Table 6.
Similarities and differences between Brugada and early repolarization syndromes and possible underlying mechanisms
| BrS | ERS | Possible Mechanism(s) | |
|---|---|---|---|
| Similarities between BrS and ERS | |||
| Male predominance | Yes (>75%) | Yes (>80%) | Testosterone modulation of ion currents underlying the epicardial AP notch |
| Average age of first event | 30–50 | 30–50 | |
| Associated with mutations or rare variants in KCNJ8, CACNA1C, CACNB2, CACNA2D, SCN5A, ABCC9, SCN10A | Yes | Yes | Gain of function in outward currents (IK-ATP) or loss of function in inward currents (ICa or INa) |
| Relatively short QT intervals in subjects with Ca channel mutations | Yes | Yes | Loss of function of ICa |
| Dynamicity of ECG | High | High | Autonomic modulation of ion channel currents underlying early phases of the epicardial AP |
| VF often occurs during sleep or at a low level of physical activity | Yes | Yes | Higher level of vagal tone and higher levels of Ito at the slower heart rates |
| VT/VF trigger | Short-coupled PVC | Short-coupled PVC | Phase 2 reentry |
| Ameliorative response to quinidine and bepridil | Yes | Yes | Inhibition of Ito and possible vagolytic effect |
| Ameliorative response to isoproterenol denopamine and milrinone | Yes | Yes | Increased ICa and faster heart rate |
| Ameliorative response to cilostazol | Yes | Yes | Increased ICa, reduced Ito and faster heart rate |
| Ameliorative response to pacing | Yes | Yes | Reduced availability of Ito due to slow recovery from inactivation |
| Vagally mediated accentuation of ECG pattern | Yes | Yes | Direct effect to inhibit ICa and indirect effect to increase Ito (due to slowing of heart rate) |
| Effect of sodium channel blockers on unipolar epicardial electrogram | Augmented J waves | Augmented J wave | Outward shift of balance of current in the early phases of the epicardial AP |
| Fever | Augmented J waves | Augmented J waves (rare) | Accelerated inactivation of INa and accelerated recovery of Ito from inactivation. |
| Hypothermia | Augmented J waves mimicking BrS | Augmented J waves | Slowed activation of ICa, leaving Ito unopposed. Increased phase 2 reentry but reduced pVT due to prolongation of APD358 |
| Differences between BrS and ERS | |||
| Region most involved | RVOT | Inferior LV wall | Higher levels of Ito and/or differences in conduction |
| Leads affected | V1–V3 | II, II a, VF, V4, V5, V6; I, aVL, Both: inferolateral | |
| Regional difference in prevalence | Europe: BrS = ERS | ||
| Asia: BrS > ERS | |||
| Incidence of late potential in signal- averaged ECG | Higher | Lower | |
| Prevalence of atrial fibrillation | Higher | Lower | |
| Effect of sodium channel blockers on surface ECG | Increased J-wave manifestation | Reduced J-wave manifestation | Reduction of J wave in the setting of ER is thought to be due largely to prolongation of QRS. Accentuation of repolarization defects predominates in BrS, whereas accentuation of depolarization defects predominates in ERS. |
| Structural changes, including mild fibrosis and reduced expression of Cx43 in RVOT or fibrofatty infiltration in cases of arrhythmogenic right ventricular cardiomyopathy. Imaging studies have also revealed wall motion abnormalities and mild dilation in the region of the RVOT. | Higher in some forms of the syndrome | Unknown | Some investigators have hypothesized that some of these changes may be the result of, rather than the cause of the BrS substrate, which may create a hibernation-like state due to loss of contractility in the RVOT secondary to loss of the AP dome. |
AP = action potential; APD = action potential duration; BrS = Brugada syndrome; ERS = early repolarization syndrome; RVOT = right ventricular outflow tract; PVC = premature ventricular contraction; pVT=polymorphic ventricular tachycardia; VF = ventricular fibrillation; VT = ventricular tachycardia.