Anne Rollin

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.

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.

Outcome After Implantation of a Cardioverter-Defibrillator in Patients With Brugada SyndromeClinical Perspective: A Multicenter Study–Part 2

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.

Prevalence and prognostic role of various conduction disturbances in patients with the Brugada syndrome.

Prevalence and prognostic value of conduction disturbances in patients with the Brugada syndrome (BrS) remains poorly known. Electrocardiograms (ECGs) from 325 patients with BrS (47 ± 13 years, 258 men) with spontaneous (n = 143) or drug-induced (n = 182) type 1 ECG were retrospectively reviewed. Two hundred twenty-six patients (70%) were asymptomatic, 73 patients (22%) presented with unexplained syncope, and 26 patients (8%) presented with sudden death or implantable cardioverter-defibrillator appropriated therapies at diagnosis or during a mean follow-up of 48 ± 34 months. P-wave duration of ≥120 ms was present in 129 patients (40%), first degree atrioventricular block (AVB) in 113 (35%), right bundle branch block (BBB) in 90 (28%), and fascicular block in 52 (16%). Increased P-wave duration, first degree AVB, and right BBB were more often present in patients after drug challenge than in patients with spontaneous type 1 ST elevation. Left BBB was present in 3 patients. SCN5A mutation carriers had longer P-wave duration and longer PR and HV intervals. In multivariate analysis, first degree AVB was independently associated with sudden death or implantable cardioverter-defibrillator appropriated therapies (odds ratio 2.41, 95% confidence interval 1.01 to 5.73, p = 0.046) together with the presence of syncope and spontaneous type 1 ST elevation. In conclusion, conduction disturbances are frequent and sometimes diffuse in patients with BrS. First degree AVB is independently linked to outcome and may be proposed to be used for individual risk stratification.

Increased Tpeak-Tend interval is highly and independently related to arrhythmic events in Brugada syndrome

BACKGROUND Risk stratification in Brugada syndrome (BS) remains controversial. The time interval between the peak and the end of the T wave (Tpe interval), a marker of transmural dispersion of repolarization, has been linked to malignant ventricular arrhythmias in various settings but leads to discordant results in BS. OBJECTIVE We study the correlation of the Tpe interval with arrhythmic events in a large cohort of patients with BS. METHODS A total of 325 consecutive patients with BS (mean age 47±13 years, 259 men-80%) with spontaneous (n=143, 44%) or drug-induced (n=182, 56%) type 1 electrocardiogram were retrospectively included. 235 were asymptomatic (70%), 80 presented with unexplained syncope (22%), and 10 presented with sudden death (SD) or appropriate implantable cardioverter-defibrillator therapy (AT) (8%) at diagnosis or over a mean follow-up of 48 ± 34 months. The Tpe interval was calculated as the difference between the QT interval and the QT peak interval as measured in each of the precordial leads. RESULTS The Tpe interval from lead V1 to lead V4, maximum value of the Tpe interval (max Tpe), and Tpe dispersion in all precordial leads were significantly higher in patients with SD/AT or in patients with syncope than in asymptomatic patients (P < .001). A max Tpe of ≥100 ms was present in 47 of 226 asymptomatic patients (21%), in 48 of 73 patients with syncope (66%), and in 22 of 26 patients with SD/AT (85%) (P < .0001). In multivariate analysis, a max Tpe of ≥100 ms was independently related to arrhythmic events (odds ratio 9.61; 95% confidence interval 3.13-29.41; P < .0001). CONCLUSION The Tpe interval in the precordial leads is highly related to malignant ventricular arrhythmias in this large cohort of patients with BS. This simple electrocardiographic parameter could be used to refine risk stratification.

Prevalence, characteristics, and prognosis role of type 1 ST elevation in the peripheral ECG leads in patients with Brugada syndrome

BACKGROUND Despite isolated reports of Brugada syndrome (BrS) in the inferior or lateral leads, the prevalence and prognostic value of ST elevation in the peripheral electrocardiographic (ECG) leads in patients with BrS remain poorly known. OBJECTIVE To study the prevalence, characteristics, and prognostic value of type 1 ST elevation and ST depression in the peripheral ECG leads in a large cohort of patients with BrS. METHODS ECGs from 323 patients with BrS (age 47 ± 13 years; 257 men) with spontaneous (n = 141) or drug-induced (n = 182) type 1 ECG were retrospectively reviewed. Two hundred twenty-five (70%) patients were asymptomatic, 72 (22%) patients presented with unexplained syncope, and 26 (8%) patients presented with sudden death (12 patients) or appropriated implantable cardioverter-defibrillator therapies (14 patients) at diagnosis or over a mean follow-up of 48 ± 34 months. RESULTS Thirty (9%) patients presented with type 1 ST elevation in at least 1 peripheral lead (22 patients in the aVR leads, 2 in the inferior leads, 5 in both aVR and inferior leads, and 1 in the aVR and VL leads). Patients with type 1 ST elevation in the peripheral leads more often had mutations in the SCN5A gene, were more often inducible, had slower heart rate, and higher J-wave amplitude in the right precordial leads. Twenty-seven percent (8 of 30) of the patients with type 1 ST elevation in the peripheral leads experimented sudden death/appropriate implantable cardioverter-defibrillator therapy, whereas it occurred in only 6% (18 of 293) of other patients (P < .0001). In multivariate analysis, type 1 ECG in the peripheral leads was independently associated with malignant arrhythmic events (odds ratio 4.58; 95% confidence interval 1.7-12.32; P = .0025). CONCLUSIONS Type 1 ST elevation in the peripheral ECG leads can be seen in 10% of the patients with BrS and is an independent predictor for a malignant arrhythmic event.

Monomorphic ventricular tachycardia in patients with Brugada syndrome: A multicenter retrospective study

BACKGROUND Isolated cases of monomorphic ventricular tachycardia (MVT) in patients with Brugada syndrome (BrS) have been reported. OBJECTIVE We aimed to describe the incidence and characteristics of MVT in a cohort of patients with BrS who had received an implantable cardioverter-defibrillator (ICD). METHODS Data from 834 patients with BrS implanted with an ICD in 15 tertiary hospitals between 1993 and 2014 were included. RESULTS The mean age of enrolled patients was 45.3 ± 13.9 years; 200 patients (24%) were women. During a mean follow-up of 69.4 ± 54.3 months, 114 patients (13.7%) experienced at least 1 appropriate ICD intervention, with MVT recorded in 35 patients (4.2%) (sensitive to antitachycardia pacing in 15 [42.8%]). Only QRS width was an independent predictor of MVT in the overall population. Specifically, 6 (17.1%) patients presented with right ventricular outflow tract tachycardia (successfully ablated from the endocardium in 4 and epicardial and endocardial ablation in 1), 2 patients with MVT arising from the left ventricle (1 successfully ablated in the supra lateral mitral annulus), and 2 (5.7%) patients with bundle branch reentry ventricular tachycardia. Significant structural heart disease was ruled out by echocardiography and/or cardiac magnetic resonance imaging. CONCLUSION In this retrospective study, 4.2% of patients with BrS implanted with an ICD presented with MVT confirmed as arising from the right ventricular outflow tract tachycardia in 6, patients with MVT arising from the left ventricle in 2, and patients with bundle branch reentry ventricular tachycardia in 2. Endocardial and/or epicardial ablation was successful in 80% of these cases. These data imply that the occurrence of MVT should not rule out the possibility of BrS. This finding may also be relevant for ICD model selection and programming.

Premature ventricular contraction-induced cardiomyopathy: Related clinical and electrophysiologic parameters.

BACKGROUND Factors associated with premature ventricular contraction-induced cardiomyopathy (PVCi-CMP) remain debated. OBJECTIVE The purpose of this study was to test the correlation of various factors to the presence PVCi-CMP in a large multicenter population. METHODS One hundred sixty-eight consecutive patients referred for ablation of frequent premature ventricular contractions (PVCs) were included. Patients were divided into 2 groups: group 1 with suspected PVCi-CMP (96 patients, ejection fraction 38% ± 10%, left ventricular end-diastolic diameter 62 ± 8 mm, with or without additional structural heart disease); and group 2 (control group, 72 patients with normal ejection fraction and left ventricular dimensions). Various clinical and electrophysiologic parameters were compared between groups. RESULTS In univariate analysis, left ventricular origin of PVC, lack of palpitations, long PVC coupling interval, epicardial origin of the focus, long sinus beat QRS duration, male gender, high PVC burden, presence of polymorphic PVCs, high PVC QRS duration, and older age were significantly related to the presence of PVCi-CMP. In multivariate analysis, only lack of palpitations, PVC burden, and epicardial origin remained significantly and independently correlated with the presence of cardiomyopathy. Even if sinus QRS duration or PVC left ventricular origin were also found independently linked to PVCi-CMP in the whole population, they were no longer correlated when patients with additional heart disease were excluded. CONCLUSION Lack of palpitations, PVC burden, and epicardial origin are independent factors that identify patients prone to developing PVCi-CMP.

Benign vs malignant inferolateral early repolarization: Focus on the T wave

BACKGROUND Inferolateral early repolarization (ER) is highly prevalent and is associated with idiopathic ventricular fibrillation (VF). OBJECTIVE The purpose of this study was to evaluate the potential role of T-wave parameters to differentiate between malignant and benign ER. METHODS We compared the ECGs of patients with ER and VF (n = 92) with control subjects with asymptomatic ER (n = 247). We assessed J-wave amplitude, QTc interval, T-wave/R-wave (T/R) ratio in leads II and V5, and presence of low-amplitude T waves (T-wave amplitude <0.1 mV and <10% of R-wave amplitude in lead I, II, or V4-V6). RESULTS Compared to controls, the VF group had longer QTc intervals (388 ms vs. 377 ms, P = .001), higher J-wave amplitudes (0.23 mV vs. 0.17 mV, P <.001), higher prevalence of low-amplitude T waves (29% vs. 3%, P <.001), and lower T/R ratio (0.18 vs. 0.30, P <.001). Logistic regression analysis demonstrated that QTc interval (odds ratio [OR] per 10 ms: 1.15, 95% confidence interval [CI} 1.02-1.30), maximal J-wave amplitude (OR per 0.1 mV: 1.68, 95% CI 1.23-2.31), lower T/R ratio (OR per 0.1 unit: 0.62, 95% CI 0.47-0.81), presence of low-amplitude T waves (OR 3.53, 95% CI 1.26-9.88). and presence of J waves in the inferior leads (OR 2.58, 95% CI 1.18-5.65) were associated with malignant ER. CONCLUSION Patients with malignant ER have a higher prevalence of low-amplitude T waves, lower T/R ratio (lead II or V5), and longer QTc interval. The combination of these parameters with J-wave amplitude and distribution of J waves may allow for improved identification of malignant ER.

T-Wave Oversensing in Patients With Brugada Syndrome: True Bipolar Versus Integrated Bipolar Implantable Cardioverter Defibrillator Leads Multicenter Retrospective Study

Background—It is thought that dedicated bipolar are more susceptible to T-wave oversensing when compared with integrated bipolar leads. This could be of extreme importance in patients with Brugada syndrome (BrS) because T-wave oversensing in this population is more frequent when compared with other implantable cardioverter defibrillator (ICD) recipients without BrS. We aimed to compare the incidence of T-wave oversensing in patients with BrS according to the type of lead (integrated bipolar versus true/dedicated bipolar). Methods and Results—All patients diagnosed with BrS with an ICD implant in 10 tertiary hospitals between 1993 and 2013 were included in the study. A total of 480 patients were included (mean age, 45.6±14 years). During a mean follow-up of 74.9±51.7 months (median, 69; range, 2–236), 28 patients had T-wave oversensing (5.8%), leading to inappropriate shock in 18 (3.8%). All these events occurred in patients with true bipolar ICD leads (P=0.01) and in 2 patients it was solved instantaneously by changing the configuration from a dedicated to an integrated bipolar sensing configuration. In the stepwise multivariate models, only integrated bipolar ICD leads (hazard ratio, 0.34; 95% confidence interval, 0.171–0.675; P=0.002) was independent predictor of non–T-wave oversensing. Conclusions—T-wave oversensing is a potential reason of inappropriate shocks in patients with BrS receiving ICDs. In the vast majority it can be solved by reprogramming. However, in some patients it still requires invasive intervention. Importantly, incidence is significantly lower using an integrated bipolar lead system when compared with a dedicated bipolar lead system and hence the latter should be routinely used in BrS cases.