Outcome after implantation of a cardioverter-defibrillator in patients with Brugada syndrome: a multicenter study.

BACKGROUND: Brugada syndrome is an arrhythmogenic disease characterized by an increased risk of sudden cardiac death (SCD) by ventricular fibrillation. At present, an implantable cardioverter-defibrillator (ICD) is the recommended therapy in high-risk patients. This multicenter study reports the outcome of a large series of patients implanted with an ICD for Brugada syndrome. METHODS AND RESULTS: All patients (n=220, 46+/-12 years, 183 male) with a type 1 Brugada ECG pattern implanted with an ICD in 14 centers between 1993 and 2005 were investigated. ICD indication was based on resuscitated SCD (18 patients, 8%), syncope (88 patients, 40%), or positive electrophysiological study in asymptomatic patients (99 patients, 45%). The remaining 15 patients received an ICD because of a family history of SCD or nonsustained ventricular arrhythmia. During a mean follow-up of 38+/-27 months, no patient died and 18 patients (8%) had appropriate device therapy (10+/-15 shocks/patient, 26+/-33 months after implantation). The complication rate was 28%, including inappropriate shocks, which occurred in 45 patients (20%, 4+/-3 shocks/patient, 21+/-20 months after implantation). The reasons for inappropriate therapy were lead failure (19 patients), T-wave oversensing (10 patients), sinus tachycardia (10 patients), and supraventricular tachycardia (9 patients). Among implantation parameters, high defibrillation threshold, high pacing threshold, and low R-wave amplitude occurred, respectively, in 12%, 27%, and 15% of cases. CONCLUSIONS: In this large Brugada syndrome population, a low incidence of arrhythmic events was found, with an annual event rate of 2.6% during a follow-up of >3 years, in addition to a significant risk of device-related complications (8.9%/year). Inappropriate shocks were 2.5 times more frequent than appropriate ones.

Clinical predictors and prognostic significance of electrical storm in patients with implantable cardioverter defibrillators.

AIMS: Insufficient data exists regarding predictors of electrical storms (ES) and clinical outcome in patients treated with an implantable cardioverter defibrillator (ICD). The purpose of this study was to delineate a subgroup of patients likely to experience ES and to determine the impact of ES on mortality in ICD recipients. METHODS AND RESULTS: Baseline characteristics of 307 ICD-treated patients were retrospectively analysed. ES was defined as two or more ventricular tachyarrhythmias within 24 h leading to an immediate electrical therapy (antitachycardia pacing and/or shock), separated by a period of sinus rhythm. Clinical characteristics and survival of 123 patients experiencing a total of 294 episodes of ES (median 2 ES/patient, range 1-9), were compared with those of 184 ES-free patients during a median follow-up of 826 days (inter-quartile 1141 days). Median actuarial duration for the first ES occurrence after ICD implant was 1417 days [95% confidence interval (CI) 1061-2363] with a median follow-up of 816 days (7-4642 days) in ES-free patients. Univariate analysis identified older age, depressed left ventricular ejection fraction (LVEF), ventricular tachycardia (VT) as index arrhythmia, chronic renal failure and absence of lipid-lowering drugs as variables significantly associated with an increased risk of ES. Multivariable Cox analysis confirmed an independent predictive value for chronic renal failure [hazard ratio (HR) 1.54, 95% CI 0.95-2.51, P=0.052], VT (HR 2.20, 95% CI 1.44-3.37, P=0.0003), and LVEF (HR 0.98, 95% CI 0.97-0.99, P=0.027). In contrast, diabetics (HR 0.49, 95% CI 0.27-0.90, P=0.022) were less affected by ES. There was no difference in survival between both groups. CONCLUSION: ES is frequent but does not increase mortality in ICD's recipients. Patients with severe systolic dysfunction, chronic renal failure and VT as initial arrhythmia are likely to experience ES. Diabetics are less affected by ES.

Prognostic impact of matrix metalloproteinase gene polymorphisms in patients with heart failure according to the aetiology of left ventricular systolic dysfunction.

AIMS: To assess the possible effect of functional polymorphisms in matrix metalloproteinase (MMP) gene promoters on the clinical outcome of patients with heart failure. METHODS AND RESULTS: We studied 444 consecutive patients who were referred to our centre for evaluation of left ventricular dysfunction. We extracted genomic DNA from white blood cells and determined the -1306 C >T MMP-2, -1171 5A > 6A MMP-3, and -1562 C >T MMP-9 polymorphisms. Clinical follow-up (median 717 days) was obtained for 443 patients. The MMP-3 polymorphism had a different impact on cardiac survival in HF patients with ischaemic and non-ischaemic cardiomyopathy (interaction p <0.03). The MMP-3 5A/5A genotype was an independent predictor of cardiac mortality (HR 2.92 [1.23-6.69]; p = 0.01) in patients with non-ischaemic HF. In contrast, there was no evidence for any effect of the MMP-3 genotype on cardiac events in patients with ischaemic cardiomyopathy. The MMP-9 polymorphism was associated with cardiac survival (p < 0.03) independently of HF aetiology. In multivariate analysis, the MMP-9 T allele was an independent predictor of cardiac mortality (HR 1.81 [1.09-3.02]; p = 0.02). Finally, there was no evidence for any association between MMP-2 polymorphism and cardiac survival. CONCLUSION: MMP-3 and MMP-9 polymorphisms contribute to variability in cardiac survival in HF patients. These data suggest that MMP genotyping could provide important additional information for refining risk stratification in patients with heart failure. MMP genotyping may help to select patients who could benefit from MMP inhibition.