title: Increased low-grade inflammation is associated with lack of functional response to carvedilol in patients with systolic heart failure.
abstract: BACKGROUND
  The aim of this study was to evaluate, according to functional response, the neuroendocrine and inflammatory status in patients with chronic heart failure before and after therapy with carvedilol.
  
  
  RESULTS
  Serum tumor necrosis factor-α (TNF-α) soluble receptors (sTNF-R1 and sTNF-R2), interleukin (IL)-10 and IL-18, chromogranin A (CgA) and brain natriuretic peptide (pro-BNP) were measured in 37 New York Heart Association class II to IV heart failure patients, at baseline and after 6 months of therapy with carvedilol. Patients were divided in two groups according to whether, following carvedilol, left-ventricular ejection fraction (LVEF) had increased by at least 5% (17 patients) or not (20 patients). Baseline LVEF was higher in nonresponders (38 ± 5 vs. 31 ± 7%, P = 0.002). In responders, LVEF increased from 31 ± 7 to 51 ± 7% (P < 0.0001), whereas in nonresponders it decreased from 38 ± 5 to 33 ± 7%, (P = 0.02). sTNF-R1 (P = 0.019) and sTNF-R2 (P = 0.025) increased in nonresponders, whereas they did not change in responders. After carvedilol, IL-10 was significantly higher in responders (P = 0.03). Conversely, no significant IL-18 and CgA changes were observed in either group. CgA was not significantly different between groups at baseline and after carvedilol in either group, whereas pro-BNP significantly increased in nonresponders (from 438 ± 582 to 1324 ± 1664 pg/ml, P = 0.04) and decreased in responders (from 848 ± 1221 to 420 ± 530 pg/ml, P = 0.08).
  
  
  CONCLUSIONS
  Increased inflammatory activation observed only in heart failure patients not improving left-ventricular function after carvedilol may indicate that inflammation, either as a direct cause or as a consequence, is associated with progressive ventricular dysfunction.
authors.affiliation: Heart Failure Clinic - Clinical Cardiology, Cardiothoracic and Vascular Department, San Raffaele University Hospital, Milan, Italy. gabriele.fragasso@hsr.it
authors.forename: Gabriele
authors.initials: G
authors.lastname: Fragasso
authors.forename: Roberto
authors.initials: R
authors.lastname: Spoladore
authors.forename: Francesco
authors.initials: F
authors.lastname: Maranta
authors.forename: Angelo
authors.initials: A
authors.lastname: Corti
authors.forename: Guido
authors.initials: G
authors.lastname: Lattuada
authors.forename: Barbara
authors.initials: B
authors.lastname: Colombo
authors.forename: Massimo
authors.initials: M
authors.lastname: Locatelli
authors.forename: Anna
authors.initials: A
authors.lastname: Salerno
authors.forename: Giliola
authors.initials: G
authors.lastname: Calori
authors.forename: Luis
authors.initials: L
authors.lastname: Briceno
authors.forename: Anna B
authors.initials: AB
authors.lastname: Alfieri
authors.forename: Gianluca
authors.initials: G
authors.lastname: Perseghin
authors.forename: Alberto
authors.initials: A
authors.lastname: Margonato
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000009:adverse effects / Q000627:therapeutic use*; D000368:Aged; D002227:Carbazoles / Q000009:adverse effects / Q000627:therapeutic use*; D000077261:Carvedilol; D015331:Cohort Studies; D016207:Cytokines / Q000097:blood / Q000187:drug effects; D004452:Echocardiography; D005260:Female; D054143:Heart Failure, Systolic / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology; D006801:Humans; D007249:Inflammation / Q000097:blood / Q000209:etiology*; D007333:Insulin Resistance / Q000502:physiology; D008297:Male; D008875:Middle Aged; D020097:Natriuretic Peptide, Brain / Q000097:blood / Q000187:drug effects; D010446:Peptide Fragments / Q000097:blood / Q000187:drug effects; D011412:Propanolamines / Q000009:adverse effects / Q000627:therapeutic use*; D011788:Quality of Life; D012720:Severity of Illness Index; D013318:Stroke Volume / Q000187:drug effects / Q000502:physiology*; D016896:Treatment Outcome
chemical_list: D000319:Adrenergic beta-Antagonists; D002227:Carbazoles; D016207:Cytokines; D010446:Peptide Fragments; D011412:Propanolamines; C109794:pro-brain natriuretic peptide (1-76); D000077261:Carvedilol; D020097:Natriuretic Peptide, Brain