Prevention of Inappropriate Shocks in ICD Recipients: A Review of 10,000 Tachycardia Episodes

Background: The efficacy of dual-chamber ICD arrhythmia classification algorithms is crucial to prevent inappropriate shocks. We report our experience from a meta-analysis of five prospective clinical studies with inclusion phases ranging between 1997 and 2003.
Methods: Dual-chamber ICD using standard dual-chamber arrhythmia classification algorithms were implanted in 802 patients (mean age = 64 ± 11 years, 88% men) in 74 medical centers. The ICD indication was secondary prevention in 95% of patients. Supraventricular tachyarrhythmias (SVT) were previously documented in 26% of patients. All spontaneous tachyarrhythmic events documented by the device memories were analyzed by a adjudicating committee. The episodes lasting >12 seconds and/or treated by the ICD were analyzed.
Results: Over a mean follow-up of 302 ± 113 days, 9,690 events were reported. Mean heart rate at the time of events was 131 ± 45 bpm (100–430). Events were classified as oversensing in 1.4%, sinus tachycardia (ST) in 66%, SVT in 13%, slow (<150 bpm) ventricular tachycardia (VT) in 8.7%, and VT or ventricular fibrillation (VF) in 10.3%. The sensitivity of slow VT detection was 94%, and of VT/VF detection 99.3%. The specificity of sinus rhythm/ST/SVT recognition was 94%, positive predictive value 79.3%, and negative predictive value 99.2%. A total of 1,918 episodes were treated in 330 patients: 1,472 appropriately in 213, and 446 inappropriately in 117 (15% of the overall population) patients. Only 62 episodes were inappropriately treated by shocks in 40 patients, representing 5% of the overall population.
Conclusions: In this conventional ICD population, the overall specificity of standard dual-chamber arrhythmia detection settings reached 94%. This feature allows efficient detection of fast as well as slow VT events with a very low rate of inappropriate shocks.     

Clinical and molecular characterization of a re‐established line of sheep exhibiting hemophilia A

Summary. Background: Large animal models that accurately mimic human hemophilia A (HA) are in great demand for developing and testing novel therapies to treat HA. Objectives: To re‐establish a line of sheep exhibiting a spontaneous bleeding disorder closely mimicking severe human HA, fully characterize their clinical presentation, and define the molecular basis for disease. Patients/methods: Sequential reproductive manipulations were performed with cryopreserved semen from a deceased affected ram. The resultant animals were examined for hematologic parameters, clinical symptoms, and responsiveness to human FVIII (hFVIII). The full coding region of sheep FVIII mRNA was sequenced to identify the genetic lesion. Results and conclusions: The combined reproductive technologies yielded 36 carriers and 8 affected animals. The latter had almost non‐existent levels of FVIII:C and extremely prolonged aPTT, with otherwise normal hematologic parameters. These animals exhibited bleeding from the umbilical cord, prolonged tail and nail cuticle bleeding time, and multiple episodes of severe spontaneous bleeding, including hemarthroses, muscle hematomas and hematuria, all of which responded to hFVIII. Inhibitors of hFVIII were detected in four treated animals, further establishing the preclinical value of this model. Sequencing identified a premature stop codon and frame‐shift in exon 14, providing a molecular explanation for HA. Given the decades of experience using sheep to study both normal physiology and a wide array of diseases and the high homology between human and sheep FVIII, this new model will enable a better understanding of HA and facilitate the development and testing of novel treatments that can directly translate to HA patients.     

Avoid Delivering Therapies for Nonsustained Fast Ventricular Tachyarrhythmia in Patients with Implantable Cardioverter/Defibrillator: The ADVANCE III Trial

Introduction: The purpose of this investigation is to evaluate whether a prolonged detection interval for life threatening ventricular tachyarrhythmia (VT) is able to reduce therapies (Rx) delivered by an implantable cardioverter/defibrillator (ICD). Until now, only the PREPARE trial demonstrated a reduction of ICD Rx in a cohort of primary prevention patients.
Methods and Results: The ADVANCE III study is a prospective, randomized, parallel trial with 2 arms evaluating different intervals to detect (NID), i.e., 18/24 (as currently used) versus 30/40. The primary endpoint is to demonstrate a 20% reduction of ICD Rx (antitachycardia pacing or shocks) delivered to terminate spontaneous VT with a cycle length ≤320 ms in patients with Class I-IIA indication for ICD therapy, regardless of cardiac resynchronization capabilities. The worldwide investigation started in spring 2008 and is expected to be finished in 2011.
Conclusions: The ADVANCE III trial is the first randomized investigation evaluating the reduction of ICD Rx for fast VT due to a prolongation of NID in a general ICD patient cohort.     

Potential Policies and Laws to Prohibit Weight Discrimination: Public Views from 4 Countries

Context

People viewed as “overweight” or “obese” are vulnerable to weight-based discrimination, creating inequities and adverse health outcomes. Given the high rates of obesity recorded globally, studies documenting weight discrimination in multiple countries, and an absence of legislation to address this form of discrimination, research examining policy remedies across different countries is needed. Our study provides the first multinational examination of public support for policies and legislation to prohibit weight discrimination.

Methods

Identical online surveys were completed by 2,866 adults in the United States, Canada, Australia, and Iceland. We assessed public support for potential laws to prohibit weight-based discrimination, such as adding body weight to existing civil rights statutes, extending disability protections to persons with obesity, and instituting legal measures to prohibit employers from discriminating against employees because of body weight. We examined sociodemographic and weight-related characteristics predicting support for antidiscrimination policies, and the differences in these patterns across countries.

Findings

The majority of participants in the United States, Canada, and Australia agreed that their government should have specific laws in place to prohibit weight discrimination. At least two-thirds of the participants in all 4 countries expressed support for policies that would make it illegal for employers to refuse to hire, assign lower wages, deny promotions, or terminate qualified employees because of body weight. Women and participants with higher body weight expressed more support for antidiscrimination measures. Beliefs about the causes of obesity were also related to support for these laws.

Conclusions

Public support for legal measures to prohibit weight discrimination can be found in the United States, Canada, Australia, and Iceland, especially for laws to remedy this discrimination in employment. Our findings provide important information for policymakers and interest groups both nationally and internationally and can help guide discussions about policy priorities to reduce inequities resulting from weight discrimination.     

Myocardial Injury During Radiofrequency Catheter Ablation: Comparison of Focal and Linear Lesions

The aim of study was to investigate the extent of myocardial injury incurred by creation of continuous RF current induced linear ablation lesions (LL; ablation of atrial fibrillation, right atrial procedure) in comparison to focal RF lesions (FL; AV node reentry tachycardia, WPW tachycardia). In 23 patients with LL (age 51.3 +/- 11.2 years, 18 men, 5 women) and in 16 patients with FL (age 53.9 +/- 5.1 years, 8 men and 8 women), levels of creatine kinase (CK), myoglobin (MG), CKMB mass (CKMB M), CKMB activity (CKMB A), and cardiac troponin T (cTnT) were determined before and 2, 4, 8, 24, and 48 hours after ablation. CKMB A was normal in 87% in LL and 100% in FL (< 6% of CK) with median maximum CK values of 214 (45-1583) U/L in LL and 36 (29-212) U/L in FL. Peak values of all parameters were significantly higher in LL than in FL. The sensitivity of cTnT was 50% in FL and 100% in LL. In FL MG, total CK, and CKMB M were abnormal in only 12.5% of cases while in LL MG and CKMB M were pathological in 100% and total CK was abnormal in 91.3% of patients. The amount of energy and number of RF applications correlated with cTnT, MG, and CKMB M (P = 0.01). In conclusion, (1) long linear RF current lesions for ablation of atrial fibrillation are associated with significantly greater myocardial injury than focal ablations. (2) In focal lesions only cTnT provided a sensitivity of 50% in the detection of myocardial injury while in linear lesions cTnT, CKMBM, and CKMB M seemed suitable for detection of RF current induced myocardial damage with 100% sensitivity. All biochemical parameters do not differentiate patients with coronary ischemia up to 48 hours after an ablation. (3) Further investigations are necessary to determine if RF current linear lesions lead to impaired atrial contractility in cases of extensive tissue damage.