Evolution of mapping and anatomic imaging of cardiac arrhythmias

NASPE 25th ANNIVERSARY SERIES

Evolution of Mapping and Anatomic Imaging of CardiacArrhythmiasDOUGLAS L. PACKERFrom the Division of Cardiology/Electrophysiology, Mayo School of Medicine, Rochester, Minnesota

IntroductionProgress in the understanding of cardiac ar-

rhythmias has emerged from a number of insight-ful studies elucidating the activation of and result-ing impulse propagation through cardiac tissue.The identification of specific patterns of sequentialdepolarization have enabled electrophysiologiststo recognize macro- or microreentrant, automatic,and triggered tachycardias and have also charac-terized the contribution of repolarization to thosesame arrhythmias.

This progress has been driven, to a large de-gree, by available technology designed for the de-tection of electrical signals originating in the heart.The successful recording of the surface electrocar-diogram (ECG) by Einthoven, in a sense, markedthe beginning of cardiac mapping. Although im-portant observations were made from those orig-inal surface tracings and subsequent refinementsof the ECG, further progress had to await more so-phisticated technology enabling detailed point topoint epicardial and intracardiac recordings. Inno-vative deciphering of the underlying physiologysubsequently proceeded to the edge of the resolu-tion of those techniques.

Further progress required yet higher levels oftechnology in the form of multichannel recordingdevices, and later electroanatomic, voltage, andnoncontact mapping techniques with computer-assisted, three-dimensional displays. Each of theseclarified further the role of fundamental elec-trophysiological properties in arrhythmogenesis.The more recent development of charge-coupledand photodiode-based optical mapping systemsand the accompanying application to ex situ my-ocardium has permitted an even more careful ex-amination of the recovery of cardiac tissue, in ad-dition to its activation. Clearly, progress in tech-nology has led to the disclosure of progressivelymore mysteries of arrhythmogenesis. Neverthe-less, rather than focusing on mapping technol-ogy, per se, this article considers a limited num-ber of sentinel observations enabled by that evolv-

Address for reprints: Douglas L. Packer, M.D., 2-416Alfred Bldg., Saint Mary’s Hospital Complex, Mayo Foun-dation, Rochester, MN 55902. Fax: (507) 255-3292; e-mail:[email protected]

ing technology and the resulting emerging under-standing of cardiac arrhythmias. This article fo-cuses exclusively on reentry. In so doing, only alimited number of the many meritorious studieswill be reviewed.

Elucidation of Macroreentrant ArrhythmiasEarly in the 20th Century, it was unclear if

the arrhythmias recorded on an ECG originatedfrom a single site or were due to reentry withincardiac tissue. In an attempt to understand themechanisms of repetitive activation so recorded,Mayer1,2 demonstrated reentrant contraction of ajellyfish ring around a natural central obstacle. In1914, Mines3 studied the patterns of impulse prop-agation from the origin of stimulation in tortoisemyocardium. He demonstrated repetitive impulsepropagation, as evidenced by muscle contraction,proceeding around an anatomic obstacle createdby blunt dissection. Based on additional observa-tions, Mines3,4 suggested the requirement of threecritical components to a reentrant arrhythmia: (1)the presence of two dissociated pathways, (2) theneed for electrical block of the impulse in onepathway with subsequent propagation through thesecond, and (3) the termination of the reentry bycutting through the pathway. These observationssupported the plausibility of reentry as a specificmechanism underlying the arrhythmias observedon ECGs and provided the theoretical underpin-nings for nonpharmacologic therapy for arrhyth-mias. Despite these landmark observations, thelimitations of available technology hampered fur-ther dissection of clinical arrhythmias.

Accessory Pathway Related Tachycardias

The arrhythmias of the Wolff-Parkinson-White (WPW) syndrome provided an excellentschoolmaster for studying the concepts of reentry.The presence of two distinct pathways was evidentin the combination of the “bundle branch block”QRS morphology along with a short PR intervalduring sinus rhythm on the one hand, and a nar-row QRS complex during paroxysmal tachycardiaon the other, as codified into syndrome format byWolff, Parkinson, and White in 1930.5

The proof of the contribution of these path-ways to reentry awaited the development of

Reprinted from PACE July 2004, Vol. 27, and JCE July 2004, Vol. 15. PACE and JCE are published by Blackwell Publishing. Heart Rhythm (2004) 153C–176C©2004 Heart Rhythm Society

EVOLUTION OF MAPPING AND ANATOMIC IMAGING OF CARDIAC ARRHYTHMIAS

Figure 1. Ventricular epicardial activation map during sinus rhythm showing ventricular pre-excitation along the right atrioventricular (AV) groove. Earliest ventricular activation occurred110 ms after the onset of the P wave and > 40 ms before the onset of the surface QRS. (Withpermission from reference 8.)

intracardiac catheters with recording electrodes6,7

and the development of hand held probes for spa-tial and temporal mapping of the patterns of reen-try seen on intraoperative mapping.8−10 At thetime of the first successful surgical intervention,Sealy and Gallagher confirmed the role of theaccessory pathway in preexcitation of the rightventricle as seen in Figure 1, and they cured aNorth Carolina fisherman of his supraventriculartachycardia.8 Additional studies using multielec-trode catheters further localized pathways basedon the site of earliest retrograde activation dur-ing orthodromic reciprocating tachycardia. Figure2 shows an eccentric sequence of activation on theatrial side of the tricuspid annulus at the path-way site. These studies also proved that tachycar-dias could be initiated by premature impulses thatblocked in one pathway, conducted via the secondto an alternative cardiac chamber, with subsequent

return activation via the first pathway now recov-ered from the original resulting “block.”11

Subsequent detailed studies demonstrated theimportance of a prolongation of the ventriculoa-trial (VA) interval with the emergence of bundlebranch block ipsilateral to the accessory pathway,not only as an indicator of the location of that path-way, but its participation in the macroreentrantarrhythmia.12 Observations made by others show-ing advancement of the retrograde atrial activationsequence with a premature ventricular stimulusintroduced at a time when the His bundle wasrefractory, further established the accessory con-nection as a critical component of that reentrantcircuit.13

Conversely, the pattern of preexcitation andthe site of earliest ventricular activation mappedthe location of the ventricular insertion ofthe pathway. The reversal of the tachycardia

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Figure 2. Activation mapping of the right and left AVgrooves during ventricular pacing mimicking ortho-dromic reciprocating tachycardia. The earliest site ofretrograde atrial activation (VA = 105 ms) occurred inthe right lateral portion of the tricuspid annulus. Allother sites activated at later times. (With permissionfrom reference 17.) AV = atrioventricular; VA = ven-triculoatrial.

circuit, yielding maximally preexcitated QRS com-plexes during the arrhythmia, was documentedusing multipolar catheters and hand held map-ping probes during surgery and the physiology ofantidromic reciprocating tachycardias was clari-fied.14 Additional studies identified the presenceof Mahaim Fibers, and their origin from the my-ocardium of the anterolateral right atrium (RA),15

rather than from the atrioventricular (AV) node aspreviously believed.16,17

Within the context of an anatomic framework,studies conducted over the last 25 years have fur-ther characterized the nature of the pathway itself,documented the slanting nature of accessory con-nections as they cross the mitral or tricuspid valveannulus, and established the importance of thecoronary sinus and other components of the car-diac vein system in the arrhythmias of the WPWsyndrome.18,19 The ablation of cardiac tissue pro-vided further confirmation of the role of specificanatomic structures and the underlying physiol-ogy in the initiation and maintenance of WPWelated arrhythmias.

Macrorentrant Ventricular Tachycardia

The mapping of ventricular tachycardias (VTs)also began in the isolated tissue preparations of

Mines,3 here reentry, as predicted by McWilliam20

20 years earlier was found. Subsequently, in 1928Schmitt and Erlanger,21 demonstrated effectivereentry (now viewed as reflection) in a muscle bun-dle, in which conduction was depressed with el-evated extracellular K+. Using limited “mapping”techniques, other investigators demonstrated theoccurrence of reentry in the bundle branch or Purk-injie system of the ventricles more convincingly asshown in an early study by Wit and Cranefield22

(Fig. 3).

Passive Mapping of VT

Early mapping studies of VT in humanswere also facilitated by the development of mul-tielectrode catheters. Wellens et al.23,24 madeimportant fundamental observations regarding VTinitiation, its response to electrical stimuli, andpatterns of termination with pacing, strongly

Figure 3. Purkinjie network reentry in a fiber exposedto high K+ and epinephrine, as studied with multiplemicroelectrodes (Panel A). Panel B shows activation oftwo limbs of the potentially reentrant circuit. Panel Cshows impulse block in pathway 2 followed by reentryvia pathways 1 and 3 as shown in the inset. Panel Dshows two reentrant cycles following pathway 2 block.Together these demonstrate the presence of microreen-try in that Purkinjie network. (With permission from ref-erence 22.)

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suggesting reentry as the underlying mechanismof this arrhythmia. In the next 15 years, mappingat available resolution, identified a relationshipbetween specific VT circuits and underlying in-farcted myocardium,25−27 and forged a link be-tween the earliest site of activation observed inthe operating room and that seen on intracardiaccatheter mapping in the electrophysiological lab-oratory, and the morphologies seen on the surfaceECG.25 Figure 4 shows the earliest site of ventricu-lar activation seen in a periinfarct border region. Inthis regard, endocardial catheterization was foundto predict the origin of VT to within 4–8 cm2 ofthat seen during preoperative electrophysiologicalstudies. The success of surgical subendocardial re-section in the region of underlying scar in a vari-ety of centers from 1978–1983 further disclosedthe importance of those border zones to the occur-rence of VT.28−30

Multielectrode recording arrays applied in an-imal models of VT extended these catheter-limitedstudies to establish (1) the actual reentrant mecha-nism underlying these arrhythmias,26 (2) the spe-cific characteristics of the reentry observed,31 and(3) the location and characteristics of compo-

Figure 4. Intraoperative mapping of ventricular tachy-cardia in a patient with an apical aneurysm. Shownare anterior, lateral, and posterior views with epicardialmapping sites as shown in the lower left-hand panel.The earliest endocardial breakthrough occurs at the on-set of the surface QRS as shown as the filled circle,which corresponded with the earliest site recorded uponcatheterization. (With permission from reference 25.)

nents of those circuits.26,27 El-Sherif et al.,31 inexamining patterns of ventricular activation in 1-day-old canine infarcts, demonstrated that someventricular arrhythmias had a focal origin arisingwithin the surviving endocardial Purkinjie net-work, while others were due to figure of eight reen-trant activation in epicardial layers overlying theinfarct (Fig. 5).32

Correlative mapping studies further indicatedthat conduction at the infarct border proceeded viazigzagging, relatively normal muscle fibers inter-spersed around islands of infarct scar.24 DeBakkeret al.,26 using simultaneous recordings from 64 en-docardial sites during VT also demonstrated thatthe “apparent” focal origin of tachycardias, occur-ring in the chronic phase of myocardial infarction,could be caused by discrete impulse exits from acircuitous pathway of surviving myocardial fibersat the border of the infarction. The presence andcharacteristics of a slow zone of conduction atthe core of reentrant VT was also established.27

Intramyocardial reentry was later documented ina canine model of myocardial infarction as well.33

Interactive Mapping of VT

In most early studies, mapping observationsduring ventricular arrhythmias were obtained pas-sively, that is with simple recordings made fromthe body surface, His-bundle region, or from theendocardial surface using intracardiac electrodecatheters to identify the earliest site of ventricularactivation during VT or to replicate the VT QRSmorphology through pacemapping during sinusrhythm. While the accuracy of passive mappingfor guiding an extensive subendocardial resectionwas less demanding, more precise localization hasbeen required in patients undergoing focal ablativetherapy for VT.

This required a new interactive approachbased on the entrainment or reset response of thatarrhythmia to single or trains of impulses deliv-ered during VT. This approach was based on sim-ilar studies of atrial flutter showing characteristicpatterns of response, which was a function of thepacing site used.34 A variety of studies showed thatsuch stimulation not only allowed validation ofthe reentrant mechanism underlying the arrhyth-mia, but also provided clues as to the participa-tion of specific tissue at that stimulation site inthe VT circuit.35,36 Stevenson et al.37 later pre-dicted and chronicled these patterns of responseand established the mechanism underlying con-cealed entrainment with pacing from the protectedslow zone of conduction at the core of VT. Figure6 shows the characteristic single and repetitive re-setting response with pacing from this protectedsite. The observation of matching postpacing


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Figure 5. Epicardial and endocardial isochronal maps during pacing induced ventricular tachycardia. The left sideof the figure shows simultaneous mapping of the epicardial and endocardial surfaces with maps showing evidenceof reentrant activation in the form of two synchronous wavefronts circulating in opposite directions around regionsof functional conduction block (shown as thick solid lines). The infarct zone is shown as the stippled area E. (Withpermission from reference 32.)

intervals and VT cycle lengths and the stim-QRSand local electrogram to QRS intervals, in thesetting of manifest entrainment with fusion ofthe QRS morphology, alternatively correlated withpacing from an outer or exposed zone. In contrast,Figure 7 shows the response when pacing from abystander pathway. The contribution of entrain-ment mapping to the success of ablation of VT hasbeen extensively documented in a number of clin-ical studies.38

Computer-Assisted Mapping of VT

The development of computer-based mappingtechnologies greatly facilitated advanced mappingand, therefore, the understanding of the mecha-nisms of both ventricular and atrial arrhythmias.A major breakthrough in this process came withthe development of electroanatomic mapping.39

This approach used a catheter with a three-coilsensor embedded in its tip. With the patient po-sitioned over a low level, three-beam magneticfield, the coils respond to the various fields, andthe exact location of the tip can thereby be tri-angulated and specified in three-space. A sur-rogate three-dimensional geometry of the actual

chamber being mapped is created through thecollection of multiple points within a cardiacchamber during an arrhythmia or sinus rhythm.Figure 8 shows one of the original maps created us-ing this CARTO (Biosense, Webster, Diamond Bar,CA, USA) system. Onto this anatomy, activationtimes at each site, occurring during a given ar-rhythmia, are registered and represented in an acti-vation color scale. In its simplest application, thisapproach provided a three-dimensional conceptu-alization of reentrant arrhythmias at a potential1–2-mm spatial resolution. This approach, whichis particularly well suited to activation mapping ofstable arrhythmias, has been applied by a numberof investigators to guide the ablation of atrial andventricular arrhythmias.40−42 Since early sites ofventricular activation, as displayed on the three-dimensional activation maps, convey only the lo-cation of the exit site of the arrhythmia, combinedpacing paradigms within the context of this surro-gate anatomy are required to further elucidate thelocations of specific components of the arrhythmiacircuit. Mapping of nonsustained or unstable VTsis difficult given the time required to generate thetotal activation map in a point by point approach.



Figure 6. Schematics of a figure eight circuit with ac-companying surface tracings representing activationduring ventricular tachycardia (VT), single stimulus re-setting, and during entrainment from a protected slowzone of conduction within infarcted myocardium. PanelA shows activation through a protected slow zone (site15), through to the VT exit (site 33), which proceedsaround the infarct scar (22, 25, 30) back to the protectedslow zone. A bystander loop is also shown. The reset re-sponse shows a postpacing interval equal to the VT cy-cle length (391 ms) with matching EG-QRS and S-QRSintervals of 248 ms. Panel B shows entrainment with-out change in QRS morphology followed by an equalpostpacing interval and VT cycle length and S-QRS andEG-QRS intervals. (With permission from reference 38.)

Noncontact mapping has also been developedfor the characterization of ventricular arrhythmias.This approach records voltage signals originatingfrom the endocardial surface, as detected on the64-electrode elements of a central recording bal-loon. Using a boundary-element approach and theinverse solution to La Place’s equations, those volt-ages are displayed in terms of 3,300 interpolatedvirtual electrograms registered on the chamber sur-face geometry, created by point to point samplingat multiple sites within the chamber.43 A color dis-play is again used to identify regions of earliestdepolarization, traceable to an arrhythmic origin,and subsequent propagation. Figure 9 shows ven-tricular activation during the systolic and diastoliccomponents of the VT cycle.43 Since the electri-cal activity of a single chamber is simultaneously

recorded, this approach is well suited to the map-ping of nonsustained arrhythmias, but its utilitycan be limited by signal distortions occurring atvirtual endocardium distances > 4 cm from themultiple electrode array. Either mapping approachis more difficult in patients with rapid tachycar-dias. Nevertheless, both provide a means of effec-tive mapping even during unstable arrhythmias.In the case of noncontact mapping, voltages re-flecting activation of the entire endocardial surfacecan be obtained from 1 or 2 beats of the arrhyth-mia. Alternatively, the electroanatomic approachprovides the means of mapping an arrhythmia bythe recording of other parametric values. Variousinvestigators have demonstrated the use of volt-age mapping during sinus rhythm to guide abla-tion of unstable VTs.44−46 Linear ablation, at theborder zone or interface between apparently ab-normal and normal myocardium, can enable theelimination of up to 75% of such unstable VTs.Figure 10 shows the linear ablation of periinfarctborder zones as guided by voltage mapping.44

Alternative Three-Dimensional Mapping

In a parallel approach, intracardiac ultra-sound was used to identify the substrate under-lying VT in patients in whom electroanatomicor noncontact mapping provided incomplete in-formation.47 The infarct regions were identi-fied on phased-array, two-dimensional intracar-diac ultrasound images. Circuit-traversing abla-tive lines were made between such scar and other

Figure 7. Schematic and tracings of the response to asingle stimulus within the bystander pathway withouttrue resetting of the VT circuit. Note that the postpac-ing interval of 431 ms is substantially longer than theVT cycle length of 391 seconds. (With permission fromreference 38.) VT = ventricular tachycardia.


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Figure 8. Right lateral view of an electroanatomic map of the left ventricle in a pig. The earliestsite of activation (red) was located at the mid-septum, with subsequent spread to the rest of theendocardium in lateral and posterobasal directions. Latest activation is in blue and purple. (Withpermission from reference 39.)

naturally occurring anatomic obstacles to elimi-nate VT in 75% of cases. As is the case with abla-tion guided by electroanatomic voltage mapping,ablation along the rim of aneurisms or other infarctscar was also effective in treating unstable VTs.

Other mapping utilities have also beendeveloped to reflect myocardial activation dur-ing ventricular arrhythmias within the context ofspecific underlying anatomy. In each of these, anassessment of the location of the mapping tipin three space, has been based on the propaga-tion of different energy waveforms through theheart. In one ultrasound-based system, the map-ping catheter, and multiple reference cathetersare fitted with small ultrasound transducers forsending and receiving ultrasound wavelengths ofenergy. Using these, the time required for the emis-sion, propagation, and reception of the ultrasoundsignal from a specific site to another is deter-

mined.48 Extrapolating from the expected veloc-ity of propagation of this waveform through theheart, the distance between the sending and re-ceiving transducers is established (Fig. 11). Usinga multiple catheter/transducer triangulation ap-proach, the specific location and orientation of acatheter tip in three space is determined, and theactivation time at that site displayed. This has beenshown to be particularly useful in the mappingof macroreentrant circuits by chronicling of mul-tisite activation times throughout the chamber ofinterest.

Alternatively, the specific location of a map-ping catheter tip in space can be determined us-ing high frequency current (1 mA, ∼ 30 kHz)introduced from three sets of orthogonal surfaceelectrode patches. This approach determines thedistance of specific catheter electrodes from theskin patches based on the voltage drop occurring



Figure 9. Sequential frames showing unipolar isopotential noncontact maps. Point of activation occurs aswhite/colored areas on a purple background. Frame 1 shows the VT exit, with frames 2 and 3 showing progressivesystolic activation. Activation via a return diastolic pathway is shown in frames 5–8. With permission from reference43.)

over that interval.49 The three orthogonal distancesare then used to create a three-dimensional geome-try. This methodology has been more widely usedfor guiding the ablation of SVTs and atrial flutter,although it can be effective in chronicling ablationsites during VT ablation. The generation of three-dimensional activation maps with this approachhas not yet been feasible.

Epicardial Mapping of Reentrant VT

A variety of investigators have demonstratedthat some critical components of reentrant VTcircuits are confined to the epicardial or subepi-cardial layers of the heart. Kaltenbrunner et al.50

found that at least 15% of patients with mappableVT have a critical epicardial component to theirreentrant circuits, explaining the poor operativeoutcome in patients undergoing exclusive surgicalsubendocardial resection alone. Svenson et al.51

reported that epicardial ablation was required inmany patients with ventricular arrhythmias under-going open laser ablation. Building on those obser-vations, Sosa et al.52 developed an intrapericardialapproach and demonstrated the utility of epicar-dial mapping and ablation for the elimination ofVT in patients with Chagas’ disease. Similar find-ings reported by others have provided support for

intrapericardial mapping as an alternative venuefor VT ablation.53,54 In these studies, 70–80% ofVTs, which could not be eliminated by an endocar-dial approach, were successfully ablated from theepicardial surface as approached using an epiduralneedle introduced into the pericardial space usinga subxyphoid approach.

Elucidation of Microreentrant ArrhythmiasEvolution of Mapping of Ventricular Fibrillation

By its very nature, ventricular fibrillation(VF) defied mapping with originally availablepoint to point techniques. Nevertheless, simpleobservations of the surface of the heart duringVF suggested the presence of multiple waveletsof activation and reactivation.55,56 Over the past30 years, 16-, 24-, and 48-channel recording de-vices have given way to 512+ channel, computer-based mapping capabilities for the simultaneousrecording of more closely spaced unipolar andbipolar electrograms. This evolution has resultedin more precise temporal and spatial resolutionof VF to disclose the mechanisms of emergenceand generalization of VF, the role of specific car-diac structures in that process, the physiologyof defibrillation with monophasic and biphasicwave forms, the graded responses occurring with


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Figure 10. Electroanatomic activation map of a patient with an inferoapical infarction and multi-ple VTs. Voltage maps of the septal, inferior, and anterolateral surfaces are as shown. Red reflectsmembrane potentials <0.5 MV in amplitude with purple regions showing potentials > 1.5 MV.The infarct border zone is shown as a spectrum of colors between these two boundaries. Threelinear ablative lesions were created along the septal, inferior, and anterolateral portions of theheart, as shown in the mesh diagram. This resulted in elimination of the multiple VT morphology.(With permission from reference 44.) VT = ventricular tachycardia.

ineffective defibrillating shocks, and other electro-physiological phenomena.

Initial electrode studies of VF used only oneto three epicardial, surface or intracellular record-ing sites.57,58 These studies demonstrated ultrara-pid activation rates in excess of 500 cycles/min inthe region of the electrodes, but could not discrimi-nate between focal firing or reentrant activation, asthe mechanism underlying VF. Studies by Moe etal.59 used three electrograms to assess the origin ofVF produced by an electrical shock, and suggestedthat fibrillation originated from a focal site produc-ing the first 2–4 cycles of tachycardia at the on-set of fibrillation. This supported the observationby Wiggers55 made from camera images of musclecontraction on the epicardial surface. In later ob-servations, Wiggers56 reported that such local ac-tivity occurring in the “first VF or tachysystolicstage” was more likely due to reentrant waveletsfollowing after the first several beats of this ar-rhythmia.

Later Ideker et al.,60 using 27 epicardial elec-trodes positioned over the right and left ventri-cles, mapped the initial 3 seconds of the transitionfrom sinus rhythm or VT to VF. In a model ofischemic reperfusion, these investigators foundthat activation in early VF arose near theborder of an ischemic reperfused region, butsubsequently conducted across ischemic or non-ischemic portions of the ventricles in more orga-nized wavefronts (Fig. 12). With arrhythmia pro-gression, the cycle length of activation wavefrontsdecreased, while the conduction times increasedwith each successive cycle. Despite these discrete,organized activation wavefronts seen on epicar-dial mapping, the surface ECG appeared disor-ganized. Because of the limited number of elec-trodes, the specific site of origin of VF withinthe ventricular wall could not be established norcould these investigators completely differenti-ate between a focal origin or a microreentrantprocess.



Figure 11. Ultrasound ranging map of isthmus depen-dent atrial flutter.

Figure 12. Isochronal maps of epicardial activation for the first six even numbered cycles re-flecting ventricular activation before and after the transition to ventricular fibrillation. Note theappearance of organized repeating cycles with increasing conduction delay. (With permissionfrom reference 60.)

Other studies, using intramural electrodessuggested a reentrant mechanism occurring at theonset of VF. Chen et al.61 examined this issue us-ing 40 plunge electrodes with multiple recordingsites at 5-mm interplunge distances to make a to-tal of 120 simultaneous endocardial, intramyocar-dial, and epicardial recordings. These investiga-tors identified complete reentrant circuits (in somecases a figure eight) around arcs of block producedby premature ventricular contraction (PVC) pro-longed refractoriness occurring at the onset of VFor repetitive responses. This reentry was causedby premature stimulus induced prolongation ofrefractoriness near that pacing site and a propa-gated response in a more distant region. Nonuni-form dispersion of refractoriness was not found tobe a crucial factor in the overall initiation of VF.To underscore the complexity of the process, stillother studies have documented a focal source ofVF during ventricular stimulation in the presenceof aconitine or strophanthidine.62

The understanding of ventricular dysrhyth-mias again progressed with the development of


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Figure 13. Panel A shows clockwise-rotating spiral waves in canine epicardial muscle. Maximal depolarization isshown in white with resting potentials are in black. Numbers below each panel reflect time given in milliseconds.Panel B shows time course of local activation in the upper left corner of the tissue over the last 10 cycles. Panel Cshows spiral waves obtained in a computer simulation using the Fitz-Gugh-Nagumo model. (With permission fromreference 66.)

charge-coupled or photo diode-based optical map-ping.63−65 The resulting enhanced temporal andspatial resolution has extended the understandingof the core pathophysiology of VT and VF. Davi-denko et al.66 used potentiometric dye in combi-nation with a charged-couple device to opticallyimage repetitive activity occurring in thin slicesof sheep and dog epicardial muscle. They demon-strated that repetitive activation occurred becauseof spiral waves of excitation traveling through ven-tricular myocardium (Fig. 13). In other cases, thecore of the spiral wave drifted from its site of originto other regions of tissue, providing a more disor-ganized arrhythmia appearance.

This phenomena was examined to a greater ex-tent in computer simulations and additional sheepventricular epicardial muscle by members of thesame laboratory.67 Using these technologies, theshape of spiral waves was found to be depen-dent on fiber orientation with a period of rotationthat was uniformly longer than tissue refractori-ness. In both simulations and actual preparations,spirals anchoring around discontinuities withinthe simulated matrix, or around small arteries orother heterogeneities in actual tissue, gave rise toa “monomorphic” VT. Without anchoring, spiralsdrifted, giving a more disorganized appearance of

torsades de pointes or polymorphic tachycardia. Insome cases, a single, rapidly drifting rotor gave riseto the ECG pattern seen in VF.68 Others have pro-posed the requirement of multiple rotors to morecompletely account for the ECG patterns of fibril-lation.69

With further extensions of technology, addi-tional dissection of VF has been possible. Wu etal.,70 using a 100 x 100 optical array to examineactivation over a 40 x 40 mm3 area of tissue, haverecently demonstrated the occurrence of two typesof VF. A fast VF, with a dominant frequency of19.1 ± 1.8 Hz, has been tracked and found to rarelyconvert to more stable VT. Fast VF was also asso-ciated with steep action potential duration resti-tution and flatter conduction velocity restitution,producing wandering wavelets of ventricular acti-vation. Optical maps showed wandering waveletsin fast VF, but also showed more marked spatial-temporal density in slower VF. The latter VF wasassociated with a flatter action potential restitutioncurve and steeper conduction velocity restitutionwith more spatial-temporal density. Extensions ofthese techniques to models of the long QT syn-drome also demonstrate the tissue level correlateof early after depolarizations (EADs) in the form ofmultiple, migratory spiral waves.



Figure 14. Color maps showing functional reentry in a right atrial preparation. Panel A showsa basic interval beat with superimposed atrial architecture. Panel B shows a premature beat,which blocks in a counterclockwise direction, with subsequent activation in a clockwise direction.Panels C and D show the first and second cycles of reentrant tachycardia around a central coreof functional block. (With permission from reference 83.)

Equally important, the most recent opticalmapping studies have demonstrated that activa-tion in VF can occur as a localized, quasi-focal,dominant frequency.71 As seen in atrial fibrillation(AF), this suggests that VF can occur because ofspecific focal or microreentrant triggers, and canbe maintained by repetitively activating dominantfrequencies, in addition to multiple wavelet reen-try in a critical mass of ventricular myocardium.That these optical mapping techniques cannot beapplied to in situ human myocardium provides anobstacle to identifying similar mechanisms in hu-man VF.

Nevertheless, more conventional clinicalmapping has recently provided support for theimportance of such triggers in producing VF. Hais-saguerre et al.72,73 reported 45 patients with VF

occurring following a relatively distinct monomor-phic PVCs in patients with underlying disease likesarcoid related cardiomyopathies. This investiga-tion demonstrated that > 50% of carefully selectedtachycardias could be eliminated simply by map-ping the source of the PVC triggering VF and ab-lating in that location.

In addition to providing information detailingthe activation of cardiac tissue during VF, opticalmapping has the additional advantage of capturingthe recovery process occurring over the course ofa reentrant cycle, and demonstrating its temporaland spatial relationship to activation. This is a ma-jor step beyond the elucidation of repolarizationbased on the QT interval, the downslope of the Twave, or the monophasic action potential record-ing.74 While each of these provide a useful marker


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Figure 15. The onset of focal atrial fibrillation from a right inferior pulmonary vein (above) and a left superiorpulmonary vein (below). Initial activation appears organized and repetitive at cycle of 170 and 160 ms cycle lengths,respectively. (With permission from reference 91.)

Figure 16. Contribution of anatomy to the ablative process. Schematic diagram shows multiple forms of atrial tachy-cardia along with the estimated contribution of physiology versus anatomy to the ablative process. (With permissionfrom reference 100.)



Figure 17. Postablation electroanatomic map showing a wide area circumferential ablation in apatient with persistent atrial fibrillation. Shown are the left superior (LS), left inferior (LI), rightsuperior (RS), and right inferior (RI) pulmonary veins (PVs). Ablative rings circumscribe the leftand right PV sets. The carinal lines between the veins, a line connecting the right to the left PVrings, and an ablative line (white arrow) from the LIPV to the mitral valve annulus are also shown.(With permission from Packer DL. Catheter ablation for atrial fibrillation: A promising alternativeto drug therapy. Mayo Clinic Cardiovascular Update 2004; 2:5–7.)

for prolonged repolarization with antiarrhythmicdrugs or genetic abnormalities, like long QT syn-drome, the accompanying resolution of repolariza-tion was inadequate to allow full appreciation ofthe underlying physiology to arrhythmogenesis.

Evolution of Mapping of AF and Atrial Flutter

In no arrhythmia is the progress in mappingand its contribution to the characterization of theunderlying physiology more evident than occur-ring with AF. In 1920, Sir Thomas Lewis proposedthat atrial arrhythmias could occur due to reen-try around multiple anatomic obstacles in general,and around the superior and inferior vena cavain specific.75 Wiener and Rosenblueth76 proposedthat an obstacle the size of the inferior vena cavamight be large enough to facilitate atrial flutter,while a smaller obstacle, like the superior venacava, could lend itself more readily to the creationof AF. Scherf77 and subsequently Kimura et al.78

alternatively demonstrated that AF could be gen-erated from a single firing focus, as created withaconitine applied to the RA appendage. In thelate 1950s and early 1960s Moe et al.79−81 com-pared vagally mediated AF with that producedby aconitine. Based on studies as detailed as pos-sible with available recording technologies, Moeprovide support for a multiple wavelet hypothe-sis of AF.80 This was founded on eight critical ob-servations. (1) A grossly irregular wavefront canbecome fractionated as it divides around eyeletsor strands of refractory tissue. (2) Each resultingdaughter wavelet may be considered an indepen-dent offspring. (3) Wavelets may accelerate or de-celerate as they encounter tissue in a more or lessadvanced state of recovery. (4) Wavelets may beextinguished as they encounter refractory tissue,only to divide again or combine with a neigh-bor. (5) Wavelets may be expected to fluctuate insize and change direction. (6) Its course would be


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Figure 18. Multirow spiral CT showing a posterior coronal image of the pulmonary veins in apatient with atrial fibrillation. The right superior (RS) and right inferior (RI) pulmonary veinsenter posteriorly into the right atrium. The left superior (LS) and the left inferior (LI) pulmonaryveins combine to form an antrum (black arrows) before entering the left atrium. (With permissionfrom reference 101.) CT = computed tomography.

determined by the excitability or refractoriness ofsurrounding tissue. (7) Fully developed fibrillationwould then be a state in which many randomlywandering wavelets coexist. (8) The likelihood ofpersistence of the process should depend on thenumber of wavelets present.

Allessie et al.82−84 made landmark observa-tions in a study performed using intracellular andextracellular electrodes positioned in isolated rab-bit myocardium. These investigators found that inthe absence of an anatomic central obstacle, circusmovement reentry could proceed around a func-tionally refractory core produced by centripetal ac-tivation towards the center of the reentry. Figure 14shows such reentry following an atrial prematurecomplex (APC) that blocks in one direction butpropagates in the other. These observations leadto the “leading circle” hypothesis of circus move-ment in the presence of AF and provided ampleevidence that any atrial tissue could participate inmicroreentry.

Allessie subsequently demonstrated the im-portance of the electrophysiological properties ofthe involved tissue, including conduction veloc-ity and refractoriness, in the initiation and mainte-nance of AF.85 Taken together, these two propertiesspecified the required length of the reentrant path-way needed to permit reentry uninterrupted by tis-sue refractoriness. The presence of five to sevenmultiple reentrant wavelets were also found to beresponsible for continued AF.

The development of multielectrode spoonand plaque techniques subsequently disclosed thehighly complex and variable nature of AF inhumans.86 Several studies showed the relativelystraightforward propagation of an activation wave-front in some AF patients with other patientsdemonstrating multiple, simultaneous waveletswith splitting and recombining wavefronts ormany divergent wavefronts undergoing fractiona-tion and reactivation as suggested 30 years earlierby Moe.



Figure 19. Helical row, CT imaging of the distal and proximal venous system of the heart. PanelA shows an oblique view of the heart displaying the greater cardiac vein, and its extension intothe anterior, interventricular vein (black arrows). Panel B shows a three-dimensional, segmentedrendering of the heart from a posterior view. Shown are the coronary sinus (white arrow), themiddle cardiac vein, a posterior branch of the coronary sinus (white arrow), and the greatercardiac vein extending laterally around the oblique margin of the heart. AO = aortic root; CT =computed tomography; LA = left atrium; LM = left main coronary artery; LV = left ventricle; RA= right atrium; RAA = right atrial appendage; RS = right superior pulmonary vein.


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With the advent of optical and ultra highdensity mapping techniques, additional featuresof AF have been more readily disclosed. Localhigh density classical electrode or optical map-ping in AF showed the presence of dominantfrequencies of repetitive activation in the poste-rior left atrium (LA) near the pulmonary veins(PVs), found to drive AF.87−89 Optical mappingprovided substantially better spatial and tempo-ral resolution of activation, extending the con-cept of AF from microreentry to fixed or migrating“mother” rotors with “daughter” wavelets occur-ring through activation and fractionation at breakpoints.90

In an additional revolutionary step to under-standing AF, and in somewhat of a paradoxicalshift back to more straightforward multipolar map-ping, Haissaguerre et al.91 demonstrated the re-sponsibility of triggering foci originating in the PVsfor the initiation of AF, as shown in an originaltracing in Figure 15. This has paved the way fornonpharmacologic therapy in the form of ablation,which has since been highly successful in elim-inating AF through isolation of these triggeringfoci.

The train of knowledge elucidating the mecha-nisms of atrial flutter has proceeded down a morestraightforward track. Although this arrhythmia,as seen in animal and interoperative mappingstudies, has been shown to precede via a variety ofdifferent reentrant pathways, studies from a num-ber of investigators more clearly established theimportance of macroreentry around fixed or func-tional obstacles,92 including the tricuspid valve asthe site of reentry for isthmus dependent and atyp-ical flutters.93 In the former case, propagation viathe cavotricuspid isthmus has been critical as acentral corridor of activation around the tricuspidvalve. Mapping studies using multipolar cathetersperformed by others added another dimension: thepresence of a figure eight reentry as a more accu-rate reflection of the circuit of classical atrial flut-ter.94,95 In addition to that portion of the circuittraveling around the tricuspid valve, the secondactivation wavefront proceeds superiorly along theinteratrial septum and posterior wall of the RA,around a line of fixed and functional block at thecrista terminalis or within the sinus venosus re-gion, with reentry from a superior to the inferiordirection along the lateral aspect of the cavotricus-pid isthmus.

Anatomic Mapping of Cardiac ArrhythmiasThe Role of Anatomy in Cardiac Arrhythmias

For the first half century of clinical car-diac electrophysiology, the fundamentalunderstanding of reentrant circuits or point

source tachycardias was based almost exclusivelyon the electrophysiology of the arrhythmia. Map-ping was typically used to identify the earliestsite of atrial or ventricular activation or evidenceof a slow zone of conduction, critical to a scardependent arrhythmia like VT or atrial flutter.With the experience provided by ablation camea realization that most arrhythmias were at leastpartially anatomically based and that ablativetreatment in some arrhythmias could be totallyanatomically guided. For example, accessorypathways bridge the mitral or tricuspid annulus,or may be connected to the coronary sinus venoussystem. The catheter used in the ablation ofleft-sided accessory pathways must be positionedappropriately underneath the mitral valve leafletsin the retrograde aortic approach, along the mitralannulus in a transseptal approach, or within thecoronary sinus. Obviously, the surgical divisionor ablation of these connections also requiresthe determination of the sites of earliest atrial orventricular activation as previously described.With the elucidation of the pathophysiologyof typical atrial flutter, also came a realizationthat an anatomic structure, the cavotricuspidisthmus, was critically important to the oc-currence of this arrhythmia, and warranted achange in the nomenclature of this arrhythmiato “isthmus-dependent,” counter-clockwise atrialflutter. A number of investigators have shown thatsuccessful ablation can be completely anatomi-cally guided by the fluoroscopic position of thisanatomic landmark, even in the absence of anymapping.

In point of fact, most of the arrhythmias in-vestigated by clinical electrophysiologists have acritically important anatomic component. The in-terventional approach to left bundle, inferior-axisidiopathic VT in the absence of heart disease, isdependent on an understanding of right ventricu-lar outflow tract anatomy. The occurrence of idio-pathic right bundle, left-axis VT is localized to theposterior septum, two thirds of the distance fromthe base to the left ventricular apex. Using intrac-ardiac ultrasound, this arrhythmia has also beenlocalized by some investigators to the false tendonor trabecula in this region.96 Certain VTs have alsobeen mapped to the coronary cusps of the aorticand pulmonic valves.97,98

An extreme example of the importance ofanatomy is the mapping of most repetitively fir-ing triggers, critical in the arrhythmogenesis ofparoxysmal AF, to the PVs. Although 5–6 yearsago, ablation was directed at a specific site of ear-liest activation within the vein, this has evolvedfrom lasso-guided, segmental ablation directednear the orifice of the vein to eliminate PVpotentials,99 into a largely anatomically based



Figure 20. Intracardiac, phased-array echocardiographic image of the left pulmonary veins. Shown are the left supe-rior (LS), and the left inferior (LI) pulmonary veins. This image is obtained with the ICE transducer on the right sideof the interatrial septum. (With permission from reference 101.)

procedure, guided by electroanatomic mapping.One of the strengths of the lasso-type catheteris the demarcation of the PV. Even here, fur-ther anatomic imaging with intracardiac ultra-sound has demonstrated the potential catheterdrift into the PV, requiring continued surveil-lance to avoid inadvertent ablation too far intothe vein. The more recently adopted wide areacircumferential ablative approach, in which ab-lation energy is directed at atrial tissue aroundtwo or more PVs (Fig. 16),100 has underscoredthe specific utility of electroanatomic, surrogateanatomy for guiding the mapping of the three-dimensional origins of the arrhythmia and the in-terruption of potential sites of dominant frequen-cies, circuits, rotors, or parasympathetic ganglia inthe posterior LA. The relative contribution fromanatomy versus physiology in understanding thesearrhythmias varies depending on the arrhyth-mia. A proposed contribution of each is seen inFigure 17.

Computed Tomography and Magnetic ResonanceImaging of Arrhythmogenic Substrate

Each of these considerations now provides theincentive for an entirely new generation of cardiacimage-based mapping using traditional imagingtechniques. Computed tomographic (CT) and mag-netic resonance imaging (MRI) approaches havealready provided critical information establishingthe number, location, and size of PVs, as needed inplanning the ablation (Fig. 18) and selecting appro-priately sized ablation devices. Resulting imagesalso identify branching patterns of potentially ar-rhythmogenic PVs, disclose the presence of fusedsuperior and inferior veins into antral structures,and clarify the potentially confounding origins offar-field electrograms that masquerade as PV po-tentials. This has been recently reviewed in greaterdetail elsewhere.101

These imaging modalities are also useful inmapping the presence and location of cardiac


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Figure 21. Intracardiac ultrasound image of the left atrium as obtained from the right atrium. Shown (white pluses)is a left atrial occlusion device positioned into the left atrial appendage. When expanded, this device measured 2.2cm in diameter.

veins draining into the coronary sinus. Using avail-able software protocols, the entire venous systemcan be segmented out from surrounding structuresto provide clear-cut candidate pacing sites for car-diac resynchronization therapy. Figure 19 showsthe distal portion of the coronary venous system,as visualized by multirow helical CT imaging anda segmented three-dimensional view of the proxi-mal coronary sinus with several candidate veinsfor use in biventricular pacing. In the near fu-ture, image-based tissue characterization, whenmatched to the underlying venous anatomy, mayprovide ever better means of selecting more effec-tive LV pacing sites. As the spatial and temporalresolution of these modalities improve, three-dimensional imaging may also find use in clari-fying other targets for anatomic-based therapies.While the CT/MRI approach to three-dimensionalimaging provides exquisite images of the underly-ing structures relevant in arrhythmogenesis, it islimited by its off-line acquisition and inability toreflect all phases of the cardiac cycle during an ar-rhythmia. Nevertheless, it is highly likely that sub-sequent generations of CT or MRI scanners will be

sufficiently fast to permit real-time, or nearly real-time imaging for interventional guidance.

Intracardiac Ultrasound Imaging for Ablation

Additional inroads into anatomic mappingwere made with the use of transesophagealechocardiography. In early studies, Packer et al.102

demonstrated the utility of this approach for track-ing the position of an ablation catheter, and estab-lishing its relationship to the underlying anatomyof the mitral valve in patients with WPW syn-drome and left free-wall accessory pathways (APs).An unexpected finding was the extent of changein tissue appearance with the delivery of ra-diofrequency energy, including the visualizationof showers of microbubbles and abrupt tissue al-teration with the occurrence of an impedance rise.Others showed similar utility in transesophagealechocardiography (TEE) imaging during VT ab-lation. The prolonged esophageal intubation re-quired for this approach and the need for a secondoperator to acquire the echocardiographic imageslimited any widespread application in the electro-physiological laboratory.



Figure 22. Epicardial activation of the canine ventricle before and after quinidine administration as examined with anexternal fitted epicardial mapping sock. Here, quinidine results in progressive delay of ventricular activation from theright ventricular stimulation site (red) to the anterolateral left ventricular wall (deep blue). The images were obtainedwith registration of that epicardial activation map to a three-dimensional electron beam computed tomographicsegmented rendering of the heart. (With permission from Packer et al.).

Subsequent studies showed the greater suit-ability of intracardiac imaging systems to abla-tive interventions. These had the advantage ofreal-time imaging by the interventionalist withoutpatient discomfort or aspiration risk.103 Initially,single element, mechanical devices were validatedfor use in imaging RA structures, particularly thecavotricuspid isthmus and the crista terminalisrelevant to the occurrence of typical atrial flut-ter.104,105 This approach was limited by incompletetissue penetration and the requisite imaging in aplane cross sectional to the long axis of most cham-bers of the heart and ablation catheters.

Real-time interventional applications havebeen fostered by the development of miniaturized,phased-array technology that provides images ofleft heart structures from an RA venue.103 This

approach has since been used in AF ablation toidentify the number and position of PVs (Fig. 20),establish the presence of a left PV antrum, de-termine the branching patterns of the right PVsneeded for total vein isolation, guide the position-ing of interventional catheters, verify catheter tipto tissue contact, assess the degree of PV occlu-sion during balloon-based ablative interventions,visualize evolving lesions during energy delivery,and image microbubble formation during tissueheating. The latter is important, as microbubbleformation during ablation can indicate excessivetissue heating, which could lead to thrombus orchar formation, tissue disruption, or PV stenosis.Beyond mere imaging utility, several studies havenow shown the clinical benefit of ultrasound guid-ance in the successful treatment of AF.101,106,107


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Figure 23. Five-dimensional map of an atrial premature complex (APC) initiating atrial fibrilla-tion in a patient with a left superior pulmonary vein focus of tachycardia. Here, earliest activationproceeds from the left superior pulmonary vein (light blue wavefront) with subsequent spread intothe left atrium (purple). This noncontact map activation sequence is registered onto the renderedand segmented left atrial and pulmonary vein volumes obtained from matching spiral computedtomographic scan images. (With permission from reference 108.)

Other studies have shown the utility of ultra-sound in mapping the anatomic origin of SVTs.Given the consistent location of the sinus node atthe superior end of the crista terminalis immedi-ately below the superior vena cava/RA junction,intracardiac ultrasound has been useful in ablat-ing inappropriate sinus tachycardia or sinus nodereentrant arrhythmias. Recently, LA appendage oc-clusive devices have been implanted under ultra-sound guidance (Fig. 21). This approach has alsobecome the standard of imaging for guiding theplacement of closure devices for repair of atrialseptal defects.

Other parametric imaging modalities havealso been applied in the electrophysiologylaboratory. Phased angle imaging has been used tovisualize mechanical preexcitation of the ventri-cle for the localization of accessory connections.Alternative tissue Doppler imaging of ventricularmyocardium is also being developed as an indirectmeans of assessing ventricular activation. Whilethis is of potential interest for examining mid-myocardial activation, an even greater applicationmay be in establishing the presence and degree ofventricular dissynchrony, guiding the placementof left ventricular pacing leads, and determiningthe response to cardiac resynchronization therapyover long-term follow-up. Whether this approachwill serve in predicting which patients will best

respond to biventricular pacing is yet to be es-tablished. In some cases, the spatial and tempo-ral resolving power of these alternative imagingapproaches also remain limited by imaging framerates.

Combined Anatomic and Physiological ImagingOver the past 3 years substantial progress has

been made in the integration of anatomic andmultisite, computer-assisted mapping. This pro-cess requires multiple steps, beginning with the ac-quisition of cross-sectional or “axial” CTs or MRIsat sufficient resolution to delineate cardiac struc-tures < 1–2 mm in thickness. Images at 0.625-mmthickness can be reconstructed from images ob-tained at 1.25-mm intervals with currently avail-able multirow, helical scanners. Similar MRIs arelikewise obtainable, although at slightly less spa-tial resolution.

Rendering a “volume” or reconstructing anycardiac chamber in three dimensions from the ax-ial images is a straightforward process using anyone of a variety of software packages. The processof “extracting” that chamber or volume from itssurrounding structures, or “segmentation,” is notdifficult, providing there are sharp contrasts in theimage between the chamber or structure of interestand neighboring tissue. These segmented volumescan also be viewed from an external perspective or



from within the chamber using virtual endoscopicor cardioscopic displays.

While such segmented structures are highlyuseful in visualizing the cardiac structures andcharacteristics of the tissue forming that struc-ture, they do not convey the physiology of an ar-rhythmia. Integrating that physiology, as capturedby electroanatomic or noncontact mapping, withthe spatial information contained in the CTs andMRIs requires “registration” of activation or volt-age data to an appropriate location on a three-dimensional representation of a chamber. In theearly 1990s, a map demonstrating the impact ofquinidine on ventricular activation, as recorded byan epicardial sock, was registered onto an under-lying CT-acquired anatomic framework (Fig. 22).Shown in Figure 22 is an increase in the pro-portion of the LV with delayed activation (blueand dark blue) because of the use dependent con-duction slowing with this membrane active drug.Global LA activation during sinus rhythm and atthe onset of AF, as recorded in noncontact andelectroanatomic mapping, have likewise been reg-istered to rendered CT volumes and matched tospecific surfaces of the LA (Fig. 23).108 This con-cept will rapidly expand to include the registrationof activation maps, voltage maps, and information

from other technologies measuring physiologicalvariables. This is of critical importance in that itestablishes the relationship between anatomy andphysiology as required for the structure/activity-based understanding of arrhythmias and for en-abling image-guided intervention.

These approaches are limited by therequirement of off-line generation of the CTand MRI libraries. To overcome this time lim-itation, current efforts are now underway tofuse real-time ICE images with those gener-ated by CT/MRI scans,109 and provide a morereal-time interactive display. In the future, it isanticipated that these real-time ultrasound andoff-line CTs and MRIs will be fully fused anddisplayed with registered activation maps. Ananticipated future approach to the ablation ofcardiac arrhythmias should include guidanceby these virtual images to fully immerse theoperator in the field of intervention. While muchwork in this arena is still required, the interven-tional electrophysiology lab of the future willundoubtedly be enabled by this kind of anatomicimaging and mapping. Here again, progress intechnology will undoubtedly drive an even greaterunderstanding of arrhythmias than previouslypossible.

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Evolution of mapping and anatomic imaging of cardiac arrhythmias

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