A A J Adgey, S J Walsh

Transcription

1 Eletrophysiology THEORY AND PRACTICE OF DEFIBRILLATION: (1) ATRIAL FIBRILLATION AND DC CONVERSION A A J Adgey, S J Walsh 1493 D Heart 2004; 90: doi: /hrt efibrillation has been used to treat disturbanes of the ardia rhythm sine the late 1800s. 1 w1 In order to appreiate the mehanisms of defibrillation, one must also understand the basi eletrophysiologial priniples of fibrillation. ELECTROPHYSIOLOGICAL BASIS OF FIBRILLATION Atrial and ventriular fibrillation are both based upon a re-entrant mehanism, a phenomenon that was first reognised almost 100 years ago and initially desribed by Mines and Garrey. w1 Mines also suggested that ondution blok was neessary to failitate re-entry. w1 It was not until the 1950s that Moe and olleagues advaned the irus movement theory of re-entry when they suggested the multiple wavelet hypothesis of atrial fibrillation (AF). 2 This proposed that AF ourred in the presene of inhomogeneous atrial tissue. 2 It was postulated that multiple wavelets propagated randomly through the atria. These waves of exitation were presumed apable of spreading through the atrial myoardium at a time when some of its omponents had reovered while others remained partially or fully refratory as a result of a preeding ativation. 2 Thus AF ould be maintained as a turbulent arrhythmia in a stable state for long periods of time. By 1985, after the development of high resolution eletrode mapping systems, Allessie and olleagues provided evidene of multiple propagating wavelets that reated turbulent atrial ativity in the anine heart. 2 Subsequent experiments have proven Moe s idea that multiple wavelets distributed randomly throughout the atria gave rise to the haoti ativation patterns observed on the ECG. 2 More reent studies have further expanded on some of the experimental findings of Allessie and olleagues, suggesting that some forms of AF may atually be the result of high frequeny ativation by a single re-entrant soure in some patients. 2 The drivers of AF may be relatively stationary rotors of eletrial ativity that are anhored to an unexited (anatomial) ore in the posterior left atrium. 2 The atrial anatomy may failitate this re-entry proess by providing areas of ondution blok (for example, pulmonary vein ostia). It is also inreasingly reognised that etopi foi originating from the pulmonary veins may be responsible for initiation of AF in patients, and that eletrial isolation of these foi may provide long term orretion of AF in some patients. 3 Thus, AF is based upon re-entry. Multiple wavelets of eletrial ativity propagate randomly in the atrial tissue produing a haoti but ontinuous ativation of the atrial tissue. Defibrillation (or diret urrent ardioversion) in this setting aims to bring an abrupt halt to this proess and restore sinus rhythm. See end of artile for authors affiliations Correspondene to: Professor Jennifer Adgey, Regional Medial Cardiology Centre, Royal Vitoria Hospital, Grosvenor Road, Belfast BT12 6BA, UK; jennifer.adgey@ royalhospitals.n-i.nhs.uk MECHANISMS OF ATRIAL DEFIBRILLATION There are only limited data that examine the interation between an eletrial shok and atrial tissue. 4 w2 w3 Researh into the mehanisms of defibrillation has ourred almost exlusively in the setting of ventriular fibrillation. While there may be distint differenes between the preise mehanisms of atrial and ventriular defibrillation, none has been desribed. There are several theories of the mehanisms of defibrillation that are derived by ventriular defibrillation. It is thought that shoks defibrillate by altering the potential differene aross the ell membrane (that is, the transmembrane potential). 5 However, the situation in the heart is extremely omplex with the intraellular spae and extraellular spae both possessing different eletrial properties than the ell membrane that divides them. 5 Unfortunately, there is no urrent onsensus on how the extraellular potential gradient relates to the transmembrane potential gradient. Thus, the exat mehanism of eletrial defibrillation remains inompletely understood. The ritial mass theory proposes that defibrillation an be suessfully ahieved by the depolarisation of a suffiient or ritial mass of tissue. Zipes and olleagues demonstrated that hemial depolarisation of a ritial mass of ventriular myoardium (,75%), using seletive infusion of potassium hloride into the left oronary artery, would suessfully abolish ventriular

2 1494 fibrillation. 5 6 Therefore, if a suffiient voltage potential gradient ould be generated by a shok to halt the fibrillation ativation fronts in the myoardium, fibrillation ould be abolished. 5 When an eletrial field with strength of 5 V/m or less is introdued to ventriular myoardium, it exhibits an all or nothing response. 5 Therefore, reovered myoardium produes a new ation potential, while the stimulus has no effet on even partially refratory ells. 5 Above 5 V/m a graded response an be produed in refratory ells. 5 The result of this graded response is a prolongation of both refratoriness and the ation potential, although of shorter duration than the prodution of a new ation potential. 5 These observations form the basis of the extension of refratoriness hypothesis. This hypothesis states the defibrillating shok interats primarily with ells during their refratory period and prolongs refratoriness in most of the myoardium so that fibrillation wavefronts annot propagate and fibrillation eases. w4 A lower limit of vulnerability also exists for ventriular myoardium. 7 This is the minimum voltage required by an eletrial stimulus to indue fibrillation during the vulnerable period. It was noted in the 1960s that there was an upper limit to the strengths of shoks delivered during the vulnerable period that indue ventriular fibrillation. 7 It was also observed that the strengths of these shoks at the upper limit of vulnerability were approximately equivalent to the shoks at defibrillation threshold. 7 The upper limit of vulnerability hypothesis for defibrillation states to defibrillate, a shok not only must halt the ativation fronts of fibrillation, but it also must not reinitiate fibrillation by the same mehanism that a shok of the same strength during the vulnerable period of sinus or paed rhythm initiates fibrillation. 7 These theories are supported by the Fundamental Law of Eletrostimulation, whih was adapted by Irnih and applied to ventriular defibrillation. w5 If the onept of nearfield and farfield rheobase (lowest urrent strength whih suessfully stimulates myoardium) are introdued, then attempted defibrillation with shoks of too low voltage may be effetive lose to the eletrode (nearfield) but fail to stimulate ardia tissue at a remote site (farfield). w6 In order to gain a more aurate piture of the ellular response to eletrial stimuli, optial mapping tehniques were developed. This involves the use of potentiometri fluoresent dyes that bind to ell membranes in proportion to the polarisation of the membrane aused by a shok. 7 Using this tehnique, Kwaku and Dillon reported that ativation fronts in the ventriles arose from the border of shok-depolarised areas and that these fronts propagated unidiretionally away from these regions. 7 8 They also found that inreasing refratoriness dereased the likelihood of a reativation wavefront, and onluded that for suessful defibrillation a shok must depolarise myoardial tissue, even during its refratory period. 8 Transmembrane potentials have been reorded from the atria during AF and after biphasi shoks. 4 The shoks have been shown to produe four types of responses: immediate essation of epiardial ativity, single post-shok ativation, organised ativation for seonds followed by termination, and organised ativity followed by degeneration bak into AF. 4 These experiments led the authors to onlude, These results are onsistent with both the ritial mass hypothesis and the upper limit of vulnerability hypothesis. 4 Therefore, given the similarity between atrial and ventriular myoytes, it seems reasonable to assume that the effets of an eletri shok are similar in both hambers. DEFIBRILLATION WAVEFORMS Early devies employed both alternating and diret urrent for defibrillation. However, by the 1960s it was apparent that Volts Figure 1 Examples of some monophasi, biphasi, and triphasi waveforms (3 20 ms in duration). 0 Damped sine wave Monophasi trunated exponential waveform Time (ms) Volts 0 Time (ms) Biphasi trunated exponential waveform Triphasi trunated exponential waveform

3 alternating urrent was more detrimental to the heart and diret urrent has been used in defibrillators sine. w7 There are a variety of different waveforms in use today (fig 1). The ritially damped monophasi waveforms have been the mainstay of external defibrillation for over three deades. However, these are produed with indutors used in onjuntion with apaitors. w7 Indutors are eletrial omponents that are too large for implantable devies. Interest in more reent years has therefore foused on straightforward apaitor disharges, as apaitors were suitable for use in implantable defibrillators. Consider fig 2. When the swith is in position X, the apaitor C will harge until the potential differene aross it is equivalent to the potential differene aross the battery. When the swith is moved to position Y, exponential disharge ours through the resistor R (as shown in the graph of voltage versus time). The rate of apaitor disharge is desribed by the equation Q=Q 0 e 2t/CR. Q represents the harge on the apaitor at a given time, Q 0 is the harge at time zero, t is time and e is the exponential funtion. The time onstant of the iruit (amount of time required for harge to redue to 37% of its initial value) is therefore proportional to CR (the apaitane value and the resistane through whih the disharge ours). Adjusting apaitane allows the slope or tilt of the resultant waveform to be ontrolled. Duration an be trunated at the desired point. Swithing the polarity of the iruit during the disharge produes biphasi and triphasi waveforms. The energy produed by a waveform is alulated from the produt of voltage and urrent (power) multiplied by time. There has been a gradual swith to biphasi waveforms in more reent years due to improved performane in various linial trials over their monophasi ounterparts. It is generally agreed that the first phase of a biphasi waveform should have a positive polarity and duration of equal to or greater than the seond phase of the waveform. The atual eletrode polarity (plaing the anode in the apial or alternative pad position) does not influene the effiay of biphasi waveforms. It has been shown that biphasi shoks produed less dispersion of refratory period extension and suggested that a more homogeneous dispersion of refratory period extension was a more important fator in explaining why biphasi shoks are more effiaious in ventriular defibrillation. 9 In effet a biphasi shok produes less heterogeneous repolarisation and is therefore less likely to re-indue fibrillation. PRACTICE OF ATRIAL DEFIBRILLATION (DIRECT CURRENT CARDIOVERSION) Waveforms Several studies of epiardial and endoardial atrial defibrillation have demonstrated biphasi waveforms to be superior to their monophasi ounterparts of equivalent overall duration. The biphasi waveforms offer superior effiay in terms of peak voltage, urrent and total energy delivered. This has been shown in animal models w8 of AF as well as in w9 w10 patients. The development of devies that deliver impedane ompensated biphasi (ICB) waveforms for use in ardia arrest has stimulated interest in their use for diret urrent ardioversion. The evidene to date shows that the biphasi devies offer suessful ardioversion rates omparable to or superior to standard monophasi defibrillators, but at signifiantly lower energies (table 1) w11 w12 Some physiians may argue that biphasi devies do not offer a lear advantage over monophasi defibrillators. Arguments inlude: there is no large inrease in overall suess of the proedure (when both protools are ompleted to the highest energy); there does not appear to be any funtional advantage for the patient from the use of biphasi waveforms; biphasi devies have not been shown to influene the duration of sinus rhythm; and exposure to high umulative energies does not lead to troponin release. w13 However, skin burns are less ommon with biphasi waveforms 11 with the likelihood of a skin burn inreasing proportionally with the total energy delivered for both monophasi and biphasi waveforms. 11 w14 Biphasi ardioversion is also assoiated with less skeletal musle damage. w12 In addition, fewer shoks are needed with a biphasi devie, 11 potentially leading to shorter ardioversion proedures. Biphasi waveforms have been shown to be effiaious for patients with previously failed attempted ardioversion with monophasi waveforms. w15 Finally, given the lear advantages of impedane ompensated biphasi waveforms, monophasi devies in hospital are likely to be phased out and replaed by their biphasi ounterparts. This will result in an inevitable shift in pratie toward biphasi diret urrent ardioversion of atrial arrhythmias. Eletrode positions Historially, anteroposterior (AP) onfigurations have been onsidered to provide a superior shok vetor through the atria w16 w17 ompared with the antero-apial (AA) onfiguration X Y Voltage Figure 2 A apaitor resistor iruit and a graph showing exponential apaitor disharge. C R Time

4 Table 1 Suess of monophasi (MP) and biphasi (BP) waveforms at umulative energy levels in ardioversion of atrial fibrillation (AF) Study MP energy seletion protool (J) Overall MP suess (%) BP devie BP energy seletion protool (J) Overall BP suess (%) 1496 Mittal et al , 200, 300, Zoll PD , 120, 150, Page et al , 150, 200, Heartstream XL 100, 150, 200, Sholten et al w11 200, Zoll M-Series 120, Marinsek et al w12 100, 200, 300, Heartstream XL 70, 100, 150, However, the atual path taken by urrent through human tissue is omplex, with a small perentage (,4%) of urrent delivered by the transthorai route reahing the heart in the AA onfiguration. w18 The route taken by urrent during AP defibrillation has not been desribed. Two studies have suggested that an AP eletrode onfiguration is superior to an AA eletrode onfiguration when monophasi waveforms are used for diret urrent ardioversion of AF However, neither study reported whether there was a differene in transthorai impedane for the onfigurations studied. Transthorai impedane (TTI) has been shown to be an important determinant of atrial w19 and ventriular defibrillation w20 and is now widely aepted as an important preditor of suess. w21 We have reently shown in a large series of patients (using ICB waveforms) that the AP pad position is assoiated with lower transthorai impedane than the AA onfiguration. w22 It is likely that this explains the findings of the older monophasi studies, and it is therefore reasonable to reommend the AP eletrode positions for monophasi diret urrent ardioversion. Several AP pad positions have been desribed. Some authors feel that a right anterior to left posterior onfiguration is better where the underlying pathology involves both atria, while a left anterior to posterior onfiguration is better when the left atrium is primarily affeted. w17 The right anterior to left posterior onfiguration is desribed, as are the left anterior to right posterior 11 and AP midline onfigurations. 13 No data have been published showing superiority of one AP onfiguration over the other. Finally, our omparison of AP and AA eletrode onfigurations using ICB waveforms demonstrated no differene between these approahes with a modern defibrillator. w22 Internal atrial defibrillation Internal atrial defibrillation an also be reliably ahieved using eletrodes plaed in the right atrium and distal oronary sinus. w23 This approah has been widely used in patients and subsequently led to the development of a single hamber atrial defibrillator. This devie has been shown to be sensitive and speifi in the detetion of AF and R wave synhronised shoks were delivered appropriately. w24 Follow up of initial implants revealed treatment to be highly effiaious 96% of 227 AF episodes were onverted to sinus rhythm. w25 Unfortunately, the frequeny of short lived nontreated episodes does not appear to be dereased by this devie, and the thromboemboli risk from paroxysmal AF is therefore likely to remain. w26 In addition, a signifiant number of patients an expet to have the devie explanted w27 w28 beause of unontrolled AF. The single hamber atrial defibrillator is now superseded by dual hamber alternatives. Several of these are urrently available. They also offer AF preventative paing, atrial antitahyardia paing, and atrial defibrillation funtions in addition to ventriular defibrillation. w29 However, the effiay of these devies for the prevention of AF is unproven and long term linial benefit has not been demonstrated in large numbers of patients. The role of implantable devies for the treatment of AF alone is undefined at present. The plae of transvenous atrial defibrillation as a stand alone proedure has not been established in the era of ICB waveforms. However, there may be a use for low energy internal ardioversion for sustained arrhythmia in the eletrophysiology laboratory or in seleted patient groups (suh as the very obese, after ardia surgery, or in those where external ardioversion fails). Energy seletion for diret urrent ardioversion There are two approahes to energy seletion for diret urrent ardioversion. After developing the tehnique of ardioversion, Lown favoured the esalating energy approah. The rationale for this was to minimise post-shok arrhythmia. w16 This approah also allows ardioversion at the lowest energy for eah individual patient and may prevent high umulative doses in some. Some pratitioners prefer to begin the proedure at the highest energy in order to minimise the total number of shoks delivered and the duration of the proedure (inluding exposure to sedation or anaesthesia) for the majority of patients, while aepting that a proportion will be relatively overdosed. The most reent guidelines for AF suggest a starting energy of at least 200 J for attempted ardioversion of AF using monophasi waveforms. This reommendation is made on the basis that energies lower than this are unlikely to be suessful. 15 However, AF of very short duration (for example, after ardia surgery) may be 14 w30 amenable to lower energy shoks. Variable energies have been reommended for defibrillators that deliver impedane ompensated biphasi waveforms in the orretion of AF. The reommended energy depends on the manufaturer of the devie. Published evidene suggests that a shok of 150 J will result in suess for,80% of patients with these new devies and there does not appear to be a signifiant additional benefit in the seletion of energies above 200 J (table 2). Indeed, this manoeuvre may result in an exess of skin burns. w14 Using an ICB defibrillator, we favour an initial energy of 150 J followed by a 200 J shok. ROLE OF DIRECT CURRENT CARDIOVERSION FOR AF IN THE ERA OF THE RATE CONTROL STRATEGY The high likelihood of relapse into AF after a suessful ardioversion has been reognised for some time. AF has been shown to reur in 88% of patients over 19 months of follow up on optimal antiarrhythmi treatment. 16 Thus, withdrawal of antioagulation during periods of sinus rhythm is likely to arry a risk of thromboembolism in a number of patients. Two large linial studies have reently

5 Table 2 Suess of umulative shoks for different biphasi devies in ardioversion of AF Study Biphasi devie Suess at 70 J (%) Suess at 100 J (%) Suess at 120 J (%) Suess at 150 J (%) Suess at 170 J (%) Suess at 200 J (%) Suess at 360 J (%) Mittal et al 10 Zoll PD Page et al 11 HS-XL Sholten et al w11 Zoll M series Walsh et al w22 HS-XL Marinsek et al w12 HS-XL Neal et al w14 Lifepak Neal et al w14 Zoll M series hallenged the rationale of reurrent ardioversion and pharmaologial prophylaxis for the maintenane of sinus rhythm in AF patients (table 3). A total of 4060 patients were enrolled in the AFFIRM study. In the rhythm ontrol group (2033 patients), the antiarrhythmi drugs used were hosen by the treating physiian. Attempts to maintain sinus rhythm ould inlude ardioversion as neessary. In the rate ontrol group (2027 patients), drugs that were aeptable in the protool for this purpose were b blokers, verapamil, diltiazem, digoxin, and ombinations of these drugs. The goal for antioagulation with warfarin was an international normalised ratio (INR) of In the rhythm ontrol group, ontinuous antioagulation was enouraged but ould be stopped at the physiian s disretion if sinus rhythm had apparently been maintained for at least four, and preferably 12, onseutive weeks with antiarrhythmi drug treatment. In the rate ontrol group, ontinuous antioagulation was mandated by the protool. For patients in the rate ontrol group, 35% were in sinus rhythm at five years and over 80% of those in AF had adequate heart rate ontrol. The prevalene of sinus rhythm in the rhythm ontrol group at follow up was 82%, 73%, and 63% at one, three, and five years, respetively. Eletrial ardioversion was attempted one during follow up in 368 patients, twie in 214 patients, and three or more times in 187 patients in this group. There were 356 deaths among the patients assigned to rhythm ontrol treatment and 310 deaths among those assigned to rate ontrol treatment (mortality at five years, 24% and 21%, respetively; hazard ratio 1.15, 95% onfidene interval 0.99 to 1.34; p = 0.08). More patients in the rhythm ontrol group than in the rate ontrol group were hospitalised, and there were more adverse drug effets in the rhythm ontrol group. In both groups, the majority of strokes ourred after warfarin had been stopped or when the INR was subtherapeuti. The authors onluded that management of AF with the rhythm-ontrol strategy offers no survival advantage over the rate-ontrol strategy, and there are potential advantages, suh as a lower risk of adverse drug effets, with the rate-ontrol strategy. Additionally, antioagulation should be ontinued in this group of high risk patients. 17 The RACE study was smaller, with 522 patients enrolled, but of similar design. 18 Patients in the rate ontrol group reeived oral antioagulant drugs and rate slowing mediation. The rhythm ontrol group had a more rigorous management protool. These patients initially underwent eletrial ardioversion without previous treatment with antiarrhythmi drugs. Thereafter, patients reeived sotalol. If there was a reurrene within six months, eletrial ardioversion was repeated and sotalol was replaed by fleainide or propafenone. If there was a reurrene within six months after the start of this regimen, a loading dose of amiodarone was given, and eletrial ardioversion was repeated. The dose of amiodarone was then lowered to 200 mg daily. If sinus rhythm was maintained beyond one month, warfarin ould be stopped or substituted by aspirin. A total of 35 thromboemboli ompliations ourred (14 rate ontrol group and 21 rhythm ontrol group). These ourred more ommonly during periods of no or subtherapeuti antioagulation. The onlusion of the authors was strikingly similar to the AFFIRM study: rate ontrol is not inferior to rhythm ontrol for the prevention of death and morbidity from ardiovasular auses and may be appropriate therapy in patients with a reurrene of persistent AF after eletrial ardioversion. 18 The STAF pilot study provides further support for a rate ontrol strategy. 19 Despite these studies, diret urrent ardioversion is still an important treatment option for patients with symptomati AF. Many of our patients will omplain of lethargy or poor exerise apaity when in AF. It is still reasonable to ardiovert these patients and attempt to maintain sinus rhythm for symptom ontrol. An important lesson from AFFIRM and RACE is that antioagulation should be ontinued in those patients who are at risk from thromboembolism. Cardioversion will also be useful where AF is seondary to another ondition (for example, postoperative, pneumonia or an exaerbation of thyrotoxiosis, et), where Table 3 Rate ontrol versus rhythm ontrol studies in AF Study Number of patients Primary end point Events for rate ontrol group Events for rhythm ontrol group p Value AFFIRM Overall mortality RACE Composite* STAF Pilot CompositeÀ *Death from ardiovasular auses, heart failure, thromboemboli ompliations, bleeding, implantation of a paemaker, and severe adverse effets of drugs. ÀDeath, ardiopulmonary resusitation, erebrovasular event, and systemi embolism. AFFIRM, atrial fibrillation follow-up investigation of rhythm management; RACE, rate ontrol versus eletrial ardioversion for persistent atrial fibrillation study; STAF, strategies of treatment of atrial fibrillation.

6 1498 AF and diret urrent onversion: key points Atrial fibrillation (AF) is mainly re-entry assoiated with multiple propagating wavelets in the atria probably initiated by etopi foi originating from the pulmonary veins Diret urrent ardioversion is an important treatment for patients with symptomati AF Impedane ompensated biphasi defibrillators are replaing monophasi defibrillators sine suessful ardioversion is ahieved with lower energies and fewer shoks The anteroposterior eletrode onfiguration appears optimal for monophasi diret urrent ardioversion (lower transthorai impedane). There is no differene between the anteroposterior and antero-apial eletrode onfigurations when impedane ompensated biphasi waveforms are used Where monophasi waveforms are used, the first shok should be 200 J exept for AF of very short duration Where biphasi waveforms are used, the first shok should be 150 J A rate ontrol strategy (pharmaologial inluding antioagulant treatment) is satisfatory in those where AF has reurred or in those with hroni AF restoration of sinus rhythm will often be permanent after the preipitating event has resolved. Aggressive pursuit of sinus rhythm an no longer be justified in asymptomati AF. Where the arrhythmia is symptomati but refratory, alternative strategies suh as atrioventriular nodal ablation and paing should be onsidered. FUTURE DEVELOPMENTS IN DIRECT CURRENT CARDIOVERSION Biphasi defibrillators are replaing their monophasi ounterparts for this proedure (monophasi devies are no longer available from most manufaturers). In the next few years warfarin is likely to be superseded by alternative antioagulants. New antiarrhythmi agents may revitalise the rhythm ontrol strategy in the future if these drugs have omparable effiay to amiodarone with safer side effet profiles. The role of implantable devies is still under investigation. Hybrid devies that maintain sinus rhythm by multisite atrial paing and failitate reurrent internal diret urrent ardioversion by the delivery of radiofrequeny energy 20 have potential for some patients with AF.... Authors affiliations A A J Adgey, S J Walsh, Regional Medial Cardiology Centre, Royal Vitoria Hospital, Belfast, UK REFERENCES 1 Jalife J. Ventriular fibrillation: mehanisms of initiation and maintenane. Annu Rev Physiol 2000;62: Jalife J, Berenfeld O, Mansour M. Mother rotors and fibrillatory ondution: a mehanism of atrial fibrillation. Cardiovas Res 2002;54: Review of the mehanisms of atrial fibrillation. 3 Haissaguerre M, Jais P, Shah DC, et al. Spontaneous initiation of atrial fibrillation by etopi beats originating in the pulmonary veins. N Engl J Med 1998;339: Gray RA, Ayers GM, Jalife J. Video imaging of atrial defibrillation in the sheep heart. Cirulation 1997;95: Examination of the effets of atrial defibrillation using potentiometri dyes. 5 Ideker RE, Wolf PD, Tang ASL. Mehanisms of defibrillation. In: Taker WA, ed. Defibrillation of the heart. St Louis, Missouri: Mosby-Year Book, In, 1994: Zipes DP, Fisher J, King RM, et al. Termination of ventriular fibrillation in dogs by depolarizing a ritial amount of myoardium. Am J Cardiol 1975;36: Original demonstration of the ritial mass theory in ventriular defibrillation. 7 Ideker RE, Chattipakorn N, Gray RA. Defibrillation mehanisms: the parable of the blind men and the elephant. J Cardiovas Eletrophysiol 2000;11: Authoritative review of mehanisms of defibrillation. 8 Kwaku KF, Dillon SM. Shok-indued depolarization of refratory myoardium prevents wave-front propagation in defibrillation. Cir Res 1996;79: Sims JJ, Miller AW, Ujhelyi MR. Disparate effets of biphasi and monophasi shoks on postshok refratory period dispersion. Am J Physiol 1998;274:H Demonstration of how biphasi shoks have different effets on refratory period dispersion ompared to monophasi shoks. 10 Mittal S, Ayati S, Stein KM, et al. Transthorai ardioversion of atrial fibrillation. Comparison of retilinear biphasi versus damped sine wave monophasi shoks. Cirulation 2000;101: Study demonstrating the superiority of retilinear biphasi shoks over their monophasi ounterparts for diret urrent ardioversion of AF. 11 Page RL, Kerber RE, Russell JK, et al for the BiCard Investigators. Biphasi versus monophasi shok waveform for onversion of atrial fibrillation. JAm Coll Cardiol 2002;39: Demonstrated that diret urrent ardioversion requires fewer shoks with biphasi waveforms and also showed that skin burns our less ommonly with biphasi waveforms. 12 Botto GL, Politi A, Bonini W, et al. External ardioversion of atrial fibrillation: role of paddle position on tehnial effiay and energy requirements. Heart 1999;82: Kirhhof P, Ekardt L, Loh P, et al. Anterior-posterior versus anterior-lateral eletrode positions for external ardioversion of atrial fibrillation: a randomized ontrolled trial. Lanet 2002;360: Mathew TP, Moore A, MIntyre M, et al. Randomised omparison of eletrode positions for ardioversion of atrial fibrillation. Heart 1999;81: Fuster V, Ryden LE, Asinger RW, et al. ACC/AHA/ESC Guidelines for the management of patients with atrial fibrillation. A report of the Amerian College of Cardiology/Amerian Heart Assoiation task fore on pratie guidelines and the European Soiety of Cardiology ommittee for pratie guidelines and poliy onferenes (ommittee to develop guidelines for the management of patients with atrial fibrillation) developed in ollaboration with the North Amerian Soiety of Paing and Eletrophysiology. Eur Heart J 2001;22: Exellent review of all aspets of AF, with urrent reommendations for management. 16 Israel CW, Gronefeld G, Ehrlih JR, et al. Long-term risk of reurrent atrial fibrillation as doumented by an implantable monitoring devie: impliations for optimal patient are. J Am Coll Cardiol 2004;43: The Atrial Fibrillation Follow-up Investigation of Rhythm Management (AFFIRM) Investigators. A omparison of rate ontrol and rhythm ontrol in patients with atrial fibrillation. N Engl J Med 2002;347: Large linial trial showing that a rate ontrol strategy is not inferior to a rhythm ontrol strategy. 18 Van Gelder IC, Hagens VE, Bosker HA, et al. A omparison of rate ontrol and rhythm ontrol in patients with reurrent persistent atrial fibrillation. N Engl J Med 2002;377: Further data showing that a rate ontrol strategy is not inferior to a rhythm ontrol strategy. 19 Carlsson J, Miketi S, Windeler J, et al for the STAF Investigators. Randomized trial of rate-ontrol versus rhythm-ontrol in persistent atrial fibrillation. The strategies of treatment of atrial fibrillation (STAF) study. JAm Coll Cardiol 2003;41: Manoharan G, Evans N, Kidwai B, et al. Novel passive implantable atrial defibrillator using transutaneous radiofrequeny energy transmission suessfully ardioverts atrial fibrillation. Cirulation 2003;108: Additional referenes appear on the Heart website