Electrophysiology of Ventricular Tachycardia: A …pacericd.com/documents/ARTICLES/Electrophysiology... · Electrophysiology of Ventricular Tachycardia: A Historical Perspective MARK

www.pace

ricd.c

om

NASPE HISTORY SERIES

Electrophysiology of Ventricular Tachycardia:A Historical PerspectiveMARK E. JOSEPHSONFrom the Department of Cardiology, Beth Israel Deaconess Medical Center, Boston, Massachusetts

IntroductionThe purpose of this article was to review the

history of the use of programmed electrical stim-ulation (PES) and endocardial catheter mappingto evaluate the mechanisms of ventricular tachy-cardias (VTs) and develop therapy to treat them.While most of the information initially regardingtachycardia mechanism came from studies of VTin the setting of coronary artery disease, subse-quent studies of VT in a variety of other conditionsrevealed mechanisms other than reentry were op-erative. The methods used to define mechanismswere then used to develop therapy for these ar-rhythmias. As such, this article is divided into twoparts, Mechanisms and Therapy (Tables I and II)

Mechanisms (Table III)Mode of Initiation

The electrophysiological evaluation of VT be-gan in 1972 when Wellens et al.1 described fivepatients in whom VT could be initiated and termi-nated by properly timed extrastimuli (Fig. 1) sug-gesting a reentrant mechanism. This study led tothe recognition that PES could be used to studyVT safely. Shortly thereafter, these investigatorsstudied patients with VT in acute myocardial in-farction (24 hours) and demonstrated that suchVTs could not be reproducibly initiated.2 This ledthem to suggest that the VT mechanism in acuteinfarction was different from that in chronic in-farction. These investigators went further by sug-gesting that during induction an inverse relation-ship of the coupling of the extrastimulus used toinitiate the VT and the first beat of the VT meantthat slow conduction was necessary to generatethe tachycardia, supporting reentry as the under-lying mechanism. The site of reentry was uncer-tain, but the specialized conducting system wassuggested as a possible site.3 These investigatorsalso noted that occasionally different sites of stim-ulation were required for initiation and termina-tion. The field rapidly advanced in the late 70swhen Josephson and his colleagues at the Univer-sity of Pennsylvania helped further characterize

Address for reprints: Mark E. Josephson, M.D., BethIsrael Deaconess Med. Ctr., Cardiology, One Deaconess Rd.Baker 4 Boston, MA 02215. Fax: (617) 667-8769; e-mail:[email protected]

VT by introducing a more aggressive, stimulationprotocol that included up to three extrastimuli ona routine basis, multiple drive cycle lengths (in-cluding sinus rhythm, and paced cycle lengths at600 and 400, and others if needed), and multiplesites of stimulation from the right (RV) and left ven-tricles.4−11 These investigators demonstrated thatinduction of monomorphic VT was a reproducibleand a specific response to PES, while the initi-ation of ventricular fibrillation and polymorphicVT was nonspecific. These conclusions were sup-ported by subsequent studies.12−21 All these stud-ies suggested that the optimal method to achievemaximum sensitivity and specificity for VT in-duction using PES was a protocol incorporatingthree extrastimuli from the RV apex and outflowtract, during at least 2 drive cycle lengths (600 and400 ms).

The presenting arrhythmia and underlyingpathological state also markedly influenced the ar-rhythmia induced by PES. In the setting of priorinfarction, nearly 95% of patients who presentedwith monomorphic sustained VT could have theirtachycardia reproduced by PES. In patients withcoronary artery disease presenting with cardiac ar-rest, only 55% had a monomorphic VT induced.In patients with prior infarction, a low ejectionfraction, but only nonsustained VT, only 35% hadmonomorphic VT induced. This latter observa-tion22−24 was the basis for the Multicenter Un-sustained Tachycardia Trial (MUSTT) study formanagement of nonsustained VT. The inductionof ventricular fibrillation or polymorphic VT wasconsidered nonspecific since they could be in-duced in patients without heart disease. Poll etal.25,26 also demonstrated that if monomorphicVT was the presenting arrhythmia, it was re-producibly initiated, regardless of the underlyingpathology.

In patients with coronary artery disease thepresenting arrhythmia influenced the number ofextrastimuli required to initiate the arrhythmia.Two thirds of the patients with tolerated monomor-phic VT could have their VT replicated by oneor two extrastimuli, whereas those that presentedwith cardiac arrest required two or three extrastim-uli in 66% of the cases.11 It was rare to have a car-diac arrest patient have their arrhythmia replicatedby a single extrastimulus, while it was not unusualin those presenting with a slow tolerated rhythm.

2052 October 2003 PACE, Vol. 26

www.pace

ricd.c

om

ELECTROPHYSIOLOGY OF VT

Table I.

History of Electrophysiology: Mechanisms of Ventricular Tachyarrhythmias

• 1972—first demonstration of reproducible initiation and termination of VT• 1974–78—further characterization of VT, by use of aggressive RV and LV stimulation• 1978–85—sensitivity, specificity, and reproducibility of PES• 1978–86—development of endocardial mapping to define origin, ECG correlates of sites of origin, and role of

fragmented electrograms to define electrophysiological substrate of VT, NSVT, and cardiac arrest in CAD.• 1983–88—description of pathologic correlates of fractionated electrograms; i.e., separation of viable myocytes by scar• 1980–88—use of PES and pharmacologic perturbations to understand the mechanisms of cardiac arrest and NSVT• 1981–93—entrainment and resetting of VT, implications for mechanism and therapy (ATP and ablation)

ATP = adenosine triphosphate; CAD = coronary artery disease; ECG = electrocardiographic; LV = left ventricular; RV = rightventricular; NSVT = nonsustained ventricular tachycardia; PES = programmed electrical stimulation; VT = ventricular tachycardia.

An additional RV or LV stimulation site wasrequired more often in patients presenting withcardiac arrest. Moreover, VTs induced by compa-rable extrastimuli were faster in patients present-ing with cardiac arrest than in those with toleratedVT. By the early to mid-1980s, a stimulation pro-tocol including triple extrastimuli from two sitesin the RV at two different cycle lengths becamethe minimum standard in the study of ventriculartachyarrhythmias.

The role of conduction delay in the genesisof arrhythmias was further characterized by thePhiladelphia group after Wellens’ initial sugges-tion of reentry by noting an inverse relationshipof coupling interval of the initiating extrastimulusand the onset of the tachycardia. They found an in-verse relationship between the coupling interval ofthe initiating impulse and the time to the onset ofthe tachycardia in a larger number of patients.4,27

These investigators also demonstrated that an in-verse relationship could also be observed when adecreased paced cycle length was used to initiatethe tachycardia. The inverse relationship betweenthe interval to the onset of VT and the couplinginterval of the premature beat(s) and the drive cy-cle length indirectly supported conduction delayas a requisite for reentry. These investigators also

Table II.

History of Electrophysiology: Therapy of Ventricular Tachyarrhythmias

• 1977–1986—use of PES to guide antiarrhythmic therapy for VT, cardiac arrest, and NSVT in CAD; concern in CM• 1977–85—antitachycardia pacing for VT• 1978–85—development of surgery for VT• 1980— development of the implantible defibrillator• 1984–93—development of catheter ablation for VT; fulguration to RF• 1985–91—mechanism of antiarrhythmic drug action on VT

CAD = coronary artery disease; CM = cardiomyopathy; NSVT = nonsustained ventricular tachycardia; PES = programmed electricalstimulation; RF = radiofrequency; VT = ventricular tachycardia.

suggested that site specificity for induction alsosupported reentry, since induced rhythms due totriggered activity would not depend on the direc-tion of the stimulated wavefront. They further sug-gested that the PES should be done with a sin-gle extrastimulus at each drive cycle length, fromeach site, before more aggressive therapy was used.Only in this manner could one assess the relativeease of induction from any given site. They notedthat when PES was used in this manner, 25% ofpatients could demonstrate a differential ease ofinitiation among different sites in the ventricle.5,8

An example of VT that was inducible with a singleextrastimulus from the RV outflow tract, but not in-ducible with three extrastimuli at the RV apex isshown in Figure 2.

A quantum leap in the understanding of themechanisms of VT came with the development ofcatheter endocardial mapping of the human leftventricle by Josephson et al. in the mid-1970s.28−31

These investigators demonstrated that one couldsafely and reproducibly map the endocardium ofthe LV and RV. They subsequently defined nor-mal, abnormal, fractionated, and late electrogramsusing amplitude, duration, and the ratio of am-plitude and duration measurements (Fig. 3).32−36

They related the electrogram characteristics to the

PACE, Vol. 26 October 2003 2053

www.pace

ricd.c

om

JOSEPHSON

Figure 1. Initiation of ventricular tachycardia (VT). Ini-tiation of VT with inverse relationship of iniating cou-pling interval to onset to VT from 1972. Electrocardio-graphic (ECG) leads I, III, V1 and recordings from theright atrium (RA) and His bundle are shown. (Courtesyof Hein Wellens.)

presence of arrhythmias and the underlyingpathology in patients with coronary artery diseaseand cardiomyopathy. Patients with inducible sus-tained monomorphic VT had more abnormalitiesof conduction in terms of number and percentageof the endocardium with abnormal, late, and frac-tionated electrograms than patients with coronarydisease and no inducible arrhythmia or those with-out coronary disease. The abnormal electrogramswere correlated with the underlying pathology inan elegant study by Fenoglio et al.37 who identifiedthe underlying pathology of arrhythmogenic tissuefrom pieces of endocardium removed at the timeof arrhythmia surgery (Fig. 3). This was the firsttime that abnormal and fractioned electrograms,a hallmark of arrhythmogenic tissue, was definedpathologically by islands of viable myocardialfibers inbedded in scar tissue following infarction.Later studies confirmed the relationship of thispathologic sustrate with abnormal electrogramsand potential pathways of reentry.38−40 Early stud-ies suggested that the epicardium was often thesite of fractionated and late potentials in patientswith cardiomyopathy41; however, Cassidy et al.35

demonstrated that patients with idiopathic dilatedcardiomyopathies (IDCMs) presenting with sus-tained monomorphic VT had as many abnormalelectrograms as patients with coronary disease, butfewer fractionated and late signals. Recent studiesusing three-dimensional electroanatomic mappingshowed almost as many endocardial as epicardialabnormal electrograms in patients with IDCM42

Figure 2. Site specificity of induction of VT. Inductionof VT with a single extrastimulus from the RV outflowtract, but not inducible with three extrastimuli at the RVapex. (With permission from reference 124.) RV = rightventricular; VT = ventricular tachycardia.

presenting with monomorphic VT. Thus, patientswith IDCM can have endocardial epicardial ortransmural reentrant circuits.

The Penn group was able to map VTs in pa-tients with and without coronary disease.28−31

They demonstrated that in coronary disease, 85%of VTs had their “site of origin” (the earliest di-astolic activity) located in sites with abnormal,fractionated, or late electrograms.33 They observedthat while this arrhythmogenic substrate could beidentified, one could not predict the site of originfrom the substrate. They did note that late elec-trical activity during sinus rhythm was often as-sociated with presystolic, diastolic activity dur-ing VT. They demonstrated that VT in the settingof a prior myocardial infarction almost uniformly(>98%) arose from the endocardial surfaces of theLV, while in patients with IDCM, VT could arisefrom either chamber of the heart. Idiopathic tachy-cardias could arise from either chamber as well.In addition, mapping helped characterize certainQRS morphologic patterns with “sites of origin.”These investigators demonstrated for the first timethat VT originating in the LV could have a leftbundle branch block (LBBB) morphology. Theydemonstrated that the global activation of the RVand LV determined the morphology, not the spe-cific site of origin.43,44 The activation sequenceof the ventricles could be markedly influencedby prior scar. The mapping techniques developedduring this period have been refined and form thebasis for all ablative therapy currently being usedto manage tolerated and nontolerated VTs (see sub-sequent paragraphs on ablation).

Response to Stimulation During VT

While analyzing the modes of initiation of VTyielded useful indirect evidence for arrhythmia


www.pace

ricd.c

om


Figure 3. Electrogram morphologies andanatomic sustrate of ventricular tachy-cardia in infarction. Normal, abnormal,and fractionated elecrograms (left) andunderlying anatomy of fractionated elec-trogram. (Adapted from reference 124.)

mechanism (reentry, triggered activity, automatic-ity), the response to PES during the tachycar-dia provided more diagnostic information. Waldoet al.45,46 were the first to demonstrate the phe-nomenon of entrainment of VT by overdrive pac-ing from the RV apex. These investigators de-scribed entrainment as the demonstration of fixedfusion of the paced QRS and the tachycardia at anypaced cycle length, and progressive fusion at de-creasing paced cycle lengths (QRS becomes morelike a pure paced QRS), and at each paced cyclelength the tachycardia resuming upon cessation ofpacing. The demonstration of fusion during pacingwas diagnostic of reentrant mechanism becauseit implied that two wavefronts could exist at thesame time on the heart with an interaction betweenthe paced impulse and the VT. This implies an en-trance and an exit to a reentrant VT circuit. Theseand other investigators also demonstrated that VT

Table III.

Mechanisms of Ventricular Tachycardia

• Reproducible initiation– Relationship of initiation to conduction abnormalities and/or heterogeneity of recovery– Relationship of VES coupling interval or PCL on interval to onset of VT– Site specificity for induction– Effect of antiarrhythmic agents or isoproterenol on induction of VT

• Effects of stimulation during VT– Resetting, entrainment, or termination with fusion– Effects of overdrive pacing or VES on return cycle– Site specificity for termination

• Effects of antiarrhythmic agents• Mapping techniques for successful ablation

PCL = paced cycle length; VES = ventricular extrastimuli; VT = ventricular tachycardia.

could be entrained by atrial pacing.46,47 The ap-pearance of electrocardiographic (ECG) fusion wasdependent upon the site of pacing.48 The closer thesite of pacing to the “exit” site of the circuit, theless likely fusion would be seen since the pacedQRS would look similar to the QRS of the VT, orthe paced QRS would capture the exit site not al-lowing any expression of the VT to be manifest onthe surface QRS.

Almendral and colleagues,49−53 in a series ofelegant studies, analyzed the response of a VT toa single extrastimulus. The interaction of a singleextrastimulus with a tachycardia was termed reset-ting, and its presence implied the presence of anexcitable gap in the tachycardia circuit. These in-vestigators demonstrated that resetting could qual-itatively and quantitatively characterize the extentof the temporal excitable gap of a VT circuit. Re-setting responses demonstrating identical return


www.pace

ricd.c

om

JOSEPHSON

Figure 4. Characterization of the excitable gap in the ventricular tachycardia (VT) circuit by resetting. Schema ofmechanism of resetting and types of responses (left). Analogue recordings of resetting of VT with a fully excitable gapof at least 100 ms. See text for explanation. (Adapted from reference 12.)

cycles over a range of coupling intervals (>30 ms)defined a fully excitable gap. Increasing return cy-cles mixed (flat plus increasing) responses werealso observed (Fig. 4). The excitable gap was 15–35% of the VT cycle length. Entrainment, unlikeresetting, does not characterize the tachycardia cir-cuit per se, but evaluates the effects of resetting areset circuit. As a result, entrainment was oftenassociated with what appeared to be decremen-tal conduction in the VT circuit. Callans et al.54

clarified the differences between resetting and en-trainment. With resetting only a single extrastim-ulus interacts with the VT circuit. If stimulationat the exact same coupling interval that resets theVT is continued, subsequent extrastimuli inter-act with the previously reset circuit and conduc-tion delay could occur until a longer, fixed, sta-ble conduction time was established. The extentof the excitable gap, established by resetting, de-

termined if entrainment, at any particular cyclelength, would produce decrimental conduction.Nevertheless, resetting with fusion or entrainmentwith fusion on the surface ECG or an intracar-diac (LV) electrogram was diagnostic of a reentrantmechanism. Overdrive pacing of tachycardias dueto triggered activity never demonstrates fixed fu-sion; the response to overdrive pacing usually isone of acceleration of the tachycardia, at least forthe initial beats, and a shortening of the returncycle.

Another feature suggestive of reentry is sitespecificity for termination. Since triggered activityis a focal event, depolarization of the cell respon-sible for this mechanism is all that is required fortermination, independent of the direction stimu-lated impulse. However, the wavefront of activa-tion may be important if there is an anatomic cir-cuit with separate entrance and exit sites.


www.pace

ricd.c

om


Response to Antiarrhythmic Agents

The effects of antiarrhythmic agents werealso used to sort out the underlying mecha-nisms.55−62 Most importantly was the recogni-tion that triggered activity due to delayed after-depolarizations most often occurred in responseto catecholamines. This was due to enhancedadenylcyclase activity, which subsequently ledto increased intracellular calcium, which thentriggered a nonspecific transient inward currentcarried by sodium. This phenomenon would re-sult in afterdepolarizations leading to tachycardia.Lerman et al.61,62 were the first to demonstrate thatadenosine was able to terminate such delayed af-terdepolarizations. Vagal maneuvers were also ef-fective. The rhythm that most commonly producedby this mechanism was RV outflow tract VT, whichis frequently induced by exercise. β-Blockers andverapamil could also be used to terminate such af-terdepolarizations, but this response is not specificfor triggered activity.

A diagnostically and clinically useful re-sponse to antiarrhythmic drugs is the conversionof polymorphic VT to monomorphic VT. This wasfirst noted by Horowitz et al.63 who demonstratedthat nonsustained polymorphic VT in patientswith coronary artery disease could be changed toa uniform VT with morphology similar to one ofthe complexes seen in the polymorphic run by aclass I antiarrhythmic. This was sequentially con-firmed and evaluated in more detail by Buxtonet al.64,65 who demonstrated that this phenomenonwas specific for polymorphic VT associated withinfarction. These investigators suggested that thisfinding reflected an insufficient substrate of slowconduction that was increased by the drug, result-ing in stabilized reentry. The change from poly-morphic VT to monomorphic VT was not seen incardiomyopathies or in normal patients in whompolymorphic VTs are considered to be a nonspe-cific response to PES. Confirmation of the clinicalrelevance of this observation was the demonstra-tion that map-guided operation of drug induceduniform VTs in patients who presented with syn-cope or cardiac arrest prevented recurrent syncopeor cardiac arrest (unpublished observations).

Mapping of VTs

As noted above, endocardial catheter map-ping not only provided information allowing forthe understanding of the underlying pathophys-iological substrate of VT in coronary artery dis-ease, but it also enabled investigators to localizespecific arrhythmogenic areas that could be ab-lated by surgical or catheter-based techniques. Ac-tivation mapping, while critically important forlocalizing a focal mechanism of VT by nothing

the earliest site of impulse formation using bipo-lar and/or unipolar recordings, was just as valu-able in localizing critical components of a reen-trant circuit. In fact, despite the fact that duringreentrant excitation activation is continuous, theearliest recorded sites of electrical activity in in-ducible VT due to coronary artery disease (reen-trant VT) were recorded earlier in diastole thansites of origin of “focal” (triggered or automatic)VT.28−31,66−72 Sites at which mid-diastolic poten-tials or continuous activity were recorded wereconsidered sites potentially related to the reen-trant circuit. Proof that these diastolic sites werewithin the reentrant circuit and not dead-end path-ways was required. The demonstration of a fixedrelationship of the diastolic electrogram to sub-sequent QRS complexes in response to sponta-neous or pacing induced changes in the VT cy-cle length suggested that these diastolic poten-tials were in or attached to a diastolic pathwaythat is orthodromically activated during VT.48−53

Occasionally, mid-diastolic potentials disappear,proving their lack of importance to the VT mech-anism. Occasionally, complete reentrant circuitscould be demonstrated in the operating roomor using electroanatomic mapping, but this wasuncommon.73

In the absence of demonstrating reentrant ex-citation, another method was needed to identifycritical areas of reentrant circuit that could ulti-mately be targeted for ablative procedure (i.e., thecritical central common pathway). The concept ofentrainment mapping was developed initially inthe mid-1980s by Almendral et al.48 who demon-strated that diastolic potentials that could be or-thodromically activated were in or attached to thecentral pathway in the circuit, and that entrain-ment from the exit site or within the circuit couldlead to an identical QRS as a VT itself. Return cy-cles could only equal the VT cycle length if pac-ing was produced from the circuit itself. Whileuse of the above principals of mapping was sug-gested to the investigators of the Catheter Abla-tion Registry, they were rarely applied (unpub-lished observations). It was not until several yearslater that the careful studies of Stevenson et al.69,74

presented the concept in a more understandableway. The reentrant circuit was described as be-ing anatomically created and composed of a criti-cal protected area through which the impulse con-ducted in diastole. This had been referred to as thecentral common pathway in experimental mod-els. Entrainment of VT from this critical centralcommon pathway was associated with an iden-tical QRS as the tachycardia, a stimulus to QRSapproximating that of the electrogram to QRS, areturn cycle equal to the tachycardia cycle length.Entrainment from the reentrant circuit outside the


www.pace

ricd.c

om

JOSEPHSON

isthmus (outer loop) would produce a differentQRS than the tachycardia QRS, but an identicalreturn cycle as a tachycardia cycle length. Whilepacing outside the circuit (either far from the cir-cuit or from a dead-end pathway attached to thecircuit) would produce return cycle greater thanthat of the tachycardia cycle length. Other inves-tigators75,76 used slightly different methodologieswith different tolerances and definitions of “iden-tical QRS,” equivalent return cycles and stim-ulus at QRS intervals. Nevertheless, the use ofconcealed entrainment to identify critical sites inmacroreentrant VT circuits became accepted.

Pacemapping was developed to localize thesite of origin of a focal tachycardia. This tech-nique was based on the hypothesis that an iden-tical QRS induced by pacing would identify a sitefrom which a spontaneous arrhythmia arose.77−79

Unfortunately, the area over which some of themorphologies could be reproduced was 1–4 cm2.Thus, this technique has more often been used as aconfirmation of activation mapping. Pacemappingwas noted to be less valuable for macroreentrantVT related to infarction, since similar morpholo-gies could be produced by pacing over a largerarea, including sites that were outside the reen-trant pathway. Pacing from the center of a dias-tolic isthmus during sinus rhythm generally pro-duces a totally different morphology than duringVT, since during sinus rhythm activation from thepacing site would be centrifugal resulting in or-thodromic and antidromic activation through theisthmus, while during entrainment of VT activa-tion would only be orthodromic.

Application of the different mapping tech-niques for different tachycardia mechanisms is de-scribed below under Ablative Procedures. Epicar-dial mapping has been introduced using similarmethodologies to endocardial mapping describedabove.80,83 Epicardial origins of VT may be seen in15% of cases of coronary disease (usually inferiorinfarction and in cardiomyopathies. Entrainmentmapping may be useful in either condition). Epi-cardial mapping may also be useful for arrhyth-mias that are focal in origin, arising on the epi-cardium, particularly near or at the aortic andmitral annuli. An additional site of impulse for-mation may be in the aortic coronary sinuses orthe pulmonary artery, both of which have musclefibers extending onto them, which may be sourcesof focal arrhythmic activity.83−87

Application of Electrophysiological Studiesand Developed Therapy for VT

Pharmacological Therapy

With the recognition that most VT, due to coro-nary artery disease could be reproducibly initi-

ated and terminated, the concept of the use ofPES to guide antiarrhythmic therapy evolved. Al-though the vast majority of the arrhythmias forwhich pharmacologic testing was used were re-lated to prior infarction, patients with cardiomy-opathies, particularly right ventricular dysplasia,and other disorders in which VT could be repro-ducibly initiated were also treated in this man-ner. The basic concept of this methodology wasthat the ability to initiate a tachycardia suggestedthat an arrhythmogenic substrate was present thatenabled spontaneous or induced triggers to initi-ate sustained arrhythmias. The ability of a drug toprevent initiation of a tachycardia by PES was as-sumed to be an effect of that drug on the substratethat prevented it from enabling the occurrence ofa sustained arrhythmia. Initial studies by Fisheret al.,88 Horowitz et al.,89−91 and Mason andWinkle92 demonstrated the feasibility of such drugtesting with oral and/or intravenous (IV) agents inpatients with monomorphic sustained VT. A va-riety of antiarrhythmic drugs were tried for sev-eral days to determine a drug that prevented initi-ation of VT. Ultimately, if a drug was successful inpreventing VT acutely, following achievement ofsteady-state levels shown to be acutely effective,a repeat test was done. If the VT was shown to benoninducible, the patient was sent home on thatday. This form of testing was also subsequently ap-plied to patients presenting with cardiac arrest93

and nonsustained VT.22,94−99 While these stud-ies suggested benefit to patients whose tachycar-dias were rendered noninducible, none of the tri-als were randomized and many were, in fact, acombination of prospective and retrospective data.Drug follow-up was short (12–20 months). How-ever, in all studies there was a higher reoccurrencerate and/or mortality in those patients with persis-tently inducible ventricular tachyarrhythmias. Inthe absence of other options for therapy, such test-ing was accepted. With the advent of additionaltherapies like implantable cardioverter defibrilla-tors (ICDs) and ablation (see below), the use of an-tiarrhythmic drugs and drug testing diminisheddespite the fact that the drugs were still admin-istered and this was probably the best method toevaluate efficacy.

The usefulness of the electrophysiologicalstudies was evaluated by the ElectrophysiologicStimulation versus Electrocardiographic Monitor-ing (ESVEM) study.100 This study tested the abil-ity of PES or Holter monitoring to judge effi-cacy of class I antiarrhythmic agents or sotalolin preventing spontaneous occurrences of VT.This was a highly selected patient population inwhom VT could be reproducibly initiated and inwhom spontaneous ventricular ectopy was fre-quent enough to be evaluatable by Holter monitor.


www.pace

ricd.c

om


This population represents ∼15% of patients withsustained VT. The results of ESVEM suggested thatneither method was good, both having a 40% re-currence rate of VT in a year. This was nearlydouble the recurrence rate suggested by PES innonrandomized trials.88−92,101−104 The study alsosuggested that sotalol was better than class I agents.Several criticisms arose with the analysis of thisdata. Two thirds of the patients had already failedclass I agents and prior studies by Waxman et al.,105

suggested that if procainamide failed to preventinitiation of VT, other class I agents would also fail.This resulted in a significant bias toward benefit forsotalol. Moreover, patients who had been success-fully treated with class I agents, however, were notincluded. In addition, a major limitation was an in-adequate stimulation protocol used to test drug ef-ficacy. Stimulation was never more aggressive thanbaseline, in terms of number of extrastimuli, andcompletion of a protocol of three ventricular ex-trastimuli was not even achieved at baseline if VTwas induced with a lesser number of extrastimuli.The author has observed that a number of drugsincrease the number of extrastimuli required forinitiation of VT, but that this “increase in diffi-culty” is not associated with freedom from recur-rence (104). Therefore, failing to test more aggres-sive stimulation protocols may have eliminatedpatients who normally would have been classi-fied a failure, thereby implying PES was not anaccurate method of assessing drug effectiveness.Despite these limitations, the use of PES to guidedrug therapy was reduced to a minimum and othertreatment modalities were used.

Antitachycardia Pacing (ATP) and ICDs

From 1977 through 1985 an active interest inATP as a mode to treat VT was noted. This wasnatural consequence of the electrophysiologicalstudies, which showed that most of these arrhyth-mias could be reproducibly terminated by PES.While increasing the number of stimuli from asingle extrastimulus to bursts of rapid ventricularpacing increased the ability to terminate tachycar-dias from approximately 25% to 75%, an increas-ing incidence of acceleration of the tachycardia toa faster VT or ventricular fibrillation was noted(35%).106−109 Even VTs with rates >200 beats/mincould be terminated by pacing 50% of the time;but the remainder required cardioversion. Thus,while a number of ATP modalities were devel-oped for implantable devices, stand-alone ATP de-vices were never developed because accelerationof VT and/or degeneration of VT to ventricularfibrillation by antitachycardia pacing was too un-safe. It was obvious that defibrillation backup wasneeded. Fortunately, by 1980 Mirowski et al.110 de-veloped and implanted an automatic ICD in hu-

mans. By the late 1980s, ICDs incorporated ATPand low energy cardioversion therapies and a va-riety of diagnostic features. The diminution in sizeof the device and incorporation of dual chambercapabilities in a pectoral implantable system hasrevolutionized the treatment of lethal ventriculararrhythmias. The ease and low morbidity of im-plantation, and nearly uniform success in termi-nating VT and ventricular fibrillation has madethe ICD the most popular method of treating VTor ventricular fibrillation.

Ablative Procedures

In the hierarchy of therapy of ventricular tach-yarrhythmias, prevention of the arrhythmia by pre-venting substrate formation (i.e., infarction) of de-struction of the substrate by surgical or catheterablation should be the highest goal. Terminationof VTs by drugs or ATP or slowing of the arrhyth-mia to hemodynamic tolerance would be a secondoption, and rescue by cardioversion or defibrilla-tion with an ICD should be the last goal. Despitethe recognition that the goal should be to preventthe arrhythmia, ICDs have become the major formof therapy used. Nevertheless, the concept of abla-tion of ventricular tachyarrhythmias to cure thearrhythmia evolved from early mapping studiesin the mid-70s. A variety of surgical procedureswere developed in the late 1970s that could bedescribed as map-guided or visual or electricallydetermined substrate-guided.111−119 Guiraudon etal.111 developed the first technique, the encirclingventriculotomy for patients with VT due to coro-nary disease, but his procedure was rapidly dis-continued due to the high mortality associatedwith interruption of blood supply to viable tis-sue. Shortly thereafter, Josephson et al.112 devel-oped the technique of map-guide subendocardialresection which was based on their mapping tech-niques demonstrating that most ventricular tach-yarrhythmias arose on the endocardial surface ofthe heart. These investigators ultimately operatedon more than 300 patients with a high clinicalsuccess rate (92%) and an operative mortality of15%.120 Mortality was due to pump failure, whichwas not surprising since these patients had se-vere LV dysfunction, and usually underwent si-multaneous aneurysmectomy and coronary arterybypass grafting. In the Penn series the mean ejec-tion fraction was 0.28, with 50% of patients hav-ing ejection fractions of <0.25, and 25% havingejection fractions <0.20. Nevertheless, their clini-cal success rate was remarkable. Nonmap-guidedsurgery involved modifications of Guiraudon’s en-circling ventriculotomy. Removal or isolation ofthe entire scarred endocardium, diagnosed visu-ally or the endocardium in which fragmentedelectrograms and late potentials were recorded,


www.pace

ricd.c

om

JOSEPHSON

by cryoablative therapy or subendocardial lesionswere used by a number of individuals with a suc-cess rate in the 80% range.111,115−117 With theadvent of the ICD, surgical therapy, a curative pro-cedure that ameliorated ventricular dysfunction,coronary obstruction and the arrhythmia, bacamenearly extinct.121

Catheter Ablation of VT in Coronary Disease

In the mid-1980s catheter ablation for VT wasdeveloped using direct current (DC) energy.122,123

This subsequently has envolved over the pastdecade and a half, as we have seen the energysource changed from DC energy to radiofrequencyenergy. Newer energies are being evaluated at thistime. Hemodynamically tolerated monomorphicVT associated with coronary artery disease can besuccessfully ablated using entrainment mappingtechniques to define a critical isthmus throughwhich the impulse must pass.69−72,74−76,124−127

The technique involves locating a mid-diastolicsite and demonstrating that pacing at that site ata slightly faster rate than the VT produces: (1) anidentical QRS as the VT (in all 12 ECG leads); (2) astimulus-QRS approximately equal to the electro-gram QRS (±10 ms); and (3) a return cycle equalto the VT cycle length ±10 ms).75 Other authorsallow a tolerance of up to 30 ms69,74: this mybe less specific. Entrainment from a site in thecentral common pathway of the reentrant circuitproduces and exact 12-lead match. Pacing fromoutside the common pathway but still within thecircuit (outer loop) would produce a fused QRSbut a return cycle equal to the VT cycle length anda stimulus QRS equal to the electrogram QRS. Ifthe pacing site is distant from the VT circuit, thepaced QRS will differ from that of the VT, and thereturn site will exceed the VT cycle length. Pac-ing from a bystander site attached to the centralpathway will produce a QRS identical to that ofthe VT but a longer stimulus QRS than the elec-trogram QRS and a longer return cycle than theVT cycle length. In the current experience, thevast majority of tolerated VTs can be terminatedwith a lesion at a single site using this technique,usually (75%) in less than 10 seconds (Fig. 5).75

Others have observed termination of VT by RF de-livered at sites not meeting the criteria describedabove. This demonstrates some of the limitationsof the techniques. Stimulation and recording maybe from different electrodes than that deliveringRF energy (distal electrode), and high current usedfor pacing may depolarize sites distant from therecording site. Other reasons for failure of ablationinclude an isthmus that is broader than the lesionmade by the RF energy, intramural or epicardiallocations, or the presence of a mural thrombus.Epicardial locations are suggested by more slurred

and wider QRS. Epicardial mapping through a di-rect intrapericardial approach was pioneered bySosa et al.80,82 and has been used to ablate suchtachycardias.

It is unclear whether it is necessary to ab-late all inducible (tolerated or nontolerated) VTsin such patients since the mortality from suddencardiac death in patients presenting with toleratedVT is low (2–3%/year).125 In most series of VT ab-lation there is a ∼70% success rate acutely witha recurrent rate of 10–40%.69,73−76,126−128 Theseresults depend on the accuracy of mapping, thenumber of tolerated VTs induced, and, perhaps,the extent of ablation. The shorter the time to VTtermination, the higher the success rate for abla-tion of that VT. The efficacy of catheter ablationis unclear since results are rarely reported on anintention to treat basis. In a small series Callanset al.127 reported a 60% success rate on an inten-tion to treat basis primarily due to access problemsor failure to induce or adequately map toleratedVT.

The patient with untolerated VT and coronaryartery disease is a particularly vexing problem.While mapping is possible using inotropic agentsand/or an intraaortic balloon pump for support,there is now an active interest in using substratemapping to guide ablation. This procedure is basedon the ability of catheter mapping to identify andlocalize arrhythmogenic sites, which are charac-terized by abnormal, fractionated, and/or delayedpotentials. It is now possible to accurately localizeand quantify the extent of abnormal electrogramsand scar tissue. Using the Carto electroanatomicmapping system (Biosense Cordis),129,130 the volt-age of electrograms from normal tissue exceeds1.5 mV and that from scar tissue is defined inthe author’s laboratory by ≤0.1 mV. The value forscar tissue is based on prior data from his lab-oratory (unpublished observations) that demon-strated amplitudes of <0.1 mV were associatedwith dense scar tissues seen at surgery and patho-logically. Soejima et al.131 have used electrical in-excitability as a means to identify dense scar tis-sue. This correlates with electrogram amplitudeand duration as demonstrated by Kienzle et al.132

He and his colleagues demonstrated a direct rela-tionship of excitability and electrogram durationand an inverse relationship to electrogram ampli-tude. Using the electroanatomic mapping systemone can identity dense scar. Of note, that whentolerated VTs are mapped and the central com-mon pathways are identified, these sites corre-late with scar tissue and late potentials. Pacemap-ping to identify a QRS comparable to the in-duced rapid tachycardia allows one to identify anexit point from the circuit. Linear lesions can bemade from the broder zone of infarction at the


www.pace

ricd.c

om


Figure 5. Entrainment mapping to guide ablation of infarction related VT. Perfect entrainment map (upper right),return cycle and stimulus to QRS equal to spontaneous VT cycle length and electrogram (EGM) to QRS, respectively(lower left). Termination of VT with application of radiofrequency energy at this site (lower right). VT = ventriculartachycardia.

site of the best pacemap to the dense scar.133 Theauthor and others have also targeted late poten-tials to guide ablation.134,135 Another approach isto eliminate all viable channels between densescars that could potentially develop into isth-muses of reentrant circuits. Scars can be connectedby radiofrequency lesions eliminating these chan-nels. The pathophysiological basis of substrate-guided RF ablation comes 25 years following itsuse during nonmap-guided surgery for VT. Thesuccess rate of substrate-guided catheter ablationremains unknown and awaits prospective sutdies.

Arrhythmogenic RV Dysplasia (ARVD)

A ARVD is a disorder primarily, but not ex-clusively, of the RV in which there is fibrofattyreplacement of the free wall of the RV.136−138 In-volvement of the LV, although less common patho-logically, is even rarer clinically. VT in ARVD

ranges from asymptomatic nonsustained episodesto sudden cardiac death. Besides the fibrofatty in-filtration, the hallmarks of this disorder include:inversion of T waves in the precordial leads (V1–V3), epsilon waves (which represent late poten-tials) in these leads, ventricular premature contrac-tions or VT with varying axes and LBBB patterns,and a family history of this disorder. Perhaps 30%of the patients will have a heredity basis for thedisease.

It is the author’s impression that in differ-ent stages of the disease the arrhythmia mecha-nisms may vary. Early in the disease exercise in-duced arrhythmias are common and these appearto caused by triggered activity due to delayed af-terdepolarizations. Three general areas are arry-thmogenic tissue have been noted to include theRV outflow tract, the RV inflow tract and the freewall near the apex right of the ventricle. With the


www.pace

ricd.c

om

JOSEPHSON

development of marked fibrofatty infiltration, theelectrograms of the RV become fractionated andextremely long in duration. These long electro-grams are associated with the epsilon waves seenon the ECG. These electrograms are similar to thoseseen in mycardial infarction, and most likely rep-resent the same phenomenon of viable myocytesimbedded fiberfatty tissue with poor intercellularcommunications. As such, therapy of ARVD wasaddressed in a similar manner as that for VT dueto coronary artery disease. At this stage of the dis-ease, reentrant VTs are common, most of whichare stable, but in some instances can be hemo-dynamically untolerated. Antiarrhythmic agentshave been used in ARVD, but the efficacy of phar-macologic therapy has not been determined inany prospective study. Early attempts to operateon such patients using ventriculotomies119,139 oreven disarticulartion of the right ventricle140 havelargely been abandoned. ICDs have been used inmany patients since they have the advantage ofpacing for reentrant VT and can rescue patientsthat have hemodynamically untolerated VT; how-ever, the role of ICDs in ARVD has not been es-tablished. Ablation in the author’s opinion offersan excellent opportunity to treat such patients. En-trainment mapping been successfully used to ab-late VTs in ARVD,141 although additional lesionsare often necessary because the central pathways(isthmuses) appear to be wide. VTs in which thetricuspid valve forms one barrier of a central path-way are ablatable by identifying and destroyingthe isthmus. Other ablation techniques to treatsuch VT include encircling areas of late poten-tials or connecting scars to prevent the formationof isthmuses (see ablation of VT in coronary arterydisease). Although some investigators have foundablation to be useful in the management of suchpatients, in most laboratories ICDs are addition-ally used. In the current patient population of VTin ARVD, ICDs have only been implanted in pa-tients with untolerated tachycardia. The authorhas been able to successfully ablate VT in sevenpatients with no recurrence with a follow-up aver-aging 3 years.

Idiopathic VT

Idiopathic VT falls into two major categories.Ths most common variety are due to focal mecha-nisms, primarily catechcolamine induced delayedafterdepolarizations, which are dependent uponenhanced adenyl cyclase activity.61,62,83−87,142−146

While these arrhythmias were able to be initiatedby programmed stimulation (rapid pacing easierthan timed extrasimuli), induction often requiredthe addition of isoproterenol.22,61,62 Arrhythmiasmay also be initated by phosphosdiesterase inhib-iters and modulated by other agents that influence

adenyl cyclase activity (e.g., muscarinic, puriner-gic, and alpha 1 receptors). Clinically, a commonstimulant of these arrhythmias is milrinone, par-ticularly when it is used in a setting of an intensivecare unit in combination of catacholamine stimu-lation (endogenous/exogenous). This combinationof adenyl cyclase stimulation (catecholamines)and diminished breakdown (phosphodiesteraseinhibitors) is a potent stimulant of triggered ac-tivity by increasing intacelluar calcium loadingthat induces a transient inward current carried bysodium to produce afterdepolarizations. Termina-tion of these arrhythmias may be seen with suchvagal maneuvers, administration of adenosine, cal-cium blockers, β-blockers, and sodium blockers.Since these arrhythmias most commonly occur inpatients without heart diseases, curative proce-dures like ablation are the therapy of choice.

The most common triggered VT occurring inthe general population is that arising from the RVoutflow tract. These tachycardias, which were de-scribed more than 80 years ago, present with theLBBB, right inferior, or left inferior axis depend-ing on their site of origin in the RV outflow tract.The closer to the pulmonary valve and more sep-tallly located the VT, the more right and inferiorthe axis. Wellens et al. (personal communication,September 7, 2002) have recently found VTs aris-ing above the pulmonary value in the pulmonaryartery where muscle fibers extend. Less commonly(∼10%), VTs arise from the LV outflow tract, theLV epicardium, particularly around the superiormitral annulus near the area of aortomitral con-tinuity, or in the sinuses of valsalva, where ex-tensions of myocardium are often found.83−87,146

VTs arising from the epicardium or at the mitral-aortic annulus have a right bundle branch block(RBBB), inferior axis with concordant precordialR waves. LV outflow tract VTs and those from thesinus of valsalva can have RBBB or LBBB mor-phology. When LBBB morphology is present thereis frequently an R wave in lead 1 and V1 andan early transition in V2 or V3. Characteristics ofthe LV outflow tract, LV epicardial, and coronarycusp VT QRS morphologies have been recentlydescribed by several investigators.83−87,146 Occa-sionally, these tachycardias behave more like au-tomatic tachycardias, which are also susceptibleto induction by cathecholamines, but are neitherinducible nor terminatable by PES.

The methods by which these focal VTs are ab-lated include a combination of activation mappingand pacemapping. The author always uses bothbipolar and unipolar recordings in these patients.It is critical to demonstrate the distal unipolarrecording has earlier activation that the proximalpole and correlates with the earliest onset of elec-trical activity on the bipolar recording, since the


www.pace

ricd.c

om


radiofrequency energy is delivered thru the distalpole. The unipolar recording should also have aQS morphology at the earliest site, with a rapidintrinsicoid deflection. Pacemapping can also beused, but as mentioned earlier in this article,similar pacemaps can occur over 1- or 2-cm area.The more normal the heart, the smaller the areaover which identical pacemaps can be generated.The success rates of ablation of these tachycardiasare extremely high, usually exceeding 90%. In theauthor’s opinion, ablation should be considered asa primary form of therapy in such patients.

Uncommonly, other triggered rhythms mayappear from the fascicles. These rhythms are usu-ally transient and treatment usually involves re-moving the offending trigger (e.g., digitalis, milri-none). Occasionally they require specific therapy.β-Blockers are usually quite effective, but if symp-tomatic VT persists, ablation may be undertakenusing activation mapping to lacalize the earliestPurkinje potential.

The second type of idiopathic VT is one fromthe LV septum adjacent to the posterior papillarymuscle. This VT is known as “verapamil-sensativeVT” because of its unique responsiveness to thisagent.147−159 These VTs typically have a RBBB/leftanterior descending morphology, but may have aright superior axis when located more apically.Initially many investigatores believed this rhthymwas due to triggered activity, but it is now com-monly accepted that it is due to reentry. This reen-trant arrhythmia can be intiated and terminatedby atrial or ventricular pacing and/or extrasimuli.The interval to the onset of the VT usually demon-strates an inverse relationship to the coupling in-terval of the initiating extrastimulus or paced cyclelength. It is also entrainable with fusion from theatrium or ventricle. Of note is the fact that Purk-inje spikes typically precede the onset of the QRSand local ventricular activation during VT. Thisled some investigators to call this fascicular VTthe author believes this term is inappropriate sincethe exact role of the Purkinje system in this VT isunclear. For example, atrial pacing can entrain theVT with total antegrade capture (normal QRS andHV interval) suggesting that the Purkinje system isused antegradely. Whether or not it is used retro-gradely is unproven.

Recently, several investigators have describedmild-diastolic potentials that define a protectedzone of slow conduction that can be traced overseveral centimeters on the septum to approach theexit site at the inferior septum at which site a Purk-inje spike is typically observed.150 Of note, thePurkinje spike at the “exit” of the diasolic path-way may not be the earliest Purkinje potentialrecorded. During pacing or in response to vera-pamil or lidocanie155−159 there is progressive delay

the block between the diastolic potential and thePurkinje spike. The frequency with which the di-astolic potentials are observed is variable. Multiplemapping techniques have been used to guide abla-tion of this arrhythmia, all claiming high success.They include activation mapping to define the ear-liest site of ventricular myocardial activation, theearliest Purkinje potential, the diastolic potentialand pathway, and site of concealed entrainment.Concealed entrainment is extremely difficult be-cause of the apparently small isthmus, but whenaccomplished is 100% successful. Ablation at thediastolic155−159 potential has also yielded excel-lent results. While Nakagawa et al.150 initially sug-gested ablation directed at the earliest Purkinje po-tential, this has not been uniformly successful. Ihave seen absence of Pukinje fibers at successfulablation sites, and as mentioned above, success-ful ablation sites at the diastolic potential oftendo not record the earliest Purkinje potential, as bythe earliest ventricular myocardial activation (± aPurkinje potential) and an excellent pacemap. Suc-cess of these various methods (i.e., based on Purk-inje mapping, pacemapping, or ventricular map-ping) may indicate different mechanisms and lo-cations of circuits, but more likely, it suggests thesemethods target the area incorporating the exit siteaccurately enough to successfully ablate the VT.The true accuracy of these latter methods cannot bedetermined since the number of lesions requiredfor success is usually not reported.

Ablation of VT in Cardiomyopathyand Miscellaneous Disorders

Sustained monomorphic VT is an uncommonpreseting arrhythmiain in IDCM, but appears morecommon in Chagas disease, sarcoidosis, and my-opathy due to ecchinochoccis cysts or trauma. Asnoted above, the sustrate of VT in patients IDCMcan be located endocardially or epicardially whichmay produce reentrant circuits that are difficult toablate from the endocardium. Sosa et al.80,82 de-veloped and successfully used the intrapericardialapproach to ablate VT in Chagas disease in whichthe critical components of the VT circuit werecommonly subepicardial. Another reentrant VTinitially described in cardiomyopathy and otherconditions with severe LV dysfunction, was bun-dle branch reentry.160−163 This VT circuit mostcommonly used the RBBB antegradely and theLBBB retrogradely, but the reverse could also beseen. Ablation of the RBBB or LBBB could curethis arrhythmia. More recently this VT has beennoted in myotonic dystrophy and coronary dis-ease, where it is usually confined to the fascicles,typically in patients with anterior infarction andbifascicular block. Unfortunately, in most patients,


www.pace

ricd.c

om

JOSEPHSON

other myocardial VTs are also present, mandatinguse of ICDs.

DiscussionOver the past 30 years elctrophysiologi-

cal studies have been used to understand themechanisms of a variety of VTs. They have alsobeen pivotal in developing therapy for the arrhyth-mias. In recent years there has been a great in-

terest in the molecular genetics of a variety ofarrhythmias. Mutations responsible for the longQT syndromes, Brugada syndrome, ARVD, cate-cholamine induced polymorphic VTs, and highrisk mutations with hypertrophic cardiomyopa-thy have been identified. The challenges for gene-based therapy for these disorders will be work forthe next decade and is dicussed elsewhere in thissymposium.

References1. Wellens HJJ, Schuilenburg RM, Durrer D. Electrical stimulation

of the heart in patients with ventricular tachycardia. Circulation1972; 38:216–226.

2. Wellens HJJ, Lie KI, Durrer D. Further observations on ventricu-lar tachycardia as studied by electrical stimulation of the heart.Circulation 1974; 39:647–653.

3. Wellens HJJ, Duren DR, Lie KI. Observations on mechanism ofventricular tachycardia in man. Circulation 1976; 84:237–244.

4. Josephson ME, Horowitz LN, Farshidi A, et al. Recurrent sus-tained ventricular tachycardia. 1. Mechanisms. Circulation 1976;57:431–440.

5. Spielman SR, Farshidi A, Horowitz LN, et al. Ventricular fibrilla-tion during programmed ventricular stimulation: Incidence andclinical implications. Am J Cardiol 1978; 42:913–918.

6. Josephson ME, Horowitz LN, Farshidi A, et al. Sustained ventric-ular tachycardia: Evidence for protected localized reentry. Am JCardiol 1978; 42:416–424.

7. VandePol CJ, Farshidi A, Spielman SR, et al. Incidence and clini-cal significance of induced ventricular tachycardia. Am J Cardiol1980; 45:725–731.

8. Robertson JP, Cain ME, Horowitz LN, et al. Anatomic and elec-trophysiologic correlates of ventricular tachycardia requiring leftventricular stimulation. Am J Cardiol 1981; 48:263–268.

9. Doherty JU, Kienzle MG, Waxman HL, et al. Programmed ventric-ular stimulation at a second right ventricular site: An analysis of100 patients, with special reference to sensitivity, specificity andcharacteristics of patients with induced ventricular tachycardia.Am J Cardiol 1983; 52:1184–1189.

10. Doherty JU, Kienzle MG, Waxman HL, et al. Relation of mode ofinduction and cycle length of ventricular tachycardia: Analysis of104 patients. Am J Cardiol 1983; 52:60–64.

11. Buxton AE, Waxman HL, Marchlinski FE, et al. Role of tripleextrastimuli during electrophysiologic study of patients withdocumented sustained ventricular tachyarrhythmias. Circulation1984; 69:532–540.

12. Brugada P, Abdollah H, Heddle B, et al. Results of a ventricularstimulation protocol using a maximum of 4 premature stimuli inpatients without documented or suspected ventricular arrhyth-mias. Am J Cardiol 1983; 52:1214–1218.

13. Morady F, DiCarlo L, Winston S, et al. A prospective comparisonof triple extrastimuli and left ventricular stimulation in studies ofventricular tachycardia induction. Circulation 1984; 70:52–57.

14. Brugada P, Green M, Abdollah H, et al. Significance of ventricu-lar arrhythmias initiated by programmed ventricular stimulation:The importance of the type of ventricular arrhythmia inducedand the number of premature stimuli required. Circulation 1984;69:87–92.

15. Brugada P, Wellens HJJ. Comparison in the same patient of twoprogrammed ventricular stimulation protocols to induce ventric-ular tachycardia. Am J Cardiol 1985; 55:380–383.

16. Kudenchuk PJ, Kron J, Walance CG, et al. Reproducibility of ar-rhythmia induction with intracardiac electrophysiologic testing:Patients with clinical sustained ventricular tachyarrhythmias. JAm Coll Cardiol 1986; 7:819–828.

17. Herre JM, Mann DE, Luck JC, et al. Effect of increased currentmultiple pacing sites and number of extrastimuli on induction ofventricular tachycardia. Am J Cardiol 1986; 57:102–107.

18. Estes NAM III, Garan H, McGovern B, et al. Influence of drivecycle during programmed stimulation on induction of ventriculararrhythmias: Analysis of 403 patients. Am J Cardiol 1986; 57:108–112.

19. Cooper MJ, Hunt LJ, Richards DA, et al. Effect of repetition of ex-trastimuli on sensitivity and reproducibility of mode of induction

of ventricular tachycardia by programmed stimulation. J Am CollCardiol 1888; 11:1260–1267.

20. Martinez-Rubio A, Shenasa M, Borggrefe M, et al. Electrophysio-logic variables characterizingthe induction of ventricular tachy-cardia versus ventricular fibrillation after myocardial infarction:Relation between ventricular late potentials and coupling inter-vals for the induction of sustained ventricular tachyarrhythmias.J Am Coll Cardiol 1993; 21:1624–1631.

21. Hummel JD, Strickberger SA, Daoud E. Results and efficiency ofprogrammed ventricular stimulation with four extrastimuli com-pared with one, two, and three extrastimuli. Circulation 1994;90:2827–2832.

22. Buxton AE, Waxman HL, Marchlinski FE, et al. Electrophysio-logic studies in nonsustained ventricular tachycardia: Relation tounderlying heart disease. Am J Cardiol 1983; 52:985–991.

23. Buxton AE, Marchlinski FE, Waxman HL, et al. Prognostic fac-tors in nonsustained ventricular tachycardia. Am J Cardiol 1984;53:1275–1279.

24. Veltri EP, Platia EV, Griffith LSC, et al. Programmed electricalstimulation and long-term follow-up in asymptomatic, nonsus-tained ventricular tachycardia. Am J Cardiol 1985; 56:309–314.

25. Poll DS, Marchlinski FE, Buxton AE, et al. Sustained ventriculartachycardia in patients with idiopathic dilated cardiomyopathy:Electrophysiologic testing and lack of response to antiarrhythmicdrug therapy. Circulation 1984; 70:451–456.

26. Poll DS, Marchlinski FE, Buxton AE, et al. Usefulness of pro-grammed stimulation in idiopathic dilated cardiomyopathy. AmJ Cardiol 1986; 58:992–997.

27. Josephson ME, Almendral JM, Buxton AE, et al. Mechanisms ofventricular tachycardia. Circulation 1987; 75:41–47.

28. Josephson ME, Horowitz LN, Farshidi A, et al. Recurrent sus-tained ventricular tachycardia. 2. Endocardial mapping. Circu-lation 1978; 57:440–447.

29. Josephson ME, Horowitz LN, Farshidi A. Continuous local elec-trical activity: A mechanism of recurrent ventricular tachycardia.Circulation 1978; 57:659–665.

30. Josephson ME, Horowitz LN, Farshidi A, et al. Recurrent sus-tained ventricular tachycardia. 4. Pleomorphism. Circulation1979; 59:459–468.

31. Josephson ME, Horowitz LN, Spielman SR, et al. Role of cathetermapping in the preoperative evaluation of ventricular tachycar-dia. Am J Cardiol 1982; 49:207–220.

32. Cassidy DM, Vassallo JA, Marchlinski FE, et al. Endocardial map-ping in humans in sinus rhythm with normal left ventricles: Ac-tivation patterns and characteristics of electrograms. Circulation1984; 70:37–42.

33. Cassidy DM, Vassallo JA, Buxton AE, et al. The value of cathetermapping during sinus rhythm to localize site of origin of ventric-ular tachycardia. Circulation 1984; 69:1103–1110.

34. Cassidy DM, Vassallo JA, Buxton AE, et al. Catheter mapping dur-ing sinusrhythm: Relation of local electrogram duration to ven-tricular tachycardia cycle length. Am J Cardiol 1985; 55:713–716.

35. Cassidy DM, Vassallo JA, Miller JM, et al. Endocardial cathetermapping in patients in sinus rhythm: Relationship to underly-ing heart disease and ventricular arrhythmias. Circulation 1986;73:645–652.

36. Untereker WJ, Spielman SR, Waxman HL, et al. Ventricular ac-tivation in normal sinus rhythm: Abnormalities with recurrentsustained tachycardia and a history of myocardial infarction. AmJ Cardiol 1985; 55:974–979.

37. Fenoglio JJ, Pham TD, Harken AH, et al. Recurrent sustainedventricular tachycardia: Structure and ultrastructure of


www.pace

ricd.c

om


subendocardial regions in which tachycardia originates. Circula-tion 1983; 68:518–533.

38. Gardner PI, Ursell PC, Fenoglio JJ Jr, et al. Electrophysiologic andanatomic basis for fractionated electrograms recorded from healedmyocardial infarcts. Circulation 1985; 72:596–611.

39. de Bakker JMT, van Capelle FJL, Janse MJ, et al. Reentry as a causeof ventricular tachycardia in patients with chronic ischemic heartdisease: Electrophysiologic and anatomic correlates. Circulation1988; 77:589–606.

40. DeBakker JMT, Van Capelle FJL, Janse MJ, et al. Slow conduc-tion in the infarcted human heart: “Zigzag” course of activation.Circulation 1993; 88:915–926.

41. Perlman RL, Miller J, Kindwall KE, et al. Abnormal epicardialand endocardial electrograms in patients with idiopathic dilatedcardiomyopathy: Relationship to arrhythmias. Circulation 1990;82:708.

42. Hsia HH, Marchlinski FE. Characterization of the electrophysio-logic substrate for monomorphic ventricular ventricular tachy-cardia in patients with nonischemic cardiomathy. PACE 2002;25:1114–1127.

43. Horowitz LN, Josephson ME, Harken AH. Epicardial and endocar-dial activation during sustained ventricular tachycardiain man.Circulation 1980; 61:1227–1238.

44. Josephson ME, Horowitz LN, Spielman SR, et al. Comparisonof endocardial catheter mapping with intraoperative mapping ofventricular tachycardia. Circulation 1980; 61:395–404.

45. MacLean WAH, Plumb VJ, Waldo AL. Transient entrainment andinterruption of ventricular tachycardia. PACE 1981; 4:358–366.

46. Waldo AL, Henthorn RW, Plumb VJ, et al. Demonstration of themechanism of transient entrainment and interruption of ventric-ular tachycardia with rapid atrial pacing. J Am Coll Cardiol 1984;3:422–430.

47. Almendral JM, Gottlieb C, Marchlinski FE, et al. Entrainment ofventricular tachycardia by atrial depolarizations. Am J Cardiol1985; 56:298–304.

48. Almendral JM, Gottlieb CD, Rosenthal ME, et al. Entrainmentof ventricular tachycardia: Explanation for surface electrocardio-graphic phenomena by analysis of electrograms recorded withinthe tachycardia circuit. Circulation 1986; 77:569–580.

49. Almendral JM, Rosenthal ME, Stamato NJ, et al. Analysis of theresetting phenomenon in sustained uniform ventricular tachycar-dia: Incidence and relation to termination. J Am Coll Cardiol 1986;8:294–300.

50. Almendral JM, Stamato NJ, Rosenthal ME, et al. Resettingresponse patterns during sustained ventricular tachycardia:Relationship to the excitablegap. Circulation 1986; 74:722–730.

51. Rosenthal ME, Stamato NJ, Almendral JM, et al. Influence of thesite of stimulation on the resetting phenomenon in ventriculartachycardia. Am J Cardiol 1986; 58:970–976.

52. Stamato NJ, Rosenthal ME, Almendral JM, et al. The resetting re-sponse of ventricular tachycardia to single and double extrastim-uli: Implications for an excitable gap. Am J Cardiol 1987; 60:596–601.

53. Rosenthal ME, Stamato NJ, Almendral JM, et al. Resetting of ven-tricular tachycardia with electrocardiographic fusion: Incidenceand significance. Circulation 1988; 77:581–588.

54. Callans DJ, Hook BG, Josephson ME. Comparison of resetting andentrainment of uniform sustained ventricular tachycardia: Fur-ther insights into the characteristics of the excitable gap. Circula-tion 1993; 87:1229–1238.

55. Wellens HJJ, Bar FWHM, Lie KI, et al. Effects of procainamide,propranolol and verapamil on mechanism of tachycardia in pa-tients with chronic recurrent ventricular tachycardia. Am J Car-diol 1977; 40:579–585.

56. Marchlinski FE, Buxton AE, Josephson ME, et al. Predicting ven-tricular tachycardia cycle length after procainamide by assessingcycle length-dependent changes in paced QRS duration. Circula-tion 1989; 79:39–46.

57. Marchlinski FE, Buxton AE, Kindwall KE, et al. Comparison of in-dividual and combined effects of procainamide and amiodaronein patients with sustained ventricular tachyarrhythmias. Circula-tion 1988; 78:583–591.

58. Rosen MR, Danilo P Jr. Effects of tetrodotoxin, lidocaine, ve-rapamil, and AHR-2666 on ouabain-induced delayed afterde-polarizations in canine Purkinje fibers. Circ Res 1980; 46:117–124.

59. Horowitz LN, Josephson ME, Farshidi A, et al. Recurrent sus-tained ventricular tachycardia. 3. Role of the electrophysiologic

study in selection of antiarrhythmic regimens. Circulation 1978;58:986–597.

60. Mason JW, Winkle RA. Electrode catheter arrhythmia inductionin the selection and assessment of antiarrhythmic drug therapy forrecurrent ventricular tachycardia. Circulation 1978; 58:971–585.

61. Lerman BB, Belardinelli L, West GA, et al. Adenosine sensitive,ventricular tachycardia: evidence suggesting cyclic-AMP medi-ated triggered activity. Circulation 1986; 74:270–280.

62. Lerman BB, Stein KM, Markowitz SM, et al. Ventricular tachycar-dia in patients with structurally normal hearts. In D Zipes, J Jalife(eds.). Cardiac Electrophyiology From Cell to Bedside. Philadel-phia, W.B. Saunders, 2000, pp. 265–291.

63. Horowitz LN, Greenspan AM, Spielman SR, et al. Torsades depointes: Electrophysiologic studies in patients without transientpharmacologic or metabolic abnormalities. Circulation 1981;63:1120–1128.

64. Buxton AE, Marchlinski FE, Miller JM, et al. Role of procainamidein identifying clinically relevant polymorphic tachycardias. Cir-culation 1988; 78:II–71.

65. Buxton AE, Josephson ME, Marchlinski FE, et al. Polymorphicventricular tachycardia induced by programmed stimulation: Re-sponse to procainamide. J Am Coll Cardiol 1993; 21:90–98.

66. Klein LS, Shih HT, Hackett FK, et al. Radiofrequency catheterablation of ventricular tachycardia in patients without structuralheart disease. Circulation 1992; 85:1666–1674.

67. Coggins DL, Lee RJ, Sweeney J, et al. Radiofrequency catheterablation as a cure for idiopathic tachycardia of both left and rightventricular origin. J Am Coll Cardiol 1994; 23:1333–1341.

68. Varma N, Josephson ME. Therapy of idiopathic ventricular tachy-cardia. J Cardiovasc Electrophysiol 1997; 8:104–116.

69. Stevenson WG, Khan H, Sager P, et al. Identification of reentry cir-cuit sites during catheter mapping and radiofrequency ablation ofventricular tachycardia late after myocardial infarction. Circula-tion 1993; 88:1647–1670.

70. Morady F, Harvey M, Kalbfleisch SJ, et al. Radiofrequency catheterablation of ventricular tachycardia in patients with coronaryartery disease. Circulation 1993; 87:363–372.

71. Kim YH, Sosa-Suarez G, Trouton TG, et al. Treatment of ven-tricular tachycardia by transcatheter radiofrequency ablation inpatients with ischemic heart disease. Circulation 1994; 89:1094–1102.

72. Gonska BD, Cao K, Schaumann A, et al. Catheter ablation ofventricular tachycardia in 136 patients with coronary artery dis-ease: Results and long-term follow-up. J Am Coll Cardiol 1994;24:1506–1514.

73. Miller JM, Harken AH, Hargrove WC, et al. Pattern of endocardialactivation during sustained ventricular tachycardia. J Am CollCardiol 1085; 6:1280–1287.

74. Stevenson WG, Friedman PL, Sager PT, et al. Exploring postinfarc-tion reentrant ventricular tachycardia with entrainment mapping.J Am Coll Cardiol 1997; 29:1180–1189.

75. El Shalakany A, Hadjis T, Papageorgiou P, et al. Entrainment map-ping criteria for the prediction of termination of ventricular tachy-cardia by single radiofrequency lesion in patients with coronaryartery disease. Circulation 1999; 99:2283–2289.

76. Bogun F, Bahu M, Knight BP, et al. Comparison of effective andineffective target sites that demonstrate concealed entrainment inpatients with coronary artery disease undergoing radiofrequencyablation of ventricular tachycardia. Circulation 1997; 95:183–190.

77. Waxman HL, Josephson ME. Ventricular activation during ventric-ular endocardial pacing. I. Electrocardiographic patterns relatedto the site of pacing. Am J Cardiol 1982; 50:1–10.

78. Holt PM, Smallpiece C, Dedverall PB, et al. Ventricular arrhyth-mias: A guide to their localizations. Br Heart J 1985; 53:417–430.

79. Kuchar DL, Buskin JN, Garan H. Electrocardiographic localizationof the site of origin of ventricular tachycardia in patients withprior infarction. J Am Coll Cardiol 1989; 4:893–903.

80. Sosa E, Scanavacca M, D’Avila A, et al. A new technique to per-form epicardial mapping in the electrophysiology laboratory. JCardiovasc Electrophysiol 1996; 7:531–536.

81. Sosa E, Scanavacca M, d’Avila A, et al. Endocardial and epicardialablation guided by nonsurgical transthoracic epicardial mappingto treat recurrent ventricular tachycardia. J Cardiovasc Electro-physiol 1998; 9:229–239.

82. Sosa E, Scanavacca M, d’Avila A, et al. Radiofrequency catheterablation of ventricular tachycardia guided by nonsurgical epi-cardial mapping in chronic Chagasic heart disease. PACE 1999;22:128–130.


www.pace

ricd.c

om

JOSEPHSON

83. Callans DJ, Menz V, Schwartzman DS, et al. Repetitive monomor-phic ventricular tachycardia from the left ventricular outflowtract: Electrocardiographic patterns consistent with a left ventric-ular site of origin. J Am Coll Cardiol 1997; 29:1023–1027.

84. Kanagaratnam L, Tomassoni G, Schweikert R, et al. Ventriculartachycardia as arising from the aortic sinus of Valsalva: An underrecognized variant of left outflow tract ventricular tachycardia. JAm Coll Cardiol 2001; 37:1408–1414.

85. Dixit S, Marchlinski FE. Clinical characteristics and catheter ab-lation of left ventricular outflow tract tachycardia. Curr CardiolRep 2001; 3:305–313.

86. Hachiya H, Aonuma K, Yamauchi Y, et al. How to diagnose, locate,and ablate coronary cusp ventricular tachycardia. J CardiovascElectrophysiol 2002; 13:551–556.

87. Ouyang F, Fotuhi P, Ho SY, et al. Repetitive monomorphic ven-tricular tachycardia originating from the aortic sinus cusp: Elec-trocardiographic characterization for guiding catheter abalation.J Am Coll Cardiol 2002; 39:500–508.

88. Fisher JD, Cohen HL, Mehra R, et al. Cardiac pacing and pacemak-ers. II. Serial electrophysiologic pharmacologic testing for controlof recurrent tachyarrhythmias. Am Heart J 1977; 93:658–668.

89. Horowitz LN, Josephson ME, Farshidi A, et al. Recurrent sus-tained ventricular tachycardia. 3. Role of the electrophysiologicstudy in selection of antiarrhythmic regimens. Circulation 1978;58:986–597.

90. Josephson ME, Horowitz LN. Electrophysiologic approach to thetherapy of recurrent sustained ventricular tachycardia. Am J Car-diol 1979; 43:631–642.

91. Horowitz LN, Josephson ME, Kastor JA. Intracardiac electrophys-iologic studies as a method for the optimization of drug therapy inchronic ventricular arrhythmia. Prog Cardiovasc Dis 1980; 23:81–98.

92. Mason JW, Winkle RA. Electrode catheter arrhythmia inductionin the selection and assessment of antiarrhythmic drug therapy forrecurrent ventricular tachycardia. Circulation 1978; 58:971–585.

93. Ruskin JN, DiMarco JP, Garan H. Out-of-hospital cardiac arrest:Electrophysiologic observations and selection of long-term antiar-rhythmic therapy. N Engl J Med 1980; 303:607–613.

94. Morady F, Scheinman MM, Hess DS, et al. Electrophysiologic test-ing in the management of survivors of out-of-hospital cardiac ar-rest. Am J Cardiol 1983; 51:85–89.

95. Buxton AE, Marchlinski FE, Flores BT, et al. Nonsustained ven-tricular tachycardia in patients with coronary artery disease: roleof electrophysiologic study. Circulation 1987; 75:1178–1185.

96. Klein RC, Machell C. Use of electrophysiologic testing in patientswith nonsustained ventricular tachycardia: Prognostic and thera-peutic implications. J Am Coll Cardiol 1989; 14:155–161.

97. Manolis AS, Estes NAD. Value of programmed ventricular stim-ulation in the evaluation and management of patients with non-sustained ventricular tachycardia associated with coronary arterydisease. Am J Cardiol 1990; 65:201–205.

98. Kowey PR, Waxman HL, Greenspon A, et al. Value of electrophysi-ologic testing in patients with previous myocardial infarction andnonsustained ventricular tachycardia. Philadelphia ArrhythmiaGroup. [comments] Am J Cardiol 1990; 65:594–598.

99. Wilber DJ, Kopp D, Olshansky B, et al. Nonsustained ventriculartachycardia and other high-risk predictors following myocardialinfarction: Implications for prophylactic automatic implantablecardioverter-defibrillator use. Prog Cardiovasc Dis 1993; 36:179–194.

100. Mason JW. A comparison of electrophysiologic testing with Holtermonitoring to predict antiarrhythmic-drug efficacy for ventricu-lar tachyarrhythmias. Electrophysiologic Study versus Electrocar-diographic Monitoring Investigators. [comments] N Engl J Med1993; 329:445–451.

101. Breithardt G, Borggrefe M, Seipel L. Selection of optimal drugtreatment of ventricular tachycardia by programmed electricalstimulation of the heart. Ann N Y Acad Sci 1984; 427:49–66.

102. Rae AP, Greenspan AM, Spielman SR, et al. Antiarrhythmic drugefficacy for ventricular tachyarrhythmias associated with coro-nary artery disease as assessed by electrophysiologic studies. AmJ Cardiol 1985; 55:1494–1499.

103. Reddy CP, Chen TJ, Guillory WR. Electrophysiologic studies inselection of antiarrhythmic agents: Use with ventricular tachy-cardia. PACE 1986; 9:756–763.

104. Josephson ME. Clinical Cardiac Electrophysiology: Techniquesand Interpretation. 3rd ed. Philadelphia, Lippencott Williams andWilkins, 2002, pp. 611–657.

105. Waxman HL, Buxton AE, Sadowski LM, et al. The response to pro-

cainamide during electrophysiologic study for sustained ventric-ular tachyarrhythmias predicts the response to other medications.Circulation 1983; 67:30–37.

106. Roy D, Waxman HL, Buxton AE, et al. Termination of ventriculartachycardia: Role of tachycardia cycle length. Am J Cardiol 1982;50:1346–1350.

107. Fisher JD, Kim SG, Matos JA, et al. Comparative effectiveness ofpacing techniques for termination of well-tolerated sustained ven-tricular tachycardia. PACE 1983; 6:915–922.

108. Waldecker B, Brugada P, Zehender M, et al. Importance of modesof electrical termination of ventricular tachycardia for the selec-tion of implantable antitachycardia devices. Am J Cardiol 1986;57:150–155.

109. Naccarelli GV, Zipes DP, Rahilly GT, et al. Influence of tachy-cardia cycle length and antiarrhythmic drugs on pacing termina-tion and acceleration of ventricular tachycardia. Am Heart J 1983;105:1–5.

110. Mirowski M, Reid PR, Mower MM, et al. Termination of malignantventricular arrhythmias with an implantable automatic defibril-lator in human beings. N Engl J Med 1980; 303:322–324.

111. Guiraudon G, Fontaine G, Frank R, et al. Encircling endocardialventriculotomy: A new surgical treatment for life-threatening ven-tricular tachycardias resistant to medical treatment following my-ocardial infarction. Ann Thorac Surg 1978; 26:438–444.

112. Josephson ME, Harken AH, Horowitz LN. Endocardial excision: Anew surgical technique for the treatment of recurrent ventriculartachycardia. Circulation 1979; 60:1430–1439.

113. Horowitz LN, Josephson ME, Harken AH. Epicardial and endocar-dial activation during sustained ventricular tachycardia in man.Circulation 1980; 61:1227–1238.

114. Guiraudon G, Fontaine G, Frank R, et al. Surgical treatment ofventricular tachycardia guided by ventricular mapping in 23 pa-tients without coronary artery disease. Ann Thorac Surg 1981;32:439–450.

115. Miller JM, Harken AH, Hargrove WC, et al. Pattern of endocardialactivation during sustained ventricular tachycardia. J Am CollCardiol 1985; 6:1280–1287.

116. Moran JM, Kehoe RF, Leob JM, et al. Extended endocardial resec-tion for the treatment of ventricular tachycardia and ventricularfibrillation. Thorac Surg 1982; 34:538.

117. Guiraudon GM, Thakur RK, Klein GJ, et al. Encircling endocardialcryoablation for ventricular tachycardia after myocardial infarc-tion: Experience with 33 patients. Am Heart J 1984; 128:982–989.

118. Borggrefe M, Podczek A, Ostermayer J, et al. Long-term results ofelectrophysiologically guided antitachycardia surgery in ventric-ular tachyarrhythmias. A report on 665 patients. In G Breithardt,M Borggrefe, DP Zipes (eds.): Nonpharmacological Therapy ofTachyarrhythmias. Mount Kisco, NY, Futura Publishing, 1987,p. 109.

119. Fontaine G, Guiraudon G, Frank R, et al. Stimulation studies inepicardial mapping of VT. Study of mechanisms and selection forsurgery. In HE Kulbertus (ed.): Reentrant Arrhythmias: Mecha-nisms and Treatment. Baltimore, University Park Press, 1977.

120. Fontaine G, Guiraudon G, Frank R, et al. Correlation between latepotentials in sinus rhythm and earliest activation during chronicVT. In W Bircks, F Loogen, HD Schulte, L Seipel (eds.): Medicaland Surgical Management of Tachyarrhythmias. Berlin, Springer-Verlag, 1980, p. 138.

121. DiMarco JP, Lerman BB, Kron IL, et al. Sustained ventricular tach-yarrhythmias within 2 months of acute myocardial infarction: Re-sults of medical and surgical therapy in patients resuscitated fromthe initial episode. J Am Coll Cardiol 1985; 6:759–968.

122. Josephson ME. Clinical Cardiac Electrophysiology: Techniquesand Interpretation. 3rd ed. Lippencott Williams and Wilkins,Philadelphia, 2002.

123. Hartzler GO. Electrode catheter ablation of refractory focal ven-tricular tachycardia. J Am Coll Cardiol 1983; 2:1107–1113.

124. Fontaine G, Tonet JL, Frank R, et al. Emergency treatment ofchronic ventricular tachycardia after myocardial infarction byendocavitary fulguration. Arch Mal Coeur Vaiss 1985; 78:1037–1043.

125. Sarter BH, Finkle JK, Gerszten RE, et al. What is the risk of suddencardiac death in patients presenting with hemodynamically stablesustained ventricular tachycardia after myocardial infarction? JAm Coll Cardiol 1996; 28:122–129.

126. Rothman SA, Hsia HH, Cossu SF, et al. Radiofrequency catheterablation of postinfarction ventricular tachycardia: Long-term suc-cess and the significance of inducible nonclinical arrhythmias.Circulation 1997; 96:3499–3508.


www.pace

ricd.c

om


127. Callans DJ, Zado E, Sarter BH, et al. Procedural efficacy ofradiofrequency ablation for ventricular tachycardia in patientswith healed myocardial infarction: An intention to treat analy-sis. Am J Cardiol 1998; 82:429–432.

128. Stevenson WG, Friedman PL, Kocovic D, et al. Radiofrequencycatheter ablation of ventricular tachycardia after myocardial in-farction. Circulation 1998; 98:308–314.

129. Ben-Haim SA, Osadchy D, Schuster I, et al. Nonflucroscopic, invivo navigation and mapping technology. Nat Med 1996; 2:1393–1395.

130. Gepstein L, Hayam G, Ben-Haim SA. A novel method for nonflu-oroscopic catheter-based electroanatomical mapping of the heart.In vitro and in vivo accuracy results. Circulation 1997; 95:1611–1622.

131. Soejima K, Stevenson WG, Maisel WH, et al. Electrically unex-citable scar mapping based on pacing threshold for identificationof the reentry circuit isthmus: Feasibility for guiding ventriculartachycardia ablation. Circulation 2002; 106:1678–1683.

132. Kienzle MG, Doherty JU, Cassidy D, et al. Electrophysiologic se-quelae of chronic myocardial infarction: Local Refractoriness andelectrographic characteristics of the left ventricle. Am J Cardiol1986; 58:63–69.

133. Marchlinski FE, Callans DJ, Gottlieb CD, et al. Linear ablationlesions for control of unmappable ventricular tachycardia in pa-tients with ischemic and non-ischemic cardiomyopathy. Circula-tion 2000; 101:1288–1296.

134. Harada T, Stevenson WG, Kocovic DZ, et al. Catheter ablation ofventricular tachycardia after myocardial infarction: Relation ofendocardial sinus rhythm late potentials to the reentry circuit. JAm Coll Cardiol 1997; 30:1015–1023.

135. Arenal A, Glez-Torrecilla E, Ortiz M, et al. Ablation of electro-grams with an isolated, delayed component as treatment of un-mappable monomorphic ventricular tachycardias in patients withstructural heart disease. J Am Coll Cardiol 2003; 41:81–92.

136. Marcus Fl, Fontaine GH, Guiraudon G, et al. Right ventricu-lar dysplasia: A report of 24 cases. Circulation 1982; 65:384–398.

137. Corrado D, Basso C, Nava A, et al. Arrhythmogenic right ventric-ular cardiomyopathy: Current diagnostic and management strate-gies, Cardiol Rev 2001; 9:259–265.

138. Marcus F, Towbin JA, Zareba W, et al., ARVD/C Investigators.Arrhythmogenic right ventricular dysplasia/cardiomyopathy(ARVD/C): A multidisciplinary study: Design and protocol. Cir-culation 2003; 107:2975–2978.

139. Fontaine G, Guiraudon G, Frank R, et al. Surgical managementof ventricular tachycardia unrelated to myocardial ischemia orinfarction. Am J Cardiol 1982; 49:397–410.

140. Guiraudon GM, Klein GJ, Gulamhusein SS, et al. Total disconnec-tion of the right ventricular free wall: Surgical treatment of rightventricular tachycardia associated with right ventricular dyspla-sia. Circulation 1983; 67:463–470.

141. Ellison KE, Friedman PL, Ganz LI, et al. Entrainment mappingand radiofrequency catheter ablation of ventricular tachycardiain right ventricular dysplasia. J Am Coll Cardiol 1998; 32:724–728.

142. Klein LS, Shih HT, Hackett FK, et al. Radiofrequency catheterablation of ventricular tachycardia in patients without structuralheart disease. Circulation 1992; 85:1666–1674.

143. Coggins DL, Lee RJ, Sweeney J, et al. Radiofrequency catheterablation as a cure for idiopathic tachycardia of both left andright ventricular origin. J Am Coll Cardiol 1994; 23:1333–1341.

144. Varma N, Josephson ME. Therapy of idiopathic ventricular tachy-cardia. J Cardiovasc Electrophysiol 1997; 8:104–116.

145. Morady F, Kadish AM, DiCarlo L, et al. Long term results ofcatheter ablation of idiopathic right ventricular tachycardia. Cir-culation 1990; 82:2093–2099.

146. Frey B, Kreiner G, Fritsch S, et al. Succesful treatment of idio-pathic left ventricular outflow tract tachycardia by catheter ab-lation or minimally invasive surgical cryoablation. PACE 2000;23:870–876.

147. Klein GJ, Millman PJ, Yee R. Recurrent ventricular tachycardiaresponsive to Verapamil. PACE 1984; 7:938–948.

148. Okumura K, Matsuyama K, Miyagi H, et al. Entrainmentof idiopathic ventricular tachycardia of left ventricular ori-gin with evidence for reentry with an area of slow conduc-tion and effect of verapamil. Am J Cardiol 1988; 62:727–732.

149. Okumura K, Yamabe H, Tsuchiya T, et al. Characteristics of slowconduction zone demonstrated during entrainment of idiopathicventricular tachycardia of left ventricular origin. Am J Cardiol1996; 77:379–383.

150. Nakagawa H, Beckman KJ, McClelland JH, et al. Radiofrequencycatheter ablation of idiopathic left ventricular tachycardia guidedby a Purkinje potential. Circulation 1993; 88:2607–2617.

151. Ohe T, Shimomura K, Aihara N, et al. Idiopathic sustained leftventricular tachycardia 1996; 77:379–383.

152. Tsuchiya T, Okumura K, Honda T, et al. Effect of verapamil andlidocaine on two components of the reentry circuit of verapamil-sensitive idiopathic left ventricular tachycardia. J Am Coll Cardiol2001; 37:1415–1421.

153. Maruyama M, Tadera T, Miyamoto S, et al. Demonstration ofthe reentrant circuit of verapamil-sensitive idiopathic left ven-tricular tachycardia: Direct evidence for macrorentry as the un-derlying mechanism. J Cardiovasc Electrophysiol 2001; 12:968–972.

154. Lee KL, Lauer MR, Young C, et al. Spectrum of electrophysiologicand electropharmacologic characteristics of verapamil-sensitiveventricular tachycardia in patients without structural heart dis-ease. Am J Cardiol 1996; 77:967–973.

155. Tsuchiya T, Okumura K, Honda T, et al. Significance of latediastolic potential preceding purkinje potential in verapamil-sensitive idiopathic left ventricular tachycardia. Circulation 1999;99:2408–2413.

156. Sasano T, Satake S, Azegami K, et al. Diastolic potentials observedin idiopathic left ventricular tachycardia. Jpn Circ J 1999; 63:917–923.

157. Tsuchiya T, Okumura K, Honda T, et al. Effects of verapamil andlidocaine on two components of the reentry circuit of verapamil-sensitive idiopathic left ventricular tachycardia. J Am Coll Cardiol2001; 37:1415–1421.

158. Hachiya H, Aonuma K, Yamauchi Y, et al. ElectrocardiographicCharacteristics of left ventricular outflow tract tachycardia. PACE2000; 23:1930–1934.

159. Maruyama M, Tadera T, Miyamoto S, et al. Demonstration ofthe reentrant circuit of verapamil-sensitive idiopathic left ven-tricular tachycardia: Direct evidence for macroeentry as the un-derlying mechanism. J Cardiovasc Electrophysiol 2001; 12:968–972.

160. Blanck Z, Sra J, Dhala A, Bundle branch reentry: Mechanisms,diagnosis, and treatment. In D Zipes, J Jalife (eds.): Cardiac Elec-trophyiology From Cell to Bedside. Philadelphia, W.B. SaundersCompany, 2000, pp.

161. Crijns HJGM, Smeets JLRM, Rodriguez LM, et al. Cure of interfas-cicular reentrant tachycardias by ablation of the anterior fascicleof the left bundle branch. J Cardiovsc Electrophysiol 1995; 6:486–492.

162. Touboul P, Kirkorian G, Atallah G, et al. Bundle branch reen-try tachycardia treated by electrical ablation of the right bundlebranch. J Am Coll Cardiol 1986; 7:1404–1409.

163. Tchou P, Jazayeri M, Denker S, et al. Transcatheter electrical abla-tion of the right bundle branch: A method of treating macroreen-trant ventricular tachycardia due to bundle branch reentry. Circu-lation 1988; 78:246–757.


Documents

Electrophysiology of Ventricular Tachycardia: A …pacericd.com/documents/ARTICLES/Electrophysiology... · Electrophysiology of Ventricular Tachycardia: A Historical Perspective MARK