A Vector-Based Algorithm to Differentiate Septal and Free Wall Sites of Origin of Ventricular Arrhythmias in the Right Ventricular Outflow Tract

Fengxiang Zhang; Yan Xu; Zhen Fang; Liyan Zhao; Bing Yang; Hongwu Chen; Weizhu Ju; Mohammad Bilaal Toorabally; Kejiang Cao; Minglong Chen

doi:10.4103/2352-4197.191481

ORIGINAL ARTICLE

Year : 2016 | Volume : 1 | Issue : 1 | Page : 43-49

A Vector-Based Algorithm to Differentiate Septal and Free Wall Sites of Origin of Ventricular Arrhythmias in the Right Ventricular Outflow Tract

Fengxiang Zhang, Yan Xu, Zhen Fang, Liyan Zhao, Bing Yang, Hongwu Chen, Weizhu Ju, Mohammad Bilaal Toorabally, Kejiang Cao, Minglong Chen
Section of Pacing and Electrophysiology, Division of Cardiology, The First Affiliated Hospital to Nanjing Medical University, Nanjing 210029, PR China

Date of Web Publication

30-Sep-2016

Correspondence Address:
Fengxiang Zhang
Section of Pacing and Electrophysiology, Division of Cardiology, The First Affiliated Hospital of Nanjing Medical University, Guangzhou Road 300, Nanjing 210029
PR China

Source of Support: None, Conflict of Interest: None

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DOI: 10.4103/2352-4197.191481

Abstract

Purposes: There are few vector-based electrocardiogram (ECG) algorithms to differentiate ventricular tachycardia (VT) and premature ventricular complexes (PVCs) originating from the septum (SP) or free wall (FW) in the right ventricular outflow tract (RVOT). Methods: One hundred and twenty-one patients (mean age 41 ± 13 years; 62% female) underwent mapping and ablation of symptomatic PVC or VT with left bundle branch block morphology. Inferior axis and precordial lead transition zone ≥V3 on the ECG were analyzed retrospectively. Ablation was highly successful on the 95 SP patients and among 26 cases in the FW group. The ECG morphology of VT/PVC was analyzed to derive a novel algorithm to localize VT origin within the RVOT. A VT/PVC QRS axis ≥90° or an R wave amplitude ratios ≥1 in leads II and III predicted a septal origin. If neither of these characteristics were present, the following criteria were each given a score of 1: VT/PVC QRS axis <85;°, leads II and III R wave amplitude ratio <0;.88, QRS duration in lead III ≥155 ms, and QRS duration ≥155 ms in lead aVL. A cumulative score of ≥2 predicted an FW origin whereas a total score of <2; predicted an SP origin. A prospective analysis in 99 patients was used to confirm the significance of the algorithm. Results: Retrospective analysis showed that the new algorithm predicted an SP origin with an overall sensitivity, specificity, and positive predictive values of 95.2%, 88%, and 96.3%, respectively. Prospective analysis showed that the new algorithm predicted RVOT-SP origin with a sensitivity, specificity, and positive predictive values of 97.5%, 88.9%, and 97.5%, respectively. Conclusion: The new vector-based ECG algorithm can differentiate septal from FW sites of origin in the RVOT with a high sensitivity, specificity, and positive predictive values.

Keywords: Algorithms, premature ventricular complex, radiofrequency catheter ablation, ventricular tachycardia

How to cite this article:
Zhang F, Xu Y, Fang Z, Zhao L, Yang B, Chen H, Ju W, Toorabally MB, Cao K, Chen M. A Vector-Based Algorithm to Differentiate Septal and Free Wall Sites of Origin of Ventricular Arrhythmias in the Right Ventricular Outflow Tract. Int J Heart Rhythm 2016;1:43-9

How to cite this URL:
Zhang F, Xu Y, Fang Z, Zhao L, Yang B, Chen H, Ju W, Toorabally MB, Cao K, Chen M. A Vector-Based Algorithm to Differentiate Septal and Free Wall Sites of Origin of Ventricular Arrhythmias in the Right Ventricular Outflow Tract. Int J Heart Rhythm [serial online] 2016 [cited 2023 Jun 5];1:43-9. Available from: https://www.ijhronline.org/text.asp?2016/1/1/43/191481

Introduction

Ventricular tachycardia (VT) and premature ventricular complexes (PVCs) with a left bundle branch block (LBBB) morphology and inferior axis most commonly arise from an anatomic site of origin in the right ventricular outflow tract (RVOT). Radiofrequency catheter ablation has shown to have a high success rate in eliminating RVOT VT/PVC.^{[1],[2],[3],[4],[5]} Accurate preprocedural localization of VT/PVC origin has the potential to reduce procedure duration and fluoroscopy time. VT/PVC originating from the free wall (FW) of the RVOT has already been proposed before; however, the criteria are mostly based on QRS duration and morphology.^{[6],[7],[8],[9],[10],[11]} In this study, we developed a vector-based algorithm, retrospectively and prospectively evaluated its distinguishing characteristics in differentiating RVOT-septum (SP) from FW origin.

Materials and Methods

Patient population

Patients undergoing ablation of symptomatic VT or PVC with LBBB morphology, inferior axis, and precordial lead transition zone ≥V3 were included. A PVC count of >20% total beats on 24 h Holter monitoring was required in all patients.^[12] The patients remained symptomatic despite administration of Class I or II antiarrhythmic drugs (AAD). Patients with structural heart disease, polymorphic ventricular arrhythmias (VA), preexisting LBBB or RBBB during sinus rhythm, and those with VT/PVC originating beyond the RVOT were excluded from the study. Consecutive patients undergoing ablation between June 2007 and December 2011 formed the retrospective cohort, from whom the novel electrocardiogram (ECG) algorithm was derived. This algorithm was then tested prospectively in the second cohort of consecutive patients who underwent successful ablation of RVOT PVC/VT between August 2012 and October 2014. The study protocol conforms to the ethical guidelines of the 1975 Declaration of Helsinki as reflected in a priori approval by the Institutional Human Research Ethics Committee.^[13]

Electrocardiogram parameters

All ECGs were analyzed from the recording system at a speed of 25 mm/s with digital calipers. ECG measurements were made in accordance with the previous reports.^{[6],[7],[8],[14],[15]} The following measurements of the clinical VT/PVC were made:

VT/PVC QRS axis
R wave amplitude in lead I, II, III, and aVF
S wave amplitude in lead aVR, aVL, V1, and V2
QRS wave duration in lead I, II, III, aVR, aVL, aVF, V1, and V2.

The segment between T wave andPwave (TP segment) was considered the isoelectric baseline for the measurement of R and S wave amplitudes. The QRS duration was measured from the earliest initial deflection in any given lead to the time of latest activation in that same lead.^[16] For VT cases, QRS measurements were made on the first beat of VT or isolated PVC representative of the clinical VT before the induction of sustained VT.

Electrocardiogram electrical axis measurement

The QRS axis was determined from inspection of the ECG tracings by two independent, experienced cardiac electrophysiologists. The axis was recorded and compared with automatic ECG determination and a difference of more than 3° in axis determined by the two readers was resolved by joint reevaluation of the tracings.^[17] The R or S wave amplitudes were measured by digital calipers in leads I and III. The algebraic sum of the QRS vectors was calculated in leads I and III to calculate the QRS axis according to Einthoven's Law.

Electrophysiological testing

All AADs were discontinued for at least 5 half-lives before the procedure. After written informed consent had been obtained, the electrophysiology study was performed in the fasting state. A quadripolar electrode catheter, mapping catheter, and RF ablation catheter (Cordis Webster Inc., Baldwin Park, CA, USA; EP Technologies Inc., San Jose, CA, USA) were inserted into the right femoral vein and positioned in the right ventricle apex and the RVOT. A three-dimensional (3D) mapping system (Ensite Array or NavX, St Jude Medical, St. Paul, MN, USA) was used for RVOT VT/PVC mapping. Electrograms were filtered at 30 Hz and 500 Hz. If few or no PVCs were observed at baseline, programmed ventricular stimulation was performed with intravenous administration of isoproterenol and/or epinephrine to induce VT or PVC. Systemic heparinization maintained an activated clotting time of 250–300 s throughout the procedure.

Mapping and catheter ablation

The 3D geometry of the RVOT was constructed by navigating and mapping an ablation catheter within the RV. SP and FW zones were defined by 3D computed tomography geometry. At 30° right anterior oblique position, the right anterior wall was defined as the FW and the left lateral part as the SP. In 45° left anterior oblique position, the left part was FW and the right part was the SP [Figure 1].^[18] When the EnSite multielectrode array (MEA) was used, it was placed at the optimal mapping position whereby the earliest activation (EA) site and the breakout (BO) sites of VT/PVC to the center of MEA (defined as R value) were not more than 35 mm.^[19] For identification of the EA site and BO site, a broad color band setting was used with color high (defined as unipolar electrogram baseline) at 0 mV and color low at −2 mV. The virtual unipolar high-pass filter was set at 4 Hz. The EA site was defined as the site with the earliest unipolar deflection from baseline during spontaneous PVC/VT, forming a single spot on the isopotential map, as well as characterized by a QS pattern of noncontact unipolar electrogram. The BO site was marked as the site along the depolarization pathway identified by the color-coded activation map where rapid centrifugal electrical propagation originated from and local unipolar electrograms exhibited the maximum negative dV/dt.^[20],[21] Ablation was initiated at either the EA or BO site and crossed over to the other if the initial ablation was not very successful. When the NavX electroanatomical mapping system was used, an endocardial activation map was created using bipolar electrograms recorded during either VT or PVC. Pace mapping was used to confirm the putative target site as the true site of PVC origin. Pacing was performed at the diastolic threshold and 0.5 ms pulse width with the pacing cycle length 10 ms less than the coupling interval of the PVC.

Figure 1: The schematic representation of free wall and septum of the right ventricular outflow tract by 3D computed tomography and three.dimensional electroanatomical map. Free wall and septum of the right ventricular outflow tract are shown with three-dimensional computed tomography at the projection of right anterior oblique 30° and (a) left anterior oblique 45° (b) superior view of septum and free wall of the right ventricular outflow tract with EnSite map, real line represents the free wall, dotted line represents the septum (c and d). RVOT=Right ventricular outflow tract, CT=Computed tomography, FW=Free wall, SP=Septum, RAO=Right anterior oblique, LAO=Left anterior oblique.

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Ablation was performed by delivering radiofrequency energy in temperature-control mode. The power output was titrated to as high as 40 W to achieve a target temperature of 50–60°C for 60 s. The ablation was considered acutely successful if the VT or PVC were eliminated during the ablation and/or became noninducible with programmed electrical stimulation with or without isoproterenol infusion.

Follow-up

After the procedure, ECG monitoring was performed for 24 h in all patients. All patients were seen in an outpatient clinic every month after the procedure in the first 3 months, and then followed up every 6 months. During each clinic visit, a 12-lead ECG was recorded in each patient and 24 h Holter monitoring was performed at every follow-up. Recurrence of arrhythmia was defined as the recurrence of symptoms and ECG or 24 h Holter monitoring recorded VT/PVC.

Statistical analysis

Continuous variables and categorical variables were described by means ± standard deviation and percentages, respectively. Independent sample t-test was used to compare continuous variables such as baseline characteristics and electrophysiological parameters between SP and FW groups. Chi-square test was used for nonparametric analysis. A univariate and multivariate analyses were used with the logistic forward Wald regression model to determine the independent predictors of VT/PVC origin from the RVOT-FW. Receiver-operating characteristic (ROC) analysis was used to assess the ability to predict the value of the VT/PVC originating from the RVOT-SP or FW. P < 0.05 was considered statistically significant. All confidence intervals (CIs) were calculated at a 95% interval.

Results

Patient characteristics

In total, 220 patients participated in this study, with 121 cases in the retrospective phase and a further 99 cases forming the prospective validation cohort. In the retrospective stage, 156 patients fulfilling the inclusion criteria underwent successful ablation between June 2007 and December 2011. Of these, 34 patients had PVC/VT originating from beyond the RVOT (20 with pulmonary artery printarticle.asp?issn=2352-4197;year=2016;volume=1;issue=1;spage=43;epage=49;aulast=Zhang foci, 10 with left ventricular outflow tract foci, and 4 with distal great cardiac vein foci) and ablation was unsuccessful in 1 patient. After excluding these patients, a total of 121 patients with VT/PVC with successful ablation in the RVOT were included for analysis. The mean age of these 121 patients was 40.7 ± 13.4 years, with 46 male cases. A single focus was found in all patients; 95 at the SP [Figure 2]a,[Figure 2]b,[Figure 2]c,[Figure 2]d,[Figure 2]e and 26 at the FW [Figure 2]f,[Figure 2]i,[Figure 2]j. Baseline characteristics and electrophysiological and ablation parameters were similar between the SP and FW groups [Table 1]. With follow-up of 63.7 ± 19.4 months, same morphology PVC reoccurred in three patients, SP PVC in one patient, and FW PVC in another two patients. They received repeated ablation successfully.

Figure 2: Noncontact mapping and pace mapping for premature ventricular complex originate from the septum and free wall of the right ventricular outflow tract. Premature ventricular complex originates from the septum of right ventricular outflow tract (a-e): Premature ventricular complex QRS axis 87°, III and II R wave amplitude ratio 0.92, aVL and III QRS duration 122 ms (a). Noncontact mapping disclosed the earliest activation and breakout site of premature ventricular complex at the septum (b and c). Pace mapping at the earliest activation and breakout site (d and e). Premature ventricular complex originates from the free wall of right ventricular outflow tract (f-j): Premature ventricular complex QRS axis 74°, III and II R wave amplitude ratio 0.85, aVL and III QRS duration was 160 ms (f). Noncontact mapping disclosed the earliest activation and breakout site of premature ventricular complex at the free wall (i and j). Pace mapping at the earliest activation and breakout site (g and h). NCM = Noncontact mapping, FW = Free wall, PVC: Premature ventricular complexes, RVOT=Right ventricular outflow tract.

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Table 1: Patients' characteristics and parameters were showed during the procedure

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In the prospective stage, 136 patients fulfilling the inclusion criteria underwent successful ablation between August 2012 and October 2014. Thirty-seven of them had PVC/VT originating from beyond the RVOT (9 with PA foci, 23 with left ventricular outflow tract foci, and 5 with distal great cardiac vein foci) and 99 patients underwent successful ablation of RVOT PVC/VT. The mean age was 44.3 ± 18.7 years with 37.4% male. There was no significant difference of the foci originating from the SP (78.5% vs. 80.8%) between the retrospective and prospective validation cohorts. However, there was a significant difference of the procedural duration, X-ray exposure time, and dose between the two groups [Table 2].

Table 2: Patients' characteristics between retrospective and prospective cohorts

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QRS axis, QRS duration and amplitude

The mean VT/PVC QRS axis was 87.9 ± 9.8° versus 76.5 ± 9.7° (CI 6.74–15.99, P < 0.001) in SP and FW groups, respectively [Table 3]. For all limb and V2 leads, QRS duration was wider in the FW group (P< 0.01). VT/PVC R wave amplitudes in lead III and aVF as well as the III/II ratio were significantly higher in SP group than that of FW group (P< 0.05). VT/PVC S wave amplitudes in lead aVL in SP group were significantly higher than that of FW group (P< 0.05).

Table 3: Axis, QRS wave duration, and amplitude of ventricular tachycardia/premature ventricular complexes between the septum and free wall foci in the retrospective cohort

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Predictors of ventricular tachycardia/premature ventricular complex originating from the septum and free wall of the right ventricular outflow tract

Based on univariate analysis, the following variables were significantly associated with the origin of VT/PVC and were added to the multivariate logistic regression model to predict RVOT origin: For RVOT-SP origin – VT/PVC QRS axis, VT/PVC R wave amplitude in lead III, aVF, III/II ratio, and S wave amplitude in lead aVL (P< 0.05) and for RVOT-FW origin – VT/PVC QRS durations in leads I, II, III, aVR, aVL, aVF, V2, and S wave amplitudes in V1 and V2 (P< 0.01). Multivariate analyses showed that VT/PVC QRS axis and III/II R wave amplitude ratios were independent predictors of an RVOT-SP origin (P< 0.01). VT/PVC III and aVL lead QRS durations were independent predictors of RVOT-FW origins (P< 0.05) [Table 4]. ROC analysis was performed to establish the cutoff values for each of these 4 independent parameters to distinguish between SP and FW origins [Table 5].

Table 4: Univariate and multivariate analyses for the origin of ventricular tachycardia/premature ventricular complexes

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Table 5: Receiver-operating characteristic analysis was performed to establish the cut-off value for each of these four independent parameters to discriminate between a septum and free wall origin

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A new algorithm

Based on the sites of successful ablation as confirmation of PVC/VT origin and informed by multivariate and ROC analysis of these 121 patients, a novel 3-step algorithm was proposed as follows [Figure 3]:

Step 1: VT/PVC QRS axis ≥90° (n = 39, 32.2%) predicted a RVOT-SP origin with 46.3% sensitivity, 96.2% specificity, and 97.4% positive predictive value
Step 2: VT/PVC III and II R wave amplitude ratio ≥1 (n = 8, 6.6%) predicted an RVOT-SP origin with 33.7% sensitivity, 92.3% specificity, and 93.3% positive predictive value
Step 3: The VT/PVC morphology was scored based on 4 criteria (n = 74, 61.2%): VT/PVC axis <85;°, III and II R wave amplitude ratio <0;.88, IIId ≥155 ms and AVLd ≥155 ms. A score of 1 was given for each criterion met. If the total score in step 3 is <2;, an SP origin was predicted. Conversely, if the final score is ≥2, the origin was deemed to be on the FW. The sensitivity, specificity, and positive predictive values were 96.3%, 84.6%, and 95.2%, respectively, for prediction of an RVOT-SP origin.

In general, in the retrospective phase, the new algorithm had an overall sensitivity, specificity, and positive predictive values of 95.2%, 88%, and 96.3%, respectively, to predict an RVOT-SP focus.

Figure 3: Step-wise electrocardiographic algorithms for determination of the origin of ventricular tachycardia/premature ventricular complex at the septum or free wall in the right ventricular outflow tract. VT=Ventricular tachycardia, PVC=Premature ventricular complexes, SP=Septum, FW=Free wall, RVOT=Right ventricular outflow tract, IIIa/IIa, III, and II R wave amplitude ratio, IIId, III duration; aVLd, aVL duration.

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Prospective analysis of the new electrocardiogram algorithm

The new ECG algorithm was prospectively tested in 99 patients who underwent successful ablation of RVOT-VT/PVC. The overall sensitivity, specificity, and positive predictive values to identify a successful ablation site of this newly proposed ECG algorithm were 97.5%, 88.9%, and 97.5%, respectively, for SP origin.

Follow-up

All patients completed electrocardiographic follow-up. Seventeen patients declined to physically come back to the clinic; however, Holter recordings were performed at their local hospitals and forwarded to our institution for analysis. The remaining patients completed follow-up for at least 19 months. With a mean follow-up of 64.8 ± 96.3 (19.6–1417.4) months, PVC reoccurred in 11 subjects: 6 patients in retrospective group and 5 patients in the prospective group. All 11 patients were in SP group and underwent successful repeat ablation.

Discussion

Major findings

In this study involving 220 patients with RVOT PVC/VT, a novel vectorial ECG algorithm based entirely on analysis of limb leads parameters was able to discriminate between RVOT-SP and FW foci, with an overall sensitivity, specificity, and positive predictive values of 95.2%, 88%, and 96.3%, respectively, in a retrospective cohort of 121 patients. The performance of this algorithm was validated prospectively in the second cohort of 99 patients with a high positive predictive value of 97.5%.

The advantage of vector-based algorithm

The four factors reflected by the electrical vectors, VT/PVC QRS axis, R wave amplitude III/II ratio, III, and aVL QRS duration were identified with multivariate analysis. In a normal heart, where net electrical impulse travels from approximately 11 o'clock to 5 o'clock, lead II pointing toward 5 o'clock exhibits the greatest positive deflection, resulting in a normal heart electrical axis of 30° to + 90°. The larger muscle mass of the left ventricle cancels out detection of the right ventricle's electrical activity, leaving approximately 20% of the left ventricle's electrical activity to be sensed by the ECG. Thus, the normal QRS axis is directed downward and leftward. When depolarization does not occur via an intact His-Purkinje system, the QRS axis becomes variable.

Anatomically, the RVOT-SP is posterior and leftward in relation to the FW. When the VT/PVC originates from the RVOT-SP, the QRS axis is more rightward compared to the FW (87.9 ± 9.8° vs. 76.5 ± 9.7°, P = 0.0001). In this study, we found that VT/PVC QRS axis ≥90° predicted SP origin of PVC with 96.2% specificity and 97.4% positive predictive value.

In addition, a VT/PVC R wave amplitude III/II ≥1 predicted an RVOT-SP origin with 92.3% specificity and 93.3% positive predictive value. The vectors of VT/PVC originating from the RVOT-SP shift toward the direction of lead III, resulting in taller R wave amplitudes in lead III as compared to lead II. In contrast, the net vector of VT/PVC originating from the RVOT-FW is from right to left, causing R wave amplitudes to be higher in lead II compared to lead III.^[15] QRS wave duration greater than 155 ms in leads III and aVL was independent predictor of RVOT-FW origin. The QRS duration is wider because the electrical activity is further away from the septal conducting tissue [Figure 4].

Figure 4: The scheme of QRS axis of ventricular tachycardia/premature ventricular complex originated from the septum and free wall in the right ventricular outflow tract and sinus rhythm. SP=Septum, FW=Free wall, SR=Sinus rhythm, RVOT=Right ventricular outflow tract.

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Comparison with other algorithms

Several ECG algorithms have been used to assess VT/PVC originating from the FW or SP in the RVOT.^{[6],[7],[8],[9]} These algorithms were predominantly based on QRS duration, notching, amplitude, and inferior R wave height. When applied to the RVOT PVC/VT ECGs of the 121 patients in the retrospective cohort, the overall sensitivity, specificity, and positive predictive values to correctly identify the origin within the RVOT were 64%, 72.6%, and 70.6% using the algorithm proposed by Dixit et al.;^[6] 92%, 41.7%, and 53.2% proposed by Joshi and Wilber;^[7] 20%, 91.7%, and 75.2% proposed by Ito et al.;^[8] and 38.5%, 90.3%, and 53.2% proposed by Shima et al.,^[23] respectively. Tada et al. also revealed that lead III QRS duration was significantly longer in FW group than SP group; however, the VT/PVC QRS axis was not considered.^[9] The proposed ECG algorithm demonstrates an excellent performance in terms of sensitivity, specificity, and positive predictive values because of the different score criteria.

Clinical implications

This ECG algorithm allows for rapid and accurate differentiation of VT/PVC originating from the FW or SP in the RVOT. This algorithm may facilitate mapping and reduce fluoroscopic exposure and procedural duration.

Limitation

It is difficult to differentiate the PA and LVOT originating VA from RVOT-SP origin. VT/PVC originating from above the PA valve has been reported. We did not investigate whether the new score system was useful in differentiating the PA origin from the RVOT origin because VT/PVC originating from the PA and LVOT was excluded in this present study.

Conclusion

A new vector-based algorithm predicted the VT/PVC site of origin from the RVOT-SP and RVOT-FW with high sensitivity, specificity, and positive predictive values.

Acknowledgments

The authors would like to thank Roderick Tung, MD (The University of Chicago Medicine Center for Arrhythmia Care and Heart and Vascular Center) for his review of this manuscript and language editing.

Financial support and sponsorship

This work was supported by the grants from the National Natural Science Foundation of China (Grant no. 81470456, 81170160), by National “Twelfth Five-Year” Plan for Science and Technology Support (Grant no. 2011BAI11B13), by “A Project Funded by the Priority Academic Program Development of Jiangsu Higher Education Institutions,” by the Six Peak Talents Foundation of Jiangsu Province (Grant no. 2011-WS-071), and by the Program for Development of Innovative Research Team in the First Affiliated Hospital of Nanjing Medical University (Grant no. IRT-004).

Conflicts of interest

There are no conflicts of interest.

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