TY - JOUR
T1 - Low-dose nesiritide in human anterior myocardial infarction suppresses aldosterone and preserves ventricular function and structure
T2 - A proof of concept study
AU - Chen, H. H.
AU - Martin, F. L.
AU - Gibbons, R. J.
AU - Schirger, J. A.
AU - Wright, R. S.
AU - Schears, R. M.
AU - Redfield, M. M.
AU - Simari, R. D.
AU - Lerman, A.
AU - Cataliotti, A.
AU - Burnett, J. C.
PY - 2009/8
Y1 - 2009/8
N2 - Background: B-type natriuretic peptide (BNP, nesiritide) has anti-fibrotic, anti-hypertrophic, anti-inflammatory, vasodilating, lusitropic and aldosterone-inhibiting properties but conventional doses of BNP cause hypotension, limiting its use in heart failure. Objective: To determine whether infusion of low-dose BNP within 24 h of successful reperfusion for anterior acute myocardial infarction (AMI) would prevent adverse left ventricular (LV) remodelling and suppress aldosterone. Methods: A translational proof-of-concept study was carried out to determine tolerability and biological activity of intravenous BNP at 0.003 and 0.006 μg/kg/min, without bolus started within 24 h of successful reperfusion for anterior AMI. 24 patients with first anterior wall ST elevation AMI and successful revascularisation were randomly assigned to receive 0.003 (n = 12) or 0.006 (n = 12) μg/kg/min of IV BNP for 72 h in addition to standard care during hospitalisation for anterior AMI. Results: Baseline characteristics, drugs and peak cardiac biomarkers for myocardial damage were similar between both groups. Infusion of BNP at 0.006 μg/kg/min resulted in greater biological activity than infusion at 0.003 μg/kg/ min as measured by higher mean (SEM) plasma cGMP levels (8.6 (1) vs 5.5 (1) pmol/ml, p<0.05) and suppression of plasma aldosterone (8.0 (2) to 4.6 (1) ng/ dl, p<0.05), which was not seen in the 0.003 μg/kg/min group. LV ejection fraction (LVEF) improved significantly from baseline to 1 month (40 (4)% to 54 (5)%, p<0.05) in the 0.006 group but not in the 0.003 group. Infusion of BNP at 0.006 μg/kg/min was associated with a decrease of LV end-systolic volume index (61 (9) to 43 (8) ml/m2, p<0.05) at 1 month, which was not seen in the 0.003 group. No drug-related serious adverse events occurred in either group. Conclusions: 72 h infusion of low BNP at the time of anterior AMI is well tolerated and biologically active. Patients treated with low-dose BNP had improved LVEF and smaller LV end-systolic volume at 1 month.
AB - Background: B-type natriuretic peptide (BNP, nesiritide) has anti-fibrotic, anti-hypertrophic, anti-inflammatory, vasodilating, lusitropic and aldosterone-inhibiting properties but conventional doses of BNP cause hypotension, limiting its use in heart failure. Objective: To determine whether infusion of low-dose BNP within 24 h of successful reperfusion for anterior acute myocardial infarction (AMI) would prevent adverse left ventricular (LV) remodelling and suppress aldosterone. Methods: A translational proof-of-concept study was carried out to determine tolerability and biological activity of intravenous BNP at 0.003 and 0.006 μg/kg/min, without bolus started within 24 h of successful reperfusion for anterior AMI. 24 patients with first anterior wall ST elevation AMI and successful revascularisation were randomly assigned to receive 0.003 (n = 12) or 0.006 (n = 12) μg/kg/min of IV BNP for 72 h in addition to standard care during hospitalisation for anterior AMI. Results: Baseline characteristics, drugs and peak cardiac biomarkers for myocardial damage were similar between both groups. Infusion of BNP at 0.006 μg/kg/min resulted in greater biological activity than infusion at 0.003 μg/kg/ min as measured by higher mean (SEM) plasma cGMP levels (8.6 (1) vs 5.5 (1) pmol/ml, p<0.05) and suppression of plasma aldosterone (8.0 (2) to 4.6 (1) ng/ dl, p<0.05), which was not seen in the 0.003 μg/kg/min group. LV ejection fraction (LVEF) improved significantly from baseline to 1 month (40 (4)% to 54 (5)%, p<0.05) in the 0.006 group but not in the 0.003 group. Infusion of BNP at 0.006 μg/kg/min was associated with a decrease of LV end-systolic volume index (61 (9) to 43 (8) ml/m2, p<0.05) at 1 month, which was not seen in the 0.003 group. No drug-related serious adverse events occurred in either group. Conclusions: 72 h infusion of low BNP at the time of anterior AMI is well tolerated and biologically active. Patients treated with low-dose BNP had improved LVEF and smaller LV end-systolic volume at 1 month.
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U2 - 10.1136/hrt.2008.153916
DO - 10.1136/hrt.2008.153916
M3 - Article
C2 - 19447837
AN - SCOPUS:68049144936
SN - 1355-6037
VL - 95
SP - 1315
EP - 1319
JO - Heart
JF - Heart
IS - 16
ER -