TY - JOUR
T1 - Changes in plasma endothelin-1 levels reflect clinical response to β- blockade in chronic heart failure
AU - Krum, Henry
AU - Gu, Anguo
AU - Wilshire-Clement, Michelle
AU - Sackner-Bernstein, Jonathon
AU - Goldsmith, Rochelle
AU - Medina, Norma
AU - Yushak, Madeline
AU - Miller, Myron
AU - Packer, Milton
N1 - Funding Information:
From the aDivisiono f CirculatoryP hysiology, Collegeo f Physicians & Sm~ geons, ColumbiaU niversity, and bMount Sinai School of Medicine. Dr. Krum was supported by a National Heart Foundation of Australia Overseas Research Fellowship. Received for publication Mar. 15, 1995; accepted June 16, 1995. Reprint requests: Henry Krum, MB, PhD, Departmento f Medicine, Austin Hospital, Heidelberg, Victoria 3084 Australia. Copyright © 1996 by Mosby-YearB ook, Inc. 0002-8703/96/$5.00 + O 411/68075 Plasma levels of the potent endothelial-derived peptide endothelin-1 and other neurohormonal vasoconstrictor factors are elevated in patients with congestive heart failure, t,2 These elevations may be of physiologic and prognostic significance. 3, 4 Furthermore, plasma levels ofendothelin-1 may be a marker of disease severity because levels have been found to be proportional to the severity of pulmonary hypertension in these patients. 5 However, the ability of plasma levels of endothelin-1 to reflect clinical efficacy of drug therapy for heart failure has not been previously determined. Accordingly, in the present study we measured changes in plasma levels of endothelin-1 in patients with heart failure in response to treatment with either placebo or the ~-blocker-vasodilator carvedilol. Administration of carvedilol resulted in significant improvements in functional, hemodynamic, and neurohormonal status in these patients.6 We determined whether changes in plasma endothelin-1 levels in response to treatment with carvedilol and placebo would parallel changes in clinical status after these treatments.
PY - 1996
Y1 - 1996
N2 - Plasma levels of endothelin-1 are elevated in patients with chronic heart failure; however, it is unknown whether changes in plasma endothelin-1 levels accurately reflect clinical response to therapy in these patients. To determine this, we measured plasma endothelin-1 in addition to functional, hemodynamic, and other neurohormonal parameters as part of a double-blind, placebo-controlled study of the β-blocker vasodilator carvedilol in patients with moderate to severe chronic heart failure. Patients were assigned (2:1 randomization) to receive carvedilol (25 mg twice daily, n = 10) or placebo (n=5) for 14 weeks, with evaluations made before and after therapy. Compared to patients receiving placebo, patients receiving carvedilol improved significantly as assessed by the parameters described. These changes were paralleled by significant falls in endothelin-1 with carvedilol (-2.1 + 3.8 pg/ml) in comparison to placebo (2.2 ± 3.9 pg/ml; p < 0.05 for between- group differences). Changes in endothelin-1 after treatment in both groups correlated significantly with changes in symptom severity, New York Heart Association class, 6-minute walk distance (r = 0.64 to 0.80; p < 0.05), hemodynamic parameters (ejection fraction, right atrial pressure, pulmonary artery diastolic pressure, pulmonary wedge pressure, right atrial pressure, and stroke volume index; r = 0.54 to 0.86; p < 0.05), and neurohormonal parameters (serum aldosterone end plasma norepinephrine (r = 0.74 to 9.76; p < 0.05). By stepwise regression analysis, change in endothelin-1 was an independent, noninvasive predictor of functional end hemodynamic responses to therapy in these patients. These findings suggest that endothelin-1 accurately reflects functional, hemodynamic, and neurohormonal responses to β-blocker therapy in patients with congestive heart failure. Measurement of endothelin-1 may therefore be a useful, noninvasive approach to the evaluation of clinical response to drug therapy in these patients.
AB - Plasma levels of endothelin-1 are elevated in patients with chronic heart failure; however, it is unknown whether changes in plasma endothelin-1 levels accurately reflect clinical response to therapy in these patients. To determine this, we measured plasma endothelin-1 in addition to functional, hemodynamic, and other neurohormonal parameters as part of a double-blind, placebo-controlled study of the β-blocker vasodilator carvedilol in patients with moderate to severe chronic heart failure. Patients were assigned (2:1 randomization) to receive carvedilol (25 mg twice daily, n = 10) or placebo (n=5) for 14 weeks, with evaluations made before and after therapy. Compared to patients receiving placebo, patients receiving carvedilol improved significantly as assessed by the parameters described. These changes were paralleled by significant falls in endothelin-1 with carvedilol (-2.1 + 3.8 pg/ml) in comparison to placebo (2.2 ± 3.9 pg/ml; p < 0.05 for between- group differences). Changes in endothelin-1 after treatment in both groups correlated significantly with changes in symptom severity, New York Heart Association class, 6-minute walk distance (r = 0.64 to 0.80; p < 0.05), hemodynamic parameters (ejection fraction, right atrial pressure, pulmonary artery diastolic pressure, pulmonary wedge pressure, right atrial pressure, and stroke volume index; r = 0.54 to 0.86; p < 0.05), and neurohormonal parameters (serum aldosterone end plasma norepinephrine (r = 0.74 to 9.76; p < 0.05). By stepwise regression analysis, change in endothelin-1 was an independent, noninvasive predictor of functional end hemodynamic responses to therapy in these patients. These findings suggest that endothelin-1 accurately reflects functional, hemodynamic, and neurohormonal responses to β-blocker therapy in patients with congestive heart failure. Measurement of endothelin-1 may therefore be a useful, noninvasive approach to the evaluation of clinical response to drug therapy in these patients.
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U2 - 10.1016/S0002-8703(96)90363-4
DO - 10.1016/S0002-8703(96)90363-4
M3 - Article
C2 - 8579030
AN - SCOPUS:0030023824
SN - 0002-8703
VL - 131
SP - 337
EP - 341
JO - American heart journal
JF - American heart journal
IS - 2
ER -