Recording of isolated very delayed potentials on the right ventricular epicardium in a patient with Brugada syndrome.

Introduction

Epicardial mapping revealed the existence of abnormal potentials on the right ventricular outflow tract (RVOT) in patients with Brugada syndrome. It is reported that tissues of the RVOT epicardium from open-chest biopsy and autopsy showed the existence of fibrosis and fatty infiltration associated with increased interstitial collagen and decreased connexin 43. Although the abnormal potentials can be explained by repolarization abnormality of delayed upstroke of the action potential dome and concealed phase 2 reentry, these abnormal potentials are associated with epicardial tissue fibrosis and include the mechanism of delayed conduction.

Epicardial voltage mapping revealed very extensive multiple abnormal potentials, especially from below the pulmonary artery valve to above the tricuspid annulus.

Isolated very delayed potentials (IVDPs) on the right ventricle epicardium appeared 500 ms after the last stimulus beats. The appearance of IVDPs was associated with the last stimulus beats, and the response of the IVDPs to ventricular pacing was unusual.

Turning on the electricity for ablation immediately eliminated local abnormal potentials within 1–5 seconds. After the ablation, ventricular fibrillation attacks were completely suppressed.

We experienced a case of Brugada syndrome and frequent ventricular fibrillation (VF) episodes. The patient had abnormal epicardial delayed potentials that have been reported previously and also an unusual isolated very delayed potential (IVDP) that was reproducibly recorded 400–500 ms after the last ventricular activation on the epicardium of the RVOT.

Case report

The patient was a 24-year-old man without any organic heart disease. He experienced syncope after drinking alcohol at night and visited a hospital. The rhythm was atrial fibrillation, and an electrocardiogram (ECG) did not show any other abnormalities. A doctor therefore injected pilsicainide, a pure sodium channel blocker, to terminate the arrhythmia. VF occurred spontaneously during the injection of pilsicainide and was successfully terminated by cardioversion. The ECG was typical type 1 ECG (Figure 1A, Left panel), and he was diagnosed as having Brugada syndrome. Gene analysis showed that the patient did not have SCN5A mutation.

Figure 1

A: Left panel: Twelve-lead electrocardiogram (ECG) showing sinus rhythm and typical coved-type pattern with Brugada syndrome. Right panel: The ST elevation of V1 and V2 lead was reduced after the ablation. B: Multiple abnormal potentials were found on the epicardium at the right ventricular outflow tract: (a) high-voltage + low-frequency delayed potential, (b) double potential, (c) high voltage + fragmentation, (d) low voltage + fragmentation.

After implantation of an implantable cardioverter-defibrillator, frequent appropriate shocks to terminate VF were documented despite medical treatment (bepridil at 200 mg/day, cilostasol at 100 mg/day, and continuous infusion of isoproterenol). We therefore planned emergent ablation to suppress the drug-refractory VF attacks.

Under general anesthesia, 2 vascular sheaths were placed in the right femoral vein for a quadripolar catheter and an ablation catheter (Navistar ThermoCool SmartTouch; Biosense Webster, Diamond Bar, CA) with an 8F irrigated D-curve in the right ventricle (RV). We then performed endocardial RV voltage mapping using an electroanatomic mapping system (CARTO 3; Biosense Webster, Diamond Bar, CA). However, we found very few abnormal low-voltage potentials on the endocardial surface of the RV free wall. Then we performed epicardial mapping via a subxiphoid approach. A 7F decapolar catheter (DECANAV; Biosense Webster, Diamond Bar, CA) was advanced into the pericardial space via an epicardial access through an Agilis (St. Jude Medical, Minnetonka, MN) sheath under electroanatomic and fluoroscopic guidance. We performed electroanatomic mapping on the epicardial surface of the RV. Epicardial voltage mapping revealed very extensive abnormal potentials, especially from below the pulmonary artery valve to above the tricuspid annulus (Figure 1B). Clustering of prolonged split potentials, local abnormal ventricular activity, and complex fractionated ventricular signals were noted on the epicardium of the RVOT as well as the mid free wall. The total number of mapping points using a decapolar catheter and an ablation catheter was 272. We could find the variable activation time according to shortening of coupling intervals of extrastimuli. Moreover, IVDPs appeared about 400–500 ms after the last ventricular activation captured by the extrastimuli. IVDPs were discrete low-voltage potentials with 1–3 sharp spikes, and there were no electrical activities between the last ventricular activation by extrastimuli and IVDPs. This potential appeared by ventricular pacing and did not reflect any potential on the body-surface ECG (Figure 2). The interval between the stimulus (St) and IVDPs was slightly reduced by shortening of the coupling interval of extrastimuli, but it was later gradually prolonged. When the extrastimulus captured local ventricular activation with a significant delay, the appearance of IVDPs was also delayed in parallel (Figure 3). Programmed electrical stimulation and rapid pacing from the endocardium of the RV apex and RVOT and the epicardium of the RVOT failed to induce VF. We performed radiofrequency catheter ablation targeting these fractionated and late potentials using the vector of the ablation catheter. Turning on the electricity for ablation immediately eliminated local abnormal potentials within 1–5 seconds. Extensive ablations (power of 30–35 W, temperature of <42°C, 30 seconds/point) were carried out along the area of the RV epicardium having the abnormal potentials. The total number of ablations was 41 points and ablation time was 26 minutes. The ST elevation in V1-V2 leads decreased and the VF attacks were suppressed after the ablation (Figure 1A, Right panel). The patient, after the electrophysiological study, has remained asymptomatic, with no further occurrence of ventricular tachycardia/VF episodes for 15 months.

Figure 2

Isolated very delayed potentials (IVDPs) on the epicardial right ventricular outflow tract (RVOT). IVDPs appeared 400–500 ms after the last ventricular activation captured by the extrastimuli. The IVDPs were discrete low-voltage potentials with 1–3 sharp spikes, and there were no electrical activities between the last ventricular activation by extrastimuli and IVDPs. This potential appeared by ventricular pacing and did not reflect any potential on the body-surface electrocardiogram.

Figure 3

Unusual response of the isolated very delayed potentials (IVDPs) to ventricular pacing. Shortening of the S2-S3 interval abbreviated very delayed potential, but its interval was prolonged. Interestingly, the interval between S3 pacing of 400/290/230 to the isolated potential was almost the same as the interval between the local fragmented ventricular potential to the delayed potential at 400/290/210 pacing. Pacing site = right ventricular epicardium.

Discussion

We presented a case of Brugada syndrome in which frequent VF episodes occurred. Epicardial mapping of the RV showed extended delayed potentials that have been reported previously.1, 5, 6 Moreover, the patient had IVDPs on the RV epicardium that appeared 400–500 ms after the last St beats. The appearance of IVDPs was associated with the last St beats, and the response of the IVDPs to ventricular pacing was unusual. This is the first case report of IVDPs in a patient with Brugada syndrome.

The abnormal delayed potentials on the epicardium observed in patients with Brugada syndrome were usually low-voltage, prolonged, and fractionated potentials and were associated with epicardial fibrosis and fatty infiltration. Appearance of the delayed potentials accompanied the QRS complex of the ECG and the delayed potentials had a long duration with fractionation. Increased heart rate enhanced delayed potentials, and these potentials should be associated with conduction abnormality. However, the IVDPs in our case were different from delayed potentials and had unique characteristics: (1) the IVDPs appeared 400–500 ms after the last beats; (2) there were no electrical activities between the last beat and IVDPs; (3) IVDPs did not appear spontaneously and were associated with the previous beats; (4) shortening of the coupling intervals of the extrastimuli reduced the interval of St-IVDPs at first, but it was then gradually prolonged; and (5) IVDPs did not reflect surface ECGs. It is difficult to determine the mechanism of IVDPs. It seems to be difficult to explain the timing of the IVDPs by depolarization abnormality. If the epicardium had atrioventricular node-like tissue, prominent delayed conduction could be explained, but the response to the pacing of the IVDPs showed that it was not unusual conduction slowing. The repolarization abnormality hypothesis explains the mechanism of Brugada syndrome by changes of the epicardial action potential morphology and dispersion of repolarization. The repolarization abnormality hypothesis could explain the delayed potential in Brugada syndrome. The model showed delayed potential with a duration of ≈100–200 ms. If the tissue had manifest conduction slowing, phase 2 reentrant beats might explain the appearance of IVDPs. Since IVDPs did not appear spontaneously, abnormal automaticity should not be a mechanism. Another possible mechanism of the IVDPs is triggered activity from delayed afterdepolarizations (DADs). DADs appear after termination of the action potential, and IVDPs appear in association with the previous pacing beats. Shortening of the pacing cycle length enhances the occurrence of DADs and shortens the onset of DADs. Although the coupling interval of IVDPs might be too long for the appearance of DADs, the response to pacing of IVDPs seems to correspond to the characteristics of DADs. Further shortening of the coupling interval of extrastimuli prolonged the appearance of IVDPs and they might have occurred due to local conduction slowing. Recent progress in disease modeling using induced pluripotent stem cell–derived cardiomyocyte showed that induced pluripotent stem cell myocytes from patients with Brugada syndrome showed abnormal intracellular calcium handling and tended to provoke triggered activity. Indeed, body-surface mapping during VF induced by programmed electrical stimulation revealed that repetitive firing from the RVOT frequently occurred. Microreentry appears as focal firing, but the repetitive occurrence of triggered activity from DAD is also represented as a focal firing pattern. We did not evaluate the appearance of IVDPs after the ablation because of the noninducibility of VF by ventricular pacing. Although the importance of DAD and triggered activity in Brugada syndrome has not been clarified, it should be an important mechanism of arrhythmogenesis in Brugada syndrome. But we had a limitation in this case that IVDPs were artifacts of the pulmonic valve closure, because the pacing site was very near the pulmonic valve site.

Conclusion

We identified IVDPs in a patient with Brugada syndrome. The IVDPs had unique characteristics and the mechanism of IVDPs could not be explained by either depolarization or repolarization abnormalities. Occurrence of DAD and triggered activity are possible mechanisms of IVDPs, and IVDPs should be associated with arrhythmogenicity in Brugada syndrome.