Perspectives on Implementing a Multidomain Approach to Caring for Older Adults With Heart Failure

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/153220/1/jgs16183_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/153220/2/jgs16183-sup-0001-supinfo.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/153220/3/jgs16183.pd

Frailty in Advanced Heart Failure: A Consequence of Aging or a Separate Entity?

There are over 5 million Americans with heart failure (HF), the majority of whom are over age 65. Frailty is a systemic syndrome associated with aging that produces subclinical dysfunction across multiple organ systems and leads to an increased risk for morbidity and mortality. The prevalence of frailty is about 10% in community-dwelling elderly and 20% in those with advanced HF, and increases in both cohorts with age. Yet the relationship between the primary frailty of aging and frailty secondary to HF remains poorly defined. Whether the frailty of these two populations share similar etiologies or exist as separate entities is unknown. Teasing apart potential molecular, cellular, and functional differences between the frailty of aging and that of advanced HF has implications for risk stratification, quality of life, and pharmacological and therapeutic interventions for advanced HF patients

Baseline pro-inflammatory gene expression in whole blood is related to adverse long-term outcomes after transcatheter aortic valve replacement: a case control study.

BackgroundAge-associated inflammation and immune system dysfunction have been implicated as mechanisms that increase risk for adverse long-term procedural outcomes in older adults. The purpose of this study was to investigate relationships between baseline inflammatory and innate antiviral gene expression and outcomes after transcatheter aortic valve replacement (TAVR) in older adults with severe aortic stenosis.MethodsWe performed a retrospective case-control study comparing pre-procedural pro-inflammatory and Type 1 interferon (IFN) gene expression in 48 controls with favorable outcomes (alive 1 year after TAVR with improved quality of life [QoL]) versus 48 individuals with unfavorable outcomes (dead by 1 year or alive at 1 year but with reduced QoL). Gene expression was evaluated in whole blood via (1) pre-defined composite scores of 19 inflammation-associated genes and 34 Type I IFN response genes, and (2) pro-inflammatory and antiviral transcription factor activity inferred from promotor based bioinformatics analyses of genes showing > 25% difference in average expression levels across groups. All analyses were adjusted for age, gender, body mass index, diabetes, immunosuppression, cardiovascular disease (CVD), and frailty.ResultsRelative to controls, those with unfavorable outcomes demonstrated higher expression of the pro-inflammatory gene composite prior to TAVR (p < 0.01) and bioinformatic indicators of elevated Nuclear Factor kB (p < 0.001) and Activator Protein 1 (p < 0.001) transcription factor activity, but no significant differences in Type I IFN-related gene expression.ConclusionsThese results demonstrate that a pro-inflammatory state prior to TAVR, independent of CVD severity and frailty status, is associated with worse long-term procedural outcomes