The Effect of Antihistamine Cetirizine on Ventricular Repolarization in Congenital Long QT Syndrome

Anna-Mari Hekkala, M.D.; * Heikki Swan, Ph.D.; * Heikki Väänänen, M.Sc.; † Matti Viitasalo, Ph.D.; * Lauri Toivonen, Ph.D.*

Disclosures

J Cardiovasc Electrophysiol. 2007;18(7):691-695. 

In This Article

Abstract and Introduction

Abstract

Cetirizine and QT Interval in LQTS.
Introduction: Many drugs are known to block cardiac potassium channels, thus prolonging QT interval and predisposing to malignant arrhythmias. Patients with congenital long QT syndrome are particularly vulnerable, but usually electrophysiological effects of drugs have not been assessed in these patients at risk.
Methods: Fifteen asymptomatic patients with type 1 (LQT1), 15 patients with type 2 (LQT2) long QT syndrome, and 15 healthy volunteers took a placebo and cetirizine 10 mg. In addition, healthy volunteers took cetirizine 50 mg. The study was single-blinded and randomized. Exercise tests were performed during stable plasma concentrations. The electrocardiogram was recorded with a body surface potential mapping system (BSPM). Data were analyzed with an automated analyze program. QT intervals to the T wave apex and T wave end and their difference (Tp-e) were determined at rest and at specified heart rates during and after exercise.
Results: Cetirizine did not lengthen the QT intervals at rest or during exercise and recovery in any group. It shortened Tp-e at rest in LQT1 and LQT2 patients and during exercise test in LQT1 patients, thus slightly decreasing electrocardiographic transmural dispersion of repolarization.
Conclusions: Cetirizine does not adversely modify ventricular repolarization in types 1 and 2 long QT syndrome, suggesting that it might be used safely in these long QT syndrome patients.

Introduction

Patients with long QT syndrome have an abnormal cardiac repolarization, which exposes them to malignant arrhythmias. A number of pharmaceutical compounds have an affinity to the cardiac potassium channel responsible for the repolarizing IKr current. Long QT syndrome patients have increased risk for drug-induced pro-arrhythmia upon the administration of IKr-blocking agents. The clinical safety studies usually exclude patients with pre-existing cardiac repolarization abnormalities. Thus, risks of medical treatment of non-cardiac disorders in long QT syndrome are insufficiently known.

Terfenadine and astemizole were widely used second-generation H1 blockers in the 1980s and 1990s because of minimal sedative effects. Later they were reported to have potentially fatal cardiac side effects,[1,2] due to blockade of cardiac potassium current IKr,[3] which resulted in the risk of torsade de pointes ventricular tachycardia.[4,5] Soon thereafter, terfenadine and astemizole were suspended in several European countries and by the Food and Drug Administration (FDA) in the USA.[6,7]

Antihistamines are often necessary to use in the treatment of hay fever and other allergies in patients with long QT syndrome. To study the safety of one of the third-generation antihistamines for long QT syndrome patients, we tested cetirizine in patients with known defects in ventricular repolarization. Cetirizine has been shown not to have an influence on potassium currents at clinically used concentrations in in vitro models,[8,9] or produce torsades de pointes in in vivo animal models[10] or human cohort study.[11]

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