[Clinical, hemodynamic and neurohumoral effects of long-term therapy of patients with severe chronic heart failure with beta-adrenoblocker bisoprolol].
The use of beta-adrenoblockers in conjunction with angiotensin converting enzyme inhibitors improves quality of life and prognosis of patients with chronic heart failure. However basic mechanisms of these positive effects in severe heart failure remain to be elucidated.


METHODS
Patients (n=54) with NYHA class III-IV heart failure and left ventricular ejection fraction < or =35% were randomized either to treatment with bisoprolol (1.25-10 mg/day) (n=30) or in control group (n=24) and were followed up for 12 months.


RESULTS
The use of bisoprolol was associated with significant improvement of heart failure functional class, lowering of heart rate (by 14%, p<0.01), elevation of systolic blood pressure (by 7.2+/-12.3 mm Hg, p<0.01) and increase of walking distance (by 30.1+/-29.0 m, p<0.01). No significant changes of these parameters occurred in control group. After 12 months increases of left ventricular end diastolic and end systolic volumes (by 85+/-69.2 and 71+/-51.5 ml, respectively, p<0.001) and of ejection fraction (by 5.7+/-7.3%, p<0.01) took place in bisoprolol treated patients. These changes were significantly (p<0.001) higher than those in control group. After 6 months of treatment with bisoprolol noradrenaline concentration fell from 533 to 402 pg/ml (p<0.05) while in controls it rose from 369 to 474 pg/ml, p<0.01). Decreases of plasma renin activity (from 1.2 to 0.42 ng/ml/h), plasma concentrations of angiotensin II (from 17.1 to 13.1 pg/ml) and aldosterone (from 173 to 148 pg/ml, p<0.05) were also observed in bisoprolol group. No substantial dynamics of activity of main components of renin angiotensin system took place in controls. There were no significant changes of atrial natriuretic peptide in both groups. Significant positive dynamics of parameters of heart rate variability was registered only in bisoprolol group: SDNN increased by 25% (p<0.05), high frequency spectrum by 106% (p=0.03), LF/HF ratio from 2.18+/-1.41 to 1.82+/-0.7.


CONCLUSIONS
Long term use of bisoprolol was associated with improved clinical and hemodynamic status, increased systolic BP, blocked processes of pathological left ventricular remodeling, lowered activity of not only sympathetic-adrenal but also of main components of renin-angiotensin system and improved heart rate variability.
Belenkov
Iu N
IuN
Cardiology Research Complex, A. L. Myasnikov Institute of Clinical Cardiology, ul. Tretiya Cherepkovskaya 15a, 121552 Moscow, Russia.
Skvortsov
A A
AA
Mareev
V Iu
VIu
Nasonova
S N
SN
Sychev
A V
AV
Narusov
O Iu
OIu
Baklanova
N A
NA
Masenko
V P
VP
D000319:Adrenergic beta-Antagonists / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D000328:Adult; D000368:Aged; D017298:Bisoprolol / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D001794:Blood Pressure / Q000187:drug effects; D004452:Echocardiography; D005260:Female; D005500:Follow-Up Studies; D006333:Heart Failure / Q000175:diagnosis / Q000188:drug therapy*; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D008297:Male; D008875:Middle Aged; D018377:Neurotransmitter Agents; D012084:Renin-Angiotensin System / Q000187:drug effects; D013997:Time Factors
D000319:Adrenergic beta-Antagonists; D018377:Neurotransmitter Agents; D017298:Bisoprolol