Ablation of Genetically Triggered Ventricular Tachycardia/Fibrillation—Focusing on Brugada Syndrome

Brugada Syndrome Substrate

After its initial description in 1992, the BrS has drawn worldwide attention as an important clinical entity that causes premature death in young adults who are otherwise apparently healthy individuals. This has led to an abundance of research conducted worldwide. However, the pathophysiology of the BrS is not well explained and controversies exist with ongoing heated debate about the underlying pathophysiology of the syndrome–repolarization abnormality versus depolarization abnormality. Fortunately, stemming from the two opposing views is a consensus that right ventricular outflow tract (RVOT) is the most likely substrate site regardless of which mechanisms are responsible.

The observation that placing the electrodes of right precordial leads at the second and third intercostal spaces (ICS)—the location where there are no other cardiac structures except the RVOT—increases the likelihood of producing a BrS electrocardiogram (ECG) pattern compared with just placing the electrodes only on the standard fourth ICS and strongly suggests that the RVOT is a culprit substrate site. This contention is supported by the findings that VF-triggering premature ventricular contractions (PVCs) often emanated from the RVOT in patients with VF storm. Ablations of these triggering PVC from the endocardial site abated VF storms. Similarly, in an animal model, Morita et al. demonstrated that RVOT epicardium was the main substrate site. Perhaps the most compelling findings attesting that RVOT epicardium is the primary substrate sites for BrS came from our study in patients with frequent implantable cardioverter-defibrillator (ICD) discharges.

We found that all our BrS patients who underwent epicardial and endocardial mapping during sinus rhythm had abnormal low voltage, fractionated late potentials clustering in the anterior aspect of the RVOT epicardium as shown in Fig. 36.1 . Ablation at this area normalized the Brugada ECG pattern and prevented recurrent VF episodes. Of interest, the endocardial sites juxtaposed to the corresponding epicardial sites exhibit normal voltage potentials without fractionation ( Fig. 36.2 ). Fig. 36.3 shows epicardial electrograms recorded from various sites of the epicardium in both the left ventricular and right ventricular (RV) epicardium. Note that abnormal fractionated electrograms and double potential electrograms are localized only in the anterior aspect of the RVOT epicardium.

During the first decade after BrS was described, most believed that BrS is a primary electrical disease and was one of ion-channelopathy IAS subgroup with repolarization abnormalities. However, our collaborative multicenter study demonstrated epicardial and interstitial fibrosis and reduced gap junction expressions in the RVOT of sudden cardiac death victims with BrS family history and negative routine autopsy. In the same study, we also found fibrosis from the biopsies taken from RVOT epicardial sites with abnormal, fragmented, and delayed conduction in all six BrS patients who underwent open heart surgical ablation of the Brugada substrates. Fig. 36.4 shows an RVOT anatomic grid generated by computed tomography of the heart; the biopsy site demonstrates that both abnormal fractionated electrograms and fibrosis coexist. After open heart ablations at these fibrosis sites, ECG patterns normalized, and patients no longer had recurrent VF. Interestingly, the in vivo cases all had normal cardiac images on computed tomography/magnetic resonance imaging, as well as a normal-appearing heart on direct visualization during thoracotomy. Investigators from the Academic Medical Center of Amsterdam also reported similar findings from the explanted heart of a BrS patient who had SCN5A mutation with medically treated failure from VF storms, necessitating heart transplantation surgery. The explanted heart showed no evidence of repolarization abnormality. Instead, the investigators found evidence of interstitial fibrosis causing conduction delay. Thus one can reasonably conclude that interstitial fibrosis and reduced gap junction expression on the epicardial surface of the RVOT is the abnormal myocardial structure that underlies the arrhythmogenic substrate, as detected by abnormal fractionated low-voltage late potential. Similar observations were found in all of our study patients, and these findings clearly provide the strongest clinical evidence that the delayed depolarization at the anterior aspect of the RVOT is the most likely underlying electrophysiologic mechanism underlying BrS. These findings also suggest that BrS is not the primary electrical disease without structural heart disease, but the IAS category that has subclinical myopathic changes in the right ventricle.