Abstract Brugada syndrome is an inherited heart disease without structural abnormalities that is thought to arise as a result of accelerated inactivation of Na channels and predominance of transient ...outward K current ( Ito ) to generate a voltage gradient in the right ventricular layers. This gradient triggers ventricular tachycardia/ventricular fibrillation possibly through a phase 2 reentrant mechanism. The Brugada electrocardiographic (ECG) pattern, which can be dynamic and is sometimes concealed, being only recorded in upper precordial leads, is the hallmark of Brugada syndrome. Because of limitations of previous consensus documents describing the Brugada ECG pattern, especially in relation to the differences between types 2 and 3, a new consensus report to establish a set of new ECG criteria with higher accuracy has been considered necessary. In the new ECG criteria, only 2 ECG patterns are considered: pattern 1 identical to classic type 1 of other consensus (coved pattern) and pattern 2 that joins patterns 2 and 3 of previous consensus (saddle-back pattern). This consensus document describes the most important characteristics of 2 patterns and also the key points of differential diagnosis with different conditions that lead to Brugada-like pattern in the right precordial leads, especially right bundle-branch block, athletes, pectus excavatum, and arrhythmogenic right ventricular dysplasia/cardiomyopathy. Also discussed is the concept of Brugada phenocopies that are ECG patterns characteristic of Brugada pattern that may appear and disappear in relation with multiple causes but are not related with Brugada syndrome.
Objectives The present study was designed to explore the 8-year survival benefit of a nonresynchronization implantable cardioverter-defibrillator (ICD) according to a simple risk stratification ...score. Background There is limited information regarding factors that predict the benefit of primary prevention with an ICD during long-term follow-up. Methods This study used a previously developed risk score including 5 clinical factors (New York Heart Association functional class >II, age >70 years, blood urea nitrogen >26 mg/dl, QRS duration >0.12 s, and atrial fibrillation) to evaluate 8-year ICD survival benefit within risk score categories among 1,191 MADIT-II (Multicenter Automatic Defibrillator Implantation Trial II) patients. Results Patients with low (0 risk factors, n = 345) and intermediate risk (1 to 2 risk factors, n = 646) demonstrated a significantly higher probability of survival at 8-year follow-up when treated by ICD as compared with non-ICD therapy (75% vs. 58%, p = 0.004; and 47% vs. 31%, p < 0.001, respectively). By contrast, among high-risk patients (3 or more risk factors, n = 200), there was no significant difference in 8-year survival between the ICD and non-ICD subgroups (19% vs. 17%, p = 0.50). Consistently, multivariate analysis showed that ICD therapy was associated with a significant long-term survival benefit among low- and intermediate-risk patients (hazard ratio HR: 0.52, p < 0.001, and HR: 0.66, p < 0.001, respectively), whereas treatment with an ICD was not associated with a significant benefit among high-risk patients (HR: 0.84, p = 0.25). Conclusions These findings suggest that a simple risk score can identify patients who derive significant long-term benefit from primary ICD therapy. High-risk patients with multiple comorbidities composed 17% of the MADIT-II population and did not derive long-term benefit from nonresynchronization device therapy.
Objectives We aimed to evaluate the relationship between echocardiographic response to cardiac resynchronization therapy (CRT) and the risk of subsequent ventricular tachyarrhythmias (VTAs). ...Background Current data regarding the effect of CRT on the risk of VTA are limited and conflicting. Methods The risk of a first appropriate implantable cardioverter-defibrillator (ICD) therapy for VTA (including ventricular tachycardia, ventricular fibrillation, and ventricular flutter) was compared between high- and low-echocardiographic responders to CRT defibrillator (CRT-D) therapy (defined as ≥25% and <25% reductions, respectively, in left ventricular end-systolic volume LVESV at 1 year compared with baseline) and ICD-only patients enrolled in the MADIT-CRT (Multicenter Automatic Defibrillator Implantation Trial–Cardiac Resynchronization Therapy). Results The cumulative probability of a first VTA at 2 years after assessment of echocardiographic response was highest among low responders to CRT-D (28%), intermediate among ICD-only patients (21%), and lowest among high responders to CRT-D (12%), with p < 0.001 for the overall difference during follow-up. Multivariate analysis showed that high responders to CRT-D experienced a significant 55% reduction in the risk of VTA compared with ICD-only patients (p < 0.001), whereas the risk of VTA was not significantly different between low responders and ICD-only patients (hazard ratio HR: 1.26; p = 0.21). Consistently, assessment of response to CRT-D as a continuous measure showed that incremental 10% reductions in left ventricular end-systolic volume were associated with corresponding reductions in the risk of subsequent VTA (HR: 0.80; p < 0.001), VTA/death (HR: 0.79; p < 0.001), ventricular tachycardia (HR: 0.80; p < 0.001), and ventricular fibrillation/ventricular flutter (HR: 0.75; p = 0.044). Conclusions In patients with left ventricular dysfunction enrolled in the MADIT-CRT trial, reverse remodeling was associated with a significant reduction in the risk of subsequent life-threatening VTAs. (Multicenter Automatic Defibrillator Implantation Trial–Cardiac Resynchronization Therapy MADIT-CRT; NCT00180271 )
Objectives The aim of this study was to define the genetic basis of arrhythmogenic right ventricular cardiomyopathy (ARVC). Background Arrhythmogenic right ventricular cardiomyopathy, characterized ...by right ventricular fibrofatty replacement and arrhythmias, causes sudden death. Autosomal dominant inheritance, reduced penetrance, and 7 desmosome-encoding causative genes are known. The basis of low penetrance is poorly understood. Methods Arrhythmogenic right ventricular cardiomyopathy probands and family members were enrolled, blood was obtained, lymphoblastoid cell lines were immortalized, deoxyribonucleic acid was extracted, polymerase chain reaction (PCR) amplification of desmosome-encoding genes was performed, PCR products were sequenced, and diseased tissue samples were studied for intercellular junction protein distribution with confocal immunofluorescence microscopy and antibodies against key proteins. Results We identified 21 variants in plakophilin-2 ( PKP2 ) in 38 of 198 probands (19%), including missense, nonsense, splice site, and deletion/insertion mutations. Pedigrees showed wide intra-familial variability (severe early-onset disease to asymptomatic individuals). In 9 of 38 probands, PKP2 variants were identified that were encoded in trans (compound heterozygosity). The 38 probands hosting PKP2 variants were screened for other desmosomal genes mutations; second variants (digenic heterozygosity) were identified in 16 of 38 subjects with PKP2 variants (42%), including desmoplakin ( DSP ) (n = 6), desmoglein-2 ( DSG2 ) (n = 5), plakophilin-4 ( PKP4 ) (n = 1), and desmocollin-2 ( DSC2 ) (n = 1). Heterozygous mutations in non -PKP 2 desmosomal genes occurred in 14 of 198 subjects (7%), including DSP (n = 4), DSG2 (n = 5), DSC2 (n = 3), and junctional plakoglobin ( JUP ) (n = 2). All variants occurred in conserved regions; none was identified in 700 ethnic-matched control subjects. Immunohistochemical analysis demonstrated abnormalities of protein architecture. Conclusions These data suggest that the genetic basis of ARVC includes reduced penetrance with compound and digenic heterozygosity. Disturbed junctional cytoarchitecture in subjects with desmosomal mutations confirms that ARVC is a disease of the desmosome and cell junction.
Inappropriate Implantable Cardioverter-Defibrillator Shocks in MADIT II: Frequency, Mechanisms, Predictors, and Survival Impact James P. Daubert, Wojciech Zareba, David S. Cannom, Scott McNitt, ...Spencer Z. Rosero, Paul Wang, Claudio Schuger, Jonathan S. Steinberg, Steven L. Higgins, David J. Wilber, Helmut Klein, Mark L. Andrews, W. Jackson Hall, Arthur J. Moss, for the MADIT II Investigators This study sought to identify the incidence and outcome related to inappropriate implantable cardioverter-defibrillator (ICD) shocks. In the MADIT (Multicenter Automatic Defibrillator Implantation Trial) II, the stored ICD electrograms from shock episodes were adjudicated and inappropriate shocks were subclassified by triggering rhythm as atrial fibrillation, sinus or supraventricular tachycardia, or sensing abnormality/lead malfunction. One or more inappropriate shocks occurred in 83 (11.5%) of the 719 MADIT II ICD patients. Inappropriate shock episodes constituted 184 of the 590 total shock episodes (31.2%). Smoking, atrial fibrillation, diastolic hypertension, and prior appropriate shocks predicted inappropriate shock occurrence. Inappropriate shocks were associated with increased risk of mortality in follow-up.
Objectives This study was designed to assess the clinical course and to identify risk factors for life-threatening events in patients with long-QT syndrome (LQTS) with normal corrected QT (QTc) ...intervals. Background Current data regarding the outcome of patients with concealed LQTS are limited. Methods Clinical and genetic risk factors for aborted cardiac arrest (ACA) or sudden cardiac death (SCD) from birth through age 40 years were examined in 3,386 genotyped subjects from 7 multinational LQTS registries, categorized as LQTS with normal-range QTc (≤440 ms n = 469), LQTS with prolonged QTc interval (>440 ms n = 1,392), and unaffected family members (genotyped negative with ≤440 ms n = 1,525). Results The cumulative probability of ACA or SCD in patients with LQTS with normal-range QTc intervals (4%) was significantly lower than in those with prolonged QTc intervals (15%) (p < 0.001) but higher than in unaffected family members (0.4%) (p < 0.001). Risk factors ACA or SCD in patients with normal-range QTc intervals included mutation characteristics (transmembrane-missense vs. nontransmembrane or nonmissense mutations: hazard ratio: 6.32; p = 0.006) and the LQTS genotypes (LQTS type 1:LQTS type 2, hazard ratio: 9.88; p = 0.03; LQTS type 3:LQTS type 2, hazard ratio: 8.04; p = 0.07), whereas clinical factors, including sex and QTc duration, were associated with a significant increase in the risk for ACA or SCD only in patients with prolonged QTc intervals (female age >13 years, hazard ratio: 1.90; p = 0.002; QTc duration, 8% risk increase per 10-ms increment; p = 0.002). Conclusions Genotype-confirmed patients with concealed LQTS make up about 25% of the at-risk LQTS population. Genetic data, including information regarding mutation characteristics and the LQTS genotype, identify increased risk for ACA or SCD in this overall lower risk LQTS subgroup.
Nonsustained Ventricular Tachycardia Katritsis, Demosthenes G., MD, PhD; Zareba, Wojciech, MD, PhD; Camm, A. John, MD
Journal of the American College of Cardiology,
11/2012, Letnik:
60, Številka:
20
Journal Article
Recenzirano
Odprti dostop
Nonsustained ventricular tachycardia (NSVT) has been recorded in a wide range of conditions, from apparently healthy individuals to patients with significant heart disease. In the absence of heart ...disease, the prognostic significance of NSVT is debatable. When detected during exercise, and especially at recovery, NSVT indicates increased cardiovascular mortality within the next decades. In trained athletes, NSVT is considered benign when suppressed by exercise. In patients with non–ST-segment elevation acute coronary syndrome, NSVT occurring beyond 48 h after admission indicates an increased risk of cardiac and sudden death, especially when associated with myocardial ischemia. In acute myocardial infarction, in-hospital NSVT has an adverse prognostic significance when detected beyond the first 13 to 24 h. In patients with prior myocardial infarction treated with reperfusion and beta-blockers, NSVT is not an independent predictor of long-term mortality when other covariates such as left ventricular ejection fraction are taken into account. In patients with hypertrophic cardiomyopathy, and most probably genetic channelopathies, NSVT carries prognostic significance, whereas its independent prognostic ability in ischemic heart failure and dilated cardiomyopathy has not been established. The management of patients with NSVT is aimed at treating the underlying heart disease.
Risk Stratification for Primary Implantation of a Cardioverter-Defibrillator in Patients With Ischemic Left Ventricular Dysfunction Ilan Goldenberg, Anant K. Vyas, W. Jackson Hall, Arthur J. Moss, ...Hongyue Wang, Hua He, Wojciech Zareba, Scott McNitt, Mark L. Andrews, for the MADIT-II Investigators Data regarding risk markers that can be used to identify patients with a low ejection fraction who benefit from primary implantable cardioverter-defibrillator (ICD) therapy are limited. In the present study, we demonstrate that a simple clinical risk score, developed based upon mortality data from MADIT (Multicenter Automatic Defibrillator Implantation Trial)-II, can be used to identify low- and high-risk subsets in the ischemic low ejection fraction population who derive limited benefit from ICD, and a subset of intermediate-risk patients in whom primary implantation of ICD is associated with a significant survival benefit. Our findings suggest a U-shaped pattern for ICD efficacy in patients with ischemic left ventricular dysfunction.
The QT interval is a risk marker for cardiac events such as torsades de pointes. However, QT measurements obtained from a 12-lead ECG during clinic hours may not capture the full extent of a ...patient's daily QT range.
The purpose of this study was to evaluate the utility of 24-hour Holter ECG recording in patients with long QT syndrome (LQTS) to identify dynamic changes in the heart rate-corrected QT interval and to investigate methods of visualizing the resulting datasets.
Beat-to-beat QTc (Bazett) intervals were automatically measured across 24-hour Holter recordings from 202 LQTS type 1, 89 type 2, and 14 type 3 genotyped patients and a reference group of 200 healthy individuals. We measured the percentage of beats with QTc greater than the gender-specific threshold (QTc ≥470 ms in women and QTc ≥450 ms in men). The percentage of beats with QTc prolongation was determined across the 24-hour recordings.
Based on the median percentage of heartbeats per patient with QTc prolongation, LQTS type 1 patients showed more frequent QTc prolongation during the day (~3 PM) than they did at night (~3 AM): 97% vs 48%, P ~10(-4) for men, and 68% vs 30%, P ~10(-5) for women. LQTS type 2 patients showed less frequent QTc prolongation during the day compared to nighttime: 87% vs 100%, P ~10(-4) for men, and 62% vs 100%, P ~10(-3) for women.
In patients with genotype-positive LQTS, significant differences exist in the degree of daytime and nocturnal QTc prolongation. Holter monitoring using the "QT clock" concept may provide an easy, fast, and accurate method for assessing the true personalized burden of QTc prolongation.
PDF
