title: Rate-control drugs affect variability and irregularity measures of RR intervals in patients with permanent atrial fibrillation.
abstract: BACKGROUND
  Irregularity measures have been suggested as risk indicators in patients with atrial fibrillation (AF); however, it is not known to what extent they are affected by commonly used rate-control drugs. We aimed at evaluating the effect of metoprolol, carvedilol, diltiazem, and verapamil on the variability and irregularity of the ventricular response in patients with permanent AF.
  
  
  RESULTS
  Sixty patients with permanent AF were part of an investigator-blind cross-over study, comparing 4 rate-control drugs (diltiazem, verapamil, metoprolol, and carvedilol). We analyzed five 20-minute segments per patient: baseline and the 4 drug regimens. On every segment, heart rate (HR) variability and irregularity of RR series were computed. The variability was assessed as standard deviation, pNN20, pNN50, pNN80, and rMSSD. The irregularity was assessed by regularity index, approximate (ApEn), and sample entropy. A significantly lower HR was obtained with all drugs, the HR was lowest using the calcium channel blockers. All drugs increased the variability of ventricular response in respect to baseline (as an example, rMSSD: baseline 171 ± 47 milliseconds, carvedilol 229 ± 58 milliseconds; P < 0.05 vs. baseline, metoprolol 226 ± 66 milliseconds; P < 0.05 vs. baseline, verapamil 228 ± 84; P < 0.05 vs. baseline, diltiazem 256 ± 87 milliseconds; P < 0.05 vs. baseline and all other drugs). Only β-blockers significantly increased the irregularity of the RR series (as an example, ApEn: baseline 1.86 ± 0.13, carvedilol 1.92 ± 0.09; P < 0.05 vs. baseline, metoprolol 1.93 ± 0.08; P < 0.05 vs. baseline, verapamil 1.86 ± 0.22 ns, diltiazem 1.88 ± 0.16 ns).
  
  
  CONCLUSIONS
  Modification of AV node conduction by rate-control drugs increase RR variability, while only β-blockers affect irregularity.
authors.affiliation: Dipartimento di Elettronica, Informazione e Bioingegneria, Politecnico di Milano, Milano, Italy.
authors.forename: Valentina D A
authors.initials: VD
authors.lastname: Corino
authors.forename: Sara R
authors.initials: SR
authors.lastname: Ulimoen
authors.forename: Steve
authors.initials: S
authors.lastname: Enger
authors.forename: Luca T
authors.initials: LT
authors.lastname: Mainardi
authors.forename: Arnljot
authors.initials: A
authors.lastname: Tveit
authors.forename: Pyotr G
authors.initials: PG
authors.lastname: Platonov
mesh_terms: D058671:Adrenergic beta-1 Receptor Antagonists / Q000627:therapeutic use*; D000368:Aged; D000369:Aged, 80 and over; D000889:Anti-Arrhythmia Agents / Q000627:therapeutic use*; D001281:Atrial Fibrillation / Q000175:diagnosis / Q000188:drug therapy* / Q000503:physiopathology; D002121:Calcium Channel Blockers / Q000627:therapeutic use*; D002227:Carbazoles / Q000627:therapeutic use; D000077261:Carvedilol; D018592:Cross-Over Studies; D004110:Diltiazem / Q000627:therapeutic use; D015716:Electrocardiography, Ambulatory; D005260:Female; D006329:Heart Conduction System / Q000187:drug effects* / Q000503:physiopathology; D006339:Heart Rate / Q000187:drug effects*; D006801:Humans; D008297:Male; D008790:Metoprolol / Q000627:therapeutic use; D008875:Middle Aged; D009664:Norway; D011412:Propanolamines / Q000627:therapeutic use; D013997:Time Factors; D016896:Treatment Outcome; D014700:Verapamil / Q000627:therapeutic use
chemical_list: D058671:Adrenergic beta-1 Receptor Antagonists; D000889:Anti-Arrhythmia Agents; D002121:Calcium Channel Blockers; D002227:Carbazoles; D011412:Propanolamines; D000077261:Carvedilol; D014700:Verapamil; D004110:Diltiazem; D008790:Metoprolol
keywords: atrial fibrillation; calcium-channel blockers; entropy; irregularity; rate-control drugs; time domain parameters; variability; β-blockers