Reappraisal of classical electrocardiographic criteria in detecting accessory pathways with a strict para-hisian location

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1 1 Reappraisal of classical electrocardiographic criteria in detecting accessory pathways with a strict para-hisian location E. González-Torrecilla, MD, PhD, * R. Peinado, MD, PhD, J. Almendral, MD, PhD, A. Arenal, MD, * F. Atienza, MD, PhD, * J. García Fernández, MD, PhD, y F. Fernández-Avilés, MD, PhD * From the * Cardiology Department, Hospital General Universitario Gregorio Marañón, Universidad Complutense de Madrid, Madrid, Spain, y Cardiology Department, Hospital Universitario La Paz, Madrid, Spain, z Grupo Hospital de Madrid, Universidad San Pablo-CEU, Madrid, Spain and y Cardiology Department, Complejo Hospital Universitario de Burgos, Burgos, Spain. BACKGROUND Identification of electrocardiographic (ECG) criteria for para-hisian accessory pathways (APs) is based on a small series of patients. The presence of a negative delta wave in leads V 1 and V 2 has been suggested as an ECG marker of this AP location. OBJECTIVE To validate these ECG findings in a large series of patients with strict invasive criteria for that location. METHODS We included 105 patients (39 women, 66 men; mean age years, range 5 82 years) with an ECG pattern compatible with preexcitation through an anteroseptal or midseptal AP following established ECG criteria. A para-hisian AP was defined when the location of its successful catheter ablation coincided with either the largest recordable His bundle electrogram or a His bundle potential of 40.1 mv. Patients without that definition were included in the control group. RESULTS A para-hisian location of the AP was found in 52 patients. AP locations of the remaining 53 patients (control group) were anteroseptal (n ¼ 39), midseptal (n ¼ 9), and fasciculoventricular (n ¼ 5). A negative delta wave in leads V 1 and V 2 was observed in 13 patients with para-hisian APs (sensitivity 25%; specificity 92%). However, the sum of initial r-wave amplitudes in those leads was o0.5 mv in 44 of the patients with para-hisian APs and in 13 patients of the control group (sensitivity 85%; specificity 75.5%; area under receiver-operator characteristic curve 0.85). CONCLUSIONS The presence of negative delta waves in leads V 1 and V 2 indicates a poor sensitivity and high specificity to detect APs with a strict definition of para-hisian location. The sum of initial r-wave amplitudes in those ECG leads could be a useful, adjunctive marker in the noninvasive identification of these challenging APs. KEYWORDS Accessory pathway; Electrocardiogram; Preexcitation; His bundle ABBREVIATIONS AP ¼ accessory pathway; AV ¼ atrioventricular; ECG ¼ electrocardiographic/electrocardiogram; ROC ¼ receiveroperator characteristic (Heart Rhythm 2013;10:16 21) I 2013 The Heart Rhythm Society. All rights reserved. 3 3 Introduction Over the last 2 decades, several attempts have been made to correlate electrocardiographic (ECG) findings with precise anatomic locations of accessory pathways (APs) However, no single published algorithm offers extremely high sensitivity/specificity for all pathway locations, particularly when differentiating septal APs. 1,7 Specifically, the ECG criteria to identify a para-hisian accessory bypass are based on a small series of patients. 5,13 In fact, the presence of a negative delta wave in the right precordial leads V 1 and V 2 Address reprint requests and correspondence: Dr Esteban González- Torrecilla, MD, PhD, Arrhythmia Unit, Cardiology Department, Hospital General Universitario Gregorio Marañón, Universidad Complutense de Madrid, Doctor Esquerdo 46, Madrid 28007, Spain. address: etorrecilla@telefonica.net. has been proposed as a classic, noninvasive marker of this bypass location. 13 However, these criteria were based on the observation of a small series of 7 patients by Haïssaguerre et al, 13 with a strict definition of para-hisian location mainly based on the His bundle amplitude prior to successful radiofrequency ablation. Para-Hisian APs have frequently been included in a broader anatomic concept of anteroseptal atrioventricular (AV) bypass. 2,3,7,9 However, the discrimination of such a risky location from other anteroseptal or high midseptal ventricular insertions of the bypass by ECG criteria would be valuable in planning the subsequent catheter ablation procedure. The aim of this study was therefore to validate those classical ECG features in a large cohort of patients with strict invasive criteria 13 for that challenging location. The description of other possible useful ECG signs for identifying these specific APs is a secondary objective of our study /$-see front matter B 2013 The Heart Rhythm Society. All rights reserved.

2 González-Torrecilla et al Reappraisal of Classical Electrocardiographic Criteria 17 Methods Patients characteristics and group definitions From April 2003 to January 2012, a total of 105 consecutive patients (39 women, 66 men; mean age years, range 5 82 years), who were referred to our 4 participating institutions for catheter ablation, were included in our study as they fulfilled the following inclusion criteria: (1) ECG pattern compatible with preexcitation (QRS width 4110 ms) through an anteroseptal or midseptal AP following established ECG criteria 3 ; (2) following prior algorithm, 3 midseptal AP had to have a sum of delta-wave polarities equal to 0 or þ1 to be included in the study; and (3) acute successful catheter ablation, in the current study, defined as the disappearance of ventricular preexcitation in the first 10 seconds of a radiofrequency pulse or during 4 6 minutes of a cryoablation application. Briefly, we included patients with right-side APs showing a precordial transition ov 4, delta wave in lead II Z1 mv, and a sum of delta polarities in inferior leads between 0 and Z2. 3 After successful ablation attempts, a waiting period of minutes followed by repeated extrastimulation was required to define successful ablation. The latter criterion was not applied when a fasciculoventricular bypass tract was finally diagnosed. Patients with traumatic elimination of AP AV conduction followed by successful ablation in the same point, ensured by a navigation mapping system, were also included in this study. A para-hisian AP was defined when the location of its successful catheter ablation coincided with either the largest recordable His bundle electrogram or a His bundle potential of 40.1 mv. 13 Patients without this definition were included in the control group. The presence of a His bundle deflection was sought at the location of successful bypass ablation or shortly after the disappearance of ice artifacts during successful cryoablation (Figure 1). The mean amplitude of 3 consecutive His bundle deflections was calculated. The procedure was supported by the navigation mapping system in 36 patients. ECG measurements ECG recordings were obtained in all patients during the electrophysiologic study. The ECGs were recorded at a paper speed of 25 mm/s and an amplification of 10 mm/mv. All ECGs showed a clear delta wave, with a combined delta and QRS width of at least 120 ms. Preexcited 12-lead ECGs were obtained during sinus rhythm. The initial 40 ms of the preexcited QRS complex in each of the frontal leads and the initial 60 ms of the preexcited QRS complex in each of the precordial leads were taken as the delta wave. If the delta wave was above the baseline without any part below the baseline in a given lead, it was designated as positive for that lead. If the delta wave was below the baseline without any part above the baseline, it was designated as negative. The isoelectric delta wave was designated as the whole delta wave on the baseline. The delta wave that was composed of both positive and negative components was designated as biphasic. When present, the sum of initial r-wave amplitudes in leads V 1 and V 2 were measured in every patient (Figure 2). A zero value was assigned when no initial positive deflections were observed in those leads. All the ECGs were evaluated by 2 independent electrophysiologists who were blinded to the data of the electrophysiologic studies. In redo procedures, the ECG and mapping findings of the last successful ablation session were considered. Statistical analysis Data are given as mean SD if continuous and as counts and percentages if categorical. Student t test, w 2 test, and Fisher exact test were used to compare differences between groups. The optimal cutoff value of selected continuous variables to detect a strict para-hisian AP location was determined by using receiver-operator characteristic (ROC) curve analysis. Parameter performance was assessed by the use of areas under the ROC curves. All analyses were performed with the use of SPSS software, version 15.0 Figure 1 Left panel: Successful cryoablation pulse in a true para-hisian accessory pathway (AP). The presence of a His bundle deflection was sought at the location of successful bypass ablation or shortly after the disappearance of ice artifacts during successful cryoablation. The mean amplitude of 3 consecutive His bundle deflections (H) was measured. Right panel: Intracavitary electrograms in a successful site prior to cryoapplication in the same patient. Line shows the onset of delta wave and the earliness of local ventriculogram ( 16 ms) with AV continuity. From top to bottom: Surface ECG leads, distal pair of cryoablation catheter (Abl d), unipolar lead of distal ablation electrode (Uni d), high right atrium (HRA), and right ventricular apex (RVA).

3 18 Heart Rhythm, Vol 10, No 1, January 2013 followed by successful AP elimination at the same point in 6 patients. Permanent AV block did occur in just one of the index procedures in a 61-year-old man with an anteroseptal AP and inadvertent catheter movement to more septal positions during radiofrequency pulse. Figure 2 Top panels: The initial 40 ms of the QRS complex was used to determine delta-wave polarity and the presence of a negative delta wave in leads V 1 and V 2 in a patient with true para-hisian accessory pathway (AP) (left panel). The amplitudes of initial r waves in these leads (arrows) are measured in patients with para-hisian (middle panel) and anteroseptal (right panel) APs, respectively. Lower panels: Corresponding successful sites of the ablation (Abl) catheter for each case in fluoroscopic (left anterior oblique view) and 3-dimensional electroanatomic right atrial map (modified right anterior oblique view; NavX system, St Jude Medical, Endocardial Solutions Inc, St Paul, MN) images. Asterisk denotes His position in fluoroscopic images. CS ¼ coronary sinus catheter. Other abbreviations as in Figure 1. (SPSS Inc, Delaware, CA). For all tests, P o.05 (2-sided) was considered significant. Results Study groups Successful ablation identified 52 patients as having para- Hisian APs (18 women; mean age years). Demographic, procedural, and ECG characteristics of these patients are listed in Table 1. The mean bipolar His bundle potential amplitude was mv. In 11 of these patients, the largest obtainable His bundle electrogram was o0.1 mv (range mv). AP locations of the remaining 53 patients (control group; 15 women; mean age years) were anteroseptal (n ¼ 39), midseptal (n ¼ 9; left midseptal in 1), and fasciculoventricular (n ¼ 5). The mean follow-up was months. AP recurrence after the index procedure was observed in 17 patients (16%). A dormant posteroseptal AP was observed 2 years after a successful procedure on a prior para-hisian bypass. The traumatic abolition of AP AV conduction was observed in 19 patients (14 para-hisian APs, 4 anteroseptal, and 1 midseptal). This event was more frequently observed in true para-hisian vs anteroseptal APs (27% vs 10%; P o.05). It was transient in 13 cases or ECG findings and diagnostic yield Thirteen patients with para-hisian APs had a predominantly negative delta wave in leads V 1 and V 2, whereas this was observed in just 2 patients with anteroseptal and midseptal APs in the control group (P o.001). Therefore, this ECG finding led to sensitivity, specificity, and positive, and negative predictive values of 25%, 92%, 87%, and 57%, respectively, for a para-hisian AP location. However, the sum of initial r-wave amplitudes leads V 1 and V 2, was clearly greater in the control group ( mv vs mv; P o.001; Figure 3). Figure 4 shows the ROC curve for the diagnostic performance of different values of the sum of initial r-wave amplitudes in leads V 1 and V 2, with a significant area under the curve of 0.85 (95% confidence interval ; P o.0001). The cutoff value that best optimizes the values of sensitivity and specificity was for values o 0.5 mv. This cutoff value leads to sensitivity, specificity, positive, and negative predictive values of 85%, 75.5%, 77%, and 83.3%, respectively, for a true para-hisian AP location. The delta wave in lead III was isoelectric or negative in 9 (17%) patients with para-hisian APs and 8 (20.5%) patients with anteroseptal APs (P ¼ ns). Discussion Main findings This study represents a reappraisal of classical ECG localizing criteria for a true para-hisian location in a large series of patients with prior anteroseptal or high midseptal ECG features following a known ECG algorithm. 3 Our findings demonstrate that the presence of a negative delta wave in the first 2 precordial leads shows a modest sensitivity of 25% but a high specificity to detect the ventricular insertion of APs with a strict invasive definition of para-hisian location during acute successful ablation pulses. In addition, a sum of initial r-wave amplitudes in those precordial ECG leads of o0.5 mv could be a useful, adjunctive marker in the noninvasive identification of these APs. ECG considerations and clinical implications The low prevalence of a negative delta-wave polarity in leads V 1 and V 2 may even be overestimated by some selection bias in referred patients given the known diagnostic value of that classical ECG criterion. In addition, uncommon anteroseptal APs such as those located at the noncoronary aortic cusp 14 or aortomitral continuity 11 are not represented in our series. Less experience in the first unusual location may explain in part that a required successful ablation would be less likely to achieve. Moreover, no His bundle deflection is obtainable after a successful procedure at an uncommon site such as the aortomitral continuity. 11 The specificity of 2

4 Table 1 Patient no. Characteristics of patients with preexcitation through para-hisian accessory pathways Age/Sex Energy source No. of pulses Polarity of delta wave Transition of Sum of initial His bundle V-delta A/V electrogram I II III avr avl avf V 1 V 2 V 3 V 4 V 6 R/S ratio * r wave in V 1 V 2 amplitude interval ratio 1 28/M Cryo 2 þ þ þ þ þ þ þ V 2 V 3 1þ2(3) ms /M RF/Cryo þ þ bi þ þ þ þ þ þ V 3 V 4 1.5þ2.5(4) ms /F Cryo þ þ þ bi þ þ þ þ þ þ V 3 1.5þ2(3) 0.1 0ms /F RF/Cryo þ þ bi þ þ þ þ þ þ V 2 V 3 1þ2.5(3.5) ms /M RF/Cryo þ þ þ bi þ þ þ þ þ V 3 2þ2(4) ms /M RF 3 þ þ bi þ þ þ þ V 3 0þ0(0) ms /M Cryo 2 þ þ iso þ þ biþ þ þ V 3 1þ2.5(3.5) ms /M Cryo 1 þ þ iso þ þ þ þ þ V 2 V 3 0þ5(5) ms /M RF/Cryo þ þ þ þ þ þ þ þ þ V 2 V 3 1þ5.5(6.5) ms /M Cryo 6 þ þ þ þ þ þ V 3 V 4 0þ0(0) ms /F RF/Cryo þ þ iso iso þ þ þ þ V 3 V 4 0þ1.5(1.5) ms /F RF 7 þ þ þ þ þ bi þ þ þ V 3 1þ4(5) ms /M Cryo 1 þ þ þ bi þ þ þ þ þ þ V 2 V 3 2þ2(4) ms /M RF 1 þ þ iso þ þ þ þ þ þ V 3 1þ2.5(3.5) ms /F RF/Cryo þ þ bi þ þ þ þ V 2 V 3 0þ0(0) ms /F Cryo 3 þ þ bi þ þ þ þ V 3 V 4 0þ0(0) ms /M RF 6 þ þ þ þ þ bi þ þ þ V 3 V 4 1.5þ1.5(3) ms /M RF 10 þ þ þ bi þ bi þ þ þ V 3 V 4 1þ1.5(2.5) ms /F RF 4 þ þ þ þ þ þ þ þ þ V 3 V 4 1þ1.5(2.5) ms /F RF 10 þ þ þ þ þ þ þ þ þ V 3 V 4 1þ2(3) ms /F Cryo 2 þ þ þ bi þ isoþ V 3 0þ0(0) ms /M RF 2 þ þ þ iso þ þ þ V 3 0þ4(4) ms /M Cryo 9 þ þ þ þ þ þ þ þ þ V 3 1.5þ3.5(5) ms /F Cryo 2 þ þ þ bi bi bi þ V 3 0þ0.5(5) ms /M Cryo þ þ þ þ þ bi þ V 2 V 3 0þ0(0) ms /F Cryo 6 þ þ þ þ þ þ þ þ þ V 2 V 3 2þ4(6) 0.1 0ms /F Cryo 3 þ þ þ bi þ þ þ V 3 0þ0(0) ms /M Cryo 7 þ þ bi þ þ bi þ V 3 V 4 0þ0(0) ms /M Cryo 5 þ þ þ iso þ þ þ þ þ V 3 V 4 3þ2(5) ms /F RF/Cryo þ þ þ iso þ þ þ þ þ V 3 V 4 2þ2.5(4.5) ms /M Cryo þ þ þ iso þ þ þ þ þ V 2 V 3 1.5þ2(3.5) ms /M Cryo 2 þ þ þ bi þ þ þ þ þ V 3 V 4 1.5þ1.5(3) 0.1 0ms /M RF 2 þ þ þ bi þ þ þ þ þ þ V 3 1þ1.5(2.5) ms /M RF 3 þ þ þ bi þ þ þ þ þ þ V 3 1.5þ2.5(4) ms /M Cryo þ þ þ þ þ þ þ þ V 2 V 3 0þ3(3) 0.1 1ms /M y RF 2 þ þ þ iso þ þ þ þ þ V 2 V 3 2þ7(9) ms /M RF 1 þ þ þ bi þ þ þ þ þ V 2 V 3 1þ1(2) 0.1 5ms /M RF 3 þ þ þ þ þ þ þ þ þ V 3 V 4 1þ4(5) ms /F RF 3 þ þ þ þ bi þ V 3 V 4 0þ0(0) ms /F RF 2 þ þ þ þ þ þ þ þ þ V 2 V 3 1þ3.5(4.5) ms /F RF 2 þ þ iso þ þ þ þ V 3 V 4 0þ0(0) ms /M Cryo þ þ iso þ þ þ þ þ þ V 3 V 4 0.5þ0.5(1) ms /M Cryo 4 þ þ þ bi þ þ þ þ V 3 V 4 0þ0.5(0.5) ms /M Cryo þ þ þ iso þ þ þ V 3 V 4 0þ0(0) ms /F RF 3 þ þ þ þ þ þ þ V 3 V 4 0þ0(0) 0.1 0ms /M Cryo 1 þ þ þ þ þ þ þ þ V 2 V 3 0.5þ1.5(2) ms /M Cryo 2 þ þ iso iso þ þ þ V 3 V 4 0þ0(0) ms /M Cryo 1 þ þ þ þ þ þ þ V 2 V 3 0.5þ1.5(2) ms /F RF 2 þ þ þ þ þ þ þ þ V 3 1.5þ1(2.5) ms /M Cryo 1 þ þ þ bi þ þ þ þ V 2 V 3 0þ0.5(0.5) 0.1 2ms /M Cryo 1 þ þ þ þ þ þ þ þ V 3 2þ2(4) ms /M Cryo 3 þ þ þ þ þ þ þ þ V 2 V 3 2þ4(6) ms 0.3 bi ¼ biphasic delta wave; Cryo ¼ cryoenergy; F ¼ female; iso ¼ isoelectric delta wave; M ¼ male; RF ¼ radiofrequency. *Values in mv 10. Values in mv. Patients with recurrences after ablation in the index procedure. yintermittent preexcitation. González-Torrecilla et al Reappraisal of Classical Electrocardiographic Criteria 19

5 20 Heart Rhythm, Vol 10, No 1, January 2013 Figure 4 Area under receiver-operator characteristic curve ( ) for values of the sum of initial r-wave amplitudes in the first 2 precordial leads. The cutoff value of the maximizing levels of sensitivity and specificity was o0.5 mv. Figure 3 Scatterplot showing the individual values of the sum of initial r-wave amplitudes in leads V 1 and V 2 in patients with true para-hisian accessory pathway (n ¼ 52) and control group (n ¼ 53). Gray line indicates the selected cutoff point. nearly identical monopolar surface leads equidistant from the midline to identify a superoanterior septal structure such as a para-hisian bypass is clear. In fact, orthogonal anterior projection of the superior membranous septum falls on the sternum roughly midway between V 1 and V 2 positions. 15,16 However, even minor changes in normal cardiothoracic anatomic variability may account for the low sensitivity of these classical criteria. The absence of maximal preexcitation and variable branching of ventricular insertions also prevents pinpointing the exact location of some midseptal, true para- Hisian and anteroseptal bypass tracts, which arise within the range of cm of each other. In addition, the possible effect of different initial QRS forces in right precordial leads of nonpreexcited complexes is not analyzed in this study. The sum of initial r-wave amplitudes in the same precordial leads above the estimated cutoff value could represent the presence of more intervening myocardium in other anteroseptal or high midseptal APs not fulfilling strict invasive criteria for a para-hisian location. In fact, the higher incidence of catheter-induced trauma in true para-hisian APs does suggest a more superficial endocardial location of their ventricular insertions. This ECG information before commencing the procedure could optimize patient counseling and permit the operator to plan an appropriate, definitive invasive mapping and ablation strategy with the selection of different energy sources. Limitations The results of this study should be interpreted in the face of certain limitations. ECG findings exclusively reflect the ventricular insertion of the AP and inherent limitations of the selected ECG algorithm, as the inclusion criterion could lead to the exclusion of some true para-hisian APs. 3 The absence of discernible electrograms during cryoapplications along with the possible inadvertent dislodgement of the cryocatheter tip early on rewarming is a clear limitation inherent in cryoablation procedures. In addition, the definition of high midseptal AP is questionable and directed at the specific differential diagnosis we addressed in this study. This definition is based on previous series 3,4,10 and tried to select midseptal APs with ventricular insertion in the superior half of that wide anatomic location. In addition, the pediatric population is clearly underrepresented in our study and difficulties with septal AP localization seem to be magnified in children. 7 Finally, our results from this otherwise large derivation group clearly need external validation. Conclusions The classical finding of a negative delta wave in the first 2 precordial leads shows a poor sensitivity and high specificity to detect APs with a strict definition of para- Hisian location. In addition, the sum of initial r-wave amplitudes in those ECG leads could be a useful, adjunctive marker in the noninvasive identification of these challenging APs.

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