In recent years there has been considerable interest in the diagnosis and understanding of ventricular repolarisation, particularly the QT interval prolongation and abnormal T and T/U wave morphology associated with torsades de pointes. Advances in ion channel cloning have greatly improved our understanding of the role of ionic channels in mediating cardiac repolarisation. Unfortunately, it is increasingly recognised that a number of drugs, both those associated with altering repolarisation, and others for non-cardiac conditions can increase the propensity for polymorphic ventricular tachycardia, syncope and even ventricular fibrillation and sudden death.

In this volume, arrhythmia specialists from St. Georges Hospital Medical School, London discuss the mechanisms behind QT prolongation and torsades de pointes. They focus particularly on the risk of individual cardiac and non-cardiac drugs in provoking long QT syndrome, providing a comprehensive review which will be useful for all electrophysiologists treating polymorphic ventricular tachycardias, and will expose important regulatory issues for pharmaceutical authorities and for the wider medical community.

A. John Camm, MD, FRCP, FESC, FACC Professor of Clinical Cardiology and Head, Department of Cardiological Sciences, St. Georges Hospital Medical School, London

Marek Malik, PhD, MD, DSc, FACC, FECS Professor of Cardiac Electrophysiology, Department of Cardiological Sciences, St. Georges Hospital Medical School, London

Yee Guan Yap, BMedSci, MBBS, MRCP British Heart Foundation Research Fellow in Cardiology, Department of Cardiological Sciences, St. Georges Hospital Medical School, London

Preface vi

1 Introduction 1

2 Mechanisms of acquired QT prolongation and torsades de pointes 8

3 Measurement of the QT interval and repolarization assessment 24

4 Introduction to drug-induced long QT syndrome 60

5 Risk of QT prolongation and torsades de pointes with antiarrhythmic drugs 69

6 Risk of QT prolongation and torsades de pointes with antihistamines 87

7 Risk of QT prolongation and torsades de pointes with psychotropic drugs 102

8 Risk of QT prolongation and torsades de pointes with antimicrobial and antimalarial drugs 121

9 Risk of QT prolongation and torsades de pointes with prokinetics and miscellaneous other drugs 140

10 Acquired long QT syndrome secondary to cardiac conditions 163

11 Acquired long QT syndrome secondary to noncardiac conditions 171

12 Perspective on drug-induced repolarization changes 182

Index 191