Rate-control drugs affect variability and irregularity measures of RR intervals in patients with permanent atrial fibrillation

J Cardiovasc Electrophysiol. 2015 Feb;26(2):137-41. doi: 10.1111/jce.12580. Epub 2014 Dec 2.

Abstract

Introduction: 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.

Methods and 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).

Conclusion: Modification of AV node conduction by rate-control drugs increase RR variability, while only β-blockers affect irregularity.

Keywords: atrial fibrillation; calcium-channel blockers; entropy; irregularity; rate-control drugs; time domain parameters; variability; β-blockers.

Publication types

  • Comparative Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenergic beta-1 Receptor Antagonists / therapeutic use*
  • Aged
  • Aged, 80 and over
  • Anti-Arrhythmia Agents / therapeutic use*
  • Atrial Fibrillation / diagnosis
  • Atrial Fibrillation / drug therapy*
  • Atrial Fibrillation / physiopathology
  • Calcium Channel Blockers / therapeutic use*
  • Carbazoles / therapeutic use
  • Carvedilol
  • Cross-Over Studies
  • Diltiazem / therapeutic use
  • Electrocardiography, Ambulatory
  • Female
  • Heart Conduction System / drug effects*
  • Heart Conduction System / physiopathology
  • Heart Rate / drug effects*
  • Humans
  • Male
  • Metoprolol / therapeutic use
  • Middle Aged
  • Norway
  • Propanolamines / therapeutic use
  • Time Factors
  • Treatment Outcome
  • Verapamil / therapeutic use

Substances

  • Adrenergic beta-1 Receptor Antagonists
  • Anti-Arrhythmia Agents
  • Calcium Channel Blockers
  • Carbazoles
  • Propanolamines
  • Carvedilol
  • Verapamil
  • Diltiazem
  • Metoprolol