• 2018-07
  • 2019-04
  • 2019-05
  • 2019-06
  • The circadian variation of VF shows a


    The circadian variation of VF shows a similar nocturnal pattern in patients with BS and ERS [32] (Fig. 2). This is in contrast to the circadian pattern of VTAs in patients with ischemic heart diseases [33]. In a Korean cohort of patients with ERS and BS who underwent implantable cardioverter defibrillator (ICD) implantation, the timing of VTAs, including that of cardiac arrest and appropriate shocks, peaked between midnight and early morning (12 AM and 6 AM). A significant seasonal peak of appropriate shocks was observed between spring and summer in patients with ERS, whereas no such consistent seasonal pattern was observed in patients with BS [33]. VTAs in patients with structural heart diseases occur more commonly during the daytime and in winter when the ventricular myocardium is more vulnerable to ischemia. This is associated with neurohumoral activation (plasma catecholamine concentration) that results in increased cardiac workload, higher coronary resistance, higher blood pressure, and increased blood viscosity during the daytime and in the winter. Ventricular refractoriness shows a consistent variation, with the shortest refractory period observed during waking hours and the longest observed during sleep. This ventricular myocardial status may provide additional risk in the maintenance of VF under acute ischemia [34]. The similarity in the circadian patterns of ERS and BS may be due to their shared effect of vagal activity. Vagal activity is highest during the night when the incidence of cardiac arrest and appropriate shock peaks in ERS and BS patients, whereas sympathetic activity is highest in the morning and in winter when the incidence of VTAs peaks in patients with structural heart diseases [35]. The loss of the epicardial AP dome is the basis for an elevated J point and ST segment elevation, and phase 2 reentry serves as a trigger of circus movement reentry that are responsible for VF in patients with BS. The loss of the epicardial dome (BS) or the depression of epicardial plateau (ERS) is caused by an outward shift in the balance of currents at the end of phase 1 of the AP. Vagal stimulation or autonomic neurotransmitters such as CA-074 Me facilitate loss of the epicardial AP dome by suppressing ICa and/or augmenting potassium current, whereas β-adrenergic agonists restore the dome by augmenting ICa. These experimental results are in line with the circadian distribution of VF in BS and ERS patients. Atrial tachyarrhythmias have been documented in a significant proportion of patients with BS and are an important cause of inappropriate shock. The incidence of atrial tachyarrhythmias and the development of inappropriate shock is also similar in patients with BS and ERS [36]. In our Korean patient cohort of BS and ERS, during a mean follow-up of approximately 5 years, no significant differences were found in the prevalence of atrial tachyarrhythmias (mostly atrial fibrillation) and in the incidence of inappropriate shocks due to these atrial tachyarrhythmias. It is speculated that the arrhythmogenic substrate in both BS and ERS is not restricted to the ventricular level but may be extended to the atrium [37].
    Cellular electrophysiologic basis of BS and ERS Ventricular AP exhibits considerable variation or regional difference across the transmural direction of the ventricular myocardium. The J wave originates from the heterogeneous distribution of a transient outward current-mediated spike-and-dome morphology of the AP across the ventricular wall. The presence of a prominent AP notch in the epicardium but not in the endocardium provides a voltage gradient that manifests as a J wave or as an elevated J-point in the ECG [38,39]. This unique epicardial AP shape indicates that epicardial repolarization is more susceptible to changes in response to drive cycle lengths, extrastimulation, drugs, or ischemia [40–42]. The heterogeneous loss of the AP dome caused by ischemia, bradycardia, or pharmacologic interventions (sodium channel blocker flecainide or acetylcholine) results in the development of a large dispersion of repolarization within the epicardium by abbreviation and marked prolongation of AP durations [40–42]. A dispersion of repolarization also occurs between the epicardial and M cell APs. This exaggerated dispersion of repolarization is followed by local re-excitation (phase 2 reentry) because of the AP dome propagating from sites where it was maintained to sites where it was abolished. The ECG J wave, a clinical marker of the AP notch, represents the vulnerability of the epicardial AP to a sudden disappearance of the AP dome (known as all-or-none repolarization) and susceptibility to fatal VTAs (Fig. 3A).