry a small long-term risk of sudden death (12). Automatic implantable cardioverter-defibrillatorr have been demon-

Conclwinnr. Low ettelgy cardiiversion ofatrial fibrillatiatt to sinusrhythm is feasibk with useof P riebt atrial mrinelculamws

xrated

to r&ably terminate ventricular arrhythmias (13) and IO improvc long-term survival (14,151.In some patients witb recurrent refractory atrial fibrillation, an implantable cardiovener might provide rauid restoration of sinus rhythm after recnrrenca of the arrh$hmia. To be useful, such a device would have to reliablv tetminate atrial fibrillation by cardioversion at a low l&l of energy without precipitaiing ventricular fibrillation. In this study, our objectives were I) to determine the feasibility of achieving reliable. safe cardiovenion of atrial fibrillation to sinus rhythm in an animal model. using an electrode eotdigun.ticm that would WI require thoracotomy for placement; and 2) to examine the relation between the energy required for atrial defibrillation and the probability of successful cardioversion.

Methods Experimenta! preprrrtiw. The protocol was approved by the Massachusetts General Hospital Subcommittee on Rcasarch Animal Care and the experiments were conducted in accordance with the guidelines of the “Position of the American Heart Association on Research Animal Use” adopted on November II, 1984. Twenty-one adult sheep weighing 25 to 45 kg were

anesthetized with intravenous pentobarbital (30 mglkg body weight), intubarcd and mechanically ventilated with room air by using a Harvard respirator. Three surface electrocardiographic (ECG) limb lead- ..w displayed on an oscilloscope WR 16 Simultrace). The left chest wall was shaved and a chloride gel cutaneous patch electrode with a surface area oi 50.3 cm’ (R2 Medical Systems) was placed over the left precordml remon. Femoral artery and venous catheters were &cd for co&uous pressure &nitoring and intravenous fluid administration. The heart was exposed through a right thoracotomy and two pacing plunge electrodes (O.M12-in. 15.08.cm1diameter Teflon-coated steel) were pieced on the right atrial appendage and connected externally to a programmable electronic stimulator (Medtronics model 2346).A silver and stainless steel defibrillating spring-coil electrode with a surf;lce area of 655 mm’ (Cardiac Pacemakers) was insettcd in the right external jugular vein by surgical cutdown and positioned in the right atrium. The spring electrode (cathode) and patch electrode (anode) were connected to a Ventritex HVS-02 external programmable defibrillator. which can deliver biphasic shocks with truncated exponential waveforms of a programmable energy level (50 to 750 V) and duration. The chest wall was then closed with surgical clamps. Arrhythmia induction and cardioversion pr&oi. A&l fibrillation/flutter, defined as a narrow complex rhythm witbout P waves and with an irregular ventric&r response, was induced by atrial pacing at short cycle lengths (90 to 120ms) with trains of rectaneular oulses of 2.ms duration and IO- to 20.mA current strength (16-19). in five sheep, 107episodes of electricallv induced atrial fibrillation lastine for at least 30 s were observed without cardioversion. 1; this control wouo. the duration of atrial fibrillation before soontaneous ~emt~nation raoged front 38 s to 25 min; the &.n duration was 109, 212, 129, 413 and 404 6. resoectiveiv. in the five animals. in the remaining 16 sheep, after atrial fibrillation/flutter was established for at least 30 s, cardioversion to restore sinus rhythm was attempted by using the external programmable defibrillator to deliver biphasic cathodal shocks of S-ms duration. Shocks were synchronized with the limb lead of the surface electrocardiogram (ECG) that gave the ootimal QRSIT wave ratio. The energy requirements for cardioverston were determined by using methods similar to those described by Davy et al. (20). Low energy levels (~5 .I! were initially selected, and the countershock energy was decreased in steps of0.2 13 0.5 I. The lowest energy level that resulted in successful conversion to sinus rhythm was termed the cardioversion threshold. Then 4 to 5 energy levels higher and lower than the initial cardioversion threshold in steps of 0.5 to 0.2 1 were chosen, and each energy level was tested 5 to 8 times in balanced random order (according to a standard table of random numbers) (21) to determine rhe atria1 cardiovmion CWVP for each sheep (20). After each successful cardioversion. a stabilization period of ~2 min was allowed before atrial fibrillation was reinduced and cardioversion was at-

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tempted at the next randomly selected energy level. High energy rescue defibrillation using internal paddles was available in the event of ventricular fibrillation. All data were recorded on photographic paper to document that conversion to sinus rhythm was temporally related to the electrical countershock. Successful cardioversion WBE defined es the return of sinus rhythm no later than three ventricular complexes after direct current shock. in I2 experiments. right ventricular bipolar plunge electrodes were attached to the right ventricle for recording local right ventricular electrograms. These electragrams were used in six experiments for synchronization during some of the cardioversions, to compare the effects of synchronization with the sutface ECG versus the right ventricular electmgnm oo the risk of ventricular fibrillation. Pathologic and histologic examination of atria1 e&ions. Hearts from eight sheep were removed and fixed in formalin for gross pathologic and histologic examination of tke atria1 seclions after staining with bematoxylin-eosin. Data analysis. Re<s are expre&ed as mean value + SD. The relation between the probabdity of successful cardioversion and the energy used for cardioversion was analyzed by using logistic regression analysis (BMDP Statistical Software inc. 1990 version). The roles of other potential predictor uiabies of successful cardioversion, such as sheep number, cardioversion attempt number within a sii:gle experiment. duration of atrial fibrillation and heart weight we& also examined. Logistic regression analysis was used to examine the relation between the induction of ventricular fibrillation and the level of energy applied for cardioversion. Statistical significance was defined asp 5 0.05

RWUltS Cardiiversion of atria1 Ahriiinllon. Sustained atriai fibtiilation could be induced repeatedly in all 16 sheep in which cardioversion was attempted; a total of 168 cardioversions were attempted in this group. The mean cardioversian threshold initially estimated by cardioversion energy testing (see Methods) was 2 ? 3.6 J. The probability of successful cardioversion increased as the energy level used for cardio. version increased (p < O.OW), reaching a plateau at approximately 5 1 (Fig. I). The success of co:diovcrsion varied among sheep (p < 0.0001). Representative cardioversion curves for two sheep are shown in Figure 2. The results of all 768 cardioversions are summarized in Table I. Cardioversion was successful in 31% of attempts performed at energy levels of 50.3 1. in 41% of attempts at energy levels of si J and in 83% of attempts at energy levels of 56 1 (Table I). Successful cardioversion could be demonstrated at energy levels of