BACKGROUND Heart failure patients with primary prevention implantable cardioverter-defibrillators (ICD) may experience an improvement in left ventricular ejection fraction (LVEF) over time. However, it is unclear how LVEF improvement affects subsequent risk for mortality and sudden cardiac death (SCD). OBJECTIVES We sought to assess changes in LVEF after ICD implantation and the implication of these changes on subsequent mortality and ICD shocks. METHODS We conducted a prospective cohort study of 538 patients with repeated LVEF assessments after ICD implantation for primary prevention of SCD. The primary endpoint was appropriate ICD shock, defined as a shock for ventricular tachyarrhythmias. The secondary endpoint was all-cause mortality. RESULTS Over a mean follow-up of 4.9 years, LVEF decreased in 13.0%, improved in 40.0%, and was unchanged in 47.0% of the patients. In the multivariate Cox models comparing patients with an improved LVEF to those with an unchanged LVEF, the hazard ratios were 0.33 (95% confidence interval [CI]: 0.18 to 0.59) for mortality and 0.29 (95% CI: 0.11 to 0.78) for appropriate shock, respectively. During follow-up, 25% of patients showed an improvement in LVEF to >35% and their risk of appropriate shock decreased but was not eliminated. CONCLUSION Among primary prevention ICD patients, 40.0% had an improved LVEF during follow-up and 25% had LVEF improved to >35%. Changes in LVEF were inversely associated with all-cause mortality and appropriate shock for ventricular tachyarrhythmia. In patients whose follow-up LVEF improved to >35%, the risk of an appropriate shock remained but was markedly decreased.

Objective-We proposed and tested a novel ECG marker of risk of ventricular arrhythmias (VA).Methods-Digital orthogonal ECGs were recorded at rest before ICD implantation in 508 participants of a primary prevention ICDs prospective cohort study (mean age 60±12; 377 male [74%]). The sum magnitude of the absolute QRST integral in 3 orthogonal leads (SAI QRST) was calculated. A derivation cohort of 128 patients was used to define a cutoff; a validation cohort (n=380) was used to test a predictive value.Results-During a mean follow-up of 18 months, 58 patients received appropriate ICD therapies. SAI QRST was lower in patients with VA (105.2±60.1 vs. 138.4±85.7 mV*ms, P=0.002). In the Cox proportional hazards analysis, patients with SAI QRST ≤145 mV*ms had about 4-fold higher risk of VA (HR3.6; 95% CI: 1.96-6.71, p<0.0001), and a 6-fold higher risk of monomorphic ventricular tachycardia [MMVT] (HR 6.58; P=0.014), whereas prediction of polymorphic ventricular tachycardia or ventricular fibrillation did not reach statistical significance.Conclusion-High SAI QRST is associated with low risk of sustained VA in patients with structural heart disease.Sudden cardiac death (SCD) strikes about 350,000 victims in the United States every year. 1 Implantable cardioverter-defibrillators (ICDs) are the treatment of choice2 -4 for patients at risk for SCD. The need to extend risk stratification beyond use of ejection fraction is well recognized.5 , 6 A U-shaped curve for ICD benefit was shown in the analysis of the MADIT II study, 5 prompting a search for markers that identify low-risk patients who do not benefit from ICD implantation. © 2010 Elsevier Inc. All rights reserved.Correspondence to Larisa G. Tereshchenko, MD, Carnegie 568, 600 N. Wolfe St., Baltimore, MD 21287. lteresh1@jhmi.edu Phone: 410-502-2796; Fax: 410-614-8039. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. During the century of electrocardiography multiple attempts were made to decipher complex information carried by cardiac electrical signal to obtain important clinical diagnostic and prognostic information. Several approaches have been proposed to develop composite ECG metrics that account for both amplitude and duration of ECG waveforms, with the goal to diagnose hypertrophy 7, 8, to determine localization and size of the scar9 -11, and to assess heterogeneity of action potential 12 . Although modern imaging modalities question utility of diagnostic ECG, prognostic ECG markers remain of interest. Arrhythmogenic substrate in susceptible to ventricular arrhythmia (VA) patients with structural heart disease is ...

BackgroundPrimary‐prevention implantable cardioverter‐defibrillators (ICDs) reduce total mortality in patients with severe left ventricular systolic function. However, only a minority of patients benefit from these devices. We designed the Prospective Observational Study of Implantable Cardioverter‐Defibrillators (PROSE‐ICD) to identify risk factors and enhance our understanding of the biological mechanisms that predispose to arrhythmic death in patients undergoing ICD implantation for primary prevention of sudden death.Methods and ResultsThis is a multicenter prospective cohort study with a target enrollment of 1200 patients. The primary end point is ICD shocks for adjudicated ventricular tachyarrhythmias. The secondary end point is total mortality. All patients undergo a comprehensive evaluation including history and physical examination, signal‐averaged electrocardiograms, and blood sampling for genomic, proteomic, and metabolomic analyses. Patients are evaluated every 6 months and after every known ICD shock for additional electrocardiographic and blood sampling. As of December 2011, a total of 1177 patients have been enrolled with more nonwhite and female patients compared to previous randomized trials. A total of 143 patients have reached the primary end point, whereas a total of 260 patients died over an average follow‐up of 59 months. The PROSE‐ICD study represents a real‐world cohort of individuals with systolic heart failure receiving primary‐prevention ICDs.ConclusionsExtensive electrophysiological and structural phenotyping as well as the availability of serial DNA and serum samples will be important resources for evaluating novel metrics for risk stratification and identifying patients at risk for arrhythmic sudden death.Clinical Trial RegistrationURL: http://clinicaltrials.gov/ Unique Identifier: NCT00733590.

Summary:Numerous lines of preclinical and clinical evidence support the existence of a graft-versus-leukemia effect, but less evidence supporting a comparable graft-versus-lymphoma effect exists. We review here current clinical data addressing the graft-versus-lymphoma effect, including comparisons of autologous, syngeneic, and allogeneic transplantation; responses to immunomodulation; and responses to nonmyeloablative stem cell transplantation. Despite several limitations of the data, we believe that there is sufficient evidence suggesting a significant graftversus-lymphoma effect. In addition, we discuss approaches for clinical management of lymphoma patients, opportunities for mechanistic studies afforded by donor leukocyte infusions and nonmyeloablative transplantation, and suggestions for clinical studies to further define the magnitude and applicability of the graft-versus-lymphoma effect. For over two decades, scientists and clinicians have recognized the existence of a graft-versus-tumor effect, whose role has become increasingly important in the treatment of hematologic malignancies. Initially suggested by numerous animal studies and corroborated by considerable retrospective analysis of clinical data, this effect is most directly supported by durable responses to withdrawal of immunosuppression, administration of donor leukocytes, and more recently, nonmyeloablative stem cell transplantation. Most studies to date have investigated the graft-versusleukemia effect, while comparable studies of a graft-versuslymphoma effect have been limited. Current data regarding graft-versus-lymphoma activity, however, have increasingly supported the likelihood of its existence. We review below the most recent evidence, composed of case reports and small series, larger retrospective analyses, and few prospective studies, suggesting a graft-versus-lymphoma effect.