Prognostic utility of T-wave alternans in a real-world population of patients with left ventricular dysfunction: the PREVENT-SCD study.

BACKGROUND: The predictive value of T-wave alternans (TWA) for lethal ventricular tachyarrhythmia in patients with left ventricular (LV) dysfunction is controversial. Also, long-term arrhythmia risk of patients ineligible for the TWA test is unknown. METHODS: This was a multicenter, prospective observational study of patients with LV ejection fraction ≤40% due to ischemic or non-ischemic cardiomyopathies, designed to evaluate the prognostic value of TWA for lethal ventricular tachyarrhythmia. The primary end point was a composite of sudden cardiac death, sustained rapid ventricular tachycardia (VT) or ventricular fibrillation (VF), and appropriate defibrillator therapy for rapid VT or VF. RESULTS: Among 453 patients enrolled in the study, 280 (62%) were eligible for the TWA test. TWA was negative in 82 patients (29%), who accounted for 18% of the total population. The median of follow-up was 36 months. The 3-year event-free rate for the primary end point was significantly higher in TWA-negative patients (97.0%) than in TWA non-negative patients (89.5%, P = 0.037) and those ineligible for the TWA test (84.4%, P = 0.003). Multivariable analysis identified both non-negative TWA [hazard ratio (HR) 4.43; 95% confidence interval (CI) 1.02-19.2; P = 0.047) and ineligibility for the TWA test (HR 6.89; 95% CI 1.59-29.9; P = 0.010) to be independent predictors of the primary end point. CONCLUSIONS: TWA showed high negative predictive ability for lethal ventricular tachyarrhythmia in patients with LV dysfunction, although the TWA-negative patients accounted for only 18% of the entire population. Those ineligible for the TWA test had the highest risk for lethal ventricular tachyarrhythmia.

Three-year outcomes after sirolimus-eluting stent implantation for unprotected left main coronary artery disease: insights from the j-Cypher registry.

BACKGROUND: Long-term outcomes after stenting of an unprotected left main coronary artery (ULMCA) with drug-eluting stents have not been addressed adequately despite the growing popularity of this procedure. METHODS AND RESULTS: j-Cypher is a multicenter prospective registry of consecutive patients undergoing sirolimus-eluting stent implantation in Japan. Among 12 824 patients enrolled in the j-Cypher registry, the unadjusted mortality rate at 3 years was significantly higher in patients with ULMCA stenting (n=582) than in patients without ULMCA stenting (n=12 242; 14.6% versus 9.2%, respectively; P<0.0001); however, there was no significant difference between the 2 groups in the adjusted risk of death (hazard ratio 1.23, 95% confidence interval 0.95 to 1.60, P=0.12). Among 476 patients whose ULMCA lesions were treated exclusively with a sirolimus-eluting stent, patients with ostial/shaft lesions (n=96) compared with those with bifurcation lesions (n=380) had a significantly lower rate of target-lesion revascularization for the ULMCA lesions (3.6% versus 17.1%, P=0.005), with similar cardiac death rates at 3 years (9.8% versus 7.6%, P=0.41). Among patients with bifurcation lesions, patients with stenting of both the main and side branches (n=119) had significantly higher rates of cardiac death (12.2% versus 5.5%; P=0.02) and target-lesion revascularization (30.9% versus 11.1%; P<0.0001) than those with main-branch stenting alone (n=261). CONCLUSIONS: The higher unadjusted mortality rate of patients undergoing ULMCA stenting with a sirolimus-eluting stent did not appear to be related to ULMCA treatment itself but rather to the patients' high-risk profile. Although long-term outcomes in patients with ostial/shaft ULMCA lesions were favorable, outcomes in patients with bifurcation lesions treated with stenting of both the main and side branches appeared unacceptable.

Case of atrial tachycardia originating from giant coronary sinus connected to persistent left superior vena cava: successful catheter ablation guided by noncontact mapping.

Radiofrequency (RF) catheter ablation is widely applied to tachyarrhythmia associated not only with structurally normal hearts but also with relatively mild cardiac anomalies. We present a case of 35 year-old female complaining of exercise-induced frequent palpitations caused by atrial tachycardia (AT) originating from giant coronary sinus (CS) connected to persistent left superior vena cava. AT was sensitive to intravenous ATP administration. Electrophysiological study partly using noncontact balloon of EnSite system clarified that two foci of AT were located at the orifice and the distal inner lumen of giant CS. After repetitive applications of RF energy to these origins, AT was not induced by drip infusion of isoproterenol. AT was not evoked by exercise without antiarrhythmic drugs 15 months after the RF ablation. This case indicates that RF ablation guided by noncontact mapping technique should be considered as a therapeutic regimen for AT associated with mild cardiac malformations.

Relationship between amiodarone-induced subclinical lung toxicity and Th1/Th2 balance.

BACKGROUND: Although amiodarone is a potent antiarrhythmic agent, its clinical use is limited by serious lung toxicity. This study investigated the mechanisms of amiodarone-induced lung toxicity from an immunological perspective. Because interferon gamma (IFN-gamma: Th1 cytokine) inhibits pulmonary fibroblast proliferation whereas interleukin-4 (IL-4: Th2 cytokine) augments fibroblast growth and collagen production, we hypothesized that amiodarone lung toxicity is related to Th1/Th2 balance. METHODS: Twenty-six consecutive Japanese patients with ventricular arrhythmias treated with amiodarone were enrolled in this study and were divided into two groups. Group A contained patients demonstrating amiodarone lung toxicity diagnosed by chest X-ray, KL-6 or D(LCO) (n=6), whereas group B included patients treated without any adverse effects (n=20). Th1/Th2 balance was investigated by the ratio of IFN-gamma and IL-4 produced by activated peripheral CD4(+) T cells. RESULTS: Clinical baseline characteristics prior to oral amiodarone did not show any differences between group A and group B except for D(LCO) (82.0+/-5.2% vs. 90.8+/-9.0%, p=0.032) and Th1/Th2 balance (7.98+/-1.68 vs. 13.34+/-5.10, p=0.020). This balance was not altered three months after withdrawal of amiodarone in group A and under continued treatment in group B, suggesting patient-specific rather than amiodarone-induced. After starting amiodarone, serum concentration of desethylamiodarone was greater in group A than in group B (p=0.009) and was inversely proportional to Th1/Th2 ratio (p=0.013). Multilogistic regression analysis indicated that Th1/Th2 balance was the most powerful indicator of amiodarone lung toxicity (p=0.046, odds ratio of 0.424). CONCLUSIONS: Although large cohort is required, the present study indicates that Th1/Th2 balance may influence amiodarone metabolism and may be a powerful indicator of amiodarone-induced subclinical lung toxicity at least in Japanese.

Influence of interferon therapy on signal-averaged and ambulatory electrocardiograms in patients with chronic active hepatitis.

Although interferon (IFN) shows cardiotoxicity and arrhythmogenesis, the influence of IFN on signal-averaged electrocardiography remains to be clarified. The aim of this study was to test a clinical hypothesis that IFN therapy for hepatitis C virus may induce ventricular late potentials (LPs) and related arrhythmias in patients with chronic active hepatitis. Signal-averaged and ambulatory electrocardiograms were recorded sequentially in patients with chronic active hepatitis C (n = 22) throughout the entire period of IFN therapy. The filtered QRS duration (fQRS) and low amplitude (< 40 microV) signal duration (LAS40) were significantly increased (95.5 +/- 8.5 to 99.6 +/- 9.4 msec, P < 0.0001, and 32.8 +/- 3.1 to 36.3 +/- 3.0 msec, P < 0.0001, respectively), whereas the root mean square voltage in the terminal 40 msec of the fQRS (RMS40) was significantly decreased (25.5 +/- 5.4 to 22.3 +/- 5.2 microV, P < 0.005) 1 month after starting the IFN therapy. The ventricular LP was negative in all subjects before starting therapy, but became positive in 7 patients after the therapy commenced. There were no differences in clinical baseline characteristics between the LP-positive (n = 7) and LP-negative (n = 15) groups. Significant increases in mean heart rate, fQRS, and LAS40 were observed after starting the therapy, irrespective of the appearance of the ventricular LP, whereas a decrease in RMS40 was observed only in the LP-positive group. No sustained ventricular arrhythmias were documented in the ambulatory electrocardiography and no cardiac events were encountered in the follow-up period. Therefore, the results indicate a reversible and subclinical risk of IFN-induced arrhythmogenesis.

Arrhythmogenic and inotropic effects of interferon investigated in perfused and in vivo rat hearts: influences of cardiac hypertrophy and isoproterenol.

Although the arrhythmogenic effects of interferon (IF) have been reported in clinical practice, the experimental data are limited. Therefore, these effects were investigated in in vivo and Langendorff-perfusion studies using 3 different groups of rats (ie, control, aorta-banded, and deoxycorticosterone acetate (DOCA)-salt hypertension groups) in the presence or absence of isoproterenol. In the perfusion study, human recombinant IF-alpha (< or =15,000 U/ml) alone induced irreversible atrioventricular blockade in all groups, whereas this agent (< or =1,500 U/ml) caused negative inotropism and ventricular tachyarrhythmias (arrhythmic score greater in the order of DOCA-salt>aorta-banded = control group) in the preparations pretreated with isoproterenol (10(-9) mol/L). In an in vivo study, IF-alpha (6x10(6) U/kg) resulted in ventricular tachyarrhythmias only in the presence of isoproterenol (10 mg/kg), as in the perfusion study (arrhythmic score; DOCA-salt>aorta-banded>control). In conclusion, the arrhythmogenesis of IF-alpha is potentiated in pathophysiological conditions such as cardiac hypertrophy or elevated sympathetic activity.