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Recently, the routine use of dual-chamber implantable cardioverter defibrillators (DC-ICD) has been advocated over the single-chamber version (SC-ICD), but there are few reports of the frequency of complications between the 2 types of ICDs. Between July 1997 and April 1999, 178 consecutive patients underwent implantation of either a transvenous SC-ICDs (n=104) or a DC-ICDs (n=74). Twelve (16%) of the 74 patients with a DC-ICD had a total of 16 major complications compared with 6 (6%) of the 104 patients with a SC-ICD (p=0.01). The 16 DC-ICD complications included atrial lead dislodgment (4), ventricular lead malfunction (4), and pocket infection/hematoma (3), and the 6 SC-ICD complications included ventricular lead dislodgment (2) and pocket hematoma (3). Patients with a DC-ICD had less left ventricular function (29% vs 35%, p=0.035) and a higher prevalence of non-ischemic cardiomyopathies (48% vs 28%, p=0.0076). In conclusion, the DC-ICD may have a higher frequency of device- and lead-related major complications.

Objective: Recently, a novel missense mutation (R534C) in the S4 region of human ether-a-go-go-related gene ( HERG ) was identified in one Japanese LQT2 family. The S4 region presumably functions as a voltage sensor. However, it has not yet been addressed whether the S4 region of HERG indeed functions as a voltage sensor, and whether these residues play any role in abnormal channel function in cardiac repolarization. Methods: We characterized the electrophysiological properties of the R534C mutation using the heterologous expression system in Xenopus oocytes. Whole cell currents were recorded in oocytes injected with wild-type cRNA, R534C cRNA, or a combination of both. Results: Clinical features – QTc intervals of all affected patients with R534C mutation in HERG are prolonged ranging from 460 to 680 ms (averaged QTc interval>540 ms). One member of this family had experienced sudden cardiac arrest, and other suffered from recurrent palpitation. Electrophysiology – Oocytes injected with R534C cRNA did express functional channels with altered channel gating. Kinetic analyses revealed that the R534C mutation shifted the voltage-dependence of HERG channel activation to a negative direction, accelerated activation and deactivation time course, and reduced steady-state inactivation. Quantitative analyses revealed that this mutation did not cause apparent dominant-negative suppression. Computer simulation – Incorporating the kinetic alterations of R534C, however, did not reproduce prolonged action potential duration (APD). Conclusions: The data revealed that arginine at position 534 in the S4 region of HERG is indeed involved in voltage-dependence of channel activation as a voltage sensor. Our examination indicated that HERG current suppression in R534C mutation was the least severe among other mutations that have been electrophysiologicaly examined, while affected patients did show significant QT prolongation. This suggest that another unidentified factor(s) that prolong APD might be present.