title: Inflammatory Mediators and Clinical Outcome in Patients With Advanced Heart Failure Receiving Cardiac Resynchronization Therapy.
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.
authors.affiliation: David Geffen School of Medicine, University of California, Los Angeles, California.
authors.forename: John
authors.initials: J
authors.lastname: Belperio
authors.affiliation: David Geffen School of Medicine, University of California, Los Angeles, California.
authors.forename: Tamara
authors.initials: T
authors.lastname: Horwich
authors.affiliation: Ohio State University, Columbus, Ohio.
authors.forename: William T
authors.initials: WT
authors.lastname: Abraham
authors.affiliation: David Geffen School of Medicine, University of California, Los Angeles, California.
authors.forename: Gregg C
authors.initials: GC
authors.lastname: Fonarow
authors.affiliation: University of Pittsburgh, Pittsburgh, Pennsylvania.
authors.forename: John
authors.initials: J
authors.lastname: Gorcsan
authors.affiliation: David Geffen School of Medicine, University of California, Los Angeles, California; VA Greater Los Angeles Healthcare System, Los Angeles, California.
authors.forename: Malcolm M
authors.initials: MM
authors.lastname: Bersohn
authors.affiliation: Massachusetts General Hospital, Boston, Massachusetts.
authors.forename: Jagmeet P
authors.initials: JP
authors.lastname: Singh
authors.affiliation: University of Pittsburgh, Pittsburgh, Pennsylvania; VA Pittsburgh Healthcare System, Pittsburgh, Pennsylvania.
authors.forename: Ali
authors.initials: A
authors.lastname: Sonel
authors.affiliation: St. Jude Medical, Sylmar, California.
authors.forename: Li-Yin
authors.initials: LY
authors.lastname: Lee
authors.affiliation: St. Jude Medical, Sylmar, California.
authors.forename: Jasmina
authors.initials: J
authors.lastname: Halilovic
authors.affiliation: New York Medical College, Valhalla, New York.
authors.forename: Alan
authors.initials: A
authors.lastname: Kadish
authors.affiliation: University of Pittsburgh, Pittsburgh, Pennsylvania; New York Medical College, Valhalla, New York. Electronic address: Alaa.Shalaby@va.gov.
authors.forename: Alaa A
authors.initials: AA
authors.lastname: Shalaby
mesh_terms: D000368:Aged; D015415:Biomarkers / Q000097:blood; D058406:Cardiac Resynchronization Therapy / Q000379:methods*; D016207:Cytokines / Q000097:blood*; D004452:Echocardiography; D005260:Female; D005500:Follow-Up Studies; D006333:Heart Failure / Q000097:blood* / Q000503:physiopathology / Q000628:therapy; D006801:Humans; D007249:Inflammation / Q000097:blood*; D036341:Intercellular Signaling Peptides and Proteins / Q000097:blood*; D008297:Male; D011379:Prognosis; D012189:Retrospective Studies; D013318:Stroke Volume / Q000502:physiology*; D013997:Time Factors; D016896:Treatment Outcome; D020257:Ventricular Remodeling / Q000502:physiology*
chemical_list: D015415:Biomarkers; D016207:Cytokines; D036341:Intercellular Signaling Peptides and Proteins