The role of clinical assessment and electrophysiology study in Brugada syndrome patients with syncope.

BACKGROUND: Cardiogenic syncope in Brugada syndrome (BrS) increases the risk of major events. Nevertheless, clinical differentiation between cardiogenic and vasovagal syncope can be challenging. We characterized the long-term incidence of major events in a large cohort of BrS patients who presented with syncope. METHODS: From a total of 474 patients, syncope was the initial manifestation in 135 (28.5%) individuals (43.9 ±â€¯13.9 years, 71.1% male). The syncope was classified prospectively as cardiogenic, vasovagal, or undefined if unclear characteristics were present. Clinical, electrocardiographic, genetic, and electrophysiologic features were analyzed. Cardiogenic syncope, sustained ventricular arrhythmias, and sudden death were considered major events in follow-up. RESULTS: In 66 patients (48.9%), the syncope was cardiogenic; in 51 (37.8%), vasovagal and in 18 (13.3%); undefined. The electrophysiology study (EPS) inducibility was more frequent in patients with cardiogenic syncope and absent in all patients with undefined syncope (28 [53.8%] vs 5 [12.2%] vs 0 [0%]; P < .01). During follow-up (7.7 ±â€¯5.6 years), only patients with cardiogenic syncope presented major events (16 [11.9%]). Among patients with inducible EPS, 7 (21.2%) presented major events (P = .04). The negative predictive value of the EPS for major events was 92.4%. The incidence rate of major events was 2.6% person-year. Parameters associated with major events included cardiogenic syncope (hazard ratio [HR] 6.3; 95% CI 1.1-10.4; P = .05), spontaneous type 1 electrocardiogram (HR 3.7; 95% CI 1.3-10.5; P = .01), and inducible EPS (HR 2.8; 95% CI 1.1-8.8; P = .05). CONCLUSIONS: An accurate syncope classification is crucial in BrS patients for risk stratification. In patients with syncope of unclear characteristics, the EPS may be helpful to prevent unnecessary implantable cardioverter defibrillators.

Patients With Brugada Syndrome and Implanted Cardioverter-Defibrillators: Long-Term Follow-Up.

BACKGROUND: Implantable cardioverter-defibrillator (ICD) indications for primary prevention in Brugada syndrome (BrS) are still debated. OBJECTIVES: The authors investigated the long-term outcome after ICD implantation in a large cohort of BrS patients. METHODS: Of a total of 370 patients with BrS in follow-up (age 43 ± 14 years; 74% male), 104 patients (28.1%) were treated with ICDs. The authors analyzed the long-term incidence of shocks and complications. RESULTS: An ICD was implanted for secondary prevention in 10 patients (9.6%) and for primary prevention in 94 patients (90.4%). After a follow-up of 9.3 ± 5.1 years, 21 patients (20.2%) experienced a total of 81 appropriate shocks (incidence rate 2.2 per 100 person-years). The rate of appropriate shocks was higher in secondary prevention patients (p < 0.01). However, 4 of the 45 asymptomatic patients (8.9%) experienced appropriate ICD therapy, all with a spontaneous type 1 electrocardiogram and inducible ventricular arrhythmias. In the multivariable analysis, type 1 electrocardiogram with syncope (hazard ratio: 4.96; 95% confidence interval: 1.87 to 13.14; p < 0.01) and secondary prevention indication (hazard ratio: 6.85; 95% confidence interval: 2.29 to 20.50; p < 0.01) were significant predictors of appropriate therapy. Nine patients (8.7%) experienced 37 inappropriate shocks (incidence rate 0.9 per 100 person-years). Twenty-one patients (20.2%) had other ICD-related complications (incidence rate 1.4 per 100 person-years). Three patients (2.9%) died (1 electrical storm and 2 noncardiovascular deaths). CONCLUSIONS: ICD therapy is an effective therapy in high-risk patients with BrS. However, it is also associated with a significant risk of device-related complications. Special care during ICD implantation, adequate device programming, and regular follow-up may allow reducing the number of adverse events.

Role of Electrocardiographic Tpeak-Tend for the Prediction of Ventricular Arrhythmic Events in the Brugada Syndrome.

Some previous studies have proposed the electrocardiographic Tpeak-Tend (TpTe) as a possible predictor of ventricular arrhythmic events in patients with Brugada syndrome (BrS). We sought to analyze the association between the parameters of repolarization dispersion (TpTe, TpTe/QT, TpTe dispersion, QTc, and QTd) and ventricular fibrillation/sudden cardiac death in a large cohort of patients with type 1 BrS. A total of 448 consecutive patients with BrS (men 61%, age 45 ± 16 years) with spontaneous (n = 96, 21%) or drug-induced (n = 352, 79%) type 1 electrocardiogram were retrospectively included. At the time of the diagnosis or during a mean follow-up of 93 ± 47 months (median 88 months), 43 patients (9%) documented ventricular arrhythmias. No significant difference was observed in TpTe, TpTe/QT, maximum TpTe, and TpTe dispersion between asymptomatic patients and those with syncope and malignant arrhythmias. TpTe/QT ratio did not also significantly differ between patients with ventricular fibrillation/sudden cardiac death and those asymptomatic ones. In conclusion, TpTe was not significantly prolonged in those patients with type 1 BrS presenting with unexplained syncope or malignant arrhythmic events during follow-up.

Brugada Syndrome and Exercise Practice: Current Knowledge, Shortcomings and Open Questions.

Since its recognition as a clinical entity in 1992, the Brugada Syndrome (BrS), a hereditary disease characterized by a typical electrocardiogram (ECG) pattern potentially predisposing to sudden cardiac death (SCD), has attracted the attention of many physicians for its circadian pattern of ventricular arrhythmias (VA), mostly occurring at rest. Exercise may potentially worsen the ECG abnormalities in BrS patients, resulting in higher peak J-point amplitudes during the vasovagal reaction of the recovery period, possibly leading to an increased risk of cardiac events. Moreover, the enhanced vagal tone in athletes could be both a BrS risk factor and an exercise effect. Therefore, the true risk of a BrS patient during exercise is still unclear. This review summarizes current knowledge, shortcomings and open questions on BrS and exercise. The paper, in particular, underlines specific considerations including BrS diagnostic criteria and differential diagnosis in athletes, the genetic basis, the autonomic imbalance during exercise practice and the recommendations for athletic participation in this patient group.

Brugada syndrome in the young: an assessment of risk factors predicting future events.

AIMS: To investigate the clinical characteristics, prognoses, and presence of risk factors in young patients with Brugada syndrome (BS). METHODS AND RESULTS: A consecutive cohort of 128 young BS patients (≤25 years old at diagnosis) was analysed. Eighty-eight patients (69%) were asymptomatic, whereas 40 (31%) presented with clinical manifestations of BS. Markers of prognosis and risk were identified upon comparison of these two groups. A history of malignant syncope was strong predictors of ventricular arrhythmic events. Family history of sudden cardiac death (SCD) and mutations in the SCN5A gene did not associate with increased risk. Symptomatic patients presented with significantly abnormal baseline electrical characteristics when compared with the asymptomatic cohort, including spontaneous type I electrocardiograph (ECG) patterns, sinus node dysfunction (SND), first-degree atrioventricular (AV) block, and intra-ventricular conduction delay. The symptomatic group more frequently exhibited atrial arrhythmias. Electrophysiological studies resulted positive more frequently in symptomatic patients, but no risk association for future events could be determined. During the follow-up period (mean: 65 months), 10 arrhythmic events occurred in nine symptomatic patients (event rate: 4.5% per year). No events occurred in the asymptomatic group. Variables significantly associated with arrhythmic events during follow-up were presence of symptoms at diagnosis and spontaneous type I ECG. The presence of atrial arrhythmias and conduction abnormalities was also associated with the risk of arrhythmic events during follow-up. CONCLUSION: Symptomatic BS in the young age is a rare but malignant condition that can manifest with a spectrum of electrical abnormalities (i.e. SND, atrial tachycardias, AV block, and infra-nodal conduction delay) and result in the extreme cases in lethal arrhythmic events and SCD.

Phrenic nerve injury during ablation with the second-generation cryoballoon: analysis of the temperature drop behaviour in a large cohort of patients.

AIMS: The present study sought to analyse the relationship between the temperature drop during the cryoenergy application and the occurrence of phrenic nerve injury (PNI) in a large cohort of patients having undergone second-generation cryoballoon ablation (CB-A). METHODS AND RESULTS: The first 550 consecutive patients having undergone CB-A for atrial fibrillation were enrolled. Attained temperatures at 20, 30, 40, and 60 s during cryoablation in the right-sided pulmonary veins (PVs) were collected. Diagnosis of PNI was made if reduced motility or paralysis of the hemidiaphragm was detected. The incidence of PNI in the study population was 7.3% (40/550); among them, only four (0.7%) did not resolve until discharge and one (0.2%) still persisted at 23 months. Patients with PNI exhibited significantly lower temperatures at 20, 30, and 40 s after the beginning of the cryoapplication in the right superior PV (RSPV) (P = 0.006, P = 0.003, and P = 0.003, respectively). The temperature drop expressed as Δ temperature/Δ time was also significantly higher in patients with PNI. Low temperature during the early phases of the freezing cycle (less than -38°C at 40 s) predicted PNI with a sensitivity of 80.5%, a specificity of 77%, and a negative predictive value of 97.9%. Among patients with a fast temperature drop during RSPV ablation, an RSPV diameter >23.55 × 17.95 mm significantly predicted PNI occurrence. CONCLUSION: The analysis of the temperature course within the first 40 s after the initiation of the freezing cycle showed that the temperature dropped significantly faster in patients with PNI during ablation in the RSPV.

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.

Effect of rosuvastatin on diabetic polyneuropathy: a randomized, double-blind, placebo-controlled Phase IIa study.

BACKGROUND: Diabetic neuropathy affects 50%-66% of patients with diabetes mellitus. Oxidative stress generates nerve dysfunction by causing segmental demyelinization and axonal degeneration. Antioxidants are considered to be the only etiologic management for diabetic polyneuropathy, and statins such as rosuvastatin increase nitric oxide bioavailability and reduce lipid peroxidation. The aim of this study was to evaluate the antioxidant effect of rosuvastatin in diabetic polyneuropathy. METHODS: We conducted a randomized, double-blind, placebo-controlled Phase IIa clinical trial in patients with type 2 diabetes and diabetic polyneuropathy (DPN) stage ≥1b. We allocated subjects to two parallel groups (1:1) that received rosuvastatin 20 mg or placebo for 12 weeks. Primary outcomes were neuropathic symptom score, disability score, and nerve conduction studies, and secondary outcomes were glycemic control, lipid and hepatic profile, lipid peroxidation, and nerve growth factor beta (NGF-ß) levels. RESULTS: Both groups were of similar age and duration since diagnosis of diabetes and DPN. We observed improvement of DPN in the rosuvastatin group from stage 2a (88.2%) to stage 1b (41.2%), improvement of neuropathic symptom score from 4.5±2 to 2.4±1.8, and significant (P=0.001) reductions of peroneal nerve conduction velocity (from 40.8±2.2 to 42.1±1.6 seconds) and lipid peroxidation (from 25.4±2 to 12.2±4.0 nmol/mL), with no significant change in glycemic control or ß-NGF. CONCLUSION: The severity, symptoms, and nerve conduction parameters of DPN improved after 12 weeks of treatment with rosuvastatin. These beneficial effects appear to be attributable to reductions in lipid peroxidation and oxidative stress.

The effect of ubiquinone in diabetic polyneuropathy: a randomized double-blind placebo-controlled study.

INTRODUCTION: Diabetic polyneuropathy aetiology is based on oxidative stress generation due to production of reactive oxygen species. Ubiquinone is reduced to ubiquinol and redistributed into lipoproteins, possibly to protect them from oxidation. AIMS: To evaluate the impact of oral ubiquinone in diabetic polyneuropathy, and the role of lipid peroxidation (LPO) and nerve growth factor (NGF-ß). METHODS: We conducted a double-blind, placebo-controlled clinical trial, patients were randomized to ubiquinone (400 mg) or placebo daily for 12 weeks. Main outcomes were clinical scores, nerve conduction studies, LPO, NGF-ß and safety. RESULTS: Twenty four patients on experimental group and twenty five on control group met the inclusion criteria (mean age 56 years, 22% male and 78% female, mean evolution of type 2 diabetes mellitus 10.7 years). Significant improvement on experimental vs control group was found in neuropathy symptoms score (from 2.5 ± 0.7 to 1 ± 0.8, p<0.001), neuropathy impairment score (5.5 ± 4 to 3.1 ± 2.6, p<0.001), sural sensory nerve amplitude (13.0 ± 6.1 to 15.8 ± 5.1 µV, p=0.049), peroneal motor nerve conduction velocity (39.7 ± 5.0 to 47.8 ± 4.9 m/s, p=0.047), and ulnar motor nerve conduction velocity (48.8 ± 6.8 to 54.5 ± 6.1m/s, p=0.046). There was a significant reduction of LPO in subjects treated with ubiquinone vs placebo (16.7 ± 8.6 and 23.2 ± 15.8 nmol/mL, respectively) with p<0.05, and NGF-ß did not change (control 66.5 ± 26.7 vs. experimental 66.8 ± 28.4 pg/mL, p=0.856). No drug-related adverse reactions were reported. CONCLUSIONS: Twelve weeks treatment with ubiquinone improves clinical outcomes and nerve conduction parameters of diabetic polyneuropathy; furthermore, it reduces oxidative stress without significant adverse events.