QT interval
Lucy Adkinson
July 2013
What we are going to cover
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Reminder of ECGs and what is the QT interval
How to work out QTc
Why do we care?
What should we do or avoid?
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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
Psychotropic drugs
•Chlorporomazine
•Droperidol
•Haloperidol
•Pimozide
Antimicrobials
•Macrolides: clarithromycin,
erythromycin,
Antimalarials
•Chloroquine
Misc
•Aresenic
•Domperidone
•Methadone
•Saquniavir
•Toremifine
www.azcert.org
http://www.azcert.org/medical-pros/druglists/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:
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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
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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/Domperidonecontaining_medicines/human_referral_prac_000021.jsp&mid=WC0b01ac
05805c516f