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Radiofrequency catheter ablation of the left ventricular epicardium as an electrophysiological substrate in a patient with idiopathic ventricular fibrillation associated with early repolarization
Address reprint requests and correspondence: Dr Ikutaro Nakajima, Division of Cardiology, St. Marianna University School of Medicine, 2-16-1 Sugao Miyamae-ku, Kawasaki, Kanagawa, Japan 〒216-8511.
The main underlying pathophysiological mechanism of early repolarization syndrome (ERS) remains debatable and is likely heterogeneous.
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Previous reports suggested there are 2 phenotypes of ERS: one with a late depolarization abnormality predominantly in the right ventricular epicardium, and the other with pure ERS without a ventricular fibrillation (VF) substrate but with VF triggers associated with Purkinje sites.
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There have been several experimental studies that explain the pathophysiology of ERS and the epicardial bipolar fractionated potentials as repolarization abnormalities.
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Our report suggests that there is a subset of patients with ERS in whom both local fractionated potentials and local J waves are present only on the LV epicardium, probably with repolarization features, and that the VF triggering premature ventricular contraction is associated with this arrhythmic substrate.
Introduction
Early repolarization syndrome (ERS), recognized as a specific electrocardiogram (ECG) pattern of J-point elevation in the inferior or lateral leads with unexplained ventricular fibrillation (VF), has been described in recent years.
The main underlying pathophysiological mechanism of ERS remains debatable, and previous studies have described both depolarization and repolarization abnormalities.
To date, there are still limited data that directly and fully show the electrophysiological findings of ERS. In this report, we described a VF storm patient with ERS that underwent an electrophysiological study on both the endocardium and epicardium and a successful radiofrequency catheter ablation (RFCA) of a triggering premature ventricular contraction (PVC).
Case report
A 43-year-old male patient with no prior medical history presented after an out-of-hospital cardiac arrest owing to VF terminated by an automated external defibrillator. After a shock delivery, his 12-lead ECG showed normal sinus rhythm with a J-point elevation in the inferior and lateral leads (I, II, aVL, aVF, and V5 to V6) (Figure 1A). He had no family history of sudden cardiac death, and further investigations including echocardiography, coronary angiography, and cardiac magnetic resonance imaging did not show any structural heart disease. Intravenous provocation tests with a sodium channel blocker (pilsicainide: 1 mg/kg for 5 minutes) did not lead to any augmentation of a Brugada-type ST-segment elevation. His genetic testing did not reveal any pathogenic mutations. He was diagnosed with idiopathic VF associated with ERS. During his hospitalization, paroxysmal atrial fibrillation was identified as well. He was administered ablation therapy for his symptomatic atrial fibrillation and an implantable cardioverter-defibrillator was implanted.
Figure 1A: Twelve-lead electrocardiogram (ECG) at baseline. The J waves were recorded in the inferior and lateral leads. B: Spontaneous clinical premature ventricular contraction (PVC) with a right bundle branch block morphology and inferior axis. C: A monitored ECG in lead II shows a monomorphic PVC (∗) that induced ventricular fibrillation.
During his follow-up, he was readmitted to our hospital because of multiple implantable cardioverter-defibrillator shocks owing to repeated VF episodes. After his admission, despite the intravenous application of isoproterenol and oral quinidine,
he developed a VF storm, which was preceded by a PVC with the same morphology (Figure 1B and 1C). Hence, we performed an electrophysiological study and radiofrequency ablation to eliminate the PVC triggering the VF.
Electrophysiological study
Under general anesthesia, multipolar catheters were advanced from the femoral vein. The pericardial space was accessed via a subxiphoid approach. Ventricular mapping and ablation were performed with a 3.5-mm-tip irrigated catheter (NaviStar ThermoCool SmartTouch; Biosense Webster, Inc, Diamond Bar, CA) using an electroanatomic map (CARTO 3; Biosense Webster). Unipolar electrograms were band-pass filtered from 0.05 to 100 Hz and bipolar were from 30 to 100 Hz and digitally recorded along with a 12-lead surface ECG using the Cardiolab EP System (General Electric Healthcare, Chicago, IL). Those electrograms were evaluated during appropriate catheter contact by using catheter-based contact force monitoring.
Endocardial electroanatomic bipolar mapping of the left ventricle (LV) during sinus rhythm exhibited a normal voltage (>1.5 mV) and normal electrograms. Moreover, no J waves were detected by unipolar mapping. Extensive pace mapping from the LV endocardium failed to reproduce a matched QRS morphology to the clinical PVC, while that from a multipolar catheter placed into the left lateral coronary vein was well matched; thus epicardial mapping was sequentially performed.
Epicardial electroanatomic bipolar mapping revealed an abnormal voltage (0.5–1.0 mV) in basal posterolateral LV during sinus rhythm (Figure 2A); however, a normal voltage was recorded in the right ventricle (RV). Of note here, no abnormal electrograms including fractionated or delayed potentials were demonstrated on the epicardial aspect of the RV free wall and RV outflow tract that suggested Brugada syndrome.
Interestingly, the area where the J waves were identified in the unipolar recording was located on the lateral to posterior LV wall as a clear segment, and all exhibited notched-type J waves (Figure 2A). Moreover, in the unipolar recording of the basal posterolateral LV epicardium, prominent J waves that coincided with ER in the 12-lead ECG were identified, and spiky fragmented signals at the end of the QRS complex were observed simultaneously in the bipolar recordings (Figure 2B). Abnormal bipolar electrograms were observed in a more localized area of the lateral LV epicardium within the area where J waves were observed in the unipolar recordings (Figure 2A). Those abnormal potentials exhibited no significant delay when the propagations changed during RV apical or LV endocardial pacing. The transmural conduction time from those abnormal potentials during pacing to the anatomical opposite LV endocardium was 40 ms, and was considered to be normal.
Figure 2A: Epicardial bipolar voltage (upper) and location map (lower) of the left ventricle (LV). Bipolar fractionated electrograms were observed on the posterolateral LV epicardium (blue dots). Prominent J waves in the unipolar electrograms were observed on the lateral to posterior LV wall as a clear segment (light blue). The white dots indicate locations where J waves are not observed in the unipolar recordings. The perfect pace map site of the clinical premature ventricular contraction (PVC) is shown as the white star. Radiofrequency ablation lesions (red dots) concentrated on the basal lateral LV epicardium. B: Unipolar (Uni) and bipolar (Bi) recordings on the lateral LV epicardium and on the opposite area on the endocardium. Prompt J waves (arrow) in the unipolar recordings and fractionated spiky potential (arrowhead) in the bipolar recordings were observed, while no J waves were recorded on the lateral LV endocardium. C: The 12-lead electrocardiogram of the spontaneous clinical PVC and paced beat at the ablation site on the basal lateral LV epicardium. LL = left lateral; Epi = epicardium; Endo = endocardium.
During constant atrial pacing, the voltages of the J waves both in the 12-lead ECG and in the unipolar recording became diminished, and conversely, that of the first postpacing beat became augmented with a pause dependency (Figure 3A). Similarly, when isoproterenol was administered at a dose of 3 μg, the J waves in the 12-lead ECG became diminished. After a pilsicainide infusion at a dose of 1 mg / kg for 5 minutes, the J waves in the 12-lead ECG became diminished; however, in the unipolar recording they became accentuated with a prolonged change in the potentials in the local bipolar recordings (Figure 3B).
Figure 3A: Unipolar (Uni) and bipolar (Bi) electrograms during and after constant atrial pacing (cycle length = 800 ms and 500 ms). The local ablation mapping catheter was placed on the lateral LV epicardium (Epi). B: The 12-lead electrocardiogram before and after isoproterenol administration (left). Unipolar and bipolar electrograms before and after a pilsicainide administration (right). Of note, pilsicainide administration did not lead to any augmentation of the Brugada-type ST-segment elevation.
Because of the decreasing frequency and inducibility of spontaneous PVCs after general anesthesia, extensive pace mapping on the epicardial LV was performed. On the basal lateral wall of the epicardial LV, an excellent QRS match without any stimulus-QRS delay was identified (Figure 2A and 2C), and prominent J waves in the unipolar recording with the coincidence of fragmented potentials in the bipolar recording were also observed. Then, a radiofrequency application in this region was delivered at a maximum power of 35 W after confirming no capture of the phrenic nerve. After several ablation applications, the clinical PVC was no longer induced by RV and LV stimulation or an isoproterenol administration. Consolidation lesions were delivered throughout the area where the prominent bipolar fractionated potentials were identified. Finally, the J waves in the 12-lead ECG remained; however, no VF was induced with triple extrastimulation performed from the RV apex and LV lateral epicardium at twice the pacing threshold (S1S1: 400 ms; S1S2: 200 ms; S2S3: 200 ms; S3S4: 180 ms). The patient tolerated the procedure well, with no complications recognized.
After discharge without any antiarrhythmic drugs, the patient has remained asymptomatic, with no further tachyarrhythmic episodes requiring device therapy, for more than 12 months.
Discussion
The main findings in the present case of idiopathic VF with early repolarization can be summarized as follows: (1) unipolar J-point elevation was found only on the posterolateral LV epicardium, (2) the unipolar J-point elevation became diminished during constant atrial pacing and conversely became augmented after the first postpacing beat with a pause dependency, (3) bipolar fractionated potentials coincided with the unipolar J-point elevation, and (4) the VF triggering PVC could be successfully ablated on the lateral LV epicardium where the unipolar J-point elevation with bipolar fragmented potentials was found.
VF substrates
A recent study has shown that patients with ERS with recurrent VF episodes can be classified into 2 distinct phenotypes, a group with abnormal potentials (low-voltage and split or fractionated electrograms lasting 70 ms on the bipolar records) on the epicardium and a group with no abnormal potentials despite detailed epicardial mapping.
Those abnormal potentials are considered delayed depolarizations and are located predominantly in the RV epicardium, with no cases of abnormal potentials in the LV epicardium alone. Boukens and colleagues
described a case of a patient with ERS in whom localized interstitial fibrosis in the RV sub-epicardium was the cause of the electrocardiographic pattern and VF storms. That finding supports depolarization abnormalities especially within the RV epicardium as the potential mechanism of arrhythmogenic substrates in some patients with ERS. However, as proposed by Antzelevitch and Yan,
ERS could be a disorder that is associated with repolarization abnormalities. They explained the mechanism as an outward shift in the repolarization current during the early phase of the action potential, and it could lead to the development of phase 2 reentry and VF. Recently, Yoon and colleagues
successfully displayed epicardial low-voltage fractionated and late potentials in an experimental model of ERS. In that study, they used coronary-perfused canine LV wedge preparations that pharmacologically mimicked the effects of genetic defects associated with ERS. Based on that study, concealed phase 2 reentry gives rise to discrete high-frequency spikes when the action potential dome is lost at some epicardial sites but not others. Accordingly, a repolarization abnormality could not be excluded as a possible explanation for the presence of the epicardial bipolar fractionated potentials.
Our case exhibited a regional distribution of low-voltage fractionated electrogram activity only on the posterolateral LV epicardium (and not the RV epicardium), and our electrophysiological findings suggested repolarization features. It was inconclusive whether the pathophysiology in this case should be considered as a group of repolarization abnormalities proven in basic experiments
or as a subtype of local structural abnormalities of the LV epicardium. However, our case suggested a heterogeneous electrophysiologic mechanism of ERS.
Ablation of VF associated with ERS
The effectiveness of RFCA to treat VF storms associated with ERS initiated by PVCs has been reported
Radiofrequency catheter ablation for treatment of premature ventricular contractions triggering ventricular fibrillation from the right ventricular outflow tract in a patient with early repolarization syndrome.
and RFCA may be considered to minimize the risk of VF storms in such patients. To date, the most frequent origins of triggering PVCs are reported to be the His-Purkinje system and RV outflow tract.
In the present case, the VF-triggering PVC originated from the lateral LV epicardium area, and prominent unipolar J waves and bipolar fragmented potentials were found. The cause of the culprit PVC and its correlation to ERS remained unsolved in our study. However, although it had a very small and limited population, a great report showed that the PVC origins in patients with ERS were located in epicardial lesions with marked J waves and steep repolarization gradients.
Moreover, in an experimental model, it was successfully demonstrated that the area dispersion where a loss or maintenance of the epicardial action potential dome leads to the development of phase 2 reentry gives rise to closely coupled extrasystoles.
Those findings suggested that the cause of the triggering PVC in our case originated from an arrhythmogenic substrate associated with a repolarization abnormality.
The main limitation of our present case was that activation mapping of the culprit PVC was not available owing to a decreasing frequency during the procedure, and thus our ablation was performed based on pace mapping. Hence, the effectiveness and endpoint of ablation were not eventually clear. We delivered additional ablation applications to bipolar fractionated potentials as a substrate modification in some local areas; however, low-voltage dull potentials remained extensively around this area and no significant change was found regarding the J waves on the 12-lead ECG. The clinical significance of this additional substrate modification was totally uncertain. In the study previously mentioned, Yoon and colleagues
demonstrated RFCA of the myocardium displaying abnormal repolarization cells could suppress the J wave and development of VF in an experimental model. Further studies are needed to clarify the validity of this issue.
Conclusion
We report, to the best of our knowledge, the first case of a VF storm with inferior and lateral ERS in which a successful RFCA of the triggering PVC on the LV lateral epicardium with a complete electrophysiological study was performed. The abnormal epicardial J waves were found in localized regions with fractionated potentials in the bipolar recordings, and the electrophysiological findings regarding the J waves in the unipolar and 12-lead ECG recordings suggested repolarization features. The triggering PVC originated from that specific local area, and RFCA of that PVC could suppress the recurrence of VF.
References
Haïssaguerre M.
Derval N.
Sacher F.
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Sudden cardiac arrest associated with early repolarization.
Radiofrequency catheter ablation for treatment of premature ventricular contractions triggering ventricular fibrillation from the right ventricular outflow tract in a patient with early repolarization syndrome.
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