th th The Basics patient education pieces are written in plain language, at the 5 to 6 grade reading level, and they answer the four or five key questions a patient might have about a given https://www.uptodate.com/contents/congenital-long-qt-syndrome-diagnosis/print 12/29 7/6/23, 11:06 AM Congenital long QT syndrome: Diagnosis - UpToDate condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more th th sophisticated, and more detailed. These articles are written at the 10 to 12 grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon. Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.) Basics topic (see "Patient education: Long QT syndrome (The Basics)") SUMMARY AND RECOMMENDATIONS Long QT syndrome (LQTS) is a disorder of ventricular myocardial repolarization characterized by a prolonged QT interval on the electrocardiogram (ECG) ( waveform 1), ventricular arrhythmias, and an increased risk of sudden cardiac death (SCD) caused by torsades de pointes or "twisting of the points" ( waveform 2). (See 'Introduction' above.) LQTS may be congenital or acquired. Pathogenic variants in up to 17 genes have been identified thus far in patients with genetic LQTS; the major and most important genetic subtypes are designated LQT1 through LQT3, while the minor LQTS-susceptibility genes are designated by their genetic substrate such as CALM1-LQTS, for example ( table 1). (See 'Introduction' above.) The initial diagnostic strategy includes evaluation of the presenting event (eg, syncope, seizures, sudden cardiac arrest, or SCD), obtaining a careful family history, careful evaluation of the QTc, exclusion of secondary causes of QT prolongation, ambulatory ECG monitoring (with 12-lead ECG if at all possible), exercise testing, and calculation of the LQTS diagnostic score (the "Schwartz score"). (See 'Our approach' above.) Obtaining a detailed personal medical history and multi-generation family history is crucial in determining the pretest likelihood of congenital LQTS. The personal clinical history should focus on signs and symptoms suggestive of tachyarrhythmia, particularly ventricular tachyarrhythmias, as many LQTS families have pre-sudden death warning signs including syncope suggestive of cardiac etiology, syncope followed by generalized seizures, or resuscitated sudden cardiac arrest. (See 'Clinical and family history' above.) https://www.uptodate.com/contents/congenital-long-qt-syndrome-diagnosis/print 13/29 7/6/23, 11:06 AM Congenital long QT syndrome: Diagnosis - UpToDate All patients being evaluated for congenital LQTS should have a 12-lead ECG performed. The QT interval should be measured manually on serial ECGs using multiple leads (preferably leads II and V5), and then corrected for heart rate. The heart rate corrected QT interval (QTc) is the most useful diagnostic and prognostic parameter for LQTS. The computer- derived QTc should always be confirmed or corrected manually. Since the QTc varies in response to physiologic factors and drugs, the sensitivity of a QTc from a single ECG is less than 100 percent, and serial ECG testing is required frequently. (See '12-lead ECG' above.) The average QTc values in healthy adults are 420 20 milliseconds with 99th percentile values being 460 milliseconds (prepuberty), 470 milliseconds (postpubertal males), and 480 milliseconds (postpubertal females). (See 'Normal QTc ranges' above.) Other ECG features of LQTS include abnormal T wave morphology, T wave alternans, and increased QT dispersion. (See 'Other ECG features' above.) In nearly all patients (ie, those who are old enough to cooperate and are capable of performing an exercise protocol) with known or suspected congenital LQTS, we perform an exercise (treadmill or bicycle) ECG stress test as part of the initial diagnostic evaluation to assess for exercise-associated arrhythmias, changes in T wave morphology, and the presence of maladaptive QT response during the recovery phase. (See 'Exercise testing' above.) In patients with known or suspected congenital LQTS, we perform ambulatory ECG monitoring (with 12-lead ECG if available) to help establish the diagnosis of LQTS and to add corroborative information in borderline cases. (See 'Ambulatory ECG monitoring' above.) The LQTS diagnostic score ("Schwartz score") may be helpful in evaluating individuals with suspected LQTS but is not adequate for screening of family members of affected individuals. (See 'Diagnosis' above.) Genetic testing will identify a specific LQTS-causative variant in approximately 80 percent of patients with a definite diagnosis of LQTS. Genetic testing should be viewed as standard of care in the diagnostic and prognostic evaluation of LQTS on par with the ECG itself. It may establish the diagnosis when it is uncertain, allow for efficient identification of affected family members, and have prognostic and therapeutic utility by determining which gene is involved. By all major cardiac societies throughout the world, genetic testing is indicated clinically for any patient in whom the diagnosis of LQTS is being considered or for whom the diagnosis of LQTS has been established already. (See 'Genetic testing' above.) https://www.uptodate.com/contents/congenital-long-qt-syndrome-diagnosis/print 14/29 7/6/23, 11:06 AM Congenital long QT syndrome: Diagnosis - UpToDate Among families with genetically proven/confirmed LQTS, it is unacceptable to tell family members/relatives that they do or do not have LQTS based solely on their ECG. Only a negative variant-specific genetic test result and a normal ECG in that relative can prompt the conclusion that the relative does not have LQTS and can be dismissed from follow-up. (See 'Genetic testing' above.) Use of UpToDate is subject to the Terms of Use. REFERENCES 1. Schwartz PJ, Ackerman MJ. The long QT syndrome: a transatlantic clinical approach to diagnosis and therapy. Eur Heart J 2013; 34:3109. 2. Roden DM. Drug-induced prolongation of the QT interval. N Engl J Med 2004; 350:1013. 3. Khan IA. Clinical and therapeutic aspects of congenital and acquired long QT syndrome. Am J Med 2002; 112:58. 4. Wehrens XH, Vos MA, Doevendans PA, Wellens HJ. Novel insights in the congenital long QT syndrome. Ann Intern Med 2002; 137:981. 5. Camm AJ, Janse MJ, Roden DM, et al. Congenital and acquired long QT syndrome. Eur Heart J 2000; 21:1232. 6. Chiang CE, Roden DM. The long QT syndromes: genetic basis and clinical implications. J Am Coll Cardiol 2000; 36:1. 7. Schwartz PJ, Ackerman MJ, George AL Jr, Wilde AAM. Impact of genetics on the clinical management of channelopathies. J Am Coll Cardiol 2013; 62:169. 8. Funck-Brentano C, Jaillon P. Rate-corrected QT interval: techniques and limitations. Am J Cardiol 1993; 72:17B. 9. Malik M. Problems of heart rate correction in assessment of drug-induced QT interval prolongation. J Cardiovasc Electrophysiol 2001; 12:411. 10. M nnig G, Eckardt L, Wedekind H, et al. Electrocardiographic risk stratification in families with congenital long QT syndrome. Eur Heart J 2006; 27:2074. 11. Taggart NW, Haglund CM, Tester DJ, Ackerman MJ. Diagnostic miscues in congenital long-QT syndrome. Circulation 2007; 115:2613. 12. Cowan JC, Yusoff K, Moore M, et al. Importance of lead selection in QT interval measurement. Am J Cardiol 1988; 61:83. 13. Goldman MJ. Principles of Clinical Electrocardiography, 8th ed, Lange Medical Pub, Los Altos 1973. https://www.uptodate.com/contents/congenital-long-qt-syndrome-diagnosis/print 15/29 7/6/23, 11:06 AM Congenital long QT syndrome: Diagnosis - UpToDate 14. LEPESCHKIN E, SURAWICZ B. The measurement of the Q-T interval of the electrocardiogram. Circulation 1952; 6:378. 15. Al-Khatib SM, LaPointe NM, Kramer JM, Califf RM. What clinicians should know about the QT interval. JAMA 2003; 289:2120. 16. Toivonen L. More light on QT interval measurement. Heart 2002; 87:193. 17. Hnatkova K, Malik M. "Optimum" formulae for heart rate correction of the QT interval. Pacing Clin Electrophysiol 1999; 22:1683. 18. Bazett, HC . An analysis of the time-relations of electrocardiograms. Heart 1920; 7:353. 19. Schwartz PJ, Garson A Jr, Paul T, et al. Guidelines for the interpretation of the neonatal electrocardiogram. A task force of the European Society of Cardiology. Eur Heart J 2002; 23:1329. 20. Vink AS, Neumann B, Lieve KVV, et al. Determination and Interpretation of the QT Interval. Circulation 2018; 138:2345. 21. Stramba-Badiale M, Karnad DR, Goulene KM, et al. For neonatal ECG screening there is no reason to relinquish old Bazett's correction. Eur Heart J 2018; 39:2888. 22. Berul CI, Sweeten TL, Dubin AM, et al. Use of the rate-corrected JT interval for prediction of repolarization abnormalities in children. Am J Cardiol 1994; 74:1254. 23. Rautaharju PM, Zhang ZM, Prineas R, Heiss G. Assessment of prolonged QT and JT intervals in ventricular conduction defects. Am J Cardiol 2004; 93:1017. 24. Malfatto G, Beria G, Sala S, et al. Quantitative analysis of T wave abnormalities and their prognostic implications in the idiopathic long QT syndrome. J Am Coll Cardiol 1994; 23:296. 25. Zhang L, Timothy KW, Vincent GM, et al. Spectrum of ST-T-wave patterns and repolarization parameters in congenital long-QT syndrome: ECG findings identify genotypes. Circulation 2000; 102:2849. 26. Swan H, Viitasalo M, Piippo K, et al. Sinus node function and ventricular repolarization during exercise stress test in long QT syndrome patients with KvLQT1 and HERG potassium channel defects. J Am Coll Cardiol 1999; 34:823. 27. Takenaka K, Ai T, Shimizu W, et al. Exercise stress test amplifies genotype-phenotype correlation in the LQT1 and LQT2 forms of the long-QT syndrome. Circulation 2003; 107:838. 28. Sy RW, van der Werf C, Chattha IS, et al. Derivation and validation of a simple exercise-based algorithm for prediction of genetic testing in relatives of LQTS probands. Circulation 2011; 124:2187. 29. Schwartz PJ, Priori SG, Locati EH, et al. Long QT syndrome patients with mutations of the SCN5A and HERG genes have differential responses to Na+ channel blockade and to https://www.uptodate.com/contents/congenital-long-qt-syndrome-diagnosis/print 16/29 7/6/23, 11:06 AM Congenital long QT syndrome: Diagnosis - UpToDate increases in heart rate. Implications for gene-specific therapy. Circulation 1995; 92:3381. 30. Schwartz PJ, Priori SG, Spazzolini C, et al. Genotype-phenotype correlation in the long-QT syndrome: gene-specific triggers for life-threatening arrhythmias. Circulation 2001; 103:89. 31. Crotti L, Spazzolini C, Porretta AP, et al. Vagal reflexes following an exercise stress test: a simple clinical tool for gene-specific risk stratification in the long QT syndrome. J Am Coll Cardiol 2012; 60:2515. 32. Horner JM, Horner MM, Ackerman MJ. The diagnostic utility of recovery phase QTc during treadmill exercise stress testing in the evaluation of long QT syndrome. Heart Rhythm 2011; 8:1698. 33. Eggeling T, Hoeher M, Osterhues HH, et al. Significance of noninvasive diagnostic techniques in patients with long QT syndrome. Am J Cardiol 1992; 70:1421. 34. Garson A Jr, Dick M 2nd, Fournier A, et al. The long QT syndrome in children. An international study of 287 patients. Circulation 1993; 87:1866. 35. Eggeling T, Osterhues HH, Hoeher M, et al. Value of Holter monitoring in patients with the long QT syndrome. Cardiology 1992; 81:107. 36. Lupoglazoff JM, Denjoy I, Berthet M, et al. Notched T waves on Holter recordings enhance detection of patients with LQt2 (HERG) mutations. Circulation 2001; 103:1095. 37. Mauriello DA, Johnson JN, Ackerman MJ. Holter monitoring in the evaluation of congenital long QT syndrome. Pacing Clin Electrophysiol 2011; 34:1100. 38. Etienne P, Huchet F, Gaborit N, et al. Mental stress test: a rapid, simple, and efficient test to unmask long QT syndrome. Europace 2018; 20:2014. 39. 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; 10:1932. 40. 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). Heart Rhythm 2011; 8:1308. 41. Al-Khatib SM, Stevenson WG, Ackerman MJ, et al. 2017 AHA/ACC/HRS Guideline 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 on Clinical Practice Guidelines and the Heart Rhythm Society. Circulation 2018; 138:e272. https://www.uptodate.com/contents/congenital-long-qt-syndrome-diagnosis/print 17/29 7/6/23, 11:06 AM Congenital long QT syndrome: Diagnosis - UpToDate 42. Priori SG, Barhanin J, Hauer RN, et al. Genetic and molecular basis of cardiac arrhythmias: impact on clinical management parts I and II. Circulation 1999; 99:518. 43. Priori SG, Barhanin J, Hauer RN, et al. Genetic and molecular basis of cardiac arrhythmias: impact on clinical management part III. Circulation 1999; 99:674. 44. Splawski I, Shen J, Timothy KW, et al. Spectrum of mutations in long-QT syndrome genes. KVLQT1, HERG, SCN5A, KCNE1, and KCNE2. Circulation 2000; 102:1178. 45. Taggart NW, Haglund CM, Ackerman MJ. Diagnostic miscues in congenital long QT syndrome. Heart Rhythm 2006; 3:S67. 46. Gaba P, Bos JM, Cannon BC, et al. Implantable cardioverter-defibrillator explantation for overdiagnosed or overtreated congenital long QT syndrome. Heart Rhythm 2016; 13:879. 47. Schwartz PJ. Idiopathic long QT syndrome: progress and questions. Am Heart J 1985; 109:399. 48. Schwartz PJ, Moss AJ, Vincent GM, Crampton RS. Diagnostic criteria for the long QT syndrome. An update. Circulation 1993; 88:782. 49. Schwartz PJ. The congenital long QT syndromes from genotype to phenotype: clinical implications. J Intern Med 2006; 259:39. 50. Schwartz PJ, Crotti L. QTc behavior during exercise and genetic testing for the long-QT syndrome. Circulation 2011; 124:2181. Topic 1053 Version 31.0 https://www.uptodate.com/contents/congenital-long-qt-syndrome-diagnosis/print 18/29 7/6/23, 11:06 AM Congenital long QT syndrome: Diagnosis - UpToDate GRAPHICS Single-lead electrocardiogram showing a prolonged QT interval The corrected QT interval (QTc) is calculated by dividing the QT interval (0.60 seconds) by the square root of the preceding RR interval (0.92 seconds). In this case, the QTc is 0.625 seconds (625 milliseconds). Graphic 77018 Version 7.0 https://www.uptodate.com/contents/congenital-long-qt-syndrome-diagnosis/print 19/29 7/6/23, 11:06 AM Congenital long QT syndrome: Diagnosis - UpToDate Single lead electrocardiogram (ECG) showing torsades de pointes The electrocardiographic rhythm strip shows torsades de pointes, a polymorphic ventricular tachycardia associated with QT prolongation. There is a short, preinitiating RR interval due to a ventricular couplet, which is followed by a long, initiating cycle resulting from the compensatory pause after the couplet. Graphic 73827 Version 4.0 https://www.uptodate.com/contents/congenital-long-qt-syndrome-diagnosis/print 20/29 7/6/23, 11:06 AM Congenital long QT syndrome: Diagnosis - UpToDate Summary of heritable arrhythmia syndrome susceptibility genes: Long QT syndrome (LQTS) Gene Locus Protein Major LQTS genes KCNQ1 (LQT1) 11p15.5 I Ks Kv7.1) potassium channel alpha subunit (KVLQT1, KCNH2 (LQT2) 7q35-36 I Kr Kv11.1) potassium channel alpha subunit (HERG, SCN5A (LQT3) 3p21-p24 Cardiac sodium channel alpha subunit (NaV1.5) Minor LQTS genes AKAP9 7q21-q22 Yotiao CACNA1C 12p13.3 Voltage gated L-type calcium channel (CaV1.2) CALM1 14q32.11 Calmodulin 1 CALM2 2p21 Calmodulin 2 CALM3 19q13.2-q13.3 Calmodulin 3 CAV3 3p25 Caveolin-3 KCNE1 21q22.1 Potassium channel beta subunit (MinK) KCNE2 21q22.1 Potassium channel beta subunit (MiRP1) KCNJ5 11q24.3 Kir3.4 subunit of I channel KACH SCN4B 11q23.3 Sodium channel beta 4 subunit SNTA1 20q11.2 Syntrophin-alpha 1 TRDN 6q22.31 Triadin Adapted from: Tester DJ, Ackerman MJ. Genetics of cardiac arrhythmias. In: Braunwald's Heart Disease: A Textbook of Cardiovascular Medicine, 10th ed, Mann DL, Zipes DP, Libby P, et al (Eds), Elsevier, Philadelphia 2015. Graphic 114927 Version 2.0 https://www.uptodate.com/contents/congenital-long-qt-syndrome-diagnosis/print 21/29 7/6/23, 11:06 AM Congenital long QT syndrome: Diagnosis - UpToDate Some reported causes and potentiators of the long QT syndrome Congenital Jervell and Lange-Nielsen syndrome (including "channelopathies") Romano-Ward syndrome Idiopathic Acquired Metabolic disorders Other factors Androgen deprivation therapy Hypokalemia Myocardial ischemia or infarction, GnRH agonist/antagonist therapy Hypomagnesemia Bilateral surgical orchiectomy Hypocalcemia Diuretic therapy via electrolyte disorders particularly hypokalemia and hypomagnesemia especially with prominent T-wave inversions Starvation Anorexia nervosa Herbs Liquid protein diets Cinchona (contains quinine), iboga (ibogaine), licorice extract in overuse via electrolyte disturbances Intracranial disease Hypothyroidism Bradyarrhythmias HIV infection Sinus node dysfunction Hypothermia Toxic exposure: Organophosphate AV block: Second or third degree insecticides Medications* High risk Adagrasib Cisaparide (restricted availability) Lenvatinib Selpercatinib Ajmaline Levoketoconazole Sertindole Amiodarone Methadone Sotalol Delamanid Arsenic trioxide Mobocertinib Terfenadine Disopyramide Astemizole Papavirine (intracoronary) Vandetanib Dofetilide Bedaquline Vernakalant Dronedarone Procainamide Bepridil Ziprasidone Haloperidol (IV) Quinidine Chlorpromazine Ibutilide Quinine Ivosidenib Moderate risk Amisulpride (oral) Droperidol Inotuzumab Propafenone ozogamacin Azithromycin Encorafenib Propofol Isoflurane Capecitabine Entrectinib Quetiapine Carbetocin Erythromycin Ribociclib https://www.uptodate.com/contents/congenital-long-qt-syndrome-diagnosis/print 22/29 7/6/23, 11:06 AM Congenital long QT syndrome: Diagnosis - UpToDate Certinib Escitalopram Levofloxacin (systemic) Risperidone Chloroquine Etelcalcetide Saquinavir Lofexidine Citalopram Fexinidazole Sevoflurane Meglumine antimoniate Clarithromycin Flecainide Sparfloxacin Clofazimine Floxuridine Sunitinib Midostaurin Clomipramine Fluconazole Tegafur Moxifloxacin Clozapine Fluorouracil (systemic) Terbutaline Nilotinib Crizotinib Thioridazine Olanzapine Flupentixol Dabrafenib Toremifene Ondansetrol (IV > oral) Gabobenate dimeglumine Dasatinib Vemurafenib Deslurane Voriconazole Osimertinib Gemifloxacin Domperidone Oxytocin Gilteritinib Doxepin Pazopanib Halofantrine Doxifluridine Pentamidine Haloperidol (oral) Pilsicainide Imipramine Pimozide Piperaquine Probucol Low risk Albuterol Fingolimod Mequitazine Ranolazine (due to bradycardia) Alfuzosin Fluoxetine Methotrimeprazine Relugolix Amisulpride (IV) Fluphenazine Metoclopramide (rare reports) Rilpivirine Amitriptyline Formoterol Metronidazole Romidepsin Anagrelide Foscarnet (systemic) Roxithromycin Apomorphine Fostemsavir Mifepristone Salmeterol Arformoterol Gadofosveset Mirtazapine Sertraline Artemether- Glasdegib Mizolastine lumefantrine Siponimod Goserelin Nelfinavir Asenapine Solifenacin Granisetron Norfloxacin Atomoxetine Sorafenib Hydroxychloroquine Nortriptyline Benperidol (rare reports) Sulpiride Ofloxacin (systemic) Bilastine Hydroxyzine Tacrolimus Olodaterol (systemic) Bosutinib Iloperidone Osilodrostat Tamoxifen Bromperidol Indacaterol Oxaliplatin Telavancin Buprenorphine Itraconazole Ozanimod Telithromycin Buserelin Ketoconazole (systemic) Pacritinib Teneligliptin Ciprofloxacin (Systemic) Lacidipine Paliperidone Tetrabenazine Cocaine (Topical) Lapatinib Panobinostat Trazodone Degarelix Lefamulin Pasireotide Triclabendazole https://www.uptodate.com/contents/congenital-long-qt-syndrome-diagnosis/print 23/29 7/6/23, 11:06 AM Congenital long QT syndrome: Diagnosis - UpToDate Desipramine Leuprolide Pefloxacin Triptorelin Deutetrabenazine Leuprolide- norethindrone Periciazine Tropisetron Dexmedetomidine** Pimavanserin Vardenafil Levalbuterol Dolasetron Pipamperone Vilanterol Levomethadone Donepezil Pitolisant Vinflunine Lithium Efavirenz Ponesimod Voclosporin Loperamide in Eliglustat Primaquine Vorinostat overdose Eribulin Promazine Zuclopenthixol Lopinavir Ezogabine Radotinib Macimorelin Mefloquine This is not a complete list of all corrected QT interval (QTc)-prolonging drugs and does not include drugs with either a minor degree or isolated association(s) with QTc prolongation that appear to be safe in most patients but may need to be avoided in patients with congenital long QT syndrome depending upon clinical circumstances. A more complete list of such drugs is available at the CredibleMeds website. For clinical use and precautions related to medications and drug interactions, refer to the UpToDate topic review of acquired long QT syndrome discussion of medications and the Lexicomp drug interactions tool. AV: atrioventricular; IV: intravenous; QTc: rate-corrected QT interval on the electrocardiogram. Classifications provided by Lexicomp according to US Food & Drug Administration guidance: Clinical Evaluation of QT/QTc Interval Prolongation and Proarrhythic Potential for Non-Antiarrhythmic Drugs Questions and Answers; Guidance for Industry US Food and Drug Administration, June 2017 (revision 2) available at: https://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM [1,2] 073161.pdf with additional data from CredibleMeds QT drugs list criteria may lead to some agents being classified differently by other sources. . The use of other classification Not available in the United States. In contrast with other class III antiarrhythmic drugs, amiodarone is rarely associated with torsades de pointes; refer to accompanying text within UpToDate topic reviews of acquired long QT syndrome. Withdrawn from market in most countries due to adverse cardiovascular effects. IV amisulpride antiemetic use is associated with less QTc prolongation than the higher doses administered orally as an antipsychotic. Other cyclic antidepressants may also prolong the QT interval; refer to UpToDate clinical topic on cyclic antidepressant pharmacology, side effects, and separate UpToDate topic on tricyclic antidepressant poisoning. The "low risk" category includes drugs with limited evidence of clinically significant QTc prolongation or TdP risk; many of these drugs have label warnings regarding possible QTc effects or recommendations to avoid use or increase ECG monitoring when combined with other QTc prolonging drugs. https://www.uptodate.com/contents/congenital-long-qt-syndrome-diagnosis/print 24/29 7/6/23, 11:06 AM Congenital long QT syndrome: Diagnosis - UpToDate Rarely associated with significant QTc prolongation at usual doses for treatment of opioid use disorder, making buprenorphine a suitable alternative for patients with methadone-associated QTc prolongation. Refer to UpToDate clinical topic reviews. * The United States FDA labeling for the sublingual preparation of dexmedetomidine warns against use in patients at elevated risk for QTc prolongation. Both intravenous (ie, sedative) and sublingual formulations of dexmedetomidine have a low risk of QTc prolongation and have not been implicated in TdP. Over-the-counter; available without a prescription. Not associated with significant QTc prolongation in healthy persons. Refer to UpToDate clinical topic for potential adverse cardiovascular (CV) effects in patients with CV disease. Data from: 1. Lexicomp Online. Copyright 1978-2023 Lexicomp, Inc. All Rights Reserved. 2. CredibleMeds QT drugs list website sponsored by Science Foundation of the University of Arizona. Available at http://crediblemeds.org/. Graphic 57431 Version 142.0 https://www.uptodate.com/contents/congenital-long-qt-syndrome-diagnosis/print 25/29 7/6/23, 11:06 AM Congenital long QT syndrome: Diagnosis - UpToDate Triggers for cardiac events in long QT syndrome are related to genotype In a study of 670 patients with long QT syndrome and known genotype, all symptomatic (syncope, aborted cardiac arrest, or sudden death), the occurrence of a lethal cardiac event (n = 110) provoked by a specific trigger (exercise, emotion, and sleep/rest without arousal) differed according to genotype. LQT1 patients experienced most of their events (90%) during exercise or emotion. These percentages were almost reversed among LQT2 and LQT3 patients who had most of their events during rest or sleep (63 and 80%, respectively); by contrast, they were at almost no risk of major events during exercise (arrows), which is explained by their having a normal I current. Ks ACA: aborted cardiac arrest; SCD: sudden cardiac death. Modi ed from: Schwartz PJ, Priori SG, Spazzolini C, et al. Genotype-phenotype correlation in the long-QT syndrome: gene-speci c triggers for life-threatening arrhythmias. Circulation 2001; 103:89. Graphic 64239 Version 3.0 https://www.uptodate.com/contents/congenital-long-qt-syndrome-diagnosis/print 26/29 7/6/23, 11:06 AM Congenital long QT syndrome: Diagnosis - UpToDate Schwartz score diagnostic criteria for long QT syndrome (LQTS) Points Electrocardiographic findings* A. QTc 3 480 ms 2 460 to 479 ms 1 450 to 459 ms (in males) 1 B. QTc fourth minute of recovery from exercise stress test 480 ms 2 C. Torsades de pointes 1 D. T wave alternans 1 E. Notched T wave in 3 leads 0.5 F. Low heart rate for age Clinical history A. Syncope 2 With stress 1 Without stress 0.5 B. Congenital deafness Family history 1 A. Family members with definite LQTS 0.5 B. Unexplained sudden cardiac death below age 30 among immediate family members SCORE: 1 point = low probability of long QT syndrome (LQTS). 1.5 to 3 points = intermediate probability of LQTS. 3.5 points = high probability of LQTS. In the absence of medications or disorders known to affect these electrocardiographic features. QTc calculated by Bazett's formula where QTc = QT/ RR. Mutually exclusive. Resting heart rate below the second percentile for age. https://www.uptodate.com/contents/congenital-long-qt-syndrome-diagnosis/print 27/29 7/6/23, 11:06 AM Congenital long QT syndrome: Diagnosis - UpToDate The same family member cannot be counted in A and B. From: Schwartz PJ, Crotti L. QTc behavior during exercise and genetic testing for the long-QT syndrome. Circulation 2011; 124:2181. DOI: 10.1161/CIRCULATIONAHA.111.062182. Copyright 2011 American Heart Association. Reproduced with permission from Lippincott Williams & Wilkins. Unauthorized reproduction of this material is prohibited. Graphic 113828 Version 4.0 https://www.uptodate.com/contents/congenital-long-qt-syndrome-diagnosis/print 28/29 7/6/23, 11:06 AM Congenital long QT syndrome: Diagnosis - UpToDate Contributor Disclosures Peter J Schwartz, MD No relevant financial relationship(s) with ineligible companies to disclose. Michael J Ackerman, MD, PhD Consultant/Advisory Boards: Abbott [Education around ICD/device therapy for genetic heart diseases including LQTS]; ARMGO Pharma [Novel therapies for genetic heart diseases, CPVT in particular]; Boston Scientific [Education around ICD/device therapy for genetic heart diseases including LQTS]; Daiichi Sankyo [Drug-induced QT prolongation for one of their drugs]; Invitae [Genetic testing for genetic heart diseases]; LQT Therapeutics [Development of a novel QT-shortening medication]; Medtronic [Education around ICD/device therapy for genetic heart diseases including LQTS]; UpToDate [Genetic heart diseases, especially LQTS]. Other Financial Interest: AliveCor [QTc analytics for smartphone-enabled mobile ECG]; Anumana [Artificial intelligence ECG for early detection of hypertrophic cardiomyopathy]; Pfizer [Gene therapy for genetic heart diseases including LQTS]. All of the relevant financial relationships listed have been mitigated. John K Triedman, MD Consultant/Advisory Boards: Biosense Webster and Sentiar [Supraventricular and ventricular topics]. All of the relevant financial relationships listed have been mitigated. Samuel Asirvatham, MD Grant/Research/Clinical Trial Support: Medtronic [Defibrillators]; St Jude's [Sudden Cardiac Death]. Consultant/Advisory Boards: BioTronik [Defibrillators]; Boston Scientific [Sudden Cardiac Death]. All of the relevant financial relationships listed have been mitigated. Nisha Parikh, MD, MPH No relevant financial relationship(s) with ineligible companies to disclose. Contributor disclosures are reviewed for conflicts of interest by the editorial group. When found, these are addressed by vetting through a multi-level review process, and through requirements for references to be provided to support the content. Appropriately referenced content is required of all authors and must conform to UpToDate standards of evidence. Conflict of interest policy https://www.uptodate.com/contents/congenital-long-qt-syndrome-diagnosis/print 29/29