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Background: Heart failure (HF) is associated with inflammation characterized by the formation of the inflammasome, which triggers maturation of inflammatory cytokines. Apoptosis-associated speck-like protein with a caspase recruitment domain (ASC), a vital component of the inflammasome, is controlled through epigenetic modification, which may be a candidate pathway for worsening HF. This study examined the inflammasome pathway in HF and the relationships between ASC CpG methylation and outcomes in HF., Methods and Results: Stored samples from 155 HF outpatients (ejection fraction 29.9 ± 14.9%) were analyzed for percentage methylation of 7 CpG sites in the intron region preceding exon 1 of the ASC gene. ASC methylation was inversely related to ASC mRNA (r = -0.33; P < .001) and protein (r = -0.464; P < .001). ASC methylation had a positive linear relationship with ejection fraction (r = 0.85; P < .001), quality of life (r = 0.83; P < .001), and 6-minute walk test (r = 0.59; P = .023) and a negative linear relationship with depression (r = -0.81; P < .001) and anxiety (r = -0.75; P < .001). Higher ASC methylation was associated with a lower risk for clinical events (hazard ratio [HR] 0.16; P = .025), whereas higher protein (HR = 1.78; P = .045) and mRNA expression (HR = 1.18; P = .05) were associated with a greater risk., Conclusions: Increased methylation of CpG sites in the intron region of ASC is associated with improved outcomes in HF. The associated decrease in ASC expression implicates this inflammatory mediator as a possible driver of HF outcomes and may represent a therapeutic target., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Objectives: Persons with concomitant heart failure (HF) and diabetes mellitus (DM) have complicated, often competing, self-care expectations and treatment regimens that may reduce quality of life (QOL). This randomized controlled trial tested an integrated self-care intervention on outcomes of HF and DM QOL, physical function, and physical activity (PA)., Methods and Results: Participants with HF and DM (n = 134; mean age 57.4 ± 11 years, 66% men, 69% minority) were randomized to usual care (control) or intervention. The control group received standard HF and DM educational brochures with follow-up telephone contact. The intervention group received education and counseling on combined HF and DM self-care (diet, medications, self-monitoring, symptoms, and PA) with follow-up home visit and telephone counseling. Measures included questionnaires for HF- and DM-specific and overall QOL, PA frequency, and physical function (6-min walk test [6MWT]) and were obtained at baseline and 3 and 6 months. Analysis included mixed models with a priori post hoc tests. Adjusting for age, body mass index, and comorbidity, the intervention group improved in HF total (P = .002) and physical (P < .001) QOL scores at 3 months with retention of improvements at 6 months, improved in emotional QOL scores compared with control at 3 months (P = .04), and improved in health status ratings (P = .04) at 6 months compared with baseline. The intervention group improved in 6MWT distance (924 ft to 952 ft; P = .03) whereas the control group declined (834 ft to 775 ft; F1,63 = 6.86; P = .01). The intervention group increased self-reported PA between baseline and 6 months (P = .01)., Conclusions: An integrated HF and DM self-care intervention improved perceived HF and general QOL but not DM QOL. Improved physical functioning and self-reported PA were also observed with the integrated self-care intervention. Further study of the HF and DM integrated self-care intervention on other outcomes, such as hospitalization and cost, is warranted., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Background: Persons with concomitant heart failure (HF) and diabetes mellitus constitute a growing population whose quality of life is encumbered with worse clinical outcomes as well as high health resource use (HRU) and costs., Methods and Results: Extensive data on HRU and costs were collected as part of a prospective cost-effectiveness analysis of a self-care intervention to improve outcomes in persons with both HF and diabetes. HRU costs were assigned from a Medicare reimbursement perspective. Patients (n = 134) randomized to the self-care intervention and those receiving usual care/attention control were followed for 6 months, revealing significant differences in the number of hospitalization days and associated costs between groups. The mean number of inpatient days was 3 with bootstrapped bias-corrected (BCa) confidence intervals (CIs) of 1.8-4.4 d for the intervention group and 7.3 d (BCa CI 4.1-10.9 d) in the control group: P = .044. Total direct HRU costs per participant were an estimated $9,065 (BCa CI $6,496-$11,936) in the intervention and $16,712 (BCa CI 8,200-$26,621) in the control group, for a mean difference of -$7,647 (BCa CI -$17,588 to $809; P = .21) in favor of the intervention, including intervention costs estimated to be $130.67 per patient., Conclusions: The self-care intervention demonstrated dominance in lowering costs without sacrificing quality-adjusted life-years., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Patients with heart failure continue to suffer adverse health consequences despite advances in therapies over the past 2 decades. Identification of novel therapeutic targets that may attenuate disease progression is therefore needed. The inflammasome may play a central role in modulating chronic inflammation and in turn affecting heart failure progression. The inflammasome is a complex of intracellular interaction proteins that trigger maturation of proinflammatory cytokines interleukin-1β and interleukin-18 to initiate the inflammatory response. This response is amplified through production of tumor necrosis factor α and activation of inducible nitric oxide synthase. The purpose of this review is to discuss recent evidence implicating this inflammatory pathway in the pathophysiology of heart failure., (Copyright © 2015 Elsevier Inc. All rights reserved.)