The congruence between BrS and ERS
The congruence between BrS and ERS with respect to clinical manifestations and response to therapy lends further support to the repolarization hypothesis. Using an experimental model of ERS, Koncz et al. . recently provided evidence in support of the hypothesis that, similar to the mechanism operative in BrS, an accentuation of transmural gradients in the LV wall are responsible for the repolarization abnormalities underlying ERS, giving rise to J-point elevation, distinct J waves, or slurring of the terminal part of the QRS. The repolarization defect is accentuated by cholinergic agonists and reduced by quinidine, isoproterenol, cilostazol, and milrinone, accounting for the ability of these agents to reverse the repolarization abnormalities responsible for ERS [30,222]. Higher intrinsic levels of Ito in the inferior LV were also shown to underlie the greater vulnerability of the inferior LV wall to VT/VF . The advent and implementation of ECGI by Rudy and colleagues provided additional evidence for repolarization abnormalities by identifying abnormally short activation–recovery intervals in the inferior and lateral regions of LV and a marked dispersion of repolarization . More recent studies involving ECGI mapping in an ERS patient during VF have demonstrated VF rotors anchored in the inferior lateral LV wall .
Conduction delay is known to give rise to notching of the QRS complex. When it occurs on the rising phase of the R wave, it is due to a conduction defect within the ventricle. When it occurs at the terminal portion of the QRS, thus masquerading as a J wave, it may be due to either a conduction defect or a repolarization defect [21,223]. The response to prematurity or to an increase in rate can differentiate between the two . Delayed conduction invariably becomes more exaggerated at faster rates or during premature beats, thus leading to accentuation of the QRS notch, whereas repolarization defects usually are mitigated, resulting in diminution of the J wave at faster rates. Although typical J waves usually are accentuated with bradycardia or long pauses, the opposite has also been described [224,225]. J waves are often seen in young males with no apparent structural l-ascorbic acid diseases, whereas intraventricular conduction delay is often observed in older individuals or those with a history of myocardial infarction or cardiomyopathy [223,224]. The prognostic value of a fragmented QRS has been demonstrated in BrS [49,226], although fragmentation of the QRS is not associated with increased risk in the absence of cardiac disease . Factors that may aid in the differential diagnosis of J wave vs intraventricular conduction delay (IVCD)-mediated syndromes are summarized in Table 8.
Early repolarization syndrome The majority of the studies using the criteria of Haissaguerre et al. . for diagnosing the ERP have shown that ER, especially in the inferior ECG leads, predicts cardiac and arrhythmic death. Negative studies are few and may be attributable to the exclusion criteria used (e.g., atrial fibrillation, flutter, acute coronary syndrome), a relatively short follow-up period [231,232], or different definitions of ERP . The recent consensus paper by Macfarlane et al. . dealing with the terminology of J-wave–related phenomena in the setting of ER should enable us to avoid such confusion in the future. The inclusion of Africans or African-Americans, in whom ER is prevalent but apparently not associated with high risk, may alter outcomes as well . Huikuri and colleagues reported in a series of seminal papers the results of a population-based study in Finland involving long-term prognosis of subjects with an ERP in the ECG . Tikkanen et al. . showed that J-point elevation ≥0.1mV was present in 5.8% of the population and that only 0.3% of the population had significant J-point elevation ≥0.2mV. J-point elevation ≥0.1mV in the inferior leads was associated with cardiovascular death (relative risk [RR] 1.28) and arrhythmic death (RR 1.43), and J-point elevation ≥0.2mV had a markedly elevated risk of death from cardiac causes (RR 2.92) and from arrhythmia (RR 2.92). Subsequent studies confirmed the association of J wave or ER with death from all causes, death from cardiovascular disease, sudden/unexpected death, and death from arrhythmias [44–46,127,235–238]. A horizontal or descending ST segment is associated with a worse prognosis than is an ascending ST segment (Fig. 3) [237,239]. Individuals with a high-amplitude J wave ≥0.2mV followed by a horizontal or descending ST segment in the inferior/inferolateral leads have a higher risk of lethal arrhythmias than do those with a lower-amplitude J wave, especially those with a rapidly ascending ST segment following the J wave.