Although the implantable cardioverter-defibrillator (ICD) remains the main therapy for Brugada syndrome (BrS), it does not reduce life-threatening ventricular arrhythmia. Based on pathophysiologic ...mechanisms, hydroquinidine (HQ) has been suggested for effective prevention of arrhythmia.
The purpose of this study was to provide evidence-based data supporting HQ use to prevent life-threatening ventricular arrhythmia in high-risk patients with BrS.
We performed a prospective multicenter randomized (HQ vs placebo) double-blind study with two 18-month crossover phases in patients with BrS and implanted with an ICD.
Among the 50 patients enrolled (mean age 47.0 ± 11.4 years, 42 84% male), 26 (52%) fully completed both phases. Thirty-four (68%) presented HQ-related side effects, mainly gastrointestinal, which led to discontinuation of the therapy in 13 (26%). HQ lengthened the QTc interval (409 ± 32 ms vs 433 ± 37 ms; P = .027) and increased repolarization dispersion as evaluated by Tpe max in precordial leads (89 ± 15 ms vs 108 ± 27 ms; P <.0001) with no significant changes in J-point elevation. During the 36-month follow-up, 1 appropriate ICD shock (0.97% event per year), 1 self-terminating ventricular fibrillation, and 1 inappropriate ICD shock occurred under placebo therapy. No arrhythmic events were reported under HQ therapy.
Although HQ seems to be effective in preventing life-threatening ventricular arrhythmia, it could not be an alternative for ICD implantation. Its frequent side effects greatly reduce its probable compliance and therefore do not reveal a significant effect. HQ increases repolarization dispersal with no changes in BrS pattern, which could indicate a more complex action of HQ than its I
blocking effect alone.
Guidance for the evaluation of patients with idiopathic ventricular fibrillation, sudden arrhythmic death syndrome and sudden unexplained death in infancy, which includes genetic testing, are ...provided as these topics were not covered in the previous consensus statement. The most obvious difference encountered for inherited diseases is that randomized and/or blinded studies do not exist in this field. ...most of the available data derive from registries that have followed patients and recorded outcome information. The final judgment regarding care of a particular patient must be made by the health care provider and the patient in light of all relevant circumstances. The following lifestyle changes are recommended in all patients with a diagnosis of LQTS: (a) Avoidance of QT-prolonging drugs (www.qtdrugs.org) (b) Identification and correction of electrolyte abnormalities that may occur during diarrhea, vomiting, metabolic conditions or imbalanced diets for weight loss. 2.
Objectives This study evaluated the efficacy and safety of flecainide in addition to conventional drug therapy in patients with catecholaminergic polymorphic ventricular tachycardia (CPVT). ...Background CPVT is an inherited arrhythmia syndrome caused by gene mutations that destabilize cardiac ryanodine receptor Ca2+ release channels. Sudden cardiac death is incompletely prevented by conventional drug therapy with β-blockers with or without Ca2+ channel blockers. The antiarrhythmic agent flecainide directly targets the molecular defect in CPVT by inhibiting premature Ca2+ release and triggered beats in vitro. Methods We collected data from every consecutive genotype-positive CPVT patient started on flecainide at 8 international centers before December 2009. The primary outcome measure was the reduction of ventricular arrhythmias during exercise testing. Results Thirty-three patients received flecainide because of exercise-induced ventricular arrhythmias despite conventional (for different reasons, not always optimal) therapy (median age 25 years; range 7 to 68 years; 73% female). Exercise tests comparing flecainide in addition to conventional therapy with conventional therapy alone were available for 29 patients. Twenty-two patients (76%) had either partial (n = 8) or complete (n = 14) suppression of exercise-induced ventricular arrhythmias with flecainide (p < 0.001). No patient experienced worsening of exercise-induced ventricular arrhythmias. The median daily flecainide dose in responders was 150 mg (range 100 to 300 mg). During a median follow-up of 20 months (range 12 to 40 months), 1 patient experienced implantable cardioverter-defibrillator shocks for polymorphic ventricular arrhythmias, which were associated with a low serum flecainide level. In 1 patient, flecainide successfully suppressed exercise-induced ventricular arrhythmias for 29 years. Conclusions Flecainide reduced exercise-induced ventricular arrhythmias in patients with CPVT not controlled by conventional drug therapy.
Objectives Our purpose was to evaluate the efficacy of antiarrhythmic drugs (AADs) in recurrent ventricular fibrillation (VF) associated with inferolateral early repolarization pattern on the ...electrocardiogram. Background Although an implantable cardioverter-defibrillator is the treatment of choice, additional AADs may be necessary to prevent frequent episodes of VF and reduce implantable cardioverter-defibrillator shock burden or as a lifesaving therapy in electrical storms. Methods From a multicenter cohort of 122 patients (90 male subjects, age 37 ± 12 years) with idiopathic VF and early repolarization abnormality in the inferolateral leads, we selected all patients with more than 3 episodes of VF (multiple) including those with electrical storms (≥3 VF in 24 h). The choice of AAD was decided by individual physicians. Follow-up data were obtained for all patients using monitoring with implantable defibrillator. Successful oral AAD was defined as elimination of all recurrences of VF with a minimal follow-up period of 12 months. Results Multiple episodes of VF were observed in 33 (27%) patients. Electrical storms (34 ± 47 episodes) occurred in 16 and were unresponsive to beta-blockers (11 of 11), lidocaine/mexiletine (9 of 9), and verapamil (3 of 3), while amiodarone was partially effective (3 of 10). In contrast, isoproterenol infusion immediately suppressed electrical storms in 7 of 7 patients. Over a follow-up of 69 ± 58 months, oral AADs were poorly effective in preventing recurrent VF: beta-blockers (2 of 16), verapamil (0 of 4), mexiletine (0 of 4), amiodarone (1 of 7), and class 1C AADs (2 of 9). Quinidine was successful in 9 of 9 patients, decreasing recurrent VF from 33 ± 35 episodes to nil for 25 ± 18 months. In addition, quinidine restored a normal electrocardiogram. Conclusions Multiple recurrences of VF occurred in 27% of patients with early repolarization abnormality and may be life threatening. Isoproterenol in acute cases and quinidine in chronic cases are effective AADs.
Abstract Background The early repolarization (ER) pattern is associated with an increased risk of arrhythmogenic sudden death. However, strategies for risk stratification of patients with the ER ...pattern are not fully defined. Objectives This study sought to determine the role of electrophysiology studies (EPS) in risk stratification of patients with ER syndrome. Methods In a multicenter study, 81 patients with ER syndrome (age 36 ± 13 years, 60 males) and aborted sudden death due to ventricular fibrillation (VF) were included. EPS were performed following the index VF episode using a standard protocol. Inducibility was defined by the provocation of sustained VF. Patients were followed up by serial implantable cardioverter-defibrillator interrogations. Results Despite a recent history of aborted sudden death, VF was inducible in only 18 of 81 (22%) patients. During follow-up of 7.0 ± 4.9 years, 6 of 18 (33%) patients with inducible VF during EPS experienced VF recurrences, whereas 21 of 63 (33%) patients who were noninducible experienced recurrent VF (p = 0.93). VF storm occurred in 3 patients from the inducible VF group and in 4 patients in the noninducible group. VF inducibility was not associated with maximum J-wave amplitude (VF inducible vs. VF noninducible; 0.23 ± 0.11 mV vs. 0.21 ± 0.11 mV; p = 0.42) or J-wave distribution (inferior, odds ratio OR: 0.96 95% confidence interval (CI): 0.33 to 2.81; p = 0.95; lateral, OR: 1.57 95% CI: 0.35 to 7.04; p = 0.56; inferior and lateral, OR: 0.83 95% CI: 0.27 to 2.55; p = 0.74), which have previously been demonstrated to predict outcome in patients with an ER pattern. Conclusions Our findings indicate that current programmed stimulation protocols do not enhance risk stratification in ER syndrome.
Inferolateral early repolarization (ER) is highly prevalent and is associated with idiopathic ventricular fibrillation (VF).
The purpose of this study was to evaluate the potential role of T-wave ...parameters to differentiate between malignant and benign ER.
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).
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.
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.
Guidance for the evaluation of patients with idiopathic ventricular fibrillation, sudden arrhythmic death syndrome, and sudden unexplained death in infancy, which includes genetic testing, are ...provided as these topics were not covered in the previous consensus statement. Documents produced by other medical societies have acknowledged the need to define the criteria used to rank the strength of recommendation for genetic diseases. 2 The most obvious difference encountered for inherited diseases is that randomized and/or blinded studies do not exist in this field. ...most of the available data derive from registries that have followed patients and recorded outcome information. The following lifestyle changes are recommended in all patients with a diagnosis of LQTS: a. Avoidance of QT-prolonging drugs (www.qtdrugs.org) b. Identification and correction of electrolyte abnormalities that may occur during diarrhea, vomiting, metabolic conditions, or imbalanced diets for weight loss. 2. A scoring system has been established, which takes into account the age of the patient, medical and family history, symptoms, and QTc and provides a probability of the diagnosis of LQTS. 7,8 Approximately 20%–25% of the patients with LQTS confirmed by the presence of an LQTS gene mutation may have a normal range QTc. 9,10 Risk stratification
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