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Changes in plasma endothelin-1 levels reflect clinical response to beta-blockade in chronic heart failure
H Krum1, A Gu, M Wilshire-Clement
1Division of Circulatory Physiology, College of Physicians & Surgeons, Columbia University, New York, N.Y., USA.
Insights
Plasma endothelin-1 levels decrease with carvedilol treatment, reflecting improved heart failure symptoms and function. This suggests endothelin-1 is a useful marker for assessing treatment response in chronic heart failure patients.
Area of Science:
- Cardiology
- Pharmacology
- Biomarkers
Background:
- Elevated plasma endothelin-1 is observed in chronic heart failure (CHF).
- The utility of endothelin-1 levels in reflecting clinical response to therapy in CHF remains unclear.
Purpose of the Study:
- To investigate if plasma endothelin-1 levels accurately reflect clinical response to carvedilol therapy in patients with moderate to severe CHF.
- To assess the correlation between endothelin-1 changes and functional, hemodynamic, and neurohormonal parameters.
Main Methods:
- A double-blind, placebo-controlled study involving 15 patients with moderate to severe CHF.
- Patients received either carvedilol (n=10) or placebo (n=5) for 14 weeks.
- Measurements included plasma endothelin-1, functional parameters (NYHA class, 6-minute walk), hemodynamic data, and neurohormonal markers.
Main Results:
- Carvedilol treatment led to significant improvements in functional, hemodynamic, and neurohormonal parameters compared to placebo.
- Patients receiving carvedilol showed significant reductions in plasma endothelin-1 levels.
- Changes in endothelin-1 correlated significantly with improvements in symptom severity, functional capacity, and hemodynamic measures.
Conclusions:
- Plasma endothelin-1 levels accurately reflect functional, hemodynamic, and neurohormonal responses to beta-blocker therapy in CHF patients.
- Endothelin-1 measurement offers a potentially useful, noninvasive method for evaluating clinical response to drug therapy in CHF.
Abstract:
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 beta-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 and plasma norepinephrine (r = 0.74 to 0.76; p < 0.05). By stepwise regression analysis, change in endothelin-1 was an independent, noninvasive predictor of functional and hemodynamic responses to therapy in these patients. These findings suggest that endothelin-1 accurately reflects functional, hemodynamic, and neurohormonal responses to beta-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.