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Neurohormonal activation in heart failure after acute myocardial infarction treated with beta-receptor antagonists
Hans Persson1, Karin Andréasson, Thomas Kahan
1Section of Cardiology, Division of Internal Medicine, Karolinska Institutet Danderyd Hospital, S-182 88, Stockholm, Sweden. hans.persson@med.ds.sll.se
Insights
Beta-receptor antagonists like metoprolol decreased neurohormonal activity in heart failure patients post-myocardial infarction. Elevated NPY-LI and N-ANF levels at discharge predicted long-term cardiovascular mortality.
Area of Science:
- Cardiology
- Pharmacology
- Biochemistry
Background:
- Limited research exists on neurohormonal activation post-myocardial infarction (MI) with heart failure (HF) treated by beta-receptor antagonists.
- Investigating the impact of beta(1) receptor antagonists versus agonists on neurohormonal markers is crucial for HF management.
Purpose of the Study:
- To describe neurohormonal activity in HF patients after MI.
- To compare the effects of metoprolol (beta(1) antagonist) and xamoterol (partial beta(1) agonist) on neurohormonal markers.
Main Methods:
- A double-blind, randomized trial compared metoprolol (n=74) and xamoterol (n=67) in post-MI HF patients.
- Plasma levels of catecholamines, neuropeptide Y-like immunoreactivity (NPY-LI), renin activity, and N-terminal pro-atrial natriuretic factor (N-ANF) were measured.
- Clinical and echocardiographic data were collected at baseline and 3 months.
Main Results:
- N-terminal pro-atrial natriuretic factor (N-ANF) correlated closely with HF severity indicators.
- Metoprolol and xamoterol reduced catecholamines, dopamine, and renin activity.
- Metoprolol increased NPY-LI and N-ANF, while xamoterol decreased N-ANF.
Conclusions:
- Beta-receptor antagonists reduced sympathetic nervous system and renin-angiotensin system activity in HF patients post-MI.
- Elevated NPY-LI and N-ANF at discharge were associated with increased long-term cardiovascular mortality.
- Changes in N-ANF may relate to cardiac preload, renal function, and beta-receptor mediated effects.
Background:
Few studies have described how neurohormonal activation is influenced by treatment with beta-receptor antagonists in patients with heart failure after acute myocardial infarction. The aims were to describe neurohormonal activity in relation to other variables and to investigate treatment effects of a beta(1) receptor-antagonist compared to a partial beta(1) receptor-agonist.
Methods:
Double-blind, randomized comparison of metoprolol 50-100 mg b.i.d. (n=74), and xamoterol 100-200 mg b.i.d (n=67). Catecholamines, neuropeptide Y-like immunoreactivity (NPY-LI), renin activity, and N-terminal pro-atrial natriuretic factor (N-ANF) were measured in venous plasma before discharge and after 3 months. Clinical and echocardiographic variables were assessed.
Results:
N-ANF showed the closest correlations to clinical and echocardiographic measures of heart failure severity, e.g. NYHA functional class, furosemide dose, exercise tolerance, systolic and diastolic function. Plasma norepinephrine, dopamine and renin activity decreased after 3 months on both treatments, in contrast to a small increase in NPY-LI which was greater (by 3.9 pmol/l, 95% CI 1.2-6.6) in the metoprolol group. N-ANF increased on metoprolol, and decreased on xamoterol (difference: 408 pmol/l, 95% CI 209-607). Increase above median of NPY-LI (>25.2 pmol/l, odds ratio 2.8, P=0.0050) and N-ANF (>1043 pmol/l, odds ratio 2.8, P=0.0055) were related to long term (mean follow-up 6.8 years) cardiovascular mortality.
Conclusions:
Decreased neurohormonal activity, reflecting both the sympathetic nervous system and the renin-angiotensin system, was found 3 months after an acute myocardial infarction with heart failure treated with beta-receptor antagonists. The small increase in NPY-LI may suggest increased sympathetic activity or reduced clearance from plasma. The observed changes of N-ANF may be explained by changes in cardiac preload, renal function, and differences in beta-receptor mediated inhibition of atrial release of N-ANF. NPY-LI, and N-ANF at discharge were related to long term cardiovascular mortality.