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 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 Background Long QT syndrome (LQTS) is a disorder of ventricular myocardial repolarization characterized by a prolonged QT interval on the ECG ( waveform 1). LQTS can lead to symptomatic ventricular arrhythmias and an increased risk of sudden cardiac death (SCD). (See 'Introduction' above.) Symptomatic patients Our general approach to treatment of symptomatic (or previously symptomatic) patients with congenital LQTS is as follows: General measures All patients with congenital LQTS should adhere to standard general preventive measures, such as the avoidance of medications known to prolong the QT interval ( www.crediblemeds.org) and the aggressive treatment of electrolyte https://www.uptodate.com/contents/congenital-long-qt-syndrome-treatment/print 12/31 7/6/23, 3:08 PM Congenital long QT syndrome: Treatment - UpToDate imbalances (eg, hypokalemia in the setting of vomiting, diarrhea, or diuretic use). (See 'Our approach to symptomatic patients' above.) Activity After establishing the correct diagnosis of LQTS and implementing the initial treatment program, patients with LQTS can continue to be recreationally active, especially those with LQT2 and LQT3. Athletes with LQTS who desire to remain athletes should be evaluated by an LQTS specialist to enable shared decision making to occur successfully. Importantly, there are laws in some countries that supersede professional society guidelines regarding return-to-play issues. (See 'Physical activity and LQTS' above.) Asymptomatic persons who are genotype positive/phenotype negative (ie, with normal QTc at rest) can reasonably participate in all competitive sports with appropriate safety precautions. Symptomatic (or previously symptomatic) patients, or patients with LQTS (QTc >470 milliseconds in males or >480 milliseconds in females) may consider participation in competitive athletics (with the possible exception of swimming in patients with LQT1 genotype) if they remain asymptomatic after three months of treatment and with appropriate cautionary measures, including an emergency action plan with an automated external defibrillator immediately available. Local laws and regulations may apply. Experts disagree on participation in higher levels of sport for patients with an implantable cardioverter-defibrillator (ICD) in place, with some experts allowing participation following counselling of the patient of potential risks and appropriate cautionary measures, while other experts feel it is unwise to expose patients to the risk of ventricular arrhythmias and multiple shocks just to perform a competitive sport. Beta blockers For all patients with congenital LQTS and a history of syncope or seizures, we recommend treatment with a beta blocker (Grade 1B). We suggest propranolol or nadolol, given their superior efficacy in this patient population (Grade 2C). (See 'Beta blockers' above.) Implantable cardiac defibrillator Patients with LQTS-associated sudden cardiac arrest (SCA), while compliant with beta-blocker therapy, should generally receive an ICD. Importantly, self-limiting syncope/seizures, even if assessed to be LQTS-triggered (ie, secondary to TdP) are not equivalent to SCA. (See 'Implantable cardioverter-defibrillator' https://www.uptodate.com/contents/congenital-long-qt-syndrome-treatment/print 13/31 7/6/23, 3:08 PM Congenital long QT syndrome: Treatment - UpToDate above and "Secondary prevention of sudden cardiac death in heart failure and cardiomyopathy".) Treatment intensification For patients with recurrent, LQTS-triggered arrhythmic events in spite of maximally tolerated doses of a beta blocker, or for patients who discontinue beta blockers due to intolerable side effects, treatment intensification is pursued with either concomitant drug therapy, left cardiac sympathetic denervation, and/or an ICD depending on the nature of the arrhythmic event, the genotype, and the patient's degree of QT prolongation at rest (ie, their resting QTc). Treatment intensification for patients with recurrent arrhythmic events should ideally take place in a center with expertise in the management of congenital LQTS, or for patients without access to an expert center, in consultation with a specialist with expertise in congenital LQTS. (See 'Subsequent therapies' above.) Asymptomatic patients Our general approach to treatment of asymptomatic patients with congenital LQTS is as follows (see 'Our approach to asymptomatic patients' above): For most asymptomatic patients with congenital LQTS, we suggest a beta blocker (Grade 2C). In general, the choice of a beta blocker is the same as in symptomatic patients (ie, propranolol or nadolol). However, for asymptomatic patients with a QTc <470 milliseconds, beta-blocker therapy may not be required. If an asymptomatic patient with either LQT2 or LQT3 maintains a QTc >550 ms while on pharmacotherapy, we suggest either a prophylactic left cardiac sympathetic denervation (LCSD) or a prophylactic ICD (Grade 2C). For postpubertal women with LQT2, either prophylactic LCSD or a prophylactic ICD at a lower QTc threshold (QTc >500 milliseconds) is reasonable again if pharmacotherapy (namely mexiletine) has not attenuated the QTc to <500 ms. Importantly, an ICD is never indicated based solely on a family history of LQTS-associated SCD, as family history is not a personal risk factor for the patient. 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. https://www.uptodate.com/contents/congenital-long-qt-syndrome-treatment/print 14/31 7/6/23, 3:08 PM Congenital long QT syndrome: Treatment - UpToDate 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. 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. J Am Coll Cardiol 2018; 72:e91. 9. Locati EH, Zareba W, Moss AJ, et al. Age- and sex-related differences in clinical manifestations in patients with congenital long-QT syndrome: findings from the International LQTS Registry. Circulation 1998; 97:2237. 10. Zareba W, Moss AJ, Schwartz PJ, et al. Influence of the genotype on the clinical course of the long-QT syndrome. International Long-QT Syndrome Registry Research Group. N Engl J Med 1998; 339:960. 11. Dagradi F, Spazzolini C, Castelletti S, et al. Exercise Training-Induced Repolarization Abnormalities Masquerading as Congenital Long QT Syndrome. Circulation 2020; 142:2405. 12. Ackerman MJ, Zipes DP, Kovacs RJ, Maron BJ. 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. J Am Coll Cardiol 2015; 66:2424. 13. Zipes DP, Link MS, Ackerman MJ, et al. Eligibility and Disqualification Recommendations for Competitive Athletes With Cardiovascular Abnormalities: Task Force 9: Arrhythmias and Conduction Defects: A Scientific Statement From the American Heart Association and American College of Cardiology. J Am Coll Cardiol 2015; 66:2412. 14. Pelliccia A, Fagard R, Bj rnstad HH, et al. Recommendations for competitive sports participation in athletes with cardiovascular disease: a consensus document from the Study Group of Sports Cardiology of the Working Group of Cardiac Rehabilitation and Exercise https://www.uptodate.com/contents/congenital-long-qt-syndrome-treatment/print 15/31 7/6/23, 3:08 PM Congenital long QT syndrome: Treatment - UpToDate Physiology and the Working Group of Myocardial and Pericardial Diseases of the European Society of Cardiology. Eur Heart J 2005; 26:1422. 15. Turkowski KL, Bos JM, Ackerman NC, et al. Return-to-Play for Athletes With Genetic Heart Diseases. Circulation 2018; 137:1086. 16. Tobert KE, Bos JM, Garmany R, Ackerman MJ. Return-to-Play for Athletes With Long QT Syndrome or Genetic Heart Diseases Predisposing to Sudden Death. J Am Coll Cardiol 2021; 78:594. 17. 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. 18. Wilde AA, Jongbloed RJ, Doevendans PA, et al. Auditory stimuli as a trigger for arrhythmic events differentiate HERG-related (LQTS2) patients from KVLQT1-related patients (LQTS1). J Am Coll Cardiol 1999; 33:327. 19. Moss AJ, Robinson JL, Gessman L, et al. Comparison of clinical and genetic variables of cardiac events associated with loud noise versus swimming among subjects with the long QT syndrome. Am J Cardiol 1999; 84:876. 20. Ali RH, Zareba W, Moss AJ, et al. Clinical and genetic variables associated with acute arousal and nonarousal-related cardiac events among subjects with long QT syndrome. Am J Cardiol 2000; 85:457. 21. Ackerman MJ, Tester DJ, Porter CJ. Swimming, a gene-specific arrhythmogenic trigger for inherited long QT syndrome. Mayo Clin Proc 1999; 74:1088. 22. Batra AS, Silka MJ. Mechanism of sudden cardiac arrest while swimming in a child with the prolonged QT syndrome. J Pediatr 2002; 141:283. 23. 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. 24. 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 increases in heart rate. Implications for gene-specific therapy. Circulation 1995; 92:3381. 25. Chockalingam P, Crotti L, Girardengo G, et al. Not all beta-blockers are equal in the management of long QT syndrome types 1 and 2: higher recurrence of events under metoprolol. J Am Coll Cardiol 2012; 60:2092. 26. Sauer AJ, Moss AJ, McNitt S, et al. Long QT syndrome in adults. J Am Coll Cardiol 2007; 49:329. 27. Moss AJ, Zareba W, Hall WJ, et al. Effectiveness and limitations of beta-blocker therapy in congenital long-QT syndrome. Circulation 2000; 101:616. https://www.uptodate.com/contents/congenital-long-qt-syndrome-treatment/print 16/31 7/6/23, 3:08 PM Congenital long QT syndrome: Treatment - UpToDate 28. Priori SG, Napolitano C, Schwartz PJ, et al. Association of long QT syndrome loci and cardiac events among patients treated with beta-blockers. JAMA 2004; 292:1341. 29. Hobbs JB, Peterson DR, Moss AJ, et al. Risk of aborted cardiac arrest or sudden cardiac death during adolescence in the long-QT syndrome. JAMA 2006; 296:1249. 30. 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; 117:2184. 31. Vincent GM, Schwartz PJ, Denjoy I, et al. High efficacy of beta-blockers in long-QT syndrome type 1: contribution of noncompliance and QT-prolonging drugs to the occurrence of beta- blocker treatment "failures". Circulation 2009; 119:215. 32. Wilde AA, Moss AJ, Kaufman ES, et al. Clinical Aspects of Type 3 Long-QT Syndrome: An International Multicenter Study. Circulation 2016; 134:872. 33. 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. 34. Ackerman MJ, Khositseth A, Tester DJ, et al. Epinephrine-induced QT interval prolongation: a gene-specific paradoxical response in congenital long QT syndrome. Mayo Clin Proc 2002; 77:413. 35. Shimizu W, Noda T, Takaki H, et al. Epinephrine unmasks latent mutation carriers with LQT1 form of congenital long-QT syndrome. J Am Coll Cardiol 2003; 41:633. 36. Goldenberg I, Younis A, Huang DT, et al. Use of oral contraceptives in women with congenital long QT syndrome. Heart Rhythm 2022; 19:41. 37. Bos JM, Crotti L, Rohatgi RK, et al. Mexiletine Shortens the QT Interval in Patients With Potassium Channel-Mediated Type 2 Long QT Syndrome. Circ Arrhythm Electrophysiol 2019; 12:e007280. 38. Schwartz PJ, Priori SG, Cerrone M, et al. Left cardiac sympathetic denervation in the management of high-risk patients affected by the long-QT syndrome. Circulation 2004; 109:1826. 39. Collura CA, Johnson JN, Moir C, Ackerman MJ. Left cardiac sympathetic denervation for the treatment of long QT syndrome and catecholaminergic polymorphic ventricular tachycardia using video-assisted thoracic surgery. Heart Rhythm 2009; 6:752. 40. Schwartz PJ. 1970-2020: 50 years of research on the long QT syndrome-from almost zero knowledge to precision medicine. Eur Heart J 2021; 42:1063. 41. Dusi V, Pugliese L, De Ferrari GM, et al. Left Cardiac Sympathetic Denervation for the Long QT Syndrome. 50 Years experience provides guidance for management. JACC Clin https://www.uptodate.com/contents/congenital-long-qt-syndrome-treatment/print 17/31 7/6/23, 3:08 PM Congenital long QT syndrome: Treatment - UpToDate Electrophysiol 2021. 42. Bos JM, Bos KM, Johnson JN, et al. Left cardiac sympathetic denervation in long QT syndrome: analysis of therapeutic nonresponders. Circ Arrhythm Electrophysiol 2013; 6:705. 43. Schwartz PJ. The rationale and the role of left stellectomy for the prevention of malignant arrhythmias. Ann N Y Acad Sci 1984; 427:199. 44. Schwartz PJ, Stone HL. Left stellectomy and denervation supersensitivity in conscious dogs. Am J Cardiol 1982; 49:1185. 45. Dusi V, Pugliese L, De Ferrari GM, et al. Left Cardiac Sympathetic Denervation for Long QT Syndrome: 50 Years' Experience Provides Guidance for Management. JACC Clin Electrophysiol 2022; 8:281. 46. Schwartz PJ, Snebold NG, Brown AM. Effects of unilateral cardiac sympathetic denervation on the ventricular fibrillation threshold. Am J Cardiol 1976; 37:1034. 47. Schwartz PJ, Ackerman MJ. Cardiac sympathetic denervation in the prevention of genetically mediated life-threatening ventricular arrhythmias. Eur Heart J 2022; 43:2096. 48. Wedekind H, Burde D, Zumhagen S, et al. QT interval prolongation and risk for cardiac events in genotyped LQTS-index children. Eur J Pediatr 2009; 168:1107. 49. Zareba W, Moss AJ, Daubert JP, et al. Implantable cardioverter defibrillator in high-risk long QT syndrome patients. J Cardiovasc Electrophysiol 2003; 14:337. 50. Etheridge SP, Sanatani S, Cohen MI, et al. Long QT syndrome in children in the era of implantable defibrillators. J Am Coll Cardiol 2007; 50:1335. 51. Proclemer A, Ghidina M, Facchin D, et al. Use of implantable cardioverter-defibrillator in inherited arrhythmogenic diseases: data from Italian ICD Registry for the years 2001-6. Pacing Clin Electrophysiol 2009; 32:434. 52. Schwartz PJ, Spazzolini C, Priori SG, et al. Who are the long-QT syndrome patients who receive an implantable cardioverter-defibrillator and what happens to them?: data from the European Long-QT Syndrome Implantable Cardioverter-Defibrillator (LQTS ICD) Registry. Circulation 2010; 122:1272. 53. Kowlgi GN, Giudicessi JR, Barake W, et al. Efficacy of intentional permanent atrial pacing in the long-term management of congenital long QT syndrome. J Cardiovasc Electrophysiol 2021; 32:782. 54. MacIntyre CJ, Rohatgi RK, Sugrue AM, et al. Intentional nontherapy in long QT syndrome. Heart Rhythm 2020; 17:1147. 55. 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; https://www.uptodate.com/contents/congenital-long-qt-syndrome-treatment/print 18/31 7/6/23, 3:08 PM Congenital long QT syndrome: Treatment - UpToDate 67:1053. 56. Schwartz PJ, Moreno C, Kotta MC, et al. Mutation location and IKs regulation in the arrhythmic risk of long QT syndrome type 1: the importance of the KCNQ1 S6 region. Eur Heart J 2021; 42:4743. Topic 988 Version 32.0 https://www.uptodate.com/contents/congenital-long-qt-syndrome-treatment/print 19/31 7/6/23, 3:08 PM Congenital long QT syndrome: Treatment - 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-treatment/print 20/31 7/6/23, 3:08 PM Congenital long QT syndrome: Treatment - 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-treatment/print 21/31 7/6/23, 3:08 PM Congenital long QT syndrome: Treatment - 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-treatment/print 22/31 7/6/23, 3:08 PM Congenital long QT syndrome: Treatment - 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 especially with prominent T-wave Starvation particularly hypokalemia and hypomagnesemia Anorexia nervosa Herbs inversions Liquid protein diets Cinchona (contains quinine), iboga Intracranial Hypothyroidism (ibogaine), licorice extract in overuse via electrolyte disturbances disease Bradyarrhythmias HIV infection Sinus node dysfunction Hypothermia Toxic exposure: Organophosphate AV block: Second or third degree insecticides Medications* High risk Adagrasib Cisaparide Lenvatinib Selpercatinib (restricted availability) 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 ozogamacin Propafenone Azithromycin Encorafenib Propofol Isoflurane Capecitabine Entrectinib Quetiapine Carbetocin Erythromycin Ribociclib https://www.uptodate.com/contents/congenital-long-qt-syndrome-treatment/print 23/31 7/6/23, 3:08 PM Congenital long QT syndrome: Treatment - UpToDate Certinib Escitalopram Levofloxacin Risperidone (systemic) 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 > Gabobenate Dasatinib Vemurafenib oral) dimeglumine 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 (rare reports) Nortriptyline Benperidol 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-treatment/print 24/31 7/6/23, 3:08 PM Congenital long QT syndrome: Treatment - UpToDate Desipramine Leuprolide Pefloxacin Triptorelin Deutetrabenazine Leuprolide- Periciazine Tropisetron norethindrone 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-treatment/print 25/31 7/6/23, 3:08 PM Congenital long QT syndrome: Treatment - 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-treatment/print 26/31 7/6/23, 3:08 PM Congenital long QT syndrome: Treatment - UpToDate Classification of sports based on peak static and dynamic components during competition This classification is based on peak static and dynamic components achieved during competition; however, higher values may be reached during training. The increasing dynamic component is defined in terms of the estimated percentage of maximal oxygen uptake (VO max) achieved and results in an increasing cardiac output. The increasing static component is related to the estimated percentage of maximal 2 voluntary contraction reached and results in an increasing blood pressure load. The lowest total cardiovascular demands (cardiac output and blood pressure) are shown in the palest color, with increasing dynamic load depicted by increasing blue intensity and increasing static load by increasing red intensity. Note the graded transition between categories, which should be individualized on the basis of player position and style of play. Danger of bodily collision (refer to UpToDate content regarding sports according to risk of impact and educational background). https://www.uptodate.com/contents/congenital-long-qt-syndrome-treatment/print 27/31 7/6/23, 3:08 PM Congenital long QT syndrome: Treatment - UpToDate Increased risk if syncope occurs. Reproduced from: Levine BD, Baggish AL, Kovacs RJ. Eligibility and disquali cation recommendations for competitive athletes with cardiovascular abnormalities: Task force 1: Classi cation of sports: Dynamic, static, and impact: A scienti c statement from the American Heart Association and American College of Cardiology. J Am Coll Cardiol 2015; 66:2350. Illustration used with the permission of Elsevier Inc. All rights reserved. Graphic 105651 Version 9.0 https://www.uptodate.com/contents/congenital-long-qt-syndrome-treatment/print 28/31 7/6/23, 3:08 PM Congenital long QT syndrome: Treatment - 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-treatment/print 29/31 7/6/23, 3:08 PM Congenital long QT syndrome: Treatment - UpToDate Outcome with beta blocker in the long QT syndrome is good in asymptomatic patients During a five-year follow-up of 869 patients with a long QT syndrome, the estimated cumulative probability of experiencing aborted cardiac arrest or death on beta blocker therapy was significantly reduced in those who were asymptomatic (0.97 versus 0.31 events per year on therapy in probands and 0.26 versus 0.15 events per year in affected family members). Recurrent events despite beta blocker therapy were significantly higher in those with a history of syncope (hazard ratio 3.1) or aborted sudden death (hazard ratio 12.9). Data from Moss AJ, Zareba W, Hall WJ, et al, Circulation 2000; 101:616. Graphic 78184 Version 2.0 https://www.uptodate.com/contents/congenital-long-qt-syndrome-treatment/print 30/31 7/6/23, 3:08 PM Congenital long QT syndrome: Treatment - 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-treatment/print 31/31