1. QT interval Lucy Adkinson July 2013

2. What we are going to cover • Reminder of ECGs and what is the QT interval • How to work out QTc • Why do we care? • What should we do or avoid? • Risk factors • Drugs • Methadone • General recommendations for practice • Evidence

3. ECG

4. Corrected QT : QTc • Adjust the QT for the heart rate • QTc : divide the QT interval by the square root of the preceding R-R interval • QTc = QT /√RR • Interpretation:

5. The significance of prolonged QTc • Pro-arrhythmic state • Increased risk of ventricular arrythmia • Torsade de pointes

6. Long QT • Inherited • Acquired: • Hypokalaemia/hypomagnesaemia • Drugs • Cardiac disease • Bradycardia, LVH, Heart failure, recent cardioversion from AF, ventricular arrhythmia

7. Drugs and torsades • Potassium channel blockade • Modifies repolarisation and prolongs action potential • 40 + drugs linked with QT and torsade • (not all that prolong QT, cause torsade) • Drug induced torsade is relatively rare – can be as high as 2-3% with some (high risk) drugs

8. Drugs and Torsade • Greatest with anti-arrhythmic drugs (class III) • Amiodarone, disopyramide, sotalol • In some drugs, risk only present with: • High doses • IV • Drug interaction • E.g. Ketoconazole inhibits CYP3A4 and impairs methadone metabolism • Impaired metabolism • E.g. CYP2D6 poor metabolisms may have high plasma concentrations of culprit drugs with normal doses • Hepatic or renal failure

9. Which drugs? www.azcert.org http://www.azcert.org/medical-pros/drug-lists/list-01.cfm?sort=Generic_name

10. Methadone • Prolongs QT – dose dependant and risk of torsade de pointes • Serious adverse events – more so than other opioids • FDA, 59 reports, 1 confirmed death from torsade • For practice • Role of ECG monitoring • Use in caution with: • History of cardiac conduction abnormalities • Ischaemic heart disease • Liver disease • Family history of sudden death • Electrolyte abnormailites (or drugs which cause this e.g. Diuretics) • Concurrent treatment with other drugs which potentially prolong QT, inhibit CYP3A4

11. Recommendations for practice • Be aware – polypharmacy in palliative care • But put in context • 300 patients in specialist palliative care unit • 48 (16%) had prolonged QT • Only 2 severely prolonged - >500msec • They both had IHD • Commonsense at end of life • If prescribing a drug: • Understand the pharmacology, drug-drug interaction, impaired elimination • Avoid concurrent use of QT prolonging drugs • Use lowest dose effective • If known prolonged QT avoid use of risk drugs • Cardiac disease (or other risk factors), avoid if possible • If no alternative, monitor ECG before and after and ensure electrolytes monitored • Report drugs which have prolonged QT to MHRA (yellow card) • Consider torsades as possible cause of palpitations, syncope, seizure like activity

12. Summary • Review cardiac history • Review drug history prior to any new drugs • Check out drugs in PCF/ online • Avoid multiple QT drugs • In particular haloperidol, methadone, domperidone, macrolide antibiotics

13. References • PCF – pages 727-733 • www.azcert.org • European Medicines Agency http://www.ema.europa.eu/ema/index.jsp?curl=pages/medicines/human/referrals/Domperidone-containing_medicines/human_referral_prac_000021.jsp&mid=WC0b01ac05805c516f