Quantitative Comparison of Spontaneous and Paced 12-Lead Electrocardiogram During Right Ventricular Outflow Tract Ventricular Tachycardia

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1 Joural of the America College of Cardiology Vol. 41, No. 11, by the America College of Cardiology Foudatio ISSN /03/$30.00 Published by Elsevier Ic. doi: /s (03) Quatitative Compariso of Spotaeous ad Paced 12-Lead Electrocardiogram Durig Right Vetricular Outflow Tract Vetricular Tachycardia Edward P. Gerstefeld, MD, Sajay Dixit, MD, David J. Callas, MD, Yadavedra Rajawat, MD, Robert Rho, MD, Fracis E. Marchliski, MD Philadelphia, Pesylvaia OBJECTIVES BACKGROUND METHODS RESULTS CONCLUSIONS The purpose of this study was to objectively quatify the similarity of 12-lead electrocardiogram (ECG) waveforms usig two quatitative metrics, the correlatio coefficiet (CORR) ad the mea absolute deviatio (MAD). Compariso of the 12-lead ECG morphology betwee vetricular tachycardia (VT) ad a pace-map is frequetly performed; however, there are o objective criteria for quatifyig the similarity betwee two waveform morphologies. Durig ablatio of right vetricular outflow tract (RVOT) VT, 12-lead ECG pace-maps were acquired from three superior septal sites, three superior free wall sites, ad before each ablatio attempt i 15 patiets. The 12-lead ECG waveforms of the cliical tachycardia ad pace-maps were compared usig both MAD ad CORR at each site. The MAD scores were lower (i.e., more closely matched) for septal compared with free wall sites ( % vs %; p 0.001). Successful ablatio sites had a sigificatly lower MAD score compared with usuccessful sites ( % vs %; p 0.01), whereas there was oly a tred toward a higher CORR for successful ablatio sites ( % vs %; p 0.07). A MAD score 12% was 93% sesitive ad 75% specific for idetifyig a successful ablatio site. There was a iverse correlatio betwee MAD score ad distace from the site of VT origi (r 0.63, p 0.001). A MAD score 12% betwee RVOT VT ad a pace-map at ay site suggests sufficiet dissimilarity to dissuade ablatio at that site. The MAD score ca be used to stadardize 12-lead ECG waveform morphology comparisos amog differet laboratories, ad may be useful for guidig ablatio of VT. (J Am Coll Cardiol 2003;41: ) 2003 by the America College of Cardiology Foudatio Pace-mappig is a useful tool for catheter ablatio of atrial ad vetricular tachycardias (VT), particularly tachycardias of focal origi. Whe local capture from a paced stimulus results i a 12-lead electrocardiogram (ECG) waveform idetical to that durig tachycardia, the catheter is assumed to be ear the origi of the tachycardia. Although there are some limitatios to this techique (spatial resolutio, stimulus stregth) (1,2), may studies have demostrated efficacy usig pace-mappig to choose ablatio target sites (3 7). I additio, pacig durig re-etrat tachycardias is also useful to idetify critical isthmus sites (8). Although compariso of the 12-lead ECG morphology betwee a pace-map ad cliical tachycardia is frequetly performed, there are few objective criteria for quatifyig the similarity betwee two 12-lead ECG waveform morphologies. Such comparisos are frequetly completely subjective or semiquatitative, i.e., a 10/12 lead match. Discrepacies i ablatio results may result i part from subjective differeces i the opiio of a pace-map match to the cliical tachycardia. Furthermore, criteria for comparig the similarity i 12-lead ECG waveforms from oe From the Divisio of Cardiology, Departmet of Iteral Medicie, Uiversity of Pesylvaia Health System, Philadelphia, Pesylvaia. Dr. Gerstefeld is supported by a Scietist Developmet Grat from the America Heart Associatio. Mauscript received October 22, 2002; revised mauscript received Jauary 6, 2003, accepted February 20, laboratory to aother or for describig such comparisos i the literature are lackig. We used two waveform compariso metrics, the correlatio coefficiet (CORR) ad the mea absolute deviatio (MAD) (9), to objectively quatify the similarity of 12-lead ECG waveforms durig VT ad pace-mappig. Because right vetricular outflow tract (RVOT) VT ablatio is guided chiefly by pace-mappig i our laboratory ad others, we used RVOT VT as a model for testig these quatitative compariso measures. METHODS Cosecutive patiets udergoig radiofrequecy (RF) catheter ablatio of RVOT VT at the Uiversity of Pesylvaia Hospital ad Presbyteria Medical Ceter were icluded i the study. All patiets siged iformed coset forms before the procedure. A quadripolar catheter was placed at the right vetricular (RV) apex for arrhythmia iductio, ad a Navistar catheter (Biosese Webster Ic., Diamod Bar, Califoria) was used for mappig ad ablatio. A electroaatomic map of the RVOT was acquired i sius rhythm. Pacig at twice diastolic threshold, 2 ms pulse width, ad 400 ms cycle legth was performed from three superior septal RVOT sites (1 posterior, 2 mid, 3 aterior) (4), three opposite superior free wall RVOT sites (1 posterior, 2 mid, 3 aterior), ad the

2 JACC Vol. 41, No. 11, 2003 Jue 4, 2003: Gerstefeld et al. Quatitative ECG Compariso of RVOT VT 2047 Abbreviatios ad Acroyms CORR correlatio coefficiet ECG electrocardiogram MAD mea absolute deviatio PVCs premature vetricular complexes RF radiofrequecy RV right vetricular RVOT right vetricular outflow tract VT vetricular tachycardia RV apex (Fig. 1). Arrhythmia was iduced with burst atrial or vetricular pacig. If o arrhythmia occurred, isoprotereol up to 10 g/mi was ifused ad pacig was repeated. If o sustaied tachycardia was iduced, mappig ad ablatio was guided by repetitive moomorphic sigle premature vetricular beats (10). I our laboratory, mappig ad ablatio of RVOT VT is guided maily by pacemappig, fidig the best 12-lead pace-map match to the cliical tachycardia, with cofirmatio of early activatio before ablatio. Pacig at twice threshold output, 2 ms pulse width, at the tachycardia cycle legth is routiely performed i the area of the suspected tachycardia origi ad before each ablatio attempt. Whe oly isolated premature vetricular complexes (PVCs) were idetified, pacig was performed at 400 ms cycle legth. Whe a 12-lead pacemap match was idetified, RF lesios were delivered for 60 s each, ad temperature was limited to 55 cetrigrade with a maximum power of 50 W. A usuccessful ablatio attempt is defied as the delivery of a RF lesio for 30sata suspected site of tachycardia origi, after which a tachycardia of the same morphology was still iduced. A successful ablatio site is defied as the site of RF applicatio after which o tachycardia of the same morphology could be iduced with burst pacig ad the same amout of isoprotereol before the procedure. All surface ECG sigals were stored o the Cardiolab electrophysiologic recordig system (GE Medical Systems, Housto, Texas), with a samplig frequecy of 1,000 Hz/chael, frequecy bad of 0.05 to 100 Hz, ad filtered with a 60-Hz otch filter. Sigals were digitally stored, extracted to biary data files, ad aalyzed off-lie o a persoal computer after the procedure. Sigals were viewed ad aotated usig freely available software (11), ad all quatitative waveform aalysis was performed usig custom writte software i the C programmig laguage. Sigal processig. For waveform compariso, both the MAD ad the stadard CORR were used. Both are quatitative methods of waveform compariso; however, the MAD teds to be more sesitive to differeces i waveform amplitude. The ormalized MAD was calculated by removig the mea from each waveform ad the dividig the absolute value of the differece betwee the two waveforms by the absolute value of the sum of the area uder the curve of the two waveforms. X i X Y i Y MAD [1] X i X Y i Y where X ad Y are each vectors of legth cotaiig the two waveforms to be compared. This is a computatioally simple formula that is aalogous to what a electrophysiologist performs ituitively i the electrophysiology laboratory, metally superimposig two 12-lead waveforms to fid the combiatio with the smallest differece betwee them. The MAD score quatifies waveform similarity ad rages from 0%, for two idetical waveforms to 100% for completely differet waveforms (Fig. 2). Figure 1. Electroaatomic map of the right vetricular outflow tract as viewed i the coroal projectio. Superior septal (1 posterior, 2 mid, 3 aterior) ad opposig free wall pace-map sites are show by the light gree tags, ad the successful ablatio site is show by the red tag. Also oted is the His budle area (His) ad tricuspid valve (TV). The right vetricular apical pacig site was located fluoroscopically ad ot tagged i this map.

3 2048 Gerstefeld et al. JACC Vol. 41, No. 11, 2003 Quatitative ECG Compariso of RVOT VT Jue 4, 2003: Figure 2. The ormalized mea absolute deviatio (MAD) takes the sum of the differece betwee two mea subtracted waveforms ad divides by the sum of the area uder the curve of the two waveforms. The correlatio coefficiet ( ) is calculated i the stadard fashio (see text for formulas). For two completely opposite waveforms (top right pael), the MAD score therefore 1 ad the 1. For two idetical waveforms (middle right pael) the MAD score 0 ad 1. The MAD score teds to be more sesitive to this amplitude differece betwee waveforms of similar morphology tha the (bottom right pael). Two waveforms of similar morphology with oe cotaiig oe-third the area of the other have a of 1 but a MAD of oly 0.5. The CORR was calculated i the usual fashio: X i X Y i Y X i X 2 Y i Y 2 where X ad Y are vectors of legth represetig the two waveforms to be compared. The CORR typically varies from 1 for completely opposite waveform to 1 for idetical waveforms (Fig. 2). Typically, these waveform compariso measures are used to compare oly two idividual waveforms. To compare multiple waveforms, such as those i a 12-lead ECG, these formulas eed to be exteded. This was accomplished for the MAD score by summig the umerator ad deomiator of Equatio 1 for all 12 waveforms i the stadard ECG. 12-lead MAD 12 Lead 1 12 Lead 1 Y X i X Y i Y X i X Y i [2] [3] I the same maer, the CORR was calculated for the 12-lead ECG by summig the umerator ad deomiator of Equatio 2 for all 12 ECG waveforms. I this maer, a sigle overall umber ca be calculated for the compariso of two 12-lead ECG waveforms usig either MAD or CORR. Comparisos for each lead ca also be easily performed if oe eeds further iformatio about idividual lead comparisos. Pace-maps for each of the six aatomic RVOT pacig sites, usuccessful ablatio attempts, ad successful ablatio attempts were examied. After examiig all 12 leads, the user chose a sigle 12-lead ECG beat for each paced site. The VT beat was chose by choosig ay two poits before ad after the desired VT complex without the eed to choose the exact oset or offset of the waveform. Sustaied VT was used if available, otherwise repetitive moomorphic premature vetricular beats were used for compariso. To avoid operator bias, whe there was variatio i morphology from oe beat to the ext for either pace-maps or VT, the secod beat of uiform morphology was chose for compariso. This was doe because we ofte observed that the iitial beat of sustaied VT may have a subtly differet morphology from the remaiig beats. The chose VT beat was the automatically compared with each of the pace-map beats usig customized software. The two beats were aliged by automatically covolvig (slidig) the pace-map beat past the VT beat to obtai the lowest overall 12-lead MAD or highest CORR, depedig o the desired measure. The 12-lead MAD ad correlatio were the recorded for the best aligmet. This automatic aligmet elimiated ay operator bias i waveform compariso. Waveforms were viewed by the user to esure proper aligmet (Fig. 3). Each paced site ad all ablatio sites (successful ad usuccessful) were tagged usig electroaatomic mappig (Fig. 1). The distace from the fial successful ablatio site to each pace-map site was measured. The distace betwee each paced site ad the successful ablatio site was correlated with the MAD for that compariso. Studet t test was used for comparisos. A simple liear regressio was used to compare distace ad MAD; p 0.05 was cosidered sigificat. RESULTS A total of 15 patiets (age years, 9 wome) were icluded i the study. All patiets had ormal left vetricular ad RV size ad fuctio by trasthoracic echocardiography. All uderwet successful ablatio of a RVOT VT. Patiets had sustaied RVOT VT (11 patiets) or reproducible moomorphic PVCs (4 patiets) typically origiatig from the RV septum (14 patiets) or RV free wall (1 patiet). The MAD ad correlatio scores (mea SD) of the cliical VT with pace-maps from the three septal, three free wall, usuccessful, ad successful ablatio sites for the 14

4 JACC Vol. 41, No. 11, 2003 Jue 4, 2003: Gerstefeld et al. Quatitative ECG Compariso of RVOT VT 2049 Figure 3. The left pael shows a example of right vetricular outflow tract (RVOT) vetricular tachycardia (VT) i a patiet with sustaied VT. The secod VT complex has bee idetified as the target waveform by the aotatio markers placed o either side of this complex. The middle pael shows a pace-map from free wall site 1 (FW1) ext to the superimposed VT ad pace-map waveforms after automatic computer aligmet. There are substatial differeces betwee these two waveforms (highlighted i gray), resultig i a mea absolute deviatio (MAD) score of 31.5%. The right pael shows a pace-map from the successful ablatio site (Abl S) ear the posterior septum ad the superimposed pace-map ad VT waveform. Note i the Abl S pael that whe these two waveforms are aliged they are early superimposable, ad result i a very low MAD score of 5.3%. Correlatio coefficiets for these comparisos are also show. patiets with septal sites of VT origi are show i Figures 4A ad 4B. Note that MAD scores are lower (i.e., more closely matched) for septal compared with free wall sites ( % vs %; p 0.001), ad the lowest MAD occurred at septal site 2, the most commo origi for RVOT VT i this group. Although there was overlap betwee usuccessful ad successful ablatio sites, successful ablatio sites had a sigificatly lower MAD score compared with usuccessful ablatio sites ( % vs %; p 0.01). The sesitivity, specificity, positive predictive value, ad egative predictive value for various MAD scores are show i Table 1. Usig a MAD score cutoff of 12%, the sesitivity was 93%, specificity 75%, ad egative predictive value 94% for a successful ablatio site. A MAD cutoff of 15% had 100% sesitivity ad 100% egative predictive value but was ot specific. The CORR was also higher (more closely matched) for septal compared with free wall sites ( % vs %; p 0.01). There was also a tred toward a sigificat differece betwee the mea CORR for usuccessful ad successful ablatio sites; however, this differece did ot achieve statistical sigificace ( % vs %; p 0.07) (Fig. 4B). A CORR cutoff of 96% was 93% sesitive, but oly 26% specific for a successful ablatio site. Because there is ofte beat-to-beat variatio i waveforms durig sustaied VT, we also compared the chose VT beat with 10 successive moomorphic VT beats i each patiet. The MAD score foud a mea beat-to-beat compariso measuremet of %, ad the CORR yielded a mea beat-to-beat compariso of % (Figs. 4A ad 4B). A example of VT ad pace-map 12-lead ECG waveform morphologies ad correspodig MAD scores is show i Figure 5. We performed a correlatio of MAD scores betwee the cliical VT ad each paced site ad the distace of the cliical VT origi (successful ablatio site) to each pacemap site usig electroaatomic mappig. There was a sigificat correlatio betwee MAD score ad distace from the site of VT origi (r 0.63, p 0.001) (Fig. 6). DISCUSSION We have described a quatitative measure for comparig 12-lead ECG waveform morphologies betwee pace-maps ad a cliical tachycardia usig a sigle umber ragig from 0 to 1. The 12-lead MAD score performed better tha the CORR, likely related to better sesitivity to amplitude differeces betwee waveforms. Scores were better for successful compared with usuccessful ablatio sites, suggestig that a automated objective iterpretatio may have some advatage to huma iterpretatio. The MAD scores

5 2050 Gerstefeld et al. JACC Vol. 41, No. 11, 2003 Quatitative ECG Compariso of RVOT VT Jue 4, 2003: Figure 4. (A) The mea absolute deviatio (MAD) scores for the 14 patiets with septal vetricular tachycardia (VT) origi comparig the cliical VT to pacig from posterior septal site 1 (S1), mid septal site 2 (S2), aterior septal site 3 (S3), free wall site 1 (F1), free wall site 2 (F2), free wall site 3 (F3), the right vetricular apex (RVA), usuccessful ablatio sites (Abl F), successful ablatio sites (Abl S), ad comparig the chose VT beat to other similar morphology VT beats (VT). Note that the average MAD scores are sigificatly lower for septal compared with free wall sites. The average MAD score was also sigificatly lower for successful compared with usuccessful ablatio sites, ad all successful ablatio sites had a MAD score 15%. *p (B) The mea SD correlatio coefficiet ( ) scores for the same compariso as i the previous graph. The overall patter is similar to the previous graph, although there is less spread amog the sites. The average correlatio for successful ablatio sites was ot sigificatly lower tha that of usuccessful ablatio sites. were directly related to the distace from the tachycardia site of origi. Others have described quatitative multi-lead waveform measures for comparig body surface potetial maps ad the 12-lead ECG. Lux et al. (12) described three quatitative measures to compare two body surface potetial maps: the CORR, percet error, ad root-mea-square error. These authors ackowledged the limitatios of the CORR, which was sesitive to differeces i map cotour but ot amplitude, ad used % error ad root-mea-square error to describe amplitude differeces betwee maps. They also quatitatively compared body surface potetial maps durig pacig from multiple left vetricular sites, ad foud that the CORR decreased with distace (2). Goyal et al. (13) used the CORR ad root-mea-square error to compare idividual lead morphology differeces durig pacig at differet couplig itervals ad cycle legths. They foud that the root-mea-square error was a better discrimiator of idividual lead waveform differeces tha the CORR. Throe et al. (14) used the bi area method for template matchig of itracardiac electrograms. However, quatitative measures have ot bee developed that ca be used to

6 JACC Vol. 41, No. 11, 2003 Jue 4, 2003: Gerstefeld et al. Quatitative ECG Compariso of RVOT VT 2051 Table 1. Sesitivity, Specificity, ad Predictive Values Sesitivity Specificity PPD NPD MAD 5% % % <12% % CORR 99% % % % % A MAD cutoff of <12% yielded the best results. CORR correlatio coefficiet; MAD mea absolute deviatio; NPD egative predictive value; PPD positive predictive value. easily quatify the etire 12-lead ECG ad have ot bee used cliically to assess catheter ablatio. We tested both the MAD ad CORR because previous experiece with pace-mappig has revealed the importace of matchig waveform amplitude i additio to morphology i obtaiig a successful ablatio site. Although correlatio is the much more commoly used statistic, the MAD is much more sesitive to differeces i waveform amplitude. Therefore, it is ot surprisig that the MAD was a better discrimiator of successful from usuccessful ablatio sites. The most commo huma error whe turig o RF eergy was ot appreciatig subtle amplitude or precordial lead trasitio differeces betwee two ECG patters (Fig. 5). It is importat to ote that such subtle differeces i multiple leads ca be reflected i a sigle quatitative umber. We foud that durig sustaied RVOT VT, there were beat-to-beat differeces i 12-lead ECG waveform morphology quatifiable as approximately 5% differece usig the MAD score. Some degree of these beat-to-beat chages may be related to itermittet oise, baselie wader, or respiratory artifact. However, these beat-to-beat chages i QRS morphology durig sustaied VT are frequetly observed, ad their mechaism requires further ivestigatio. Cliical applicatios. There are multiple cliical applicatios of the MAD score. Most obvious would be guidig RF ablatio of RVOT VT i ceters with less experieced operators. The MAD score is computatioally simple ad should be easy to icorporate ito curret electrophysiologic recordig systems, allowig feedback to the physicia of pace-map compariso before turig o the RF eergy. A MAD score of 12% was 93% sesitive ad 75% specific for a successful ablatio site. It is ot surprisig that the MAD score is more sesitive tha specific. Characteristics other tha a 12-lead ECG match are ecessary for a successful ablatio, icludig catheter-tissue cotact, catheter orietatio, ad tissue heatig. Our data suggest that a MAD score 12%, ad certaily 15% (100% egative Figure 5. Examples of vetricular tachycardia (VT) morphology (first pael, blue tracig) ad pace-maps (red tracig) from the three septal ad free wall sites, a usuccessful ablatio site, ad a successful ablatio site after computer aligmet with correspodig mea absolute deviatio (MAD) scores below. Note the smaller amplitude i the iferior leads ad later precordial trasitio for free wall compared with septal sites. The usuccessful ablatio site has a reasoable 12-lead match ad a low MAD score, but ot as low as the successful ablatio site.

7 2052 Gerstefeld et al. JACC Vol. 41, No. 11, 2003 Quatitative ECG Compariso of RVOT VT Jue 4, 2003: Figure 6. The graph shows the relatioship betwee the mea absolute deviatio (MAD) score ad the distace of the pace-map from the successful ablatio site measured usig electroaatomic mappig. The further away the pacig site from the vetricular tachycardia site of origi, the higher (worse) the MAD score, as oe would expect (r 0.63; p 0.001). predictive value) suggests sufficiet dissimilarity betwee pace-map ad cliical tachycardia to dissuade ablatio at that site. The MAD scores 12% should be cosidered a excellet match, ad ablatio at these sites is warrated if catheter cotact ad stability are adequate. Recetly, aatomic methods of scar-based tachycardia ablatio have bee developed that create liear lesios alog scar borders based o pace-map similarity to the cliical tachycardia to defie the tachycardia exit site. Although studies describig this techique state that there was similarity betwee pace-maps ad VT waveforms at these sites (15,16), there was o existig method for describig the degree of pace-map similarity. The MAD score would allow such a quatitative compariso. Variatio i pace-map waveform morphology with distace, curret stregth, ad rate, as well as beat-to-beat waveform differeces durig sustaied tachycardia described earlier are poorly uderstood. The MAD score would allow these differeces to be aalyzed i more detail. Limitatios. Good sigal quality is clearly importat i performig these comparisos. Because this study was performed retrospectively, there was o attempt by the cliicias to obtai superior sigal quality for the purposes of this study, thus these results should be applicable to ay digital sigal acquisitio system of reasoable quality. Some laboratories rely more o activatio mappig tha pace-mappig to ablate RVOT VT. The purpose of this study was ot to compare the two but oly to use pacemappig as a model for developig a quatitative metric. This study was a retrospective oe, coducted to validate the MAD metric as a meaigful quatitative idicator of 12-lead ECG waveform morphology. Although all patiets i this study uderwet evetual successful RF ablatio, the MAD score may evetually result i fewer delivered RF lesios ad may help to quatitatively describe ad guide ablatios. Furthermore, the goal of this study was ot to demostrate superiority to covetioal ablatio techiques, but to validate a quatitative measure of multiple waveform compariso i the electrophysiology laboratory. Coclusios. The compariso of two 12-lead ECG waveforms ca be quatified usig the MAD metric. This measure grades 12-lead ECG waveform similarity as a sigle umber ragig from 0 (idetical) to 100% (completely differet). A MAD score 12% betwee RVOT VT ad a pace-map at ay site suggests sufficiet dissimilarity to dissuade ablatio at that site. The MAD score ca be used to stadardize 12-lead ECG waveform morphology comparisos amog differet laboratories, ad may be useful for guidig ablatio of RVOT VT. Reprit requests ad correspodece: Dr. Edward P. Gerstefeld, Uiversity of Pesylvaia Medical Ceter, 9 Fouders Pavilio, 3400 Spruce Street, Philadelphia, Pesylvaia edward.gerstefeld@uphs.upe.edu. REFERENCES 1. Kadish AH, Childs K, Schmaltz S, Morady F. Differeces i QRS cofiguratio durig uipolar pacig from adjacet sites: implicatios

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