[Effect of long term therapy with spironolactone on parameters of 24-hour heart rhythm variability and ventricular arrhythmias in patients with heart failure receiving optimal therapy].
Aim of the investigation was the study of influence of spironolactone (25-75 mg/day) on clinico-functional and neurohormonal, 24-hour variability of cardiac rhythm, and ventricular disturbances of heart rhythm in patients with chronic heart failure (CHF) receiving optimal therapy. Forty nine patients were included in the study--44 men (89,8%) and 5 women (10.2%) in the age from 28 to 75 years with II-IV NYHA functional class (FC) CHF, LV ejection fraction (EF) 35%, plasma levels of creatinine 150 micromol/L and potassium 5 mmol/L. Main causes of development of CHF were dilated cardiomyopathy, ischemic heart disease (large focal postinfarction cardiosclerosis) and decompensated hypertensive heart [25/20/4 (51%/40.8%/8.2%), respectively]. As a result of randomization 2 groups of observation were formed: group 1-19 patients receiving spironolactone in a 24 hour dose 25-75 mg, group 2-control group-30 patients without therapy with spironolactone. Inhibitors of angiotensin converting enzyme (ACE) took 100%, beta-adrenoblockers--63.2% of patients. Control examination was conducted before randomization, in 6 and 12 months of follow up. During period of observation no changes of FC were noted in control group. In the spironolactone group after 6 months f treatment in 6 patients FC improved (p=0.028). By the end of follow up the given effect lost its significance, but in 5 (38.5%) patients by termination of the study FC II of CHF was noted, what was accompanied with moderate increase of distance walked during 6-minute walk test from 354 to 378 m. Addition of spironolactone to conducted therapy was followed by increase of concentration of aldosterone by 153 (84; 426) microg/ml, p=0.009, what discriminated (p=0.007) the given patients from control group and provoked increase of plasma rennin activity. Median concentration of angiotensin II changed not substantially [0.78 (-1.84; 2.66) mg/ml] after 12 months of treatment. Changes of noradrenalin, vasopressin, and endothelin were insignificant in both groups of observation. After 12 months of treatment median of changes of concentration of atrial natriuretic peptide was -51.9 ( -87; -43.9) microg/ml. At the same time in control group was observed gradual growth of concentrations of the given peptide from initial 107.3 to 168.5 microg/ml by the moment of termination of the study. Basic influence on spectral and temporal indexes of HRV spironolactone exerted in day time of 24 hours with increase of by 24.5 (10; 34) ms (p=0.042) after 6 months of treatment. Maximal lowering of number of ventricular extrasystoles from initial 75 (39; 477) to 12 (0; 15) (p=0.043) were achieved with administration of spironolactone in combination with ACE inhibitor and beta-adrenoblocker after 12 months of treatment what was followed with decrease of number of patients with episodes of of ventricular tachycardia from 50 to 18% (p=0.035). Addition of spironolactone in a dose of 75 mg/day to optimal therapy including ACE inhibitor and b-adrenoblocker is accompanied with betterment of clinical state and FC of patients with CHF.


CONCLUSIONS
Neurohormonal markers of application of spironolactone in combination with ACE inhibitor appear elevation of activity of plasma renin and concentration of aldosterone in combination with lowering of concentration of atrial natriuretic peptide in plasma of patients with CHF. Long term block of aldosterone at receptor level is accompanied with betterment of parameters of HRV in patients with CHF during day time. Addition of spironolactone to therapy with ACE inhibitor and beta-adrenoblocker bisoprolol decreases quantity and severity of ventricular rhythm disturbances in patients with moderate and severe CHF.
Skvortsov
A A
AA
Mareev
V Iu
VIu
Orlova
Ia A
IaA
Chelmakina
S M
SM
Baklanova
N A
NA
Belenkov
Iu N
IuN
D000328:Adult; D000368:Aged; D001145:Arrhythmias, Cardiac / Q000188:drug therapy / Q000453:epidemiology / Q000503:physiopathology; D015716:Electrocardiography, Ambulatory; D005260:Female; D006333:Heart Failure / Q000453:epidemiology*; D006339:Heart Rate / Q000502:physiology*; D006352:Heart Ventricles / Q000503:physiopathology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D000451:Mineralocorticoid Receptor Antagonists / Q000627:therapeutic use*; D008991:Monitoring, Physiologic; D013148:Spironolactone / Q000627:therapeutic use*; D013997:Time Factors
D000451:Mineralocorticoid Receptor Antagonists; D013148:Spironolactone