Inflammatory Mediators and Clinical Outcome in Patients with Advanced Heart Failure Receiving Cardiac Resynchronization Therapy

John Belperio, Tamara Horwich, William T. Abraham, Gregg C. Fonarow, John Gorcsan, Malcolm M. Bersohn, Jagmeet P. Singh, Ali Sonel, Li Yin Lee, Jasmina Halilovic, Alan Kadish, Alaa A. Shalaby

Research output: Contribution to journalArticle

10 Scopus citations

Abstract

Expression of different cytokines and growth factors after myocardial injury has been associated with fibroplasia and dilatation versus reverse remodeling and myocardial repair. Specifically, the proinflammatory/fibrotic mediators: interleukin (IL)-6, epidermal growth factor, and fibroblast growth factor (FGF)-2 cause fibroplasia, whereas reparative cytokines including: IL-1α, IL-1β, IL-4, and IL-13 can limit fibrosis. In appropriate patients, cardiac resynchronization therapy (CRT) reverses cardiomyopathy and improves outcome. However, a significant proportion will not respond to this therapy. We conducted this study to assess the association of proinflammatory/fibrotic and/or reparative immune response mediators at baseline with outcome after CRT. In the multicenter RISK study, plasma samples were collected prospectively before CRT implantation. Plasma IL-6, epidermal growth factor, FGF-2, IL-1α, IL-1β, IL-4, and IL-13 were evaluated by Luminex technology. The primary outcome was predefined as freedom from heart failure hospitalization or death and a decrease in echocardiographic end-systolic volume of >15% at 12 months. To determine associations with the outcome, multivariate logistic regression models including baseline clinical characteristics and the specific cytokines and growth factors were constructed. On multivariate analysis of 257 patients, detectable reparative cytokine IL-13 was significantly associated with the primary outcome (odds ratio 3.79; 95% CI 2.10 to 6.82, p <0.0001). In contrast, detectable proinflammatory/fibrotic growth factor FGF-2 was negatively associated (odds ratio 0.31; 95% CI, 0.14 to 0.68; p = 0.004). In conclusion, in CRT recipients, baseline levels of inflammatory mediators affecting cardiac fibrosis versus repair were associated with subsequent clinical outcome.

Original languageEnglish
Pages (from-to)617-625
Number of pages9
JournalAmerican Journal of Cardiology
Volume117
Issue number4
DOIs
StatePublished - Feb 15 2016
Externally publishedYes

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    Belperio, J., Horwich, T., Abraham, W. T., Fonarow, G. C., Gorcsan, J., Bersohn, M. M., Singh, J. P., Sonel, A., Lee, L. Y., Halilovic, J., Kadish, A., & Shalaby, A. A. (2016). Inflammatory Mediators and Clinical Outcome in Patients with Advanced Heart Failure Receiving Cardiac Resynchronization Therapy. American Journal of Cardiology, 117(4), 617-625. https://doi.org/10.1016/j.amjcard.2015.11.049