4.2. Typical electrophysiologic remodeling in AF and SSS
Typical electrophysiologic remodeling in AF includes down-regulation of L-type Ca2+ channel (ICa,L), down-regulation ofI to, and upregulation ofI KACh andI K1.17, 18 The remodeling of ionic current could reduce the slope of phase 0, hyperpolarize membrane voltage, and reduce heart rate. Funny current down-regulation might contribute to the association between SAN dysfunction and supraventricular tachyarrhythmias.19Compared with the normal SANs, those of patients or animals with AF did not exhibit spontaneous late diastolic Ca2+ elevation or cranial shifting of the earliest atrial activation sites upon isoproterenol infusion, suggesting impaired spontaneous sarcoplasmic reticulum Ca2+release.5, 20
Patients with conditions associated with atrial remodeling, ischemia, and atrial stretch (e.g., congestive heart failure) manifest altered SAN function.21, 22 Therefore, we excluded heart failure and myocardial ischemia cases but without affecting the final results. Moreover, there is evidence to indicate that antiarrhythmic drugs used for the treatment of AF can cause SAN dysfunction.23 In this study, antiarrhythmic drug was a factor associated with SSS in patients with AF.
SSS might also be accompanied by intra-atrial conduction delay, AV nodal conduction disturbances, and paroxysmal atrial tachycardia as part of the tachycardia-bradycardia syndrome. Damage to SAN is an important factor for the formation of AF. When sinus impulse formation is depressed in the presence of SSS, during the slow atrial cycle, an atrial extrasystole may occur. Moreover, SAN may also facilitate re-entry. Thus, ischemic damage to the SAN alone, without atrial wall disturbances, such as fibrosis, stretch, or muscle loss, may result in chronic AF.