Dominique Babuty

Sudden Cardiac Arrest Associated with Early Repolarization

BACKGROUND Early repolarization is a common electrocardiographic finding that is generally considered to be benign. Its potential to cause cardiac arrhythmias has been hypothesized from experimental studies, but it is not known whether there is a clinical association with sudden cardiac arrest. METHODS We reviewed data from 206 case subjects at 22 centers who were resuscitated after cardiac arrest due to idiopathic ventricular fibrillation and assessed the prevalence of electrocardiographic early repolarization. The latter was defined as an elevation of the QRS-ST junction of at least 0.1 mV from baseline in the inferior or lateral lead, manifested as QRS slurring or notching. The control group comprised 412 subjects without heart disease who were matched for age, sex, race, and level of physical activity. Follow-up data that included the results of monitoring with an implantable defibrillator were obtained for all case subjects. RESULTS Early repolarization was more frequent in case subjects with idiopathic ventricular fibrillation than in control subjects (31% vs. 5%, P<0.001). Among case subjects, those with early repolarization were more likely to be male and to have a history of syncope or sudden cardiac arrest during sleep than those without early repolarization. In eight subjects, the origin of ectopy that initiated ventricular arrhythmias was mapped to sites concordant with the localization of repolarization abnormalities. During a mean (+/-SD) follow-up of 61+/-50 months, defibrillator monitoring showed a higher incidence of recurrent ventricular fibrillation in case subjects with a repolarization abnormality than in those without such an abnormality (hazard ratio, 2.1; 95% confidence interval, 1.2 to 3.5; P=0.008). CONCLUSIONS Among patients with a history of idiopathic ventricular fibrillation, there is an increased prevalence of early repolarization.

Long-Term Prognosis of Patients Diagnosed With Brugada Syndrome Results From the FINGER Brugada Syndrome Registry

Background— Brugada syndrome is characterized by ST-segment elevation in the right precordial leads and an increased risk of sudden cardiac death (SCD). Fundamental questions remain on the best strategy for assessing the real disease-associated arrhythmic risk, especially in asymptomatic patients. The aim of the present study was to evaluate the prognosis and risk factors of SCD in Brugada syndrome patients in the FINGER (France, Italy, Netherlands, Germany) Brugada syndrome registry. Methods and Results— Patients were recruited in 11 tertiary centers in 4 European countries. Inclusion criteria consisted of a type 1 ECG present either at baseline or after drug challenge, after exclusion of diseases that mimic Brugada syndrome. The registry included 1029 consecutive individuals (745 men; 72%) with a median age of 45 (35 to 55) years. Diagnosis was based on (1) aborted SCD (6%); (2) syncope, otherwise unexplained (30%); and (3) asymptomatic patients (64%). During a median follow-up of 31.9 (14 to 54.4) months, 51 cardiac events (5%) occurred (44 patients experienced appropriate implantable cardioverter-defibrillator shocks, and 7 died suddenly). The cardiac event rate per year was 7.7% in patients with aborted SCD, 1.9% in patients with syncope, and 0.5% in asymptomatic patients. Symptoms and spontaneous type 1 ECG were predictors of arrhythmic events, whereas gender, familial history of SCD, inducibility of ventricular tachyarrhythmias during electrophysiological study, and the presence of an SCN5A mutation were not predictive of arrhythmic events. Conclusions— In the largest series of Brugada syndrome patients thus far, event rates in asymptomatic patients were low. Inducibility of ventricular tachyarrhythmia and family history of SCD were not predictors of cardiac events.

Outcome After Implantation of a Cardioverter-Defibrillator in Patients With Brugada Syndrome A Multicenter Study

Background— Implantable cardioverter-defibrillator indications in Brugada syndrome remain controversial, especially in asymptomatic patients. Previous outcome data are limited by relatively small numbers of patients or short follow-up durations. We report the outcome of patients with Brugada syndrome implanted with an implantable cardioverter-defibrillator in a large multicenter registry. Methods and Results— A total of 378 patients (310 male; age, 46±13 years) with a type 1 Brugada ECG pattern implanted with an implantable cardioverter-defibrillator (31 for aborted sudden cardiac arrest, 181 for syncope, and 166 asymptomatic) were included. Fifteen patients (4%) were lost to follow-up. During a mean follow-up of 77±42 months, 7 patients (2%) died (1 as a result of an inappropriate shock), and 46 patients (12%) had appropriate device therapy (5±5 shocks per patient). Appropriate device therapy rates at 10 years were 48% for patients whose implantable cardioverter-defibrillator indication was aborted sudden cardiac arrest, 19% for those whose indication was syncope, and 12% for the patients who were asymptomatic at implantation. At 10 years, rates of inappropriate shock and lead failure were 37% and 29%, respectively. Inappropriate shock occurred in 91 patients (24%; 4±4 shocks per patient) because of lead failure (n=38), supraventricular tachycardia (n=20), T-wave oversensing (n=14), or sinus tachycardia (n=12). Importantly, introduction of remote monitoring, programming a high single ventricular fibrillation zone (>210–220 bpm), and a long detection time were associated with a reduced risk of inappropriate shock. Conclusions— Appropriate therapies are more prevalent in symptomatic Brugada syndrome patients but are not insignificant in asymptomatic patients (1%/y). Optimal implantable cardioverter-defibrillator programming and follow-up dramatically reduce inappropriate shock. However, lead failure remains a major problem in this population.

Antiarrhythmic effect of statin therapy and atrial fibrillation a meta-analysis of randomized controlled trials.

OBJECTIVES To improve the evaluation of the possible antiarrhythmic effect of statins, we performed a meta-analysis of randomized trials with statins on the end point of incidence or recurrence of atrial fibrillation (AF). BACKGROUND The use of statins had been suggested to protect against AF in some clinical observational and experimental studies but has remained inadequately explored. METHODS A systematic review of controlled trials with statins was performed. Eligible studies had to have been randomized controlled parallel-design human trials with use of statins that collected data on incidence or recurrence of AF. RESULTS Six studies with 3,557 patients in sinus rhythm were included in the analysis. Three studies investigated the use of statins in patients with a history of paroxysmal AF (n = 1) or persistent AF undergoing electrical cardioversion (n = 2), and 3 investigated the use of statins in primary prevention of AF in patients undergoing cardiac surgery or after acute coronary syndrome. Incidence or recurrence of AF occurred in 386 patients. Overall, the use of statins was significantly associated with a decreased risk of AF compared with control (odds ratio [OR] 0.39, 95% confidence interval [CI] 0.18 to 0.85, p = 0.02). Benefit of statin therapy seemed more marked in secondary prevention of AF (OR 0.33, 95% CI 0.10 to 1.03, p = 0.06) than for new-onset or postoperative AF (OR 0.60, 95% CI 0.27 to 1.37, p = 0.23). CONCLUSIONS Use of statins was significantly associated with a decreased risk of incidence or recurrence of AF in patients in sinus rhythm with a history of previous AF or undergoing cardiac surgery or after acute coronary syndrome.

Clinical Aspects and Prognosis of Brugada Syndrome in Children

Background— Brugada syndrome is an arrhythmogenic disease characterized by an ECG pattern of ST-segment elevation in the right precordial leads and augmented risk of sudden cardiac death. Little is known about the clinical presentation and prognosis of this disease in children. Methods and Results— Thirty children affected by Brugada syndrome who were <16 years of age (mean, 8±4 years) were included. All patients displayed a type I ECG pattern before or after drug provocation challenge. Diagnosis of Brugada syndrome was made under the following circumstances: aborted sudden death (n=1), syncope of unexplained origin (n=10), symptomatic supraventricular tachycardia (n=1), suspicious ECG (n=1), and family screening for Brugada syndrome (n=17). Syncope was precipitated by fever in 5 cases. Ten of 11 symptomatic patients displayed a spontaneous type I ECG. An implantable cardioverter-defibrillator was implanted in 5 children; 4 children were treated with hydroquinidine; and 1 child received a pacemaker because of symptomatic sick sinus syndrome. During a mean follow-up of 37±23 months, 1 child experienced sudden cardiac death, and 2 children received an appropriate implantable cardioverter-defibrillator shock; all of them were symptomatic and had manifested a type I ECG spontaneously. One child had a cardioverter-defibrillator infection that required explantation of the defibrillator. Conclusions— In the largest population of children affected by Brugada syndrome described to date, fever represented the most important precipitating factor for arrhythmic events, and as in the adult population, the risk of arrhythmic events was higher in previously symptomatic patients and in those displaying a spontaneous type I ECG.

Interventricular and intraventricular dyssynchrony in idiopathic dilated cardiomyopathy. A prognostic study with Fourier phase analysis of radionuclide angioscintigraphy

OBJECTIVES The study evaluated the prognostic value of interventricular and intraventricular dyssynchrony in idiopathic dilated cardiomyopathy (IDC). BACKGROUND Biventricular pacing is an emerging treatment for patients with dilated cardiomyopathy and ventricular dyssynchrony. The prognostic values of interventricular and intraventricular dyssynchrony have not been previously compared. METHODS A total of 103 patients with IDC were studied. Left bundle branch block was present in 25% of patients. Equilibrium radionuclide angiography was performed and Fourier phase analyses were examined in both ventricles. Difference between the mean phase of left ventricle (LV) and right ventricle (RV) assessed interventricular dyssynchrony, and standard deviations (SDs) of the mean phase in each ventricle assessed intraventricular dyssynchrony. RESULTS The QRS duration was related to both interventricular and intraventricular dyssynchrony. A degradation of the hemodynamic status was associated with an increase in intraventricular dyssynchrony but not in interventricular dyssynchrony. With a follow-up of 27 +/- 23 months, 18 patients had a major cardiac event (7 cardiac deaths; 11 worsening, leading to heart transplantation). The SDs of the LV and RV mean phase and QRS duration were predictors of cardiac event (all p < 0.0001), but interventricular dyssynchrony was not. Among 13 univariate predictors of cardiac event, the only independent predictors were an increased SD of LV mean phase (p = 0.0004) and an increased pulmonary capillary wedge pressure (p = 0.009). CONCLUSIONS Intraventricular dyssynchrony evaluated with phase analysis of radionuclide angiography is an independent predictor of cardiac event in IDC. The prognosis is related to intraventricular rather than to interventricular dyssynchrony in IDC.

Outcome After Implantation of a Cardioverter-Defibrillator in Patients With Brugada Syndrome

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. Conclusion— 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.

SCN5A mutations and the role of genetic background in the pathophysiology of Brugada syndrome

Background— Mutations in SCN5A are identified in ≈20% to 30% of probands affected by Brugada syndrome (BrS). However, in familial studies, the relationship between SCN5A mutations and BrS remains poorly understood. The aim of this study was to investigate the association of SCN5A mutations and BrS in a group of large genotyped families. Methods and Results— Families were included if at least 5 family members were carriers of the SCN5A mutation, which was identified in the proband. Thirteen large families composed of 115 mutation carriers were studied. The signature type I ECG was present in 54 mutation carriers (BrS-ECG+; 47%). In 5 families, we found 8 individuals affected by BrS but with a negative genotype (mutation-negative BrS-ECG+). Among these 8 mutation-negative BrS-ECG+ individuals, 3, belonging to 3 different families, had a spontaneous type I ECG, whereas 5 had a type I ECG only after the administration of sodium channel blockers. One of these 8 individuals had also experienced syncope. Mutation carriers had, on average, longer PR and QRS intervals than noncarriers, demonstrating that these mutations exerted functional effects. Conclusions— Our results suggest that SCN5A mutations are not directly causal to the occurrence of a BrS-ECG+ and that genetic background may play a powerful role in the pathophysiology of BrS. These findings add further complexity to concepts regarding the causes of BrS, and are consistent with the emerging notion that the pathophysiology of BrS includes various elements beyond mutant sodium channels.

Focus Issue: Atrial FibrillationClinical Research: Statins and Atrial FibrillationAntiarrhythmic Effect of Statin Therapy and Atrial Fibrillation: A Meta-Analysis of Randomized Controlled Trials

OBJECTIVES To improve the evaluation of the possible antiarrhythmic effect of statins, we performed a meta-analysis of randomized trials with statins on the end point of incidence or recurrence of atrial fibrillation (AF). BACKGROUND The use of statins had been suggested to protect against AF in some clinical observational and experimental studies but has remained inadequately explored. METHODS A systematic review of controlled trials with statins was performed. Eligible studies had to have been randomized controlled parallel-design human trials with use of statins that collected data on incidence or recurrence of AF. RESULTS Six studies with 3,557 patients in sinus rhythm were included in the analysis. Three studies investigated the use of statins in patients with a history of paroxysmal AF (n = 1) or persistent AF undergoing electrical cardioversion (n = 2), and 3 investigated the use of statins in primary prevention of AF in patients undergoing cardiac surgery or after acute coronary syndrome. Incidence or recurrence of AF occurred in 386 patients. Overall, the use of statins was significantly associated with a decreased risk of AF compared with control (odds ratio [OR] 0.39, 95% confidence interval [CI] 0.18 to 0.85, p = 0.02). Benefit of statin therapy seemed more marked in secondary prevention of AF (OR 0.33, 95% CI 0.10 to 1.03, p = 0.06) than for new-onset or postoperative AF (OR 0.60, 95% CI 0.27 to 1.37, p = 0.23). CONCLUSIONS Use of statins was significantly associated with a decreased risk of incidence or recurrence of AF in patients in sinus rhythm with a history of previous AF or undergoing cardiac surgery or after acute coronary syndrome.

Heart rate variability in idiopathic dilated cardiomyopathy: Characteristics and prognostic value

OBJECTIVES This study was designed to evaluate heart rate variability (HRV) in patients with idiopathic dilated cardiomyopathy (IDC), to determine its correlation with hemodynamic variables and ventricular arrhythmias and to evaluate its prognostic value in IDC. BACKGROUND Previous studies have shown that HRV could predict arrhythmic events in patients after infarction, but the characteristics of HRV in IDC have not been fully established. METHODS Time domain analysis of HRV on 24-h electrocardiographic (ECG) recording was performed in 93 patients with IDC, and results were compared with those in 63 control subjects. RESULTS Patients with IDC, even those without congestive heart failure, had significantly lower values for HRV than those of control subjects. HRV was related to left ventricular shortening fraction (R = 0.5, p = 0.0001) and to peak oxygen uptake (R = 0.53, p = 0.01). HRV was not different in patients with runs of ventricular tachycardia or in patients with late potentials on the signal-averaged ECG. During a mean follow-up period (+/-SD) of 49.5 +/- 35.6 months, patients with reduced HRV had an increased risk of cardiac death or heart transplantation (p = 0.006). On multivariate analysis, cardiac events were predicted by increased left ventricular end-diastolic diameter (p = 0.0001), reduced standard deviation of all normal to normal RR intervals (p = 0.02) and increased pulmonary capillary wedge pressure (p = 0.04). CONCLUSIONS Decreased HRV in patients with IDC is related to left ventricular dysfunction and not to ventricular arrhythmias. Analysis of HRV can identify patients with IDC who have an increased risk of cardiac death or heart transplantation.