[Characteristics of action of various drugs blocking atrioventricular conduction (beta-blockers, verapamil, diltiazem) in constant fibrillation tachyarrhythmia. Is monotherapy optimal?].
OBJECTIVE
To characterize actions of beta-blockers and Ca antagonists (verapamil and diltiazem) on the rate, structure and parameters of ventricular rhythm variability in constant cardiac fibrillation (CCF) and to evaluate validity of monotherapy with these drugs.


METHODS
Thirty patients with CCF (mean age 64.5 +/- 9.5 years) received beta-blockers (n = 10, atenolol in a dose 50.0 +/- 23.2 mg/day or metoprolol in a dose 45.0 +/- 20.9 mg/day), verapamil (n = 10, 192.0 +/- 83.9 mg/day) and diltiazem (n = 10, 286.6 +/- 107.2 mg/day). The patients were studied with Holter ECG monitoring (Schiller MT-100, Switzerland) and high resolution ECG (electrocardioanalyser Cardis, Geolink-electronics, RF) with construction of periodograms of ff waves and interval histograms RR (IHrr), estimation of the rhythm variability (SDRR, rMSSD, PNN50).


RESULTS
Beta-blockers (atenolol, metoprolol), verapamil and diltiazem had no significant effect on the period of ff waves. The degree of a mean heart rate lowering decreased in the following order: beta-blockers-verapamil-diltiazem (30.1 +/- 12.5, 25.0 +/- 18.8 and 22.0 +/- 23.6 beat/min, differences are insignificant), this corresponded to the degree of Rrmin increase (0.12 +/- 0.04, 0.08 +/- 0.07 and 0.07-0.08). In CCF the inhibiting effect of beta-blockers and verapamil is substrate-dependent: the shorter baseline Rrmin (and higher heart rate), the more potent is the effect due to action of beta-blockers and verapamil (r = -0.58 and r = -0.57, p < 0.05) and reduction of a mean heart rate (r = -0.74 and r = -0.84, p < 0.05). Dependence of diltiazem effect on initial Rrmin is inverse. In contrast to Ca antagonists (verapamil, diltiazem), beta-blockers increased latent conduction manifesting in a significant rise of Rrmax, range of RR intervals (the difference between Rrmax and Rrmin) and in increased latent conduction (Rrmax/Rrmin) by 0.4 versus 0 and 0.1 in the groups on verapamil and diltiazem). In addition to insufficient shift RRmod, there appeared non-optimal rhythm structure--combination of a large number of short and long RR in small number of middle ones. Verapamil and diltiazem improved the rhythm pattern due to proportional increase of RRmin shift RRmod (r = 0.72 and r = 0.71, p < 0.05) and absence of a distinct effect on latent conduction. The between groups differences by SDRR, RMSSD and PNN50 dynamics were insignificant. Diltiazem in doses 360-480 mg/ day moderately increased latent conduction, but was low effective in the presence of early peak RR (0.28-0.46 s).


CONCLUSIONS
Monotherapy with AB-blocking drugs was possible only in patients with moderate tachycardia, no waves of fibrillation of large and middle periods (0.15 s and higher) and should be conducted under Rrmin control. In the other cases, the above drugs are either low effective or promote non-optimal rhythm structure. Therefore, combined therapy with AB-blocking drugs and cardiac glycosides is indicated for CCF patients.
Blagova
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D000319:Adrenergic beta-Antagonists / Q000627:therapeutic use*; D000328:Adult; D000368:Aged; D001262:Atenolol / Q000627:therapeutic use; D001283:Atrioventricular Node / Q000187:drug effects* / Q000503:physiopathology; D002121:Calcium Channel Blockers / Q000627:therapeutic use*; D004110:Diltiazem / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D015716:Electrocardiography, Ambulatory / Q000187:drug effects; D005260:Female; D006339:Heart Rate / Q000187:drug effects*; D006801:Humans; D008297:Male; D008790:Metoprolol / Q000627:therapeutic use; D008875:Middle Aged; D016896:Treatment Outcome; D014693:Ventricular Fibrillation / Q000188:drug therapy* / Q000503:physiopathology; D014700:Verapamil / Q000627:therapeutic use*
D000319:Adrenergic beta-Antagonists; D002121:Calcium Channel Blockers; D001262:Atenolol; D014700:Verapamil; D004110:Diltiazem; D008790:Metoprolol