|24||Endocardial and Epicardial Anatomic Correlates of Repolarization Abnormalities in Arrhythmogenic Right Ventricular Dysplasia|
|Maciej Kubala, MD; Francis E. Marchlinski, MD|
The Revised Task Force diagnostic criteria for arrhythmogenic right ventricular dysplasia (ARVD) include depolarization and repolarization abnormalities on the surface electrocardiogram (ECG).1 A finding of inverted T waves in right precordial leads is the most common 12-lead ECG abnormality in ARVD.1 Normal repolarization has been found in 12% of patients.2 T-wave inversion in leads V1, V2, and V3 and beyond has been defined as major repolarization abnormality, while negative T waves limited to V1–V2 or V3–V4 have been identified as a minor repolarization abnormality by the Revised Task Force Criteria.1 It has been shown that T-wave inversions parallel the worsening of disease, and the extent of negative T waves across the surface ECG leads was associated with larger right ventricle (RV) diameter and more severe dysfunction.3,4 Common depolarization abnormalities, including epsilon waves, terminal QRS activation delay, and QRS fragmentation, have been associated with the location and extent of low-voltage areas and marked electrogram abnormalities characterized by electroanatomic mapping.5,6 A number of approaches for substrate-based mapping and ablation in sinus or paced rhythm have been described.7 Importantly, methods targeting arrhythmogenic regions defined as zones of slow conduction based on identification of abnormal electrograms within low-voltage areas are all limited by the imprecise definition of the substrate.7 The genesis of negative T waves and ST segment elevation in ARVD and their relationship to the arrhythmogenic substrate have been less investigated. Both activation and recovery occur as propagated waveforms. Increased action potential gradients between the epicardium and endocardium are required for T-wave inversion.8,9 ARVD is characterized by fibrofatty replacement of myocytes progressing from epicardium to endocardium of the RV, resulting in ventricular arrhythmias and ventricular dysfunction.10,11 Changes in local action potential duration due to an underlying pathologic process can result in intrinsic electrical heterogeneity and a reversed repolarization sequence.12,13
SURFACE ECG REPOLARIZATION ABNORMALITIES AND ELECTROANATOMIC SUBSTRATE
The first study to demonstrate the value of electrocardiographic repolarization abnormalities in estimating the electroanatomic substrate compared the extent of negative T waves in both precordial and inferior leads to the endocardial surface of electroanatomic scar.14 In this study of 49 patients with Task Force Criteria for ARVD, negative T waves were defined as ≥ 1 mm in depth in 2 or more adjacent leads, and isolated negative T waves in leads III, aVR, and V1 were considered normal. Patients with a complete right bundle branch block were excluded. An electroanatomic endocardial RV voltage map was considered abnormal in the presence of low-voltage areas ≥ 1 cm2 including 3 or more adjacent points with a bipolar signal amplitude < 1.5 mV. The median extent of total electroanatomic endocardial scar was 33 cm2 (12.4–67.8) corresponding to a median 22.5% (5.5–31.7%) of the total RV area. The extent of negative T waves across the 12-lead ECG was correlated significantly with the RV electroanatomic scar area. Median electroanatomic scar area varied from 4.9% in patients without negative T waves to 22% in patients with negative T waves in leads V1–V3, 26.8% if negative T waves extended through V1–V6, and 30.2% in the presence of T-wave inversion in both precordial and inferior leads. The extent of negative T waves was an independent predictor of RV electroanatomic scar area and was also associated with higher RV end-diastolic volume. Moreover, the authors demonstrated a statistically significant association between the extent of negative T waves and the occurrence of major clinical events, including aborted sudden cardiac death, sustained ventricular tachycardia, or appropriate implantable cardioverter-defibrillator interventions during a median follow-up of 36 months in 53% of patients with T-wave inversion versus 7% of those without negative T waves. This study was limited to evaluation of bipolar voltage abnormalities within the endocardium.
Larger areas of epicardial bipolar voltage abnormalities are typically identified in ARVD patients with only limited endocardial bipolar voltage abnormalities.15 The anatomic extent and location of the epicardial substrate can be identified using the endocardial unipolar voltage mapping with 5.5 mV cutoff value.15 Further information about the surface ECG repolarization abnormalities and the extent on endocardial and epicardial electroanatomic abnormalities was provided by this analysis.16 In this study, we aimed to correlate detailed endocardial and epi-cardial electroanatomic mapping findings with the extent of inverted T waves and the location of the ST segment elevation on the surface ECG in ARVD patients. Negative T waves were defined as ≥ 1 mm in depth in ≥ 2 adjacent leads. The downsloping elevated ST segment pattern was defined as the presence of ≥ 0.1 mV ST segment elevation at the J point in ≥ 2 V1–V3 or inferior leads with downsloping aspect of the ST segment defined as ≥ 0.1 mV decrease in amplitude between the end of the QRS and the 80 ms point (STJ/ST80 > 1) as described by Corrado (Figure 24.1).17 An endocardial electroanatomic mapping area was considered abnormal in the presence of multiple contiguous low-voltage electrogram sites < 1.5 mV bipolar or < 5.5 mV unipolar signal amplitude.18,19 On the epicardium, to limit the influence of epicardial fat and coronary vasculature, epicardial electrograms had to demonstrate more rigid low-voltage standard, which was defined as < 1.0 mV.20,21 To help distinguish low-amplitude epicardial electrograms due to fat, epicardial bipolar electrograms were defined as abnormal if they were additionally (1) wide, for example, at least 80 ms in duration; (2) split into two or more distinct components with 20 ms isoelectric segment between peaks of individual components; or (3) late, for example, distinct electrograms with onset after the end of the QRS complex.19,21
Figure 24.1 Electrocardiographic abnormality of the ST segment. Surface precordial electrograms (25 mm, 10 mm/mV) representing examples of two distinct, abnormal ST segment repolarization patterns in 4 representative patients. Vertical lines mark the J point (STJ) and the point 80 ms after the J point (ST80) where the amplitude of ST segment is calculated. In the downsloping elevated ST segment pattern, the STJ /ST80 ratio is > 1 and the decrease between the STJ and ST80 ≥ 1 mm.
To identify abnormal epicardial substrate being opposite to the endocardial anatomic shell we used a 0.5- to 1.0-cm margin from the anatomically defined right and left anterior descending coronary arteries. To facilitate the comparison of region-specific T-wave abnormalities with the corresponding RV electroanatomic substrate, a previously reported RV free wall scoring modified model was used (Figure 24.2) that assessed seven distinct anatomic segments.22
Figure 24.2 Schematic right anterior oblique view of the right ventricle divided into segments. For comparison of region-specific T wave abnormality with the corresponding RV electroanatomic substrate, segments 2 and 3 were merged forming RV mid free wall region, 5 and 6 forming inferior region, and segments 4 and 7 forming apical region. Abbreviations: PV, pulmonary valve; TV, tricuspid valve.
Abnormal unipolar RV endocardial area of 33.4 ± 19.3% was present in 8/40 (20%) patients without negative T waves. These findings show that the RV free wall may be affected by a localized pathological process before the appearance of repolarization abnormalities on 12-lead ECG. Moreover, in patients with normal repolarization, large areas of low-voltage abnormalities were identified at the stage where life-threatening arrhythmias have already occurred. Patients with negative T waves extending beyond lead V3 (n = 20) had larger low bipolar (31.4 ± 18.9% vs. 16.5 ± 14.6%, P = 0.008) and unipolar endocardial areas (66.0 ± 19.6% vs. 47.4 ± 25.1%, P = 0.013) and larger epicardial low bipolar area (56.0 ± 19.3% vs. 40.1 ± 24.9%, P = 0.030) compared to those with negative T waves limited to leads V1–V3 (n = 20) (Figures 24.3–24.5). This study also showed a correlation of the region-specific ECG repolarization abnormalities with corresponding regional electroanatomic substrate changes. T-wave inversion in leads V2–V3, which was the most common repolarization abnormality and observed in 96% of patients, was associated with RV mid free wall region bipolar voltage abnormality with a 95% sensitivity. Furthermore, anterior T-wave abnormality was associated with epicardial mid free wall substrate with 97% sensitivity and 50% specificity. Negative T-wave in leads V4–V5 was associated with low-voltage areas in apical region both on endocardium with 83% sensitivity and 42% specificity and on epicardium with 88% sensitivity and 67% specificity. A low-voltage abnormality extending inferiorly from the mid tricuspid annulus was identified in all of 14 patients with negative T waves in inferior leads with no false positive responses. These findings show the ability to identify and to locate endo- and epicardial electroanatomic substrate based on T-wave analysis on the 12-lead ECG. Accordingly, the location and extent of the substrate abnormality can be identified prior to the ablation procedure.