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Approach Considerations

Routinely check serum levels of potassium (and sometimes magnesium) and thyroid function in patients who present with QT prolongation after arrhythmic events, to eliminate secondary reasons for repolarization abnormalities.

Analysis of repolarization duration (QTc) and morphology on a patient's electrocardiogram (ECG) and on the ECGs of the patient's relatives frequently leads to an accurate diagnosis.

Hinterseer et al found that increased short-term variability of the QT interval—ie, STV(QT)—in symptomatic patients with congenital long QT syndrome (LQTS) could be a useful noninvasive additive marker for diagnostic screening to bridge the gap while waiting for results of genetic testing.^[19] This study is the first in humans to observe this association.

Imaging studies

Imaging studies (eg, echocardiography, magnetic resonance imaging [MRI]) may help only in excluding other potential reasons for arrhythmic events (eg, hypertrophic cardiomyopathy, arrhythmogenic right ventricular cardiomyopathy) or associated congenital heart diseases in a small subset of patients with LQTS, such as persons with LQT8.

Diagnostic criteria

A presentation with syncope or sudden cardiac death, in combination with a long QT interval on an ECG, typically suggests long QT syndrome (LQTS) and leads to genetic testing to diagnose the disease. In many patients, however, the presentation may not be typical. Therefore, other tests may be indicated.

Schwartz et al suggested diagnostic criteria for LQTS in 1993 that still serve as the best criteria for clinicians.^[20]In their model, the criteria are divided to three main categories, as shown in Table 2, below. The maximum score is 9—A score above 3 indicates a high probability of LQTS.

Table 2. Diagnostic Criteria for LQTS (Open Table in a new window)

Criterion	Points
Electrocardiogram findings ^*
QTc, ms^†	>480	3
	460-469	2
	450-459 in male patient	1
Torsade de pointes^‡		2
T-wave alternans		1
Notched T wave in 3 leads		1
Low heart rate for age^§		0.5
Clinical history
Syncope^║	With stress	2
	Without stress	1
Congenital deafness		0.5
Family history ^¶
A. Family members with definite LQTS^#		1
B. Unexplained sudden cardiac death at age <30 years in an immediate family member		0.5
LQTS = long QT syndrome. ^*In the absence of medications or disorders known to affect these electrocardiographic features. ^†QTc calculated by Bazett's formula. ^‡Mutually exclusive. ^§Resting heart rate below the second percentile for age. ^\|\|Mutually exclusive. ^¶The same family member cannot be counted in both A and B. ^#Definite LQTS is defined by an LQTS score above 3 (≥4).

Electrocardiography

As the criteria for long QT syndrome (LQTS) by Schwartz et al suggest, the most helpful electrocardiographic (ECG) findings are prolongation of the QT interval, the presence of torsade de pointes, the presence of T-wave alternans, and the presence of certain morphology of the T waves (wide-based T wave, and notched T wave in three leads).

Correlation between the type of mutation and T-wave morphology has been suggested. Wide-based T waves are most frequently seen in LQT1, whereas notched T waves are most commonly seen in LQT2. In LQT3, T waves may appear normal, with a long, isoelectric ST segment.

T-wave analysis also appears to have the potential to differentiate acquired QT prolongation from congenital LQTS,^[21] as well as help identify on-therapy breakthrough arrhythmic risk in LQT1 and LQT2.^[22] Using an automated T-wave analysis program to retrospectively evaluate 12-lead ECGs of 38 patients with congenital LQTS and 114 patients with drug-induced and/or electrolyte-mediated QT prolongation, Sugrue et al noted the following differences in lead V₅ of those with acquired QT prolongation could distinguish these individuals from patients with congenital LQTS in 77% of cases (90% sensitivity, 58% specificity)^[21]:

Shallower T-wave right slope
Larger T-peak to T-end interval
Smaller T-wave center of gravity on the x axis

The same investigators used a T-wave analysis program to evaluate ECGs from 407 genetically confirmed patients with LQT1 (n = 246) and LQT2 (n = 161) over a mean follow-up of 6.4 ± 3.9 years and found two independent predictors of future LQTS-associated cardiac events were left slope of T waves in lead V₆ and a T-wave center of gravity on the x axis in lead I, particularly in patients with LQTS2.^[22]

Prolongation of the QTc interval is defined on the basis of age- and sex-specific criteria (see Table 3, below). QTc is calculated by dividing the measured QT by the square root of the R-R interval, both of which are measured in seconds. QTc prolongation longer than 0.46 seconds indicates an increased likelihood of LQTS. (See the image below.)

Marked prolongation of QT interval in a 15-year-old male adolescent with long QT syndrome (LQTS) (R-R = 1.00 s, QT interval = 0.56 s, QT interval corrected for heart rate [QTc] = 0.56 s). Abnormal morphology of repolarization can be observed in almost every lead (ie, peaked T waves, bowing ST segment). Bradycardia is a common feature in patients with LQTS.

View Media Gallery

However, approximately 10-15% of gene-positive patients with LQTS present with a QTc duration in the reference range. (See the image below.)

Genetically confirmed long QT syndrome (LQTS) with borderline values of QT corrected for heart rate (QTc) duration (R-R = 0.68 s, QT interval = 0.36 s, QT interval corrected for heart rate [QTc] = 0.44 s) in a 12-year-old girl. Note the abnormal morphology of the T wave (notches) in leads V2-V4.

View Media Gallery

Table 3. Definition of QTc Based on Age- and Sex-Specific Criteria (Open Table in a new window)

Group	Prolonged QTc, sec	Borderline QTc, sec	Reference Range, sec
Children and adolescents (<15 years)	>0.46	0.44-0.46	<0.44
Men	>0.45	0.43-0.45	<0.43
Women	>0.46	0.45-0.46	<0.45

In patients with suspected LQTS with borderline QTc values (or even values in the reference range) on standard ECGs or in patients with a score of 2-3 based on the 1993 Schwartz et al diagnostic criteria, an analysis of the dynamic behavior of QTc duration during exercise ECG or long-term Holter monitoring may reveal maladaptation of the QT interval to a changing heart rate. QTc prolongation may be evident at a fast heart rate. Ventricular arrhythmias are rarely observed during exercise testing or Holter recording in patients with LQTS.

No evidence indicates that invasive electrophysiology with attempts to induce ventricular tachycardia facilitates diagnosis.

Bradycardia and tachycardia

Bradycardia and tachycardia each need special attention. Bradycardia is included in the diagnostic criteria and adds 0.5 points to the score. Tachycardia requires special attention, too, because the QTc may be overcorrected in a tachycardic situation (eg, in infants).

T-wave alternans

Visible T-wave alternans in patients with LQTS indicates an increased risk of cardiac arrhythmias (ie, torsade de pointes and ventricular fibrillation).

Detection of microvolt T-wave alternans has low sensitivity and high specificity in diagnosing LQTS. The prognostic value of microvolt T-wave alternans has not been studied systematically.

Pharmacologic provocation

Pharmacologic provocation with epinephrine or isoproterenol helps in diagnosing LQTS in patients with a borderline presentation. It may also provide information regarding the type of mutation present.

Testing family members

It is important to review the ECGs of family members of a patient with LQTS, to obtain detailed histories, and to perform physical examinations. However, an absence of ECG findings of LQTS in family members does not exclude LQTS. In the ideal setting, all family members should be tested for LQTS mutations to help limit the small, but definite, risk of arrhythmia and sudden cardiac death. Testing is especially relevant if the patient was exposed to a drug that prolongs the QT interval.

Genetic Testing

Patients with a clinical or electrocardiographic (ECG) presentation of long QT syndrome (LQTS) need genetic testing to identify the mutation. Genetic testing for known mutations in deoxyribonucleic acid (DNA) samples from patients is becoming accessible in specialized centers, although such tests can entail considerable expense, and insurance coverage for genetic testing often requires specific physician intervention.

Identification of an LQTS genetic mutation confirms the diagnosis. However, a negative result on genetic testing is of limited diagnostic value, because only approximately 50% of patients with LQTS have known mutations. The remaining half of patients with LQTS may have mutations of yet unknown genes. Therefore, genetic testing has high specificity but low sensitivity.

Response to Standing

Viskin and colleagues demonstrated that the expected shortening of the QT interval in response to sinus tachycardia induced by standing from a supine position is impaired in patients with long QT syndrome (LQTS).^[1]In fact, the QTc interval in patients with LQTS increased with standing position, and more premature ventricular contractions (PVCs) were detected during standing in these patients. Thus, the increased QTc interval in response to standing up, which is associated with increased sympathetic tone, can provide more diagnostic information in patients with LQTS.^[1]The increase in QTc in response to standing may persist in patients with LQTS even after heart rate returns to normal.^[2]

In addition, this study may reveal that standing up in patients with LQTS may be associated with more focal activities and ventricular arrhythmias. Therefore, syncope while standing up in a patient with LQTS may not be simply a vasovagal syncope but may represent a more dangerous condition.

In a more recent study, investigators evaluating the standing test in 36 congenital LQTS patients (LQT1, LQT2, LQT7, and unidentified genotypes) and 41 control subjects found that the corrected QT interval (QTc) obtained immediately after standing and the QTc change from baseline were significantly higher in the LQTS group than in the control group, and that these QTc evaluations had a high diagnostic value when compared to the baseline QTc.^[23]In addition, the use of beta-blocker therapy ameliorated the standing response in the LQTS patients.

Treatment & Management

Viskin S, Postema PG, Bhuiyan ZA, et al. The response of the QT interval to the brief tachycardia provoked by standing: a bedside test for diagnosing long QT syndrome. J Am Coll Cardiol. 2010 May 4. 55(18):1955-61. [QxMD MEDLINE Link]. [Full Text].
Adler A, van der Werf C, Postema PG, et al. The phenomenon of "QT stunning": The abnormal QT prolongation provoked by standing persists even as the heart rate returns to normal in patients with long QT syndrome. Heart Rhythm. 2012 Jun. 9(6):901-8. [QxMD MEDLINE Link].
Ackerman MJ, Priori SG, Dubin AM, et al. Beta-blocker therapy for long QT syndrome and catecholaminergic polymorphic ventricular tachycardia: Are all beta-blockers equivalent?. Heart Rhythm. 2017 Jan. 14(1):e41-e44. [QxMD MEDLINE Link].
Heemskerk CPM, Pereboom M, van Stralen K, et al. Risk factors for QTc interval prolongation. Eur J Clin Pharmacol. 2018 Feb. 74(2):183-91. [QxMD MEDLINE Link].
El-Sherif N, Turitto G, Boutjdir M. Congenital long QT syndrome and torsade de pointes. Ann Noninvasive Electrocardiol. 2017 Nov. 22(6):[QxMD MEDLINE Link].
Wei H, Wu J, Liu Z. Studying KCNQ1 mutation and drug response in type 1 long QT syndrome using patient-specific induced pluripotent stem cell-derived cardiomyocytes. Methods Mol Biol. 2018. 1684:7-28. [QxMD MEDLINE Link].
Duncan G, Firth K, George V, et al. Drug-mediated shortening of action potentials in LQTS2 human induced pluripotent stem cell-derived cardiomyocytes. Stem Cells Dev. 2017 Dec 1. 26(23):1695-705. [QxMD MEDLINE Link].
Gong Q, Zhou Z. Nonsense-mediated mRNA decay of hERG mutations in long QT syndrome. Methods Mol Biol. 2018. 1684:37-49. [QxMD MEDLINE Link].
Fukumoto D, Ding WG, Wada Y, et al. Novel intracellular transport-refractory mutations in KCNH2 identified in patients with symptomatic long QT syndrome. J Cardiol. 2018 Apr. 71(4):401-8. [QxMD MEDLINE Link].
Perez-Riera AR, Barbosa-Barros R, Daminello Raimundo R, da Costa de Rezende Barbosa MP, Esposito Sorpreso IC, de Abreu LC. The congenital long QT syndrome Type 3: An update. Indian Pacing Electrophysiol J. 2018 Jan - Feb. 18(1):25-35. [QxMD MEDLINE Link]. [Full Text].
Vatta M, Ackerman MJ, Ye B, et al. Mutant caveolin-3 induces persistent late sodium current and is associated with long-QT syndrome. Circulation. 2006 Nov 14. 114(20):2104-12. [QxMD MEDLINE Link].
Rajab A, Straub V, McCann LJ, et al. Fatal cardiac arrhythmia and long-QT syndrome in a new form of congenital generalized lipodystrophy with muscle rippling (CGL4) due to PTRF-CAVIN mutations. PLoS Genet. 2010 Mar 12. 6(3):e1000874. [QxMD MEDLINE Link]. [Full Text].
Border WL, Benson DW. Sudden infant death syndrome and long QT syndrome: the zealots versus the naysayers. Heart Rhythm. 2007 Feb. 4(2):167-9. [QxMD MEDLINE Link].
Medeiros-Domingo A, Kaku T, Tester DJ, et al. Sodium channel β4 subunit mutation causes congenital long QT syndrome. Heart Rhythm. 2006. 3(5):S34.
Wu G, Ai T, Kim JJ, et al. Alpha-1-syntrophin mutation and the long-QT syndrome: a disease of sodium channel disruption. Circ Arrhythm Electrophysiol. 2008 Aug. 1(3):193-201. [QxMD MEDLINE Link]. [Full Text].
Schwartz PJ, Crotti L, Insolia R. Long-QT syndrome: from genetics to management. Circ Arrhythm Electrophysiol. 2012 Aug 1. 5(4):868-77. [QxMD MEDLINE Link]. [Full Text].
Refsgaard L, Holst AG, Sadjadieh G, Haunso S, Nielsen JB, Olesen MS. High prevalence of genetic variants previously associated with LQT syndrome in new exome data. Eur J Hum Genet. 2012 Aug. 20(8):905-8. [QxMD MEDLINE Link]. [Full Text].
Buber J, Mathew J, Moss AJ, et al. Risk of recurrent cardiac events after onset of menopause in women with congenital long-QT syndrome types 1 and 2. Circulation. 2011 Jun 21. 123(24):2784-91. [QxMD MEDLINE Link].
Hinterseer M, Beckmann BM, Thomsen MB, et al. Relation of increased short-term variability of QT interval to congenital long-QT syndrome. Am J Cardiol. 2009 May 1. 103(9):1244-8. [QxMD MEDLINE Link].
Schwartz PJ, Moss AJ, Vincent GM, Crampton RS. Diagnostic criteria for the long QT syndrome. An update. Circulation. 1993 Aug. 88(2):782-4. [QxMD MEDLINE Link].
Sugrue A, Noseworthy PA, Kremen V, et al. Automated T-wave analysis can differentiate acquired QT prolongation from congenital long QT syndrome. Ann Noninvasive Electrocardiol. 2017 Nov. 22(6):[QxMD MEDLINE Link].
Sugrue A, Rohatgi RK, Noseworthy PA, et al. Architectural T-wave analysis and identification of on-therapy breakthrough arrhythmic risk in type 1 and Type 2 long-QT syndrome. Circ Arrhythm Electrophysiol. 2017 Nov. 10(11):[QxMD MEDLINE Link].
Munoz-Esparza C, Zorio E, Domingo Valero D, et al. Value of the "standing test" in the diagnosis and evaluation of beta-blocker therapy response in long QT syndrome. Rev Esp Cardiol (Engl Ed). 2017 Nov. 70(11):907-14. [QxMD MEDLINE Link].
Brouillette J, Nattel S. A practical approach to avoiding cardiovascular adverse effects of psychoactive medications. Can J Cardiol. 2017 Dec. 33(12):1577-86. [QxMD MEDLINE Link].
Wang M, Szepietowska B, Polonsky B, et al. Risk of cardiac events associated with antidepressant therapy in patients with long QT syndrome. Am J Cardiol. 2018 Jan 15. 121(2):182-7. [QxMD MEDLINE Link].
Ahn J, Kim HJ, Choi JI, et al. Effectiveness of beta-blockers depending on the genotype of congenital long-QT syndrome: A meta-analysis. PLoS One. 2017. 12(10):e0185680. [QxMD MEDLINE Link]. [Full Text].
Goldenberg I, Thottathil P, Lopes CM, et al. Trigger-specific ion-channel mechanisms, risk factors, and response to therapy in type 1 long QT syndrome. Heart Rhythm. 2012 Jan. 9(1):49-56. [QxMD MEDLINE Link].
Koponen M, Marjamaa A, Hiippala A, et al. Follow-up of 316 molecularly defined pediatric long-QT syndrome patients: clinical course, treatments, and side effects. Circ Arrhythm Electrophysiol. 2015 Aug. 8(4):815-23. [QxMD MEDLINE Link].
Zareba W, Moss AJ, Daubert JP, Hall WJ, Robinson JL, Andrews M. Implantable cardioverter defibrillator in high-risk long QT syndrome patients. J Cardiovasc Electrophysiol. 2003 Apr. 14(4):337-41. [QxMD MEDLINE Link].
Goldenberg I, Moss AJ, Peterson DR, et al. Risk factors for aborted cardiac arrest and sudden cardiac death in children with the congenital long-QT syndrome. Circulation. 2008 Apr 29. 117(17):2184-91. [QxMD MEDLINE Link].
Goldenberg I, Moss AJ. Long QT syndrome. J Am Coll Cardiol. 2008 Jun 17. 51(24):2291-300. [QxMD MEDLINE Link].
Goldenberg I, Moss AJ, Zareba W, et al. Clinical course and risk stratification of patients affected with the Jervell and Lange-Nielsen syndrome. J Cardiovasc Electrophysiol. 2006 Nov. 17(11):1161-8. [QxMD MEDLINE Link].
Mazzanti A, Maragna R, Faragli A, et al. Gene-specific therapy with mexiletine reduces arrhythmic events in patients with long QT syndrome type 3. J Am Coll Cardiol. 2016 Mar 8. 67(9):1053-8. [QxMD MEDLINE Link].
Ruan Y, Denegri M, Liu N, et al. Trafficking defects and gating abnormalities of a novel SCN5A mutation question gene-specific therapy in long QT syndrome type 3. Circ Res. 2010 Apr 30. 106(8):1374-83. [QxMD MEDLINE Link].
Kim JA, Lopes CM, Moss AJ, et al. Trigger-specific risk factors and response to therapy in long QT syndrome type 2. Heart Rhythm. 2010 Dec. 7(12):1797-805. [QxMD MEDLINE Link].
[Guideline] Priori SG, Wilde AA, Horie M, et al. HRS/EHRA/APHRS expert consensus statement on the diagnosis and management of patients with inherited primary arrhythmia syndromes: document endorsed by HRS, EHRA, and APHRS in May 2013 and by ACCF, AHA, PACES, and AEPC in June 2013. Heart Rhythm. 2013 Dec. 10(12):1932-63. [QxMD MEDLINE Link].
[Guideline] Priori SG, Blomstrom-Lundqvist C, Mazzanti A, et al. 2015 ESC Guidelines for the management of patients with ventricular arrhythmias and the prevention of sudden cardiac death: The Task Force for the Management of Patients with Ventricular Arrhythmias and the Prevention of Sudden Cardiac Death of the European Society of Cardiology (ESC). Endorsed by: Association for European Paediatric and Congenital Cardiology (AEPC). Eur Heart J. 2015 Nov 1. 36(41):2793-867. [QxMD MEDLINE Link]. [Full Text].
[Guideline] Ackerman MJ, Priori SG, Willems S, et al. HRS/EHRA expert consensus statement on the state of genetic testing for the channelopathies and cardiomyopathies: this document was developed as a partnership between the Heart Rhythm Society (HRS) and the European Heart Rhythm Association (EHRA). Europace. 2011 Aug. 13(8):1077-109. [QxMD MEDLINE Link]. [Full Text].
Zipes DP, Camm AJ, Borggrefe M, et al. ACC/AHA/ESC 2006 Guidelines for Management of Patients With Ventricular Arrhythmias and the Prevention of Sudden Cardiac Death: a report of the American College of Cardiology/American Heart Association Task Force and the European Society of Cardiology Committee for Practice Guidelines (writing committee to develop Guidelines for Management of Patients With Ventricular Arrhythmias and the Prevention of Sudden Cardiac Death): developed in collaboration with the European Heart Rhythm Association... Circulation. 2006 Sep 5. 114(10):e385-484. [QxMD MEDLINE Link].
[Guideline] Ackerman MJ, Zipes DP, Kovacs RJ, et al. Eligibility and Disqualification Recommendations for Competitive Athletes With Cardiovascular Abnormalities: Task Force 10: The Cardiac Channelopathies: A Scientific Statement From the American Heart Association and American College of Cardiology. Circulation. 2015 Dec 1. 132(22):e326-9. [QxMD MEDLINE Link]. [Full Text].
Roden DM. Long QT Syndrome. N Engl J Med. 2008 Jan. 358(2):169-76. [QxMD MEDLINE Link].
Ackerman MJ. Genotype-phenotype relationships in congenital long QT syndrome. J Electrocardiol. 2005 Oct. 38(4 Suppl):64-8. [QxMD MEDLINE Link].
Antzelevitch C. Arrhythmogenic mechanisms of QT prolonging drugs: is QT prolongation really the problem?. J Electrocardiol. 2004. 37 Suppl:15-24. [QxMD MEDLINE Link].
Antzelevitch C, Oliva A. Amplification of spatial dispersion of repolarization underlies sudden cardiac death associated with catecholaminergic polymorphic VT, long QT, short QT and Brugada syndromes. J Intern Med. 2006 Jan. 259(1):48-58. [QxMD MEDLINE Link].
Ching CK, Tan EC. Congenital long QT syndromes: clinical features, molecular genetics and genetic testing. Expert Rev Mol Diagn. 2006 May. 6(3):365-74. [QxMD MEDLINE Link].
Gowda RM, Khan IA, Wilbur SL, Vasavada BC, Sacchi TJ. Torsade de pointes: the clinical considerations. Int J Cardiol. 2004 Jul. 96(1):1-6. [QxMD MEDLINE Link].
Kao LW, Furbee RB. Drug-induced q-T prolongation. Med Clin North Am. 2005 Nov. 89(6):1125-44, x. [QxMD MEDLINE Link].
Lankipalli RS, Zhu T, Guo D, Yan GX. Mechanisms underlying arrhythmogenesis in long QT syndrome. J Electrocardiol. 2005 Oct. 38(4 Suppl):69-73. [QxMD MEDLINE Link].
Modell SM, Lehmann MH. The long QT syndrome family of cardiac ion channelopathies: a HuGE review. Genet Med. 2006 Mar. 8(3):143-55. [QxMD MEDLINE Link].
Mullally J, Goldenberg I, Moss AJ, et al. Risk of life-threatening cardiac events among patients with long QT syndrome and multiple mutations. Heart Rhythm. 2013 Mar. 10(3):378-82. [QxMD MEDLINE Link].
Napolitano C, Bloise R, Priori SG. Long QT syndrome and short QT syndrome: how to make correct diagnosis and what about eligibility for sports activity. J Cardiovasc Med (Hagerstown). 2006 Apr. 7(4):250-6. [QxMD MEDLINE Link].
Roden DM. Long QT syndrome: reduced repolarization reserve and the genetic link. J Intern Med. 2006 Jan. 259(1):59-69. [QxMD MEDLINE Link].
Schwartz PJ. The congenital long QT syndromes from genotype to phenotype: clinical implications. J Intern Med. 2006 Jan. 259(1):39-47. [QxMD MEDLINE Link].

Media Gallery

Marked prolongation of QT interval in a 15-year-old male adolescent with long QT syndrome (LQTS) (R-R = 1.00 s, QT interval = 0.56 s, QT interval corrected for heart rate [QTc] = 0.56 s). Abnormal morphology of repolarization can be observed in almost every lead (ie, peaked T waves, bowing ST segment). Bradycardia is a common feature in patients with LQTS.
Genetically confirmed long QT syndrome (LQTS) with borderline values of QT corrected for heart rate (QTc) duration (R-R = 0.68 s, QT interval = 0.36 s, QT interval corrected for heart rate [QTc] = 0.44 s) in a 12-year-old girl. Note the abnormal morphology of the T wave (notches) in leads V2-V4.
ECG of a 13-year-old female who had a syncopal event while running to a school bus. She awoke after a few seconds, and her subsequent clinical course was uneventful.

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Table 1. Genetic Background of Inherited Forms of LQTS (Romano-Ward Syndrome: LQT1-6, Anderson Syndrome: LQT7, Timothy Syndrome: LQT8, and Jervell and Lang-Nielsen Syndrome: JLN1-2)

Type of LQTS	Chromosomal Locus	Mutated Gene	Ion Current Affected
LQT1	11p15.5	KVLQT1 or KCNQ1 (heterozygotes)	Potassium (I_Ks)
LQT2	7q35-36	HERG, KCNH2	Potassium (I_Kr)
LQT3	3p21-24	SCN5A	Sodium (I_Na)
LQT4	4q25-27	ANK2, ANKB	Sodium, potassium and calcium
LQT5	21q22.1-22.2	KCNE1 (heterozygotes)	Potassium (I_Ks)
LQT6	21q22.1-22.2	MiRP1, KNCE2	Potassium (I_Kr)
LQT7 (Anderson syndrome)	17q23.1-q24.2	KCNJ2	Potassium (I_K1)
LQT8 (Timothy syndrome)	12q13.3	CACNA1C	Calcium (I_Ca-Lalpha)
LQT9	3p25.3	CAV3	Sodium (I_Na)
LQT10	11q23.3	SCN4B	Sodium (I_Na)
LQT11	7q21-q22	AKAP9	Potassium (I_Ks)
LQT12		SNTAI	Sodium (I_Na)
JLN1	11p15.5	KVLQT1 or KCNQ1 (homozygotes)	Potassium (I_Ks)
JLN2	21q22.1-22.2	KCNE1 (homozygotes)	Potassium (I_Ks)

Table 2. Diagnostic Criteria for LQTS

Criterion	Points
Electrocardiogram findings ^*
QTc, ms^†	>480	3
	460-469	2
	450-459 in male patient	1
Torsade de pointes^‡		2
T-wave alternans		1
Notched T wave in 3 leads		1
Low heart rate for age^§		0.5
Clinical history
Syncope^║	With stress	2
	Without stress	1
Congenital deafness		0.5
Family history ^¶
A. Family members with definite LQTS^#		1
B. Unexplained sudden cardiac death at age <30 years in an immediate family member		0.5
LQTS = long QT syndrome. ^*In the absence of medications or disorders known to affect these electrocardiographic features. ^†QTc calculated by Bazett's formula. ^‡Mutually exclusive. ^§Resting heart rate below the second percentile for age. ^\|\|Mutually exclusive. ^¶The same family member cannot be counted in both A and B. ^#Definite LQTS is defined by an LQTS score above 3 (≥4).

Table 3. Definition of QTc Based on Age- and Sex-Specific Criteria

Group	Prolonged QTc, sec	Borderline QTc, sec	Reference Range, sec
Children and adolescents (<15 years)	>0.46	0.44-0.46	<0.44
Men	>0.45	0.43-0.45	<0.43
Women	>0.46	0.45-0.46	<0.45

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Author

Ali A Sovari, MD, FACP, FACC Attending Physician, Cardiac Electrophysiologist, Cedars Sinai Medical Center and St John's Regional Medical Center

Ali A Sovari, MD, FACP, FACC is a member of the following medical societies: American College of Cardiology, American College of Physicians, American Physician Scientists Association, American Physiological Society, Biophysical Society, Heart Rhythm Society, Society for Cardiovascular Magnetic Resonance

Disclosure: Nothing to disclose.

Coauthor(s)

Abraham G Kocheril, MD, FACC, FACP, FHRS Professor of Medicine, University of Illinois College of Medicine

Abraham G Kocheril, MD, FACC, FACP, FHRS is a member of the following medical societies: American College of Cardiology, Central Society for Clinical and Translational Research, Heart Failure Society of America, Cardiac Electrophysiology Society, American College of Physicians, American Heart Association, American Medical Association, Illinois State Medical Society

Disclosure: Nothing to disclose.

Ramin Assadi, MD Assistant Professor of Medicine, Division of Interventional Cardiology, University of California, Los Angeles, David Geffen School of Medicine

Ramin Assadi, MD is a member of the following medical societies: American College of Cardiology, American College of Physicians, American Medical Association, Society for Cardiovascular Angiography and Interventions

Disclosure: Nothing to disclose.

Arnold S Baas, MD, FACC, FACP Professor of Medicine, Division of Cardiology, Fellowship Director for Advanced Heart Failure and Transplant Cardiology, Ahmanson UCLA Cardiomyopathy Center, Mechanical Circulatory Support, and Heart Transplant Program, University of California, Los Angeles, David Geffen School of Medicine; Attending Physician, Ronald Reagan UCLA Medical Center

Arnold S Baas, MD, FACC, FACP is a member of the following medical societies: American College of Cardiology, American College of Physicians, American Society of Echocardiography, International Society for Heart and Lung Transplantation

Disclosure: Nothing to disclose.

Chief Editor

Mikhael F El-Chami, MD Associate Professor, Department of Medicine, Division of Cardiology, Section of Electrophysiology, Emory University School of Medicine

Mikhael F El-Chami, MD is a member of the following medical societies: Alpha Omega Alpha, American College of Cardiology, American Heart Association, Heart Rhythm Society

Disclosure: Serve(d) as a director, officer, partner, employee, advisor, consultant or trustee for: Medtronic; Boston Scientific, Biotronik<br/>Received research grants (as part of Multicenter studies) from Medtronic and Boston Scientific.

Acknowledgements

Brian Olshansky, MD Professor of Medicine, Department of Internal Medicine, University of Iowa College of Medicine

Brian Olshansky, MD is a member of the following medical societies: American Autonomic Society, American College of Cardiology, American College of Chest Physicians, American College of Physicians, American College of Sports Medicine, American Federation for Clinical Research, American Heart Association, Cardiac Electrophysiology Society, Heart Rhythm Society, and New York Academy of Sciences

Disclosure: Guidant/Boston Scientific Honoraria Speaking and teaching; Medtronic Honoraria Speaking and teaching; Guidant/Boston Scientific Consulting fee Consulting; Novartis Honoraria Speaking and teaching; Novartis Consulting fee Consulting

Justin D Pearlman, MD, ME, PhD, FACC, MA Chief, Division of Cardiology, Director of Cardiology Consultative Service, Director of Cardiology Clinic Service, Director of Cardiology Non-Invasive Laboratory, Director of Cardiology Quality Program KMC, Dartmouth-Hitchcock Medical Center, Dartmouth Medical School

Justin D Pearlman, MD, ME, PhD, FACC, MA is a member of the following medical societies: American College of Cardiology, American College of Physicians, American Federation for Medical Research, International Society for Magnetic Resonance in Medicine, and Radiological Society of North America

Disclosure: Nothing to disclose.

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Medscape Salary Employment