Carvedilol therapy is associated with a sustained decline in brain natriuretic peptide levels in patients with congestive heart failure.
BACKGROUND
Beta-blocker therapy improves symptoms, left ventricular ejection fraction (LVEF), and survival in patients with congestive heart failure, but chronic effects on neurohormones have not been extensively investigated. Therefore, we examined the neurohumoral effects of carvedilol.


METHODS
Fifty-five patients with New York Heart Association (NYHA) classes II-III congestive heart failure and LVEF < or =35% entered the study with intention to assess LVEF, NYHA class, plasma brain natriuretic peptide (BNP), N-terminal atrial natriuretic peptide (NANP), big-endothelin, endothelin-1, norepinephrine, and angiotensin II at baseline and at 6 and 12 months after initiation of carvedilol.


RESULTS
Forty-six patients completed 12 months of follow-up. Left ventricular ejection fraction improved from 26% +/- 8% at baseline to 39% +/- 14% at 12 months. New York Heart Association class improved from 2.3 +/- 0.4 at baseline to 1.8 +/- 0.7 at 12 months. Brain natriuretic peptide fell from 453 +/- 784 to 208 +/- 393 pg/mL at 6 months and 223 +/- 334 pg/mL at 12 months ( P = .01 vs baseline). N-terminal atrial natriuretic peptide did not change between baseline and 6 months but fell at 12 months (2117 +/- 1678, 2015 +/- 1532, and 1438 +/- 1442 pg/mL, respectively, P = .001 between baseline and 12 months). Angiotensin II was lower at 6 and 12 months than at baseline (12.6 +/- 10, 7.8 +/- 5.5 pg/mL, P < 0.001, and 11.3 +/- 17.1 pg/mL, P = .02, respectively). Left ventricular ejection fraction at 12 months correlated inversely with BNP level at 12 months (r = -0.55, P = .001).


CONCLUSIONS
Carvedilol therapy is associated with a sustained decline in BNP and NANP levels. Serial BNP levels can provide some guidance regarding probability of LVEF improvement, but the relationship is not strong enough for BNP levels to supplant measurement of LVEF.
Frantz
Robert P
RP
Division of Cardiovascular Diseases and Internal Medicine, Cardiorenal Research Laboratories, Mayo Clinic and Mayo Foundation, Rochester, Minn 55905, USA. frantz.robert@mayo.edu
Olson
Lyle J
LJ
Grill
Diane
D
Moualla
Soundos K
SK
Nelson
Susan M
SM
Nobrega
Thomas P
TP
Hanna
Richard D
RD
Backes
Richard J
RJ
Mookadam
Farouk
F
Heublein
Denise
D
Bailey
Kent R
KR
Burnett
John C
JC
D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology* / Q000627:therapeutic use; D000804:Angiotensin II / Q000378:metabolism; D009320:Atrial Natriuretic Factor / Q000378:metabolism*; D015415:Biomarkers / Q000378:metabolism; D002227:Carbazoles / Q000494:pharmacology* / Q000627:therapeutic use; D000077261:Carvedilol; D019332:Endothelin-1 / Q000378:metabolism; D016232:Endothelins / Q000378:metabolism; D005260:Female; D006333:Heart Failure / Q000188:drug therapy* / Q000378:metabolism*; D006801:Humans; D008297:Male; D008875:Middle Aged; D020097:Natriuretic Peptide, Brain / Q000187:drug effects / Q000378:metabolism*; D011412:Propanolamines / Q000494:pharmacology* / Q000627:therapeutic use
D000317:Adrenergic alpha-Antagonists; D015415:Biomarkers; D002227:Carbazoles; D019332:Endothelin-1; D016232:Endothelins; D011412:Propanolamines; C075556:big-endothelin (1-22); D000077261:Carvedilol; D000804:Angiotensin II; D020097:Natriuretic Peptide, Brain; D009320:Atrial Natriuretic Factor