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Abstract BACKGROUND Although cardiac troponin is associated with outcomes in atrial fibrillation (AF), the complementary prognostic information provided by cardiac troponin I (cTnI) and cTnT is unknown. This study investigated the distribution, determinants, and prognostic value of cTnI and cTnT concentrations in patients with AF. METHODS Samples were collected. At the time of randomization, we analyzed cTnI and cTnT concentrations of 14806 AF patients in the Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation (ARISTOTLE) trial using high-sensitivity assays. Correlations (Spearman), determinants (multivariable linear regression), and outcomes (adjusted Cox models and c-statistics) were investigated. RESULTS Concentrations of cTnI and cTnT were correlated (r = 0.70) and measurable in most participants [cTnI 98.5% (median 5.4 ng/L, ≥99th percentile in 9.2%) and cTnT 93.5% (median 10.9 ng/L, ≥99th percentile in 34.4%)]. Renal impairment was the most important factor affecting the concentrations of both troponins. cTnI increase was more associated with heart failure, vascular disease, and persistent/permanent AF, and cTnT with age, male sex, and diabetes. Over a median 1.9 years of follow-up, patients with both troponins above the median had significantly higher risk for stroke/systemic embolism [hazard ratio (HR) 1.72 (95% CI 1.31–2.27)], cardiac death [3.14 (2.35–4.20)], and myocardial infarction [2.99 (1.78–5.03)] than those with both troponins below median (all P < 0.005). Intermediate risks were observed when only 1 troponin was above the median. When combined with clinical information, each marker provided similar prognostication and had comparable c-index. CONCLUSIONS cTnI and cTnT concentrations are moderately correlated and measurable in plasma of most AF patients. The risk of stroke and cardiovascular events is highest when both troponins are above median concentrations. Each troponin provides comparable prognostic information when combined with clinical risk factors. ClinicalTrials.gov/NCT00412984

Arrhythmogenic Substrate of Ventricular Arrhythmias at the AMCIntroductionCatheter ablation of ventricular arrhythmia (VA) at the fibrous aortic mitral continuity (AMC) has been described, yet the nature of the arrhythmogenic substrate remains unknown.MethodsProcedural records of 528 consecutive patients undergoing ablation of VA at Mayo Clinic, Rochester, MN, were reviewed. The electrocardiographic and electrophysiologic characteristics of patients with successful ablation at the AMC were analyzed to characterize the underlying arrhythmogenic substrate.ResultsOf the 21 patients (mean age 53.2 ± 13.4 years, 47.6% male) who underwent ablation of VA at the AMC with acute success, prepotentials (PPs) were found at the ablation sites preceding the ventricular electrogram (VEGM) during arrhythmias in 13 (61.9%) patients and during sinus rhythm in 7 (53.8%) patients. VAs with PPs were associated with a significantly higher burden of premature ventricular complexes (PVCs; 26.1 ± 10.9% vs. 14.9 ± 10.1%, P = 0.03), shorter VEGM to QRS intervals (9.0 ± 28.5 milliseconds vs. 33.1 ± 8.8 milliseconds, P = 0.03), lower pace map scores (8.7 ± 1.6 vs. 11.4 ± 0.8, P = 0.001), and a trend toward shorter V‐H intervals during VA (32.1 ± 38.6 milliseconds vs. 76.3 ± 11.1 milliseconds, P = 0.06) as compared to those without PP. A strong and positive correlation was found between V‐H interval and QRS duration during arrhythmia in those with PPs (B = 2.11, R2 = 0.97, t = 13.7, P < 0.001) but not in those without PPs.ConclusionLocal EGM characteristics and relative activation time of the His bundle suggest the possibility of conduction tissue as the origin for VA arising from the fibrous AMC. Specific identification and targeting of PPs when ablating VAs at this location may improve procedural success.

Background— Most patients with repaired tetralogy of Fallot require pulmonary valve replacement (PVR), but the evaluation for and management of ventricular arrhythmia remain unclear. This study is aimed at clarifying the optimal approach to this potentially life-threatening issue at the time of PVR. Methods and Results— A retrospective analysis was performed on 205 patients with repaired tetralogy of Fallot undergoing PVR at our institution between 1988 and 2010. Median age was 32.9 (range, 25.6) years. Previous ventricular tachycardia occurred in 16 patients (8%) and 37 (16%) had left ventricular dysfunction, defined as left ventricular ejection fraction <50%. Surgical right ventricular outflow tract cryoablation was performed in 22 patients (10.7%). The primary outcome was a combined event including ventricular tachycardia, out-of-hospital cardiac arrest, appropriate implantable cardioverter defibrillator therapy, and sudden cardiac death. Freedom from the combined event at 5, 10, and 15 years was 95%, 90%, and 79%, respectively. In the first year after PVR, 2 events occurred. Conversely, in the 22 patients who underwent surgical cryoablation, a single event occurred 7 years after PVR. A history of ventricular tachycardia and left ventricular dysfunction was associated with higher risk for the combined event (hazard ratio, 4.7; P =0.004 and hazard ratio, 0.8; P =0.02, respectively). Conclusions— Patients with repaired tetralogy of Fallot undergoing PVR with history of ventricular tachycardia or left ventricular dysfunction appear to be associated with a higher risk of arrhythmic events after operation. Events in the first year after PVR are rare, and in select high-risk patients, surgical cryoablation does not seem to increase arrhythmic events and may be protective.

Background and Purpose— NINDS (National Institute of Neurological Disorders and Stroke)-SiGN (Stroke Genetics Network) is an international consortium of ischemic stroke studies that aims to generate high-quality phenotype data to identify the genetic basis of pathogenic stroke subtypes. This analysis characterizes the etiopathogenetic basis of ischemic stroke and reliability of stroke classification in the consortium. Methods— Fifty-two trained and certified adjudicators determined both phenotypic (abnormal test findings categorized in major pathogenic groups without weighting toward the most likely cause) and causative ischemic stroke subtypes in 16 954 subjects with imaging-confirmed ischemic stroke from 12 US studies and 11 studies from 8 European countries using the web-based Causative Classification of Stroke System. Classification reliability was assessed with blinded readjudication of 1509 randomly selected cases. Results— The distribution of pathogenic categories varied by study, age, sex, and race ( P <0.001 for each). Overall, only 40% to 54% of cases with a given major ischemic stroke pathogenesis (phenotypic subtype) were classified into the same final causative category with high confidence. There was good agreement for both causative (κ 0.72; 95% confidence interval, 0.69–0.75) and phenotypic classifications (κ 0.73; 95% confidence interval, 0.70–0.75). Conclusions— This study demonstrates that pathogenic subtypes can be determined with good reliability in studies that include investigators with different expertise and background, institutions with different stroke evaluation protocols and geographic location, and patient populations with different epidemiological characteristics. The discordance between phenotypic and causative stroke subtypes highlights the fact that the presence of an abnormality in a patient with stroke does not necessarily mean that it is the cause of stroke.

The Rare Cancer Network (RCN) was formed in the early 1990's to create a global network that could pool knowledge and resources in the studies of rare malignancies whose infrequency prevented both their study with prospective clinical trials. To date, the RCN has initiated 74 studies resulting in 46 peer reviewed publications. The First International Symposium of the Rare Cancer Network took place in Nice in March of 2014. Status updates and proposals for new studies were heard for fifteen topics. Ongoing studies continue for cardiac sarcomas, thyroid cancers, glomus tumors, and adult medulloblastomas. New proposals were presented at the symposium for primary hepatic lymphoma, solitary fibrous tumors, Rosai-Dorfman disease, tumors of the ampulla of Vater, salivary gland tumors, anorectal melanoma, midline nuclear protein in testes carcinoma, pulmonary lymphoepithelioma-like carcinoma, adenoid cystic carcinoma of the trachea, osteosarcomas of the mandible, and extra-cranial hemangiopericytoma. This manuscript presents the abstracts of those proposals and updates on ongoing studies, as well a brief summary of the vision and future of the RCN.