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Notes: The Defibrillators in Nonischemic Cardiomyopathy Treatment Evaluation (DEFINITE) is a multicenter randomized trial. Patients will have nonischemic Cardiomyopathy (LVEF ± 35%), a history of symptomatic heart fail-ure and spontaneous arrhythmia (〉 10 PVCs/hour or nonsustained ventricular tachycardia defined as 3-15 beats at a rate of 〉 120 beats/min) on Holter monitor or telemetry within the past 6 months. Patients will be randomized to an implantable cardioverter defibrillator (ICD) versus no ICD. All patients will re-ceive standard oral medical therapy for heart failure including angiotensin converting enzyme inhibitors and β-blockers (if tolerated). Patients will be followed for 2-3 years. The primary endpoint will be total mortality. Quality-of-life and pharmacoeconomics analyses will also be performed. A registry will track patients who meet basic inclusion criteria but are not randomized. We estimate an annual total mortality of 15% at 2 years in the treatment arm that does not receive an ICD. The ICD is expected to reduce mor-tality by 50%. Approximately 204 patients will be required in each treatment group. Twenty-five centers will be included in a trial designed to last an estimated 4 years.

Notes: A 57-year-old man suffered multiple inappropriate shocks from an implantable cardioverter defibrillator that could not be inactivated because the magnet switch feature was deactivated. Attempts to interrogate the defibrillator caused shocks to be delivered. Emergent explantation was performed and a loose sensing lead was discovered. Sensing and defibrillation leads functioned normally, and testing of the explanted generator demonstrated no abnormalities. A new generator was put in place and the patient has been without shocks for 6 months. This case illustrates the need for robust methods of attenuating electromagnetic interference and the importance of multiple methods of device inactivation.

Notes: Most research on children and risk is heavily influenced by developmental theory. This paper is based on a study which uses a different approach, drawing on recent work within the sociology of childhood. ‘Children, Parents and Risk’ explores the ways in which risks to children are understood and managed by children and parents, focusing on children's daily lives in and around the home at the ages of 3, 9 and 12 years. Data were gathered from interviews with children and their parents at home and from children at school and in a youth club. The paper draws on the findings from the study in order to discuss and compare parents' and children's ideas about children and childhood as risk-related; it also aims to examine the findings in the context of Ulrich Beck's recent work on the risk society and individualization. Both parents and children tended to ‘externalize’ risk away from the home and into the outside world. In response to perceived risks to childhood many parents appeared to see their role as that of striking a balance between protection and compensatory provision, and their accounts included details of increasingly ‘individualized’ measures to reduce such risks. The children conceptualized their experiences of adult control as welcoming when preventing the child's exposure to risk but as constraining when it restricted their autonomy. The paper concludes that the findings accord with Beck's description of the ‘risk society’ and that they lend some limited support to Beck's individualization thesis.

Notes: Sympathetic nervous system activity (SNSA) is believed to participate in the genesis of ventricular tachyarrhythmias (VTA) but understanding has been impeded by the number and complexity of effects and the paucity of data from humans. New information from studies of genetic disorders, animal models, and spontaneous human arrhythmias indicates the importance of the temporal pattern of SNSA in arrhythmia development. The proarrhythmic effects of short-term elevations of SNSA are exemplified by genetic disorders and include enhancement of early and delayed afterdepolarizations and increased dispersion of repolarization. The role of long-term elevations of SNSA is suggested by animal models of enhanced SNSA signaling that results in apoptosis, hypertrophy, and fibrosis, and sympathetic nerve sprouting caused by infusion of nerve growth factor. Processes that overlap short- and long-term effects are suggested by changes in R-R interval variability (RRV) that precede VTA in patients by several hours. SNSA-mediated alterations in gene expression of ion channels may account for some intermediate-term effects. The propensity for VTA is highest when short-, intermediate, and long-term changes are superimposed. Because the proarrhythmic effects are related to the duration and intensity of SNSA, normal regulatory processes such as parasympathetic activity that inhibits SNSA, and oscillations that continuously vary the intensity of SNSA may provide vital antiarrhythmic protection that is lost in severe heart failure and other disorders. These observations may have therapeutic implications. The recommended use of β-adrenergic receptor blockers to achieve a constant level of inhibition does not take into account the temporal patterns and regional heterogeneity of SNSA, the proarrhythmic effects of α-adrenergic receptor stimulation, or the potential proarrhythmic effects of β-adrenergic receptor blockade. Further research is needed to determine if other approaches to SNSA modulation can enhance the antiarrhythmic effects.

Notes: Background: Nonsustained ventricular tachycardia (NSVT) predicts mortality in several disorders but its significance in patients with sustained ventricular tachyarrhythmias is unknown. We analyzed the clinical features and outcome associated with NSVT (〉; 3 beats at 〉; 100 beats/min) recorded on a 48-hour Holter in the absence of antiarrhythmic drugs.Methods: Patients enrolled in the ESVEM trial (n = 486) were grouped according to the duration of the longest recorded episode of NSVT, and in the second analysis, according to frequency of recorded episodes. Assessments were on an intention-to-treat basis.Results: Patients without NSVT were more likely to have ischemic heart disease and had significantly lower frequencies of single and paired premature ventricular complexes (PVCs). There were no significant differences with respect to age, sex, presenting arrhythmia, years since last myocardial infarction, functional class, or present ejection fraction. The cumulative probabilities of arrhythmia recurrence and all-cause mortality at 4 years in patients without NSVT (60%± 7% and 32%± 6%, respectively) were not significantly different than those of patients with NSVT (63%± 3% and 41%± 3%, respectively). Cox regression models indicated that ejection fraction and functional class were significant predictors of outcome, but variables based on the presence, duration, and frequency of recorded episodes of NSVT were not.Conclusions: NSVT is common in patients with spontaneous and inducible sustained ventricular tachyarrhythmias and at least 10 PVCs/hour (ESVEM enrollment criteria), but is not a significant predictor of arrhythmia recurrence, sudden death, or all-cause mortality in patients with these characteristics.

Notes: Background:The implantable cardioverter defibrillator (ICD) has underscored the limitations of our methods of risk assessment. ICDs should be available to patients at high risk for arrhythmic death, but because of the potential for adverse effects and high cost it should be scrupulously avoided in patients whose lives will not be prolonged. Unfortunately, discrimination between these two groups of patients remains a challenge. Recent clinical trial results have not only shown that electrophysiological studies (EPS) in combination with other risk stratifiers identify patients with ischemic heart disease at high risk for arrhythmic death, but they have linked the efficacy of ICD therapy to the results of EPS. However, to perform EPS in all potential candidates for ICD therapy would be a time-consuming and costly burden to medical services and would expose many patients to the risks and discomfort of an invasive procedure. Noninvasive identification of appropriate candidates is therefore essential to successful application of EPS. Methods:Nonsustained ventricular tachycardia (NSVT) and a reduced left ventricular ejection fraction (EF) was used to select patients for EPS in two important trials, but it is not certain that these are the optimal tests or that the optimal thresholds 〈inlineGraphic alt="geqslant R: gt-or-equal, slanted" extraInfo="nonStandardEntity" href="urn:x-wiley:1082720X:ANEC434:ges" location="ges.gif"/〉 1 episode of NSVT 〈inlineGraphic alt="geqslant R: gt-or-equal, slanted" extraInfo="nonStandardEntity" href="urn:x-wiley:1082720X:ANEC434:ges" location="ges.gif"/〉 3 beats; EF 〈inlineGraphic alt="leqslant R: less-than-or-eq, slant" extraInfo="nonStandardEntity" href="urn:x-wiley:1082720X:ANEC434:les" location="les.gif"/〉 0.35 or EF 〈inlineGraphic alt="leqslant R: less-than-or-eq, slant" extraInfo="nonStandardEntity" href="urn:x-wiley:1082720X:ANEC434:les" location="les.gif"/〉 0.40) were used. A number of studies have addressed the accuracy of clinical factors for predicting the results of EPS and a number of noninvasive tests have been proposed including the signal-averaged electrocardiogram, heart rate variability, T-wave alternans, and high spatial resolution (multilead) electrocardiography. In some contexts, combinations of factors provide significant improvements in accuracy. However, the populations studied were often highly selected, which makes comparisons between techniques or prediction of responses in the populations that would require screening difficult. Results from recently completed and ongoing clinical trials should provide important new information. A greater problem is that EPS has not been shown to consistently provide accurate discrimination of patients with nonischemic cardiac disorders. Conclusions:Effective widespread application of ICD therapy will require greater precision of patient selection. Noninvasive tests under investigation demonstrate considerable promise in selecting appropriate candidates for EPS. However, because the most precise methods of risk assessment are likely to be those most closely linked to the mechanisms of fatal arrhythmias, it is important that further development of noninvasive techniques incorporates advances in basic cardiac electrophysiology. A.N.E. 1999;4(4):434–442

Notes: RR Dynamics Before VT. Introduction: We hypothesized that autonomic activity preceding spontaneous sustained monomorphic ventricular tachycardia (VTsm) as assessed by heart rate (HR) and RR interval variability (RRV) differs between type 1 VTsm which is initiated by morphologically distinct, early cycle, possibly triggering premature ventricular complexes (PVCs) and type 2 VTsm in which the initial complex has a QRS waveform identical to subsequent complexes. Methods and Results: Baseline Holter tapes (1,646) from a clinical trial were scanned for VTsm. QRS complexes of VTsm, were compared by two-lead cross-correlation to distinguish type 1 and type 2 VTsm, Frequency domain RRV index were estimated over 5 minutes, 15 minutes, and 24 hours. Type 1 and type 2 VTsm, were present in 15 (group 1) and 33 (group 2) of 48 patients, respectively. HR did not change in group 1 (88.4 ± 15.2 to 89.7 ± 13.0 beats/min, P = 0.89), but increased before the onset of VTsm in group 2 (74.3 ± 16.3 to 81.2 ± 18.0 beats/min, P 〈 0.001). RRV index were severely depressed in both groups. No RRV index changed significantly before the onset of type 1 VTsm, whereas significant changes occurred before type 2 VTsm from 24-hour average to 30 minutes before VTsm in very low (very low-frequency power [VLFP]: 6.62 ± 1.53 to 6.20 ± 2.07 In msec2, P = 0.036), low (low-frequency power [LFP]: 5.61 ± 1.43 to 5.28 ± 1.59 in msec2, P = 0.004), normalized low (normalized low-frequency power [LFPn]: -0.48 ± 0.58 to -0.55 ± 0.64 normalized units [nu], P = 0.05) and the ratio of LFP to high-frequency power (HFP) (LPP/HFP: 4.20 ± 3.47 to 3.45 ± 2.53, P = 0.017). Declines in RRV index between 2 hours to the 30-minute period before VTsm, occurred in group 2 but not group 1 in LFP (5.85 ± 1.42 to 5.28 ± 1.59 In msec, P = 0.043) and HFP (4.94 ± 5.14 to 3.46 ± 2.52 In msec2 P = 0.008), with a downward trend in LFP/HFP (4.94 ± 5.14 to 3.45 ± 2.53, P = 0.127) and LFPn (-0.38 ± 0.36 to -0.55 ± 0.64, P = 0.15), while HFPn tended to rise (-1.47 ± 0.65 to -1.27 ± 0.64, P = 0.15). Conclusions: HR and RRV did not change before type 1 VTsm, suggesting that short-term changes in autonomic activity were not essential to initiation of apparent PVC-triggered VTsm. In contrast, RR interval dynamics before type 2 VTsm suggested that short-term changes in neurohormonal activity contributed to arrhythmia initiation. Heterogeneities in arrhythmia onset may reflect distinct triggers and substrate properties that could provide a basis for effective therapeutic targets.