Abstract
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.
Highlights
Age-associated inflammation and immune system dysfunction have been implicated as mechanisms that increase risk for adverse long-term procedural outcomes in older adults
We explore whether innate inflammatory and Type 1 interferon (IFN) antiviral gene expression prior to transcatheter aortic valve replacement (TAVR) is related to adverse long-term outcomes using two different approaches to assessing inflammatory and antiviral activity in whole blood
Sample characteristics Of the original 927 cohort, 195 were missing biosample data, 32 were missing baseline Kansas City Cardiomyopathy Questionnaire (KCCQ) data, 17 patients died within 30 days of the procedure, and 131 patients alive at one year were missing follow up KCCQ results, leaving 552 patients available for coarsened exact matching (CEM)
Summary
Age-associated inflammation and immune system dysfunction have been implicated as mechanisms that increase risk for adverse long-term procedural outcomes in older adults. Despite overall favorable safety profiles, older adults are more susceptible to adverse long-term outcomes such as mortality and Goldwater et al BMC Cardiovasc Disord (2021) 21:368 deteriorating QoL after a procedure [2]. Transcatheter aortic valve replacement (TAVR), a minimally invasive alternative to surgical aortic valve replacement, exemplifies the benefits and challenges of performing cardiovascular interventions in older adults and provides a discrete, real-world procedural stress model with which to explore the spectrum of resilience and vulnerability. Despite an average patient age of over 80 years, numerous randomized trials show survival and QoL benefit after TAVR for severe symptomatic aortic stenosis (AS) [7, 8]. The addition of these syndromes into clinical risk models has not fully accounted for the spectrum of observed outcomes
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