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{{Short description|Measurement made on an electrocardiogram}}
{{Infobox medical intervention
 | Name        = QT interval
 | Image       = File:QT interval.jpg
 | Caption     = [[Electrocardiography|Electrocardiogram]] showing QT interval calculated by tangent method
 | ICD10       = R94.31
 | ICD9        = 89.52
 | MeshID      = D004562
 | MedlinePlus = 003868
 | OtherCodes  =
}}

The '''QT interval''' is a measurement made on an [[Electrocardiography|electrocardiogram]] used to assess some of the electrical properties of the [[heart]].  It is calculated as the time from the start of the [[QRS complex|Q wave]] to the end of the [[T wave]], and approximates to the time taken from when the [[Ventricle (heart)|cardiac ventricles]] start to contract to when they finish relaxing. An abnormally long or abnormally short QT interval is associated with an increased risk of developing [[Heart arrhythmia|abnormal heart rhythms]] and [[Cardiac arrest|sudden cardiac death]]. Abnormalities in the QT interval can be caused by [[Genetics|genetic]] conditions such as [[long QT syndrome]], by certain medications such as [[fluconazole]], [[sotalol]] or [[pitolisant]], by disturbances in the concentrations of certain [[Electrolyte|salts]] within the blood such as [[Hypokalemia|hypokalaemia]], or by [[Endocrine disease|hormonal imbalances]] such as [[hypothyroidism]].

==Measurement==
[[File:QT interval measurement.jpg|left|thumb|Illustrations of the tangent and threshold methods of measuring the QT interval]]
The QT interval is most commonly measured in [[Electrocardiography#Electrodes and leads|lead]] II for evaluation of serial ECGs, with leads I and V5 being comparable alternatives to lead II. Leads III, aVL and V1 are generally avoided for measurement of QT interval.<ref name="interval">{{cite journal | vauthors = Panicker GK, Salvi V, Karnad DR, Chakraborty S, Manohar D, Lokhandwala Y, Kothari S | title = Drug-induced QT prolongation when QT interval is measured in each of the 12 ECG leads in men and women in a thorough QT study | journal = Journal of Electrocardiology | volume = 47 | issue = 2 | pages = 155–157 | year = 2014 | pmid = 24388488 | doi = 10.1016/j.jelectrocard.2013.11.004 }}</ref> The accurate measurement of the QT interval is subjective<ref name="subjective">{{cite journal | vauthors = Panicker GK, Karnad DR, Joshi R, Shetty S, Vyas N, Kothari S, Narula D | title = Z-score for benchmarking reader competence in a central ECG laboratory | journal = Annals of Noninvasive Electrocardiology | volume = 14 | issue = 1 | pages = 19–25 | date = January 2009 | pmid = 19149789 | pmc = 6932360 | doi = 10.1111/j.1542-474X.2008.00269.x }}</ref> because the end of the T wave is not always clearly defined and usually merges gradually with the baseline. QT interval in an ECG complex can be measured manually by different methods, such as the threshold method, in which the end of the T wave is determined by the point at which the component of the T wave merges with the isoelectric baseline, or the tangent method, in which the end of the T wave is determined by the intersection of a tangent line extrapolated from the T wave at the point of maximum downslope to the isoelectric baseline.<ref name="tangent method">{{cite journal | vauthors = Panicker GK, Karnad DR, Natekar M, Kothari S, Narula D, Lokhandwala Y | title = Intra- and interreader variability in QT interval measurement by tangent and threshold methods in a central electrocardiogram laboratory | journal = Journal of Electrocardiology | volume = 42 | issue = 4 | pages = 348–352 | year = 2009 | pmid = 19261293 | doi = 10.1016/j.jelectrocard.2009.01.003 }}</ref>

With the increased availability of digital ECGs with simultaneous 12-channel recording, QT measurement may also be done by the 'superimposed median beat' method. In the superimposed median beat method, a median ECG complex is constructed for each of the 12 leads. The 12 median beats are superimposed on each other and the QT interval is measured either from the earliest onset of the Q wave to the latest offset of the T wave or from the point of maximum convergence for the Q wave onset to the T wave offset.<ref name="offset">{{cite journal | vauthors = Salvi V, Karnad DR, Panicker GK, Natekar M, Hingorani P, Kerkar V, Ramasamy A, de Vries M, Zumbrunnen T, Kothari S, Narula D | display-authors = 6 | title = Comparison of 5 methods of QT interval measurements on electrocardiograms from a thorough QT/QTc study: effect on assay sensitivity and categorical outliers | journal = Journal of Electrocardiology | volume = 44 | issue = 2 | pages = 96–104 | year = 2011 | pmid = 21238976 | doi = 10.1016/j.jelectrocard.2010.11.010 }}</ref>

==Correction for heart rate==
The QT interval changes in response to the [[heart rate]] - as heart rate increase the QT interval shortens.  These changes make it harder to compare QT intervals measured at different heart rates.  To account for this, and thereby improve the reliability of QT measurement, the QT interval can be corrected for heart rate (QTc) using  a variety of mathematical formulae, a process often performed automatically by modern ECG recorders.

===Bazett's formula===
The most commonly used QT correction formula is the ''Bazett's formula'',<ref name="Bazett-1920">{{cite journal | vauthors = Bazett HC | title=An analysis of the time-relations of electrocardiograms | journal=Heart | year=1920 | issue=7 | pages=353–370}}</ref> named after [[physiologist]] [[Henry Cuthbert Bazett]] (1885–1950),<ref>{{cite journal | vauthors = Roguin A | title = Henry Cuthbert Bazett (1885-1950)--the man behind the QT interval correction formula | journal = Pacing and Clinical Electrophysiology | volume = 34 | issue = 3 | pages = 384–388 | date = March 2011 | pmid = 21091739 | doi = 10.1111/j.1540-8159.2010.02973.x | s2cid = 43739886 }}</ref> calculating the heart rate-corrected QT interval (QTcB).

Bazett's formula is based on observations from a study in 1920. 
Bazett's formula is often given in a form that returns QTc in dimensionally suspect units, square root of seconds. The dimensionally correct form of Bazett's formula is:

: <math>QTc_B = {QT \over \sqrt{RR\over 1\text{ s}}}</math>

where QTc<sub>B</sub> is the QT interval corrected for heart rate, and RR is the interval from the onset of one [[QRS complex]] to the onset of the next QRS complex. This dimensionally correct formula returns the QTc in the same units as QT, generally milliseconds.<ref name="molnar1995">{{cite journal | vauthors = Molnar J, Weiss JS, Rosenthal JE | title = The missing second: what is the correct unit for the Bazett corrected QT interval? | journal = The American Journal of Cardiology | volume = 75 | issue = 7 | pages = 537–538 | date = March 1995 | pmid = 7864010 | doi = 10.1016/S0002-9149(99)80603-1 }}</ref>

In some popular forms of this formula, it is assumed that QT is measured in milliseconds and that RR is measured in seconds, often derived from the heart rate (HR) as 60/HR. Therefore, the result will be given in seconds per square root of milliseconds.<ref name="low heart rates">{{cite journal | vauthors = Salvi V, Karnad DR, Panicker GK, Kothari S | title = Update on the evaluation of a new drug for effects on cardiac repolarization in humans: issues in early drug development | journal = British Journal of Pharmacology | volume = 159 | issue = 1 | pages = 34–48 | date = January 2010 | pmid = 19775279 | pmc = 2823350 | doi = 10.1111/j.1476-5381.2009.00427.x }}</ref> However, reporting QTc using this formula creates a "requirement regarding the units in which the original QT and RR are measured."<ref name="molnar1995"/>

In either form, Bazett's non-linear QT correction formula is generally not considered accurate, as it over-corrects at high heart rates and under-corrects at low heart rates.<ref name="low heart rates"/> Bazett's correction formula is one of the most suitable QT correction formulae for neonates.<ref name="neonates">{{cite journal | vauthors = Stramba-Badiale M, Karnad DR, Goulene KM, Panicker GK, Dagradi F, Spazzolini C, Kothari S, Lokhandwala YY, Schwartz PJ | display-authors = 6 | title = For neonatal ECG screening there is no reason to relinquish old Bazett's correction | journal = European Heart Journal | volume = 39 | issue = 31 | pages = 2888–2895 | date = August 2018 | pmid = 29860404 | doi = 10.1093/eurheartj/ehy284 | doi-access = free }}</ref>

===Fridericia's formula===
[[Louis Sigurd Fridericia|Fridericia]]<ref name="Fridericia-1920">{{cite journal | vauthors=Fridericia LS | title=The duration of systole in the electrocardiogram of normal subjects and of patients with heart disease | journal=Acta Medica Scandinavica | year=1920 | issue=53 | pages=469–486| doi=10.1111/j.0954-6820.1920.tb18266.x }}</ref> had proposed an alternative correction formula (QTcF) using the cube-root of RR.

: <math>QTc_F = {QT \over \sqrt[3]{RR \over 1\text{ s}}}</math>

===Sagie's formula===
The Framingham correction, also called as Sagie's formula based on the [[Framingham Heart Study]], which used long-term cohort data of over 5,000 subjects, is considered a better<ref name=2014-2016>{{citation|title=Which QT Correction Formulae to Use for QT Monitoring?|vauthors=Vandenberk B, Vandael E, Robyns T, Vandenberghe J, Garweg C, Foulon V, Ector J, Willems R |journal=Journal of the American Heart Association|volume=5 |issue=6 |date=2016-06-17|doi=10.1161/JAHA.116.003264 |pmid=27317349 |pmc=4937268 }}</ref> method.<ref name="Sagie-1992">{{cite journal | vauthors = Sagie A, Larson MG, Goldberg RJ, Bengtson JR, Levy D | title = An improved method for adjusting the QT interval for heart rate (the Framingham Heart Study) | journal = The American Journal of Cardiology | volume = 70 | issue = 7 | pages = 797–801 | date = September 1992 | pmid = 1519533 | doi = 10.1016/0002-9149(92)90562-D }}<!--The following wikitext is based on {{Verify source}}-->{{fix
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: <math>QTlc = 1000\left(\frac{QT}{1000} + 0.154(1 - RR)\right)</math>

Again, here ''QT'' and ''QTlc'' are in milliseconds and ''RR'' is measured in seconds.

===Comparison of corrections===
A [[retrospective study]] suggests that Fridericia's method and the Framingham method may produce results most useful for stratifying the 30-day and 1-year risks of mortality.<ref name=2014-2016/>
[[File:QT interval corrected for heart rate.png|thumb|400px|Upper limit of normal QT interval, corrected for heart rate according to ''Bazett's formula'',<ref name="Bazett-1920"/> Fridericia's formula,<ref name="Fridericia-1920"/> and subtracting 0.02&nbsp;s from QT for every 10 bpm increase in heart rate.<ref name=Yanowitz/> Up to 0.42&nbsp;s (≤&nbsp;420&nbsp;ms) is chosen as normal QTc of QT<sub>B</sub> and QT<sub>F</sub> in this diagram.<ref name=ecglibrary>{{cite web|url=http://www.ecglibrary.com/norm.html|website=ecglibrary.com|title=A normal adult 12-lead ECG| vauthors = Jenkins D, Gerred S | access-date = 28 January 2018 }}</ref>]]

Definitions of normal QTc vary from being equal to or less than 0.40&nbsp;s (≤&nbsp;400&nbsp;ms),<ref name=Yanowitz>{{cite web | url = http://library.med.utah.edu/kw/ecg/ecg_outline/Lesson3/index.html | title = Lesson III. Characteristics of the Normal ECG | vauthors = Yanowitz FG | work = University of Utah School of Medicine | access-date = 23 March 2010 }}</ref> 0.41&nbsp;s (≤&nbsp;410&nbsp;ms),<ref>{{cite web | url = http://www.meddean.luc.edu/lumen/MedEd/MEDICINE/skills/ekg/les1prnt.htm | work = Loyola University Chicago Stritch School of Medicine | title = Medicine I | vauthors = Fitz M | access-date = 23 March 2010 }}</ref> 0.42&nbsp;s (≤&nbsp;420&nbsp;ms)<ref name=ecglibrary/> or 0.44&nbsp;s (≤&nbsp;440&nbsp;ms).<ref>{{cite web | url = http://www.cvphysiology.com/Arrhythmias/A009.htm | title = Image for Cardiovascular Physiology Concepts > Electrocardiogram (EKG, ECG) | vauthors = Klabunde RE }}</ref> For risk of [[sudden cardiac death]], "borderline QTc" in males is 431–450&nbsp;ms; and, in females, 451–470&nbsp;ms. An "abnormal" QTc in males is a QTc above 450&nbsp;ms; and, in females, above 470&nbsp;ms.<ref>{{cite web | url = http://www.medscape.com/viewarticle/522879 | work = CRM News | via = medscape.com  | title = QTc Prolongation and Risk of Sudden Cardiac Death: Is the Debate Over? | date = 3 February 2006 }}</ref>

If there is not a very high or low heart rate, the upper limits of QT can roughly be estimated by taking QT&nbsp;=&nbsp;QTc at a heart rate of 60 beats per minute (bpm), and subtracting 0.02&nbsp;s from QT for every 10&nbsp;bpm increase in heart rate. For example, taking normal QTc&nbsp;≤&nbsp;0.42&nbsp;s, QT would be expected to be 0.42&nbsp;s or less at a heart rate of 60&nbsp;bpm. For a heart rate of 70&nbsp;bpm, QT would roughly be expected to be equal to or below 0.40&nbsp;s. Likewise, for 80&nbsp;bpm, QT would roughly be expected to be equal to or below 0.38&nbsp;s.<ref name=Yanowitz/>

==Abnormal intervals==
Prolonged QTc causes premature action potentials during the late phases of depolarization. This increases the risk of developing ventricular arrhythmias, including fatal [[ventricular fibrillation]].<ref name="ReferenceA">{{cite journal | vauthors = Panoulas VF, Toms TE, Douglas KM, Sandoo A, Metsios GS, Stavropoulos-Kalinoglou A, Kitas GD | title = Prolonged QTc interval predicts all-cause mortality in patients with rheumatoid arthritis: an association driven by high inflammatory burden | journal = Rheumatology | volume = 53 | issue = 1 | pages = 131–137 | date = January 2014 | pmid = 24097136 | doi = 10.1093/rheumatology/ket338 | doi-access = free }}</ref> Higher rates of prolonged QTc are seen in females, older patients, high systolic blood pressure or heart rate, and short stature.<ref name="ReferenceB">{{cite journal | vauthors = Rossing P, Breum L, Major-Pedersen A, Sato A, Winding H, Pietersen A, Kastrup J, Parving HH | display-authors = 6 | title = Prolonged QTc interval predicts mortality in patients with Type 1 diabetes mellitus | journal = Diabetic Medicine | volume = 18 | issue = 3 | pages = 199–205 | date = March 2001 | pmid = 11318840 | doi = 10.1046/j.1464-5491.2001.00446.x | s2cid = 38600053 }}</ref> Prolonged QTc is also associated with ECG findings called [[Torsades de Pointes]], which are known to degenerate into ventricular fibrillation, associated with higher mortality rates. There are many causes of prolonged QT intervals, acquired causes being more common than genetic.<ref>{{cite journal | vauthors = van Noord C, Eijgelsheim M, Stricker BH | title = Drug- and non-drug-associated QT interval prolongation | journal = British Journal of Clinical Pharmacology | volume = 70 | issue = 1 | pages = 16–23 | date = July 2010 | pmid = 20642543 | pmc = 2909803 | doi = 10.1111/j.1365-2125.2010.03660.x }}</ref>

===Genetic causes===
[[File:QT distribution.png|thumb|Distribution of QT intervals amongst healthy males and females, and amongst those with congenital long QT syndrome]]
An abnormally prolonged QT interval could be due to [[long QT syndrome]], whereas an abnormally shortened QT interval could be due to [[short QT syndrome]].

The QTc length is associated with variations in the [[NOS1AP]] gene.<ref name="pmid16648850">{{cite journal | vauthors = Arking DE, Pfeufer A, Post W, Kao WH, Newton-Cheh C, Ikeda M, West K, Kashuk C, Akyol M, Perz S, Jalilzadeh S, Illig T, Gieger C, Guo CY, Larson MG, Wichmann HE, Marbán E, O'Donnell CJ, Hirschhorn JN, Kääb S, Spooner PM, Meitinger T, Chakravarti A | display-authors = 6 | title = A common genetic variant in the NOS1 regulator NOS1AP modulates cardiac repolarization | journal = Nature Genetics | volume = 38 | issue = 6 | pages = 644–651 | date = June 2006 | pmid = 16648850 | doi = 10.1038/ng1790 | s2cid = 12942685 }}</ref> The [[autosomal recessive]] syndrome of Jervell and Lange-Nielsen is characterized by a prolonged QTc interval in conjunction with [[sensorineural hearing loss]].

===Due to adverse drug reactions===
{{main|Drug-induced QT prolongation}}
Prolongation of the QT interval may be due to an [[adverse drug reaction]].<ref name="pimdpending">{{cite journal | vauthors = Leitch A, McGinness P, Wallbridge D | title = Calculate the QT interval in patients taking drugs for dementia | journal = BMJ | volume = 335 | issue = 7619 | pages = 557 | date = September 2007 | pmid = 17855324 | pmc = 1976518 | doi = 10.1136/bmj.39020.710602.47 }}</ref>

'''Antipsychotics''' (especially first generation/"typical")

* [[haloperidol]]<ref>{{cite web |url=https://www.fda.gov/cder/drug/InfoSheets/HCP/haloperidol.htm |title=Information for Healthcare Professionals: Haloperidol (marketed as Haldol, Haldol Decanoate and Haldol Lactate) |website=[[Food and Drug Administration]] |access-date=2007-09-18 |archive-url = https://web.archive.org/web/20071011025019/https://www.fda.gov/cder/drug/InfoSheets/HCP/haloperidol.htm <!-- Bot retrieved archive --> |archive-date = 2007-10-11}}</ref>
* [[thioridazine]]<ref name=":0">{{Cite journal | vauthors = Washington NB, Brahm NC, Kissack J |title=Which psychotropics carry the greatest risk of QTc prolongation? | journal = Current Psychiatry | date = 1 October 2012 | volume = 11 | issue = 10 | pages = 36–39 |url=https://www.mdedge.com/psychiatry/article/64870/anxiety-disorders/which-psychotropics-carry-greatest-risk-qtc-prolongation |access-date=2020-05-19}}</ref>
* [[mesoridazine]]<ref name=":0" />
* [[chlorpromazine]]<ref name=":0" /> 
* [[sertindole]]<ref>{{cite journal | vauthors = Lewis R, Bagnall AM, Leitner M | title = Sertindole for schizophrenia | journal = The Cochrane Database of Systematic Reviews | issue = 3 | pages = CD001715 | date = July 2005 | volume = 2005 | pmid = 16034864 | pmc = 7025766 | doi = 10.1002/14651858.CD001715.pub2 }}</ref>

'''DMARDs and antimalarial drugs'''

* [[hydroxychloroquine]]<ref name=":1">{{Cite web| vauthors = Malloy T |date=March 25, 2020|title=Guidance on patients at risk of drug-induced sudden cardiac death from off-label COVID-19 treatments|url=https://newsnetwork.mayoclinic.org/discussion/mayo-clinic-provides-urgent-guidance-approach-to-identify-patients-at-risk-of-drug-induced-sudden-cardiac-death-from-use-of-off-label-covid-19-treatments/|access-date=2020-05-19|website=Mayo Clinic News Network|language=en-US}}</ref>
* [[chloroquine]]<ref name=":1" />
* [[quinine]]<ref name=":1" />

'''Antibiotics'''

* [[macrolide]]s
* [[fluoroquinolone]]s<ref>{{cite journal | vauthors = Briasoulis A, Agarwal V, Pierce WJ | title = QT prolongation and torsade de pointes induced by fluoroquinolones: infrequent side effects from commonly used medications | journal = Cardiology | volume = 120 | issue = 2 | pages = 103–110 | date = 2011 | pmid = 22156660 | doi = 10.1159/000334441 | s2cid = 39533896 }}</ref>

'''Other drugs'''

* [[methadone]]<ref>{{cite web|title=Cardiotoxicity of methadone|url=http://www.dhp.virginia.gov/dhp_programs/pmp/docs/May2010/HaigneyCardiotoxicMethadone5-1-10.pdf| vauthors = Haigney M |work=Director of Cardiology|access-date=21 February 2013}}</ref>
* [[vemurafenib]]
* [[pitolisant]]<ref>https://wakix.com "WAKIX prolongs the QT interval; avoid use of WAKIX in patients with known QT prolongation or in combination with other drugs known to prolong QT interval."</ref>
* [[fluconazole]]

Some second-generation antihistamines, such as [[astemizole]], have this effect. The mechanism of action of certain antiarrhythmic drugs, like [[amiodarone]] or [[sotalol]], involve intentional pharmacological QT prolongation. In addition, high blood alcohol concentrations prolong the QT interval.<ref name="pmid17454831">{{cite journal | vauthors = Aasebø W, Erikssen J, Jonsbu J, Stavem K | title = ECG changes in patients with acute ethanol intoxication | journal = Scandinavian Cardiovascular Journal | volume = 41 | issue = 2 | pages = 79–84 | date = April 2007 | pmid = 17454831 | doi = 10.1080/14017430601091698 | s2cid = 11828588 | doi-access = free }}</ref> A possible interaction between [[selective serotonin reuptake inhibitor]]s and [[thiazide]] diuretics is associated with QT prolongation.<ref name="Tatonetti">{{cite journal | vauthors = Tatonetti NP, Ye PP, Daneshjou R, Altman RB | title = Data-driven prediction of drug effects and interactions | journal = Science Translational Medicine | volume = 4 | issue = 125 | pages = 125ra31 | date = March 2012 | pmid = 22422992 | pmc = 3382018 | doi = 10.1126/scitranslmed.3003377 }}</ref>

===Due to pathological conditions===
[[Hypothyroidism]], a condition of low function of the [[thyroid]] gland, can cause QT prolongation at the [[electrocardiogram]].  Acute hypocalcemia causes prolongation of the QT interval, which may lead to ventricular dysrhythmias.

A shortened QT can be associated with [[hypercalcemia]].<ref>{{cite web | vauthors = Skugor M | date = June 2019 | url = http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/endocrinology/hypercalcemia/ | title = Hypercalcemia | work = The Cleveland Clinic }}</ref>

===Use in drug approval studies===
Since 2005, the FDA and European regulators have required that nearly all new molecular entities be evaluated in a Thorough QT (TQT) or similar study to determine a drug's effect on the QT interval.<ref>{{cite web|url=https://www.fda.gov/downloads/RegulatoryInformation/Guidances/UCM129357.pdf |title= E14 Clinical Evaluation of QT/QTc Interval Prolongation and Proarrhythmic Potential for Non-Antiarrhythmic Drugs | work = Guidance for Industry
| date = October 2005 | publisher = U.S. [[Food and Drug Administration]] |access-date=December 9, 2009 |url-status=dead |archive-url= https://web.archive.org/web/20100306221451/https://www.fda.gov/downloads/RegulatoryInformation/Guidances/ucm129357.pdf |archive-date= March 6, 2010 }}</ref> The TQT study serves to assess the potential arrhythmia liability of a drug.  Traditionally, the QT interval had been evaluated by having an individual human reader measure approximately nine cardiac beats per clinical timepoint.  However, a substantial portion of drug approvals after 2010 have incorporated a partially automated approach, blending automated software algorithms with expert human readers reviewing a portion of the cardiac beats, to enable the assessment of significantly more beats in order to improve precision and reduce cost.<ref>{{cite web|url= http://appliedclinicaltrialsonline.findpharma.com/appliedclinicaltrials/News/iCardiac-Applies-Automated-Approach-to-Thorough-QT/ArticleStandard/Article/detail/560528?contextCategoryId=44906&ref=25|title=iCardiac Applies Automated Approach to Thorough QT Study for a Leading Pharmaceutical Company – Applied Clinical Trials|date=5 October 2011|access-date=19 March 2018|url-status=bot: unknown|archive-url=https://web.archive.org/web/20111005142032/http://appliedclinicaltrialsonline.findpharma.com/appliedclinicaltrials/News/iCardiac-Applies-Automated-Approach-to-Thorough-QT/ArticleStandard/Article/detail/560528?contextCategoryId=44906&ref=25|archive-date=5 October 2011}}</ref> In 2014, an industrywide consortium consisting of the FDA, [[iCardiac Technologies]] and other organizations released the results of a seminal study indicating how waivers from TQT studies can be obtained by the assessment of early phase data.<ref>{{Cite news| vauthors = Or A |date=2014-12-16|title=Norwest-Backed iCardiac to Expand Its Market Thanks to Breakthrough|language=en-US|work=Wall Street Journal|url=https://www.wsj.com/articles/DJFLBO0120141216eacgc9mjh|access-date=2021-01-26|issn=0099-9660}}</ref>  As the pharmaceutical industry has gained experience in performing TQT studies, it has also become evident that traditional QT correction formulas such as QTcF, QTcB, and QTcLC may not always be suitable for evaluation of drugs impacting autonomic tone.<ref>{{cite web | vauthors = Garnett C |title= CSRC White Paper: QT/QTc Evaluation for Drugs with Autonomic Effects | work = THEW Annual Meeting | date = 29 April 2009 |url=http://thew-project.org/document/2009%20THEW%20meeting/Garnett.pdf|access-date=6 June 2014}}</ref>

===As a predictor of mortality===
Electrocardiography is a safe and noninvasive tool that can be used to identify those with a higher risk of mortality. In the general population, there has been no consistent evidence that prolonged QTc interval in isolation is associated with an increase in mortality from cardiovascular disease.<ref>{{cite journal | vauthors = Montanez A, Ruskin JN, Hebert PR, Lamas GA, Hennekens CH | title = Prolonged QTc interval and risks of total and cardiovascular mortality and sudden death in the general population: a review and qualitative overview of the prospective cohort studies | journal = Archives of Internal Medicine | volume = 164 | issue = 9 | pages = 943–948 | date = May 2004 | pmid = 15136301 | doi = 10.1001/archinte.164.9.943 | doi-access =  }}</ref> However, several studies{{which|date=April 2014}} have examined prolonged QT interval as a predictor of mortality for diseased subsets of the population.

===Rheumatoid arthritis===
Rheumatoid arthritis is the most common inflammatory arthritis.<ref name="Solomon, D. 1307">{{cite journal | vauthors = Solomon DH, Karlson EW, Rimm EB, Cannuscio CC, Mandl LA, Manson JE, Stampfer MJ, Curhan GC | display-authors = 6 | title = Cardiovascular morbidity and mortality in women diagnosed with rheumatoid arthritis | journal = Circulation | volume = 107 | issue = 9 | pages = 1303–1307 | date = March 2003 | pmid = 12628952 | doi = 10.1161/01.cir.0000054612.26458.b2 | doi-access = free }}</ref> Studies have linked rheumatoid arthritis with increased death from cardiovascular disease.<ref name="Solomon, D. 1307"/>
In a 2014 study,<ref name="ReferenceA"/> Panoulas et al. found a 50&nbsp;ms increase in QTc interval increased the odds of all-cause mortality by 2.17 in patients with rheumatoid arthritis. Patients with the highest QTc interval (>&nbsp;424&nbsp;ms) had higher mortality than those with a lower QTc interval. The association was lost when calculations were adjusted for C-reactive protein levels. The researchers proposed that inflammation prolonged the QTc interval and created arrhythmias that were associated with higher mortality rates. However, the mechanism by which C-reactive protein is associated with the QTc interval is still not understood.

===Type 1 diabetes===
Compared to the general population, type 1 diabetes may increase the risk of mortality, due largely to an increased risk of cardiovascular disease.<ref name="ReferenceB"/><ref>{{cite journal | vauthors = Borch-Johnsen K, Andersen PK, Deckert T | title = The effect of proteinuria on relative mortality in type 1 (insulin-dependent) diabetes mellitus | journal = Diabetologia | volume = 28 | issue = 8 | pages = 590–596 | date = August 1985 | pmid = 4054448 | doi = 10.1007/bf00281993 | doi-access = free }}</ref> Almost half of patients with type 1 diabetes have a prolonged QTc interval (>&nbsp;440&nbsp;ms).<ref name="ReferenceB"/> Diabetes with a prolonged QTc interval was associated with a 29% mortality over 10 years in comparison to 19% with a normal QTc interval.<ref name="ReferenceB"/> Anti-hypertensive drugs increased the QTc interval, but were not an independent predictor of mortality.<ref name="ReferenceB"/>

===Type 2 diabetes===
QT interval dispersion (QTd) is the maximum QT interval minus the minimum QT interval, and is linked with ventricular repolarization.<ref>{{cite journal | vauthors = Okin PM, Devereux RB, Howard BV, Fabsitz RR, Lee ET, Welty TK | title = Assessment of QT interval and QT dispersion for prediction of all-cause and cardiovascular mortality in American Indians: The Strong Heart Study | journal = Circulation | volume = 101 | issue = 1 | pages = 61–66 | year = 2000 | pmid = 10618305 | doi = 10.1161/01.cir.101.1.61 | doi-access = free }}</ref> A QTd over 80&nbsp;ms is considered abnormally prolonged.<ref name="ReferenceC">{{cite journal | vauthors = Giunti S, Gruden G, Fornengo P, Barutta F, Amione C, Ghezzo G, Cavallo-Perin P, Bruno G | display-authors = 6 | title = Increased QT interval dispersion predicts 15-year cardiovascular mortality in type 2 diabetic subjects: the population-based Casale Monferrato Study | journal = Diabetes Care | volume = 35 | issue = 3 | pages = 581–583 | date = March 2012 | pmid = 22301117 | pmc = 3322722 | doi = 10.2337/dc11-1397 }}</ref> Increased QTd is associated with mortality in type 2 diabetes.<ref name="ReferenceC"/> 
QTd is a better predictor of cardiovascular death than QTc, which was unassociated with mortality in type 2 diabetes.<ref name="ReferenceC"/> QTd higher than 80&nbsp;ms had a relative risk of 1.26 of dying from cardiovascular disease compared to a normal QTd.

== See also ==
* [[Electrocardiogram]]
* [[Long QT syndrome]]
* [[Short QT syndrome]]
* [[QT interval variability]]
* [[Drug-induced QT prolongation]]

== References ==
{{Reflist|2}}

== External links ==
* [https://web.archive.org/web/20071020132100/http://www.biopharmnet.com/cardiac.html Cardiac safety section in the Biopharmaceutical network]
* [http://www.mdcalc.com/corrected-qt-interval-qtc/ Corrected QT interval calculation]
* [http://www.thecalculator.co/health/QTc-Calculator-385.html Comprehensive QTc Calculator with 5 formulas at TheCalculator.co]

{{Cardiovascular physiology}}

{{DEFAULTSORT:Qt Interval}}
[[Category:Cardiac electrophysiology]]
[[Category:Diagnostic cardiology]]