Author + information
- Received October 28, 2016
- Revision received December 13, 2016
- Accepted December 22, 2016
- Published online March 1, 2017.
- Fengxiang Zhang, MDa,
- David Hamon, MDb,
- Zhen Fang, MDa,
- Yan Xu, MDa,
- Bing Yang, MDa,
- Weizhu Ju, MDa,
- Jason Bradfield, MDb,
- Kalyanam Shivkumar, MD, PhDb,
- Minglong Chen, MDa and
- Roderick Tung, MDc,∗ ()
- aFirst Affiliated Hospital of Nanjing Medical University, Nanjing, China
- bUCLA Cardiac Arrhythmia Center, UCLA Health System, Los Angeles, California
- cUniversity of Chicago Medicine, Center for Arrhythmia Care, Heart and Vascular Center, Chicago, Illinois
- ↵∗Address for correspondence:
Dr. Roderick Tung, The University of Chicago Medicine, Center for Arrhythmia Care, 5841 South Maryland Avenue, MC 6080, Chicago, Illinois 60637.
Objectives This study sought to prospectively evaluate the value of a dedicated electrocardiographic posterior lead to create an anteroposterior ratio to localize premature ventricular complexes (PVCs) between the right ventricular outflow tract and left ventricular outflow tract for catheter ablation.
Background The anteroposterior relationship between the right and left outflow tract has not been explored for electrocardiographic localization of ventricular arrhythmia.
Methods Standard V5 and V6 leads were placed posteriorly and ablation was performed with activation mapping. The site of successful ablation was correlated with the ratio of the R-wave in V4 to the R-wave in V8. Normalization of the V4/V8 ratio to a V4/V8 index was achieved by dividing the V4/V8 ratio by sinus V4/V8. After determination of optimal cutoffs, comparison with V2 transition ratio and V2S/V3R was subsequently performed using receiver operating characteristic curves in a prospective validation cohort.
Results A total of 134 patients underwent ablation of PVCs with 2 modified posterior leads. PVCs successfully ablated from the left side had a statistically significantly higher V4/V8 ratio compared with right-sided PVCs (11.7 ± 10.6 vs. 2.3 ± 2.4, p < 0.001). At a cutoff of >3, the V4/V8 ratio had a sensitivity of 88% with a specificity of 77% for left-sided locations. At a cutoff of >2.28, the V4/V8 index had a sensitivity of 67% with a specificity of 98%. In the prospective validation cohort (n = 40), the V4/V8 ratio exhibited the highest sensitivity of 75% with a negative predictive value of 89% compared with the V4/V8 index, V2 transition ratio, and V2S/V3R. The V4/V8 index had the highest specificity of 96% with positive predictive value of 89% compared to the other predictive ratios. When analyzing cases with a V3 transition, the V4/V8 index demonstrated 100% specificity and positive predictive value.
Conclusions A simple modification of V5 to V8 posteriorly may provide incremental diagnostic value for localizing PVCs arising from the outflow tracts. Normalizing PVC localization criteria to the sinus rhythm results in the highest specificity when compared with other validated criteria.
Idiopathic ventricular tachycardia and premature ventricular complexes (PVCs) arising from the ventricular outflow tracts (OTs) are the most common type of ventricular arrhythmias in the absence of structural heart disease. Catheter ablation has been demonstrated to be a curative therapy, with >80% success rates (1). An accurate method to predict the site of successful ablation can guide and facilitate the procedural strategy for mapping and ablation. However, the accuracy of 12-lead electrocardiographic localization can be affected and thereby limited by body surface anatomy, cardiac anatomy, rotation, and variability in electrocardiogram (ECG) lead placement (2).
Several electrocardiographic criteria have been proposed to differentiate and localize the site of origin of outflow tract PVCs (3–10). Although multiple electrocardiographic criteria have been shown to have diagnostic accuracy, the vast majority incorporate the precordial transition into the localization algorithm. Because the right ventricular outflow tract (RVOT) and left ventricular outflow tract (LVOT) have an anteroposterior anatomic relationship, we sought to prospectively evaluate the value of a dedicated electrocardiographic posterior lead to localize the site of PVC origin between the RVOT and LVOT for catheter ablation. The prospective study was conducted in 2 phases: 1) derivation cohort for optimal cutoff determination; and 2) validation cohort with comparison to 2 other published criteria.
Consecutive patients referred for ablation of idiopathic OT PVCs at 2 academic centers between 2013 and 2015 were prospectively assessed. Standard V5 and V6 leads were placed on the back of the patient, with V5 located at the inferior tip of left scapular (V8) and V6 just left of the spine at the same level (V9) (Figure 1). This method was chosen to obviate the need for additional leads beyond the standard 12-lead system because the incremental clinical value of V5 and V6 for outflow tract PVCs is low. Patients with structural heart disease, permanent pacing, and bundle branch block (BBB) were excluded. The institutional review boards at both participating centers approved review of this data.
Diagnostic catheterization and ablation were performed via the right femoral venous approach for mapping of the RVOT and retrograde aortic approach was used for mapping of the LVOT. Systemic heparinization was administered (goal: 250 to 300 s) during LVOT mapping and ablation. Isoproterenol was administered intravenously if spontaneous PVCs were not present in the baseline state or under conscious sedation. Ablation was performed with standard activation mapping using electroanatomic mapping systems (CARTO, Biosense Webster, Diamond Bar, California, or NAVX, St. Jude Medical, Minneapolis, Minnesota). Irrigated catheters were used for ablation (ThermoCool, Biosense Webster, Diamond Bar, California, or CoolFlex, St. Jude Medical, Minneapolis, Minnesota). The flow rate was 17 to 30 ml/min and applications were applied for 60 s (power: 30 to 50 W; temperature limit: 42°C). The location of the PVC was defined by the successful site where radiofrequency application permanently suppressed ventricular ectopy during the procedure. The RVOT was subcategorized into 6 sections: 1) anterior free wall; 2) free wall; 3) posterior free wall; 4) posteroseptal; 5) septal; 6) anteroseptal; and 7) pulmonary artery. The LVOT was subcategorized into: 1) right coronary cusp (RCC); 2) RCC-left coronary cusp (LCC) junction (RCC/LCC); 3) LCC; 4) aorto-mitral continuity region; and 5) coronary venous system (great cardiac vein [GCV]-interventricular vein [AIV] junction).
Electrocardiographic analysis: V4/V8 ratio
In all patients, the 12-lead ECG (V1 and V2 in the fourth intercostal space) was recorded during sinus rhythm and PVCs and measurements were made using the electronic caliper of the recording system (Prucka Cardiolab, GE Healthcare, Waukesha, Wisconsin, and EP LabSystem, Bard, Lowell, Massachusetts) at a sweep speed of 100 mm/s with uniform lead gain. Amplitudes were measured using the vertical caliper tool and ratios were manually calculated. The T-P segment was used as the isoelectric baseline for R and S amplitude measurement. R-wave duration was measure from the first deflection from baseline back to the return to baseline (T-P segment).
The following measurements were made for all patients during both sinus rhythm and the PVC:
1. R-wave duration in V1
2. R-wave amplitude in V1-V4
3. Precordial transition defined as the lead with R>S
4. R and S wave amplitude of V2
5. R-wave amplitude of V8 and V9, if there was no R-wave present on V8 or V9, this was considered to be zero
6. Ratio of PVC R-wave V4/V8
7. Ratio of sinus rhythm R-wave V4/V8
8. V4/V8 Index defined as the normalized ratio of PVC V4/V8 divided by sinus rhythm V4/V8 (Figure 1)
R-waves were measured from the isoelectric line as the reference for both amplitude and duration. In the prospective validation cohort, the V4/V8 ratio and V4/V8 index were compared with the V2 transition ratio (cutoff ≥0.6) (6) and the V2S/V3R ratio (cutoff ≤1.5) (8). Sensitivity and specificity of each test was calculated and analysis was performed using receiver operator characteristic curves.
Prospective derivation and validation
The planning of this prospective study involved 2 phases: 1) prospective derivation of optimal cutpoints (n = 134) and 2) prospective validation study (n = 40). All cases included in both phases had placement of the posterior leads prior to mapping and ablation. Our central hypothesis was that PVCs arising from the LVOT exhibit a higher V4/V8 ratio compared with RVOT origin because of earlier R-wave precordial transition (V4) with the predominant vector moving away from posterior lead (V8). Additionally, we hypothesized that comparing this ratio with the intrinsic sinus rhythm as a normalized index would improve diagnostic accuracy, as originally described by Betensky et al. As proof-of-concept, we pace-mapped from different outflow tract regions to assess if a gradient of R-wave loss in V8 was seen from right to left in the first 5 patients (Figure 2).
Continuous variable are presented as mean standard deviation. Continuous variables were compared with Student t test. Receiver operator curves were used for sensitivity and specificity analysis to calculate area under the curve (AUC). A p value < 0.05 was considered statistically significant.
A total of 134 patients underwent ablation of PVCs with 2 modified posterior leads (V5 and V6). The mean age was 45 ± 15 years, and 37% were male. The mean ejection fraction was 62 ± 7% with a PVC burden of 24 ± 12%. The PVC had a left bundle morphology in 88% of cases. Thirty-three had left-sided sites of successful ablation (aorto-mitral continuity [AMC] region: 14; GCV-AIV: 8; RCC: 4; RCC/LCC junction: 3; LCC: 4) and 101 had successful ablation from within the RVOT. The locations of the successful ablation sites are shown in Table 1. A mean 5 ± 4 radiofrequency applications were delivered in each patient to eliminate the PVC. One patient (right BBB morphology) had acute failure resulting from the proximity of the coronary artery to the GCV earliest site of activation (V4/V8 ratio: 7.44; V4/V8 index: 3.66).
Increasing values for mean V4/V8 ratios were observed from anterior to posterior locations with anterior RVOT sites exhibiting a ratio of 0.65, posteroseptal RVOT 2.29, RCC 7.77, and LCC 8.27. A similar increasing trend of mean V4/V8 index was observed, with anterior RVOT showing the lowest index of 0.33, posteroseptal RVOT 1.03, RCC 2.32, and LCC 3.95. A summary of the V4/V8 ratios and V4/V8 indices normalized to sinus rhythm is shown in Table 2.
Overall, PVCs successfully ablated from the left side had a statistically significantly higher V4/V8 ratio compared with right-sided PVCs (11.7 ± 10.6 vs. 2.3 ± 2.4, p < 0.001). At a cutoff >3, the V4/V8 ratio had a sensitivity of 88% with a specificity of 77% (AUC: 0.89 [0.83 to 0.94]) (Figure 3). When normalized to sinus rhythm, PVCs successfully ablated from the left side had a statistically significantly higher V4/V8 index compared with right-sided PVCs (4.7 ± 3.5 vs. 0.9 ± 0.7, p < 0.001). At a cutoff >2.28, the V4/V8 index had a sensitivity of 67% with a specificity of 98% (AUC: 0.85 [0.78 to 0.91]). Discrimination with the V9 lead was not as strong as the V8 lead and therefore V9 was not subsequently used. When using the V9 lead, the AUC for V4/V9 ratio was 0.86 (0.7 to 0.92) with a sensitivity of 76% and specificity of 84% at a cutoff of >6.29.
Prospective validation cohort
Forty patients underwent ablation of PVCs with modified posterior leads. The mean age was 44 ± 16 yrs, and 35% were male. The mean ejection fraction was 61 ± 8% with a PVC burden of 23 ± 12%. The PVC had a left bundle morphology in 100% of cases, and 48% (n = 19) had a V3 transition. Twelve had left-sided sites of successful ablation (LV RCC: 5; RCC/LCC junction: 3; LCC: 4) and 28 had successful ablation from within the RVOT. The locations of the successful ablation sites are shown in Table 1. A mean of 5 ± 4 radiofrequency applications were delivered in each patient to eliminate the PVC. One patient had acute failure because of the proximity of the coronary artery to the AIV’s earliest site of activation left bundle branch morphology PVC (V4/V8 ratio: 4.62). At the cutoff >3, the V4/V8 ratio had a sensitivity of 75% with a specificity of 82% (positive predictive value [PPV]: 64%; negative predictive value [NPV]: 89%) for left-sided locations. When normalized to sinus rhythm, the cutoff >2.28 for the V4/V8 index had a sensitivity of 67%, specificity of 96%, PPV of 89%, and NPV of 87% for left-sided locations. The V2 transition had a sensitivity of 67%, specificity of 67%, PPV 47%, and NPV 82% at a cutoff ≥0.6 for left-sided PVCs. The V2S/V3R ratio had a sensitivity of 36%, specificity of 71%, PPV 33%, and NPV 74% at a cutoff of ≤1.5 (Table 3). An example of an LVOT PVC ablated from the right side of the RCC/LCC commissure that was correctly predicted only by the V4/V8 ratio and index is shown (Figure 4).
When analyzing 19 patients with a V3 precordial transition, the sensitivity of V4/V8 and the V4/V8 index was 67% and 67%, whereas the V2 transition and V2S/V3R had sensitivity of 50% and 40%, respectively. The specificity of V4/V8 and the V4/V8 index was 81% and 100%, whereas the V2 transition and V2S/V3R had specificity of 54% and 62%, respectively. The V4/V8 index had a positive predictive value of 100% and both V4/V8 ratio and V4/V8 index had a negative predictive value of 87% (Table 3). An example of an RVOT PVC with V3 transition that was correctly predicted only by the V4/V8 ratio and index is shown (Figure 5).
The major findings of the present prospective study are as follows.
1. A posterior modification of positioning lead V5 to V8 allows for the calculation of a novel anteroposterior ratio, which improves the diagnostic accuracy for differentiating left from right ventricular OT locations.
2. Normalizing the V4/V8 ratio to the patient’s sinus rhythm results in improved specificity and positive predictive value for left-sided sites.
The cardiac anatomic orientation within the chest necessitates the relationship of “right” and “left” structures to be more accurately defined as “anterior” and “posterior,” respectively. Although the early precordial R-wave amplitude of V1 and V2 during PVCs arising from the aortic root is due to a leftward origin with respect to the right precordial leads, an important contribution of the R-wave amplitude may be attributed to a posterior to anterior vector.
As the RVOT rotates and wraps around the central aorta, the portion of the RVOT adjacent to the pulmonary valves is leftward of the aortic root. For this reason, a dedicated lead on the back to compare the relative amplitudes with vector analysis in an anteroposterior dimension has anatomic merit. We chose the modification of placing V5 posteriorly to V8 because it does not require additional electrocardiographic leads, simplifying its application in any clinical setting. More important, precordial transition is typically most discriminatory at V3, making V5 and V6 relatively expendable for diagnostic localization. Igarashi et al. recently evaluating the localization of PVCs with an 18-lead ECG, which included back and right-sided leads (11). In this study, an anteroposterior ratio was not evaluated and the most accurate predictor was right-sided V5R.
Several criteria have been clinically useful to differentiate right and left OTVT. Ouyang et al. reported a greater R-wave duration and R/S-wave amplitude ratio in leads V1 or V2 in LVOT origin (12). Distinctive morphologic patterns have been reported to be specific for the LCC/RCC junction (3,13). Tanner et al. reported that outflow tract VTs with V3 transitions may arise from six distinct anatomic sites (14). The proportion of patients (48%) with V3 transition in their validation group was higher than other published studies. More important, the V4/V8 index has the highest specificity (100%) in cases with a left BBB pattern with V3 transition, which is clinically most challenging to differentiate right from left locations.
The reproducibility of electrode placement between technicians and various clinic and procedural settings is limited. Further, variable chest–heart relationships resulting from cardiac orientation and rotation limits the generalizability of any ECG criteria. One logical method to mitigate these variations requires interpretation of normalized or “indexed” precordial transition with respect to the sinus rhythm transition. Betensky et al. demonstrated this concept in a series of patients with retrospective and prospective evaluation, showing that the V2 transition ratio outperformed traditional criteria (6). For the same reason, we report that the V4/V8 index has greater specificity and positive predictive value than a single PVC value in isolation. Although this does require an additional step in analysis, the rationale for this correction allows for each subject to serve as their own control when calculating an ECG parameter and the present data further support this notion.
The strength of the present study is the prospective comparison with other validated criteria. We found that this anteroposterior ratio of V4/V8 outperformed previously validated criteria with a demonstrated diagnostic accuracy >90%. The majority of the published ECG criteria to localize PVC origin have not been prospectively evaluated, with the exception of Betensky et al. (6) and Ito et al. (9). To our knowledge, this is the largest prospective (n = 174) examination of ECG criteria for differentiating left from right OT ventricular arrhythmias. A highly specific ECG criterion for left-sided successful ablation sites has several clinical advantages. First, mapping of the OT regions is conventionally performed from right to left. Unnecessary ablation and mapping can be avoided if left-sided origin is suggested, because perforations are most commonly seen in the RVOT. Additionally, non-RVOT sites of origin have been reported to have greater association with PVC-induced cardiomyopathy (15,16) as well as risk for sudden death (10). The identification of these subsets from a modified 12-lead ECG even in the clinic setting can be helpful for patient consultation and procedural planning.
We chose the inferior point of the scapula as a reference point for localization for posterior lead placement for reproducibility. As with anterior electrode placement, the relative anatomy of an individual cardiac position in relation to the scapula has inherent variability with variations in body habitus. It is not clear how anatomic variations and obesity affect the anteroposterior ratio, but we believe that the indexing to sinus rhythm helps overcome part of these limitations. Further, this anteroposterior vectoral approach is least confounded if V4 and V8 are situated at the exact same craniocaudal level. A more inferior displacement of 1 lead relative to the other could alter R-wave amplitude that is not indicative of the anteroposterior relationship. Because of improved receiver operating characteristic curves and test characteristics in lead V8 compared with V9, we did not report the details and characteristics of V9 lead data. Further, the value of alternate posterior ECG site locations was not tested in this study, but we believe that the utility of a single lead relative to the scapula is useful for ease of clinical implementation.
PVCs with a right BBB pattern pose less of a diagnostic dilemma, but these cases were only included as proof of concept in the derivation study. Last, ablation may be successful from multiple locations because of the close relationship of the RVOT and LVOT, particularly in the posterior RVOT relative to the RCC, which both provide access to the highest portion of the interventricular septum. The classification of such sites has an element of arbitrariness and likely reflects the same region of origin. This may explain the relatively larger standard deviation seen in cases successfully ablated from the RCC. Preferential exits can occur across the septum from the site of origin and also account for wide standard deviations because the 12-lead ECG only reflects the exit site (17). Because simultaneous mapping from both outflow tracts was not required before ablation, it is possible that earlier sites of activation relative to the ablation site may have been found in other regions. For this reason, we chose a clinically practical definition to serve as the PVC location gold standard, where the PVC was permanently suppressed by ablation, rather than activation timing.
A simple modification of precordial lead V5 posteriorly to V8 may provide incremental diagnostic value for localizing PVCs arising from the outflow tracts. In addition to this novel anteroposterior ratio, normalizing PVC localization criteria to the sinus rhythm results in the highest specificity when compared with other validated criteria.
COMPETENCY IN MEDICAL KNOWLEDGE: To appreciate the limitations of current precordial lead placement for localizing outflow tract PVCs that have an anatomic anterior to posterior orientation. To understand that the V4/V8 ratio outperformed previously published criteria in the largest prospective analysis of PVC localization to date.
TRANSLATIONAL OUTLOOK 1: The present study suggests that enhancement of ECG localization can be achieved by creating an anteroposterior ratio using a standard 12-lead ECG with placement of V5 on the back under the scapula.
TRANSLATIONAL OUTLOOK 2: Improved identification of left-sided successful sites of ablation may improve preprocedural consultation, planning, and identifying patient subsets that may be at higher risk.
Dr. Hamon has received a grant from the Federation Francaise de Cardiologie. Drs. Zhang, Fang, Xu, Yang, Ju, and Chen were supported by grants from the National Natural Science Foundation of China (Grant no. 81470456), by the National “Twelfth Five-Year” Plan for Science & Technology Support (Grant no. 2011BAI11B13), a by “A Project Funded by the Priority Academic Program Development of Jiangsu Higher Education Institutions, and by NIH R01 HL084261 & NIH OT2OD023848.
Drs. Zhang and Hamon contributed equally to this work.
- Abbreviations and Acronyms
- interventricular vein
- area under the curve
- bundle branch block
- great cardiac vein
- left coronary cusp
- left ventricular outflow tract
- negative predictive value
- outflow tract
- positive predictive value
- premature ventricular complex
- right coronary cusp
- right ventricular outflow tract
- Received October 28, 2016.
- Revision received December 13, 2016.
- Accepted December 22, 2016.
- American College of Cardiology Foundation
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