Based on the close relationship of the canine wedge model
Based on the close relationship of the canine wedge model to human ECGs, individuals with prominent J waves (ERS) or J/ST elevation (BS) are thought to have accentuated ventricular AP notch and the potential to lose their AP dome because of extrinsic factors such as vagal stimulation, sodium channel blocker, or ischemia. The known genetic mutations discovered in patients with BS are compatible with the above electrophysiologic abnormalities. Loss-of-function mutations in the UM 171 responsible for inward sodium current (INa) and inward calcium current (ICa) cause a decrease in the inward current components of the AP and gain-of-function mutations in the transient outward potassium current (ITo), ATP-dependent potassium current (IK-ATP) genes cause an increase in the outward current components. This results in a net outward shift in the balance of currents, rendering the AP dome more susceptible to collapse. The sudden disappearance of the AP dome markedly abbreviates the AP duration while the repolarization duration is maintained where the AP dome is preserved (Fig. 3A).
The basic electrophysiology underlying normal J/ST/T wave, ER, and BS ECGs is a continuous spectrum. In normal hearts, the J wave is not prominent, and the ST segment is isoelectric because there are no voltage gradients in the AP plateau phase. In some physiologic or pathologic conditions (genetic, hormonal, or drug induced) in which the AP notch is accentuated either by poor inward currents or increased outward currents, the voltage gradients manifest as J wave and ST segment elevation. Accentuation of the AP notch is more pronounced in the right ventricular epicardium, where the notch is intrinsically more prominent. Until these changes progress to a certain degree, the T wave remains positive because the epicardial repolarization is followed by endocardial and M cell repolarization. This explains the typical ECG features of ER pattern (Fig. 3B, left panel). As these electrophysiologic processes become more pronounced, further accentuation of the AP notch delays development of ICa, delaying the epicardial dome and repolarization even later than that of the M cell or endocardial regions. This reverses the final repolarization sequence through the transmural myocardial layers, inducing a coved-type ST segment elevation (Fig. 3B, right panel). In a profoundly abnormal condition, an extreme accentuation of the AP notch causes further shift in the balance of inward/outward currents, which leads to the loss of the AP dome and initiates phase 2 reentry, as described above (Fig. 3A). Therefore, the basic pathophysiology of malignant tachyarrhythmias in patients with BS and ERS seems identical and only differs in the severity of the background electrophysiologic milieu.
Electrocardiographic features: J wave dynamics and mode of onset of VF BS is characterized by unique ECG features of coved-type J/ST/T waves (type I Brugada ECG pattern) and a high risk of developing VF. Suggestive but less confirmative ECG findings are saddle-back type J/ST/T waves, or type II/III Brugada patterns. Prompted by the similarity in ECG features and the potential of converting this ER to Brugada ECG patterns, the benign nature of the ER pattern was questioned based on a few clinical case reports and basic electrophysiologic studies by using canine wedge preparation [25,26]. The ECG features of these two syndromes are based on the presence of J waves, in addition, the dynamic behavior of the J waves in both syndromes shows similar cycle length-dependent pattern. The J wave and ST segment elevation in BS demonstrate a pause-dependent accentuation and acceleration-dependent attenuation . The amplitudes of J waves in ERS accentuate after long cycle lengths or after long coupling intervals (Fig. 4). Although the J/ST waves show similar dynamic patterns, the mode of onset and coupling intervals of premature ventricular contractions (PVCs) initiating VF episodes are slightly different . In patients with ERS, most (42/58, 72.4%) VF episodes were precipitated by PVCs with a short–long–short sequence of activation, while this cycle length alternans was less frequently (13/86, 15.1%) observed in patients with BS (Fig. 5). Coupling intervals were significantly shorter in patients with ERS than in those with BS (Fig. 6). The reason for this distinction in the mode of onset of VF between BS and ERS is not clear. A plausible explanation is that, in BS, the electrophysiologic milieu for arrhythmogenesis is mature enough for a single VPC to initiate VF, whereas in ERS, only a critically timed PVC in the presence of maximum dispersion of refractoriness provided by long preceding coupling interval can precipitate VF . This distinction does not negate the close association between ERS and BS. Rather, it supports the idea that ERS is a “forme fruste” or a clinical variant of BS, with both being part of the same broader category of “J wave syndrome”.