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QT Interval

QT interval is measured from the beginning of the QRS complex 
to the end of the T wave on the ECG and represents the period from 
the onset of depolarisation to the completion of repolarisation of the ventricular myocardium

QTc interval of 450 ms ( men ) and 460 ms
( women ) are generally 
accepted as upper limits of normal

Recognized risk factor for the occurrence of cardiac arrhythmias
○ VT /TdP
○ syncope
○ sudden death Particularly torsades de pointes ( TdP )
○ polymorphic ventricular tachyarrhythmia
○ on ECG → continuous twisting of the vector of the QRS complex around isolelectric baseline
○ Marked feature of TdP is pronounced prolongation of the QT interval in the supraventricular beat preceding the arrhythmia
○ TdP can degenerate into ventricular fibrillation leading to sudden death Qt interval varies greatly and is affected by age , sex , sympathetic tone and diurnal pattern The magnitude of the ↑↑ in QT interval from baseline is also helpful in evaluating the risk.

QT interval is from the beginning of the QRS complex to the end of the T wave- so it represents the complete ventricular depolarisation and repolarisation phase QT prolongation usually happens when there is a delay between the onset of depolarization and the completion of repolarization -which increases the action potential duration.

A reduction of net repolarizing ion channel currents resulting in a prolonged repolarisation

QTc ( QT corrected ) QT interval is inversely proportional to heart rate ie
QT interval increases as HR falls QTc is the interval corrected for HR @ 60 Several formulas exist to correct the QT interval Drug induced TdP is more commonly seen with bradycardias

Do not use QT prolonging drugs in patients with known LQTS-Consider the risk of QT prolongation when starting a new medication-Assess for risk factors for
 QT prolongation and overall
 risk of drug 
induced QT prolongation-If patient at ↑↑ risk of QT prolongation or already taking a drug that can ↑↑ QT consider an alternative drug which does not affect QT-Not practical to consider an 
ECG every time a QT
 prolonging medication is prescribed-When risk of QT prolongation
 is high consider baseline ECG before starting the medication and when the new drug 
reaches steady state 
( five half lives )-QTC of 470 – 500 ms in men
 QTc of 480- 500 ms in women
 An increase in QTc >= 60 ms


 QTC > 500 ms

What happens QT interval is from the beginning of the QRS complex to the end of the T wave- so it represents the complete ventricular depolarisation and repolarisation phase QT prolongation usually happens when there is a delay between the onset of depolarization and the completion of repolarization -which increases the action potential duration.
A reduction of net repolarising ion channel currents resulting in a prolonged repolarisation
This can trigger oscillations of the membrane potential which can give rise to additional depolarisations during repolarisation phase – called as early afterdepolarisations 
( EADs )
When the amplitude of EADs reaches a critical threshold and involves a sufficiently large myocardial area -ectopic ventricular beats can ensue with TdP being the most common arrhythmia

Brilliant website for all QT related issues https://crediblemeds.org
registration needed for list- free when checked last.

Steps to assess the risk- Assess the medication risk –Consider using the website CredibleMeds The website can access online or use a web app. CredibleMeds classifies medications based on QT prolonging potential in 4 types.

There are numerous 
manual and automated approaches to measure the QT interval- most accurate way to measure is to use high 
resolution digital 12 lead 
ECG extracted from 
continuous 12-lead Holter monitoring

Review dose , route of administration and interactions –Risk is dose dependent – risk increases as a function of dose and plasma drug interactions Pharmacokinetic interactions can be checked via 
https://reference.medscape.com/drug-interactionchecker

Decide if an ECG is needed –Ensure that the automatic ECG machine-has correct patient data input as age and sex Consider an ECG if 
○ there is a h/o CVD or family h/o CVD
○ patient on high dose of anti-psychotic medications
○ patient has risk factors which may predispose to arrhythmia Indications for obtaining a baseline ECG and or routine / ECG monitoring prior to treatment with a QT prolonging medication is mixed in literature It is not practical to obtain an ECG each time a QT prolonging medication is prescribed

Can we minimize the risk –Optimise any identifiable & modifiable risk factor ( or factors ) Do not use a QT prolongation drug if known LQTS Assume that all anti-psychotics carry and increased risk of sudden cardiac death Consider using lowest dose possible of a QT prolonging drug is no other alternative is available

Assess the patients risk of QTc prolongation and TdP Consider the modifiable and non-modifiable risk factors Patients with underlying heart problems for e.g Long QT syndrome , myocardial infarction , cardiomyopathy , cardiac arrhythmia , bradycardia or CCF are more prone to affects of QT prolongation Tools as those developed by Tisdale can be used to assess individual risk

Cardiology advice –If seeking cardiology advice – collect the following data
 full list of prescribed medications has the patient reported faintness , near collapse or collapse episodes known cardiac history / conditions what was the patient’s heart rate and QTc before therapy prior to using a QT prolonging medication latest HR and QTc biochemical profile within last 2 weeks

References

 Drug Induced QT Interval Prolongation National Medicine Information Center Volume 21 Number 6 2015 Drug Induced QT Prolongation PostScriptExtra Issue 21 , December 2012 NHS Glasgow and Clyde Medicines Information Service The Clinical Evaluation of QT/QTc Interval Prolongation and Proarrhythmic Potential for Non-Antiarrhythmic European Medicines Agency November 2005 CHMP/ICH/2/04 Drug-induced QT interval prolongation : mechanisms and clinical management Ther Adv Drug Saf . 2012 Oct ; 3(5) : 241-253 Drug-Induced QTc Interval Prolongation : A Multicenter Study to Detect Drugs and Clinical Factors Involved in Every Day Practice Current Drug safety , 2016 , 11 , 86-98 QT Interval and drug therapy drug and Therapeutics Bulletin BMJ 2016 ; 353 :i2732 QT Interval Edward Burns from https://lifeinthefastlane.com/ecg-library/basics/qt_interval/ My Approach to the patient with a borderline long QT Interval Trends in Cardiovascular Medicine Roston Thomas MD October 1 , 2017 , Issue 7 . Pages 516-517 Long QT syndrome BMJ Best Practice Sudden Arrhythmia Death Syndrome : Importance of the Long QT Syndrome AAFP Drug and non drug – associated QT interval prolongation Br J Clin Pharmacol . 2010 Jul ; 70 ( 1) : 16-23 Website snapshot from https://crediblemeds.org


INFORMATION FOR CLINICIANS

Calculator -from MD Calc https://www.mdcalc.com/corrected-qt-interval-qtc

Credible Meds a wonderful resource https://www.crediblemeds.org/

A 35 page PP presentation by Dr Adrian Stanleyhttps://www.ukmi.nhs.uk/filestore/ukmiamt/ProlongedQTDrugsSept2015.pdf

References

  1. Lambiase, Pier D et al. “British Heart Rhythm Society Clinical Practice Guidelines on the Management of Patients Developing QT Prolongation on Antipsychotic Medication.” Arrhythmia & electrophysiology review vol. 8,3 (2019): 161-165. doi:10.15420/aer.2019.8.3.G1 
  2. Guidelines for the Management of QTc Prolongation in Adults Prescribed Antipsychotics NHS Tees , Esk and Wear Valleys NHS Foundation Trust https://www.england.nhs.uk/north/wp-content/uploads/sites/5/2018/12/QTc-flow-diagram-with-medications-final-Dec-17-A3-with-logos.pdf
  3. Giselle Sarganas, Edeltraut Garbe, Andreas Klimpel, Rolf C. Hering, Elisabeth Bronder, Wilhelm Haverkamp, Epidemiology of symptomatic drug-induced long QT syndrome and torsade de pointes in Germany, EP Europace, Volume 16, Issue 1, January 2014, Pages 101–108, https://doi.org/10.1093/europace/eut214
  4. Schwartz, Peter J et al. “Prevalence of the congenital long-QT syndrome.” Circulation vol. 120,18 (2009): 1761-7. doi:10.1161/CIRCULATIONAHA.109.863209 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2784143/
  5. Isbister, G.K. and Page, C.B. (2013), Clinical assessment of drug‐induced QT prolongation. Br J Clin Pharmacol, 76: 48-57. doi:10.1111/bcp.12040
  6. Management of prolonged Qt interval and torsades de pointes in the intoxicated patient
    A.A. Kan1*, D.W. de Lange1,2,3, D.W. Donker2, J. Meulenbelt  Netherlands The Journal of Medicine April 2014 , Vol 72 , No 3 , 119 http://www.njmonline.nl/getpdf.php?id=1423
  7. Zolezzi, M, and L Cheung. “A literature-based algorithm for the assessment, management, and monitoring of drug-induced QTc prolongation in the psychiatric population.” Neuropsychiatric disease and treatment vol. 15 105-114. 24 Dec. 2018, doi:10.2147/NDT.S186474
  8. ECG Basics from Healio com QT Interval https://www.healio.com/cardiology/learn-the-heart/ecg-review/ecg-interpretation-tutorial/qt-interval
  9. Gomez, Andrew T et al. “Evaluation and Management of Athletes With Long QT Syndrome.” Sports health vol. 8,6 (2016): 527-535. doi:10.1177/1941738116660294
  10. Drug Induced QT Interval Prolongation National Medicine Information Center Volume 21 Number 6 2015
  11. Drug Induced QT Prolongation Post ScriptExtra Issue 21 , December 2012
  12. NHS Glasgow and Clyde Medicines Information Service  The Clinical Evaluation of QT/QTc
  13. Interval Prolongation and Proarrhythmic Potential for Non-Antiarrhythmic European Medicines Agency November 2005 CHMP/ICH/2/04
  14. Drug-induced QT interval prolongation : mechanisms and clinical management Ther Adv Drug Saf . 2012 Oct ; 3(5) : 241-253
  15. Drug-Induced QTc Interval Prolongation : A Multicenter Study to Detect Drugs and Clinical Factors Involved in Every Day Practice Current Drug safety , 2016 , 11 , 86-98
  16. QT Interval and drug therapy drug and Therapeutics Bulletin BMJ 2016 ; 353 :i2732
  17. QT Interval Edward Burns from https://lifeinthefastlane.com/ecg-library/basics/qt_interval/
  18. My Approach to the patient with a borderline long QT Interval Trends in Cardiovascular Medicine Roston Thomas MD October 1 , 2017 , Issue 7 . Pages 516-517
  19. Long QT syndrome BMJ Best Practice Sudden Arrhythmia Death Syndrome
  20. Importance of the Long QT Syndrome AAFP Drug and non drug – associated
  21. QT interval prolongation Br J Clin Pharmacol . 2010 Jul ; 70 ( 1) : 16-23 
  22. McClelland, Justine, and Monica Mathys. “Evaluation of QTc prolongation and dosage effect with citalopram.” The mental health clinician vol. 6,4 165-170. 29 Jun. 2016, doi:10.9740/mhc.2016.07.165

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