QT interval

Lucy AdkinsonJuly 2013

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

ECG

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:QTc (msec) Male Female

Normal <430 <450

Borderline 430-450 450-470

Abnormal >450 >470

The significance of prolonged QTc

• Pro-arrhythmic state• Increased risk of ventricular arrythmia – Torsade de pointes

Long QT

• Inherited• Acquired:– Hypokalaemia/hypomagnesaemia– Drugs

• Cardiac disease – Bradycardia, LVH, Heart failure, recent

cardioversion from AF, ventricular arrhythmia

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

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

Which drugs?Drugs available associated with prolonged QT and torsade de pointes

Anti-arrhythmics•Amiodarone•Disopyramide•Sotalol

Antimicrobials•Macrolides: clarithromycin, erythromycin,

Antimalarials•Chloroquine

Psychotropic drugs•Chlorporomazine•Droperidol•Haloperidol•Pimozide

Misc•Aresenic•Domperidone•Methadone •Saquniavir•Toremifine

www.azcert.org

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

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

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

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

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