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BACKGROUND: The use of a Left Ventricular Assist Device (LVAD) in patients with advanced heart failure refractory to optimal medical management has progressed steadily over the past two decades. Data have demonstrated reduced LVAD efficacy, worse clinical outcome, and higher mortality for patients who experience significant ventricular tachyarrhythmia (VTA). We hypothesize that a novel prophylactic intra-operative VTA ablation protocol at the time of LVAD implantation may reduce the recurrent VTA and adverse events postimplant. METHODS: We designed a prospective, multicenter, open-label, randomized-controlled clinical trial enrolling 100 patients who are LVAD candidates with a history of VTA in the previous 5 years. Enrolled patients will be randomized in a 1:1 fashion to intra-operative VTA ablation (n = 50) versus conventional medical management (n = 50) with LVAD implant. Arrhythmia outcomes data will be captured by an implantable cardioverter defibrillator (ICD) to monitor VTA events, with a uniform ICD programming protocol. Patients will be followed prospectively over a mean of 18 months (with a minimum of 9 months) after LVAD implantation to evaluate recurrent VTA, adverse events, and procedural outcomes. Secondary endpoints include right heart function/hemodynamics, healthcare utilization, and quality of life. CONCLUSION: The primary aim of this first-ever randomized trial is to assess the efficacy of intra-operative ablation during LVAD surgery in reducing VTA recurrence and improving clinical outcomes for patients with a history of VTA.

BackgroundEffective communication with cancer patients and their families about their disease, treatment options, and possible outcomes may improve psychosocial outcomes. However, traditional approaches to providing information to patients, including verbal information and written booklets, have a number of shortcomings centered on their limited ability to meet patient preferences and literacy levels. New-generation Web-based technologies offer an innovative and pragmatic solution for overcoming these limitations by providing a platform for interactive information seeking, information sharing, and user-centered tailoring. ObjectiveThe primary goal of this paper is to discuss the advantages of comprehensive and iterative Web-based technologies for health information provision and propose a four-phase framework for the development of Web-based information tools. MethodsThe proposed framework draws on our experience of constructing a Web-based information tool for hematological cancer patients and their families. The framework is based on principles for the development and evaluation of complex interventions and draws on the Agile methodology of software programming that emphasizes collaboration and iteration throughout the development process. ResultsThe DoTTI framework provides a model for a comprehensive and iterative approach to the development of Web-based informational tools for patients. The process involves 4 phases of development: (1) Design and development, (2) Testing early iterations, (3) Testing for effectiveness, and (4) Integration and implementation. At each step, stakeholders (including researchers, clinicians, consumers, and programmers) are engaged in consultations to review progress, provide feedback on versions of the Web-based tool, and based on feedback, determine the appropriate next steps in development. ConclusionsThis 4-phase framework is evidence-informed and consumer-centered and could be applied widely to develop Web-based programs for a diverse range of diseases.

BackgroundSeveral distinct risk factors for arrhythmia recurrence and mortality following ventricular tachycardia (VT) ablation have been described. The effect of concurrent risk factors has not been assessed so far; thus, it is not yet possible to estimate these risks for a patient with several comorbidities. The aim of the study was to identify specific risk groups for mortality and VT recurrence using the Survival Tree (ST) analysis method.MethodsIn 1251 patients 16 demographic, clinical and procedure-related variables were evaluated as potential prognostic factors using ST analysis using a recursive partitioning algorithm that searches for relationships among variables. Survival time and time to VT recurrence in groups derived from ST analysis were compared by a log-rank test. A random forest analysis was then run to extract a variable importance index and internally validate the ST models.ResultsLeft ventricular ejection fraction, implantable cardioverter defibrillator/cardiac resynchronization device, previous ablation were, in hierarchical order, identified by ST analysis as best predictors of VT recurrence, while left ventricular ejection fraction, previous ablation, Electrical storm were identified as best predictors of mortality. Three groups with significantly different survival rates were identified. Among the high-risk group, 65.0% patients were survived and 52.1% patients were free from VT recurrence; within the medium- and low-risk groups, 84.0% and 97.2% patients survived, 72.4% and 88.4% were free from VT recurrence, respectively.ConclusionsOur study is the first to derive and validate a decisional model that provides estimates of VT recurrence and mortality with an effective classification tree. Preprocedure risk stratification could help optimize periprocedural and postprocedural care.

ObjectivesThis study sought to characterize ventricular tachycardia (VT) ablation outcomes across nonischemic cardiomyopathy (NICM) etiologies and adjust these outcomes by patient-related comorbidities that could explain differences in arrhythmia recurrence rates.BackgroundOutcomes of catheter ablation of VT in patients with NICM could be related to etiology of NICM.MethodsData from 2,075 patients with structural heart disease referred for catheter ablation of VT from 12 international centers was retrospectively analyzed. Patient characteristics and outcomes were noted for the 6 most common NICM etiologies. Multivariable Cox proportional hazards modeling was used to adjust for potential confounders.ResultsOf 780 NICM patients (57 ± 14 years of age, 18% women, left ventricular ejection fraction 37 ± 13%), underlying prevalence was 66% for dilated idiopathic cardiomyopathy (DICM), 13% for arrhythmogenic right ventricular cardiomyopathy (ARVC), 6% for valvular cardiomyopathy, 6% for myocarditis, 4% for hypertrophic cardiomyopathy, and 3% for sarcoidosis. One-year freedom from VT was 69%, and freedom from VT, heart transplantation, and death was 62%. On unadjusted competing risk analysis, VT ablation in ARVC demonstrated superior VT-free survival (82%) versus DICM (p ≤ 0.01). Valvular cardiomyopathy had the poorest unadjusted VT-free survival, at 47% (p < 0.01). After adjusting for comorbidities, including age, heart failure severity, ejection fraction, prior ablation, and antiarrhythmic medication use, myocarditis, ARVC, and DICM demonstrated similar outcomes, whereas hypertrophic cardiomyopathy, valvular cardiomyopathy, and sarcoidosis had the highest risk of VT recurrence.ConclusionsCatheter ablation of VT in NICM is effective. Etiology of NICM is a significant predictor of outcomes, with ARVC, myocarditis, and DICM having similar but superior outcomes to hypertrophic cardiomyopathy, valvular cardiomyopathy, and sarcoidosis, after adjusting for potential covariates.

CD4+CD25+Foxp3+ Regulatory T cells (Tregs) play a critical role in immune tolerance. The plasticity and functional adaptability of Tregs in an inflammatory microenvironment has been demonstrated in autoimmunity. Here, using a double transgenic mouse model that permits Foxp3 lineage tracing, we investigated the phenotypic plasticity of Foxp3+ Tregs in a well-characterized murine model of corneal transplantation. In order to subvert the normal immune privilege of the cornea and foster an inflammatory milieu, host mice were exposed to desiccating stress prior to transplantation. Treg frequencies and function were decreased following desiccating stress, and this corresponded to decreased graft survival. A fraction of Tregs converted to IL-17+ or IFNγ+ 'exFoxp3' T cells that were phenotypically indistinguishable from effector Th17 or Th1 cells, respectively. We investigated how Foxp3 expression is modulated in different Treg subsets, demonstrating that neuropilin-1- peripherally-derived Tregs are particularly susceptible to conversion to IL-17+/IFNγ+ exFoxp3 cells in response to cues from their microenvironment. Finally, we show that IL-6 and IL-23 are implicated in the conversion of Tregs to exFoxp3 cells. This report demonstrates that the pathological conversion of Tregs contributes to the loss of corneal immune privilege.

Over the past three years, Massive Open Online Courses, or MOOCs, have spanned the globe, educating millions with the potential to reach millions more. Taught by leading academics from top institutions, the courses are as complete as those offered in traditional settings; yet, in being web-based and tuition free, they disregard long-standing geographic and economic barriers. These qualities have led many to see MOOCs as a significant step towards universal education and the fulfillment of the United Nation's goal of education as a human right. MOOCs, however, are not without precedent. As others have noted, the twentieth century witnessed several--generally unsuccessful--attempts at using film, radio, and television for large-scale learning. What has been mostly forgotten is that combining technology and methodology to increase efficiency and reach a "massive" number of students predates all of these examples. This study argues that the attempt to use technology for the purpose of mass education dates at least to the early nineteenth century with the educational system of Joseph Lancaster (1778-1838). Furthermore, the Lancasterian system was far more successful than most pre-MOOC applications of educational technology, having a profound and global impact. As such, the Lancasterian system deserves to be reevaluated in the context of recent developments and, as a predecessor to MOOCs, its successes and failures should serve as distant guideposts to further MOOC development.

Recurrence of ventricular tachycardia (VT) after ablation in patients with previous myocardial infarction is associated with adverse prognosis. However, the impact of the timing of VT recurrence on outcomes is unclear. We analyzed data from a multicenter collaborative database of patients who underwent catheter ablation for infarct-related VT. Multivariable Cox regression analyses investigated the effect of the timing of VT recurrence on the composite outcome of death or heart transplantation using VT recurrence as a time-varying covariate. A total of 1412 patients were included (92% men; age: 66.7±10.7 years), and 605 patients (42.8%) had a recurrence after median 116 days (188 [31.1%] within 1 month, 239 [39.5%] between 1 and 12 months, and 178 [29.4%] after 12 months). At median follow-up of 670 days, 375 patients (26.6%) experienced death or heart transplantation. The median time from recurrence to death or heart transplantation was 65 and 198.5 days in patients with recurrence ≤30 days and >30 days post ablation, respectively. The adjusted hazard ratio (95% confidence interval) for the effect of VT recurrence occurring immediately post ablation on death or heart transplantation was 3.45 (2.33-5.11) in reference to no recurrence. However, the magnitude of this effect decreased statistically significantly (P

Catheter ablation of ventricular tachycardia (VT) has evolved in recent years, especially in patients with ischemic heart disease. Data from prospective studies show that VT catheter ablation reduces the risk of recurrent VT; however, there is a paucity of data on the effect of VT catheter ablation on mortality and patient-centered outcomes such as quality of life. Performing randomized clinical trials of VT catheter ablation can be fraught with challenges, and, as a result, several prior trials of VT catheter ablation had to be stopped prematurely. The main challenges are inability to blind the patient to therapy to obtain a traditional control group, high crossover rates between the 2 arms of the study, patient refusal to participate in trials in which they have an equal chance of receiving a "pill" vs an invasive procedure, heterogeneity of mapping and ablation techniques as well as catheters and equipment, rapid evolution of technology that may make findings of any long trial less relevant to clinical practice, lack of consensus on what constitutes acute procedural and long-term success, and presentation of patients to electrophysiologists late in the course of their disease. In this article, a panel of experts on VT catheter ablation and/or clinical trials of VT catheter ablation review challenges faced in conducting prior trials of VT catheter ablation and offer potential solutions for those challenges. It is hoped that the proposed solutions will enhance the feasibility of randomized clinical trials of VT catheter ablation.

BackgroundThe impact of catheter ablation of ventricular tachycardia (VT) on all-cause mortality remains unknown.ObjectiveThe purpose of this study was to examine the association between VT recurrence after ablation and survival in patients with scar-related VT.MethodsAnalysis of 2061 patients with structural heart disease referred for catheter ablation of scar-related VT from 12 international centers was performed. Data on clinical and procedural variables, VT recurrence, and mortality were analyzed. Kaplan-Meier analysis was used to estimate freedom from recurrent VT, transplant, and death. Cox proportional hazards frailty models were used to analyze the effect of risk factors on VT recurrence and mortality.ResultsOne-year freedom from VT recurrence was 70% (72% in ischemic and 68% in nonischemic cardiomyopathy). Fifty-seven patients (3%) underwent cardiac transplantation, and 216 (10%) died during follow-up. At 1 year, the estimated rate of transplant and/or mortality was 15% (same for ischemic and nonischemic cardiomyopathy). Transplant-free survival was significantly higher in patients without VT recurrence than in those with recurrence (90% vs 71%, P