Different effects of antiarrhythmic drugs on the rate-dependency of QT interval

A study with amiodarone and flecainide

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

AIMS: To describe the QT/RR relationship in normal subjects, a previous study validated experimentally and used in healthy subjects a function that separately considered rate-dependent and rate-independent components of ventricular repolarization. The analysis is now extended to the effects on the QT/RR relationship of amiodarone and flecainide, 2 widely used antiarrhythmic drugs affecting repolarization. METHODS: The QT/RR relationship was obtained in 45 subjects without heart disease (20 men, 25 women); 20 were taken as controls, and 30 were under antiarrhythmic prophylaxis for lone atrial fibrillation (15 with amiodarone, 15 with flecainide). All subjects underwent a bicycle stress test; RR and QT (V5) were measured at the end of each load step; QTc (Bazett's formula, lead II) was obtained at rest. The QT/RR relation was fitted (R ≥ 0.90) by the function QT = QTmax*R/(RR50 + RR). Here, QTmax (QT extrapolated at infinite RR) is a rate-independent measure of repolarization, RR50 (RR at which 50% of QTmax is reached) and S evaluate the rate-dependency of QT. RESULTS: In controls, QTmax was 436 ± 67 ms, RR50 was 355 ± 55 ms, and S was 2.9 ± 0.2. Amiodarone increased QTc, QTmax, and RR50 and decreased S significantly. Flecainide slightly prolonged QTc, increased QTmax but did not modify RR50 or S. CONCULSIONS: The saturating dependency of human repolarization on cycle length, described by the proposed function, is differently affected by amiodarone and flecainide. These differences might reflect the specific effects of each drug on ionic currents and their properties.

Original languageEnglish
Pages (from-to)535-540
Number of pages6
JournalJournal of Cardiovascular Pharmacology
Volume50
Issue number5
DOIs
Publication statusPublished - Nov 2007

Fingerprint

Flecainide
Amiodarone
Anti-Arrhythmia Agents
Exercise Test
Atrial Fibrillation
Heart Diseases
Healthy Volunteers
Pharmaceutical Preparations

Keywords

  • Antiarrhythmic drugs
  • Heart rate
  • QT interval
  • Ventricular repolarization

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Pharmacology

Cite this

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title = "Different effects of antiarrhythmic drugs on the rate-dependency of QT interval: A study with amiodarone and flecainide",
abstract = "AIMS: To describe the QT/RR relationship in normal subjects, a previous study validated experimentally and used in healthy subjects a function that separately considered rate-dependent and rate-independent components of ventricular repolarization. The analysis is now extended to the effects on the QT/RR relationship of amiodarone and flecainide, 2 widely used antiarrhythmic drugs affecting repolarization. METHODS: The QT/RR relationship was obtained in 45 subjects without heart disease (20 men, 25 women); 20 were taken as controls, and 30 were under antiarrhythmic prophylaxis for lone atrial fibrillation (15 with amiodarone, 15 with flecainide). All subjects underwent a bicycle stress test; RR and QT (V5) were measured at the end of each load step; QTc (Bazett's formula, lead II) was obtained at rest. The QT/RR relation was fitted (R ≥ 0.90) by the function QT = QTmax*R/(RR50 + RR). Here, QTmax (QT extrapolated at infinite RR) is a rate-independent measure of repolarization, RR50 (RR at which 50{\%} of QTmax is reached) and S evaluate the rate-dependency of QT. RESULTS: In controls, QTmax was 436 ± 67 ms, RR50 was 355 ± 55 ms, and S was 2.9 ± 0.2. Amiodarone increased QTc, QTmax, and RR50 and decreased S significantly. Flecainide slightly prolonged QTc, increased QTmax but did not modify RR50 or S. CONCULSIONS: The saturating dependency of human repolarization on cycle length, described by the proposed function, is differently affected by amiodarone and flecainide. These differences might reflect the specific effects of each drug on ionic currents and their properties.",
keywords = "Antiarrhythmic drugs, Heart rate, QT interval, Ventricular repolarization",
author = "Gabriella Malfatto and Antonio Zaza and Mario Facchini",
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TY - JOUR

T1 - Different effects of antiarrhythmic drugs on the rate-dependency of QT interval

T2 - A study with amiodarone and flecainide

AU - Malfatto, Gabriella

AU - Zaza, Antonio

AU - Facchini, Mario

PY - 2007/11

Y1 - 2007/11

N2 - AIMS: To describe the QT/RR relationship in normal subjects, a previous study validated experimentally and used in healthy subjects a function that separately considered rate-dependent and rate-independent components of ventricular repolarization. The analysis is now extended to the effects on the QT/RR relationship of amiodarone and flecainide, 2 widely used antiarrhythmic drugs affecting repolarization. METHODS: The QT/RR relationship was obtained in 45 subjects without heart disease (20 men, 25 women); 20 were taken as controls, and 30 were under antiarrhythmic prophylaxis for lone atrial fibrillation (15 with amiodarone, 15 with flecainide). All subjects underwent a bicycle stress test; RR and QT (V5) were measured at the end of each load step; QTc (Bazett's formula, lead II) was obtained at rest. The QT/RR relation was fitted (R ≥ 0.90) by the function QT = QTmax*R/(RR50 + RR). Here, QTmax (QT extrapolated at infinite RR) is a rate-independent measure of repolarization, RR50 (RR at which 50% of QTmax is reached) and S evaluate the rate-dependency of QT. RESULTS: In controls, QTmax was 436 ± 67 ms, RR50 was 355 ± 55 ms, and S was 2.9 ± 0.2. Amiodarone increased QTc, QTmax, and RR50 and decreased S significantly. Flecainide slightly prolonged QTc, increased QTmax but did not modify RR50 or S. CONCULSIONS: The saturating dependency of human repolarization on cycle length, described by the proposed function, is differently affected by amiodarone and flecainide. These differences might reflect the specific effects of each drug on ionic currents and their properties.

AB - AIMS: To describe the QT/RR relationship in normal subjects, a previous study validated experimentally and used in healthy subjects a function that separately considered rate-dependent and rate-independent components of ventricular repolarization. The analysis is now extended to the effects on the QT/RR relationship of amiodarone and flecainide, 2 widely used antiarrhythmic drugs affecting repolarization. METHODS: The QT/RR relationship was obtained in 45 subjects without heart disease (20 men, 25 women); 20 were taken as controls, and 30 were under antiarrhythmic prophylaxis for lone atrial fibrillation (15 with amiodarone, 15 with flecainide). All subjects underwent a bicycle stress test; RR and QT (V5) were measured at the end of each load step; QTc (Bazett's formula, lead II) was obtained at rest. The QT/RR relation was fitted (R ≥ 0.90) by the function QT = QTmax*R/(RR50 + RR). Here, QTmax (QT extrapolated at infinite RR) is a rate-independent measure of repolarization, RR50 (RR at which 50% of QTmax is reached) and S evaluate the rate-dependency of QT. RESULTS: In controls, QTmax was 436 ± 67 ms, RR50 was 355 ± 55 ms, and S was 2.9 ± 0.2. Amiodarone increased QTc, QTmax, and RR50 and decreased S significantly. Flecainide slightly prolonged QTc, increased QTmax but did not modify RR50 or S. CONCULSIONS: The saturating dependency of human repolarization on cycle length, described by the proposed function, is differently affected by amiodarone and flecainide. These differences might reflect the specific effects of each drug on ionic currents and their properties.

KW - Antiarrhythmic drugs

KW - Heart rate

KW - QT interval

KW - Ventricular repolarization

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