ventricular fibrillation in patients with normal electrocardiograms: results from a multicentre long-term registry. Europace 2019; 21:1670. 37. Frontera A, Vlachos K, Kitamura T, et al. Long-Term Follow-Up of Idiopathic Ventricular Fibrillation in a Pediatric Population: Clinical Characteristics, Management, and Complications. J Am Heart Assoc 2019; 8:e011172. 38. Friedlander Y, Siscovick DS, Weinmann S, et al. Family history as a risk factor for primary cardiac arrest. Circulation 1998; 97:155. 39. Jouven X, Desnos M, Guerot C, Ducimeti re P. Predicting sudden death in the population: the Paris Prospective Study I. Circulation 1999; 99:1978. 40. Behr E, Wood DA, Wright M, et al. Cardiological assessment of first-degree relatives in sudden arrhythmic death syndrome. Lancet 2003; 362:1457. 41. Wei D, Tao L, Huang M. Genetic variations involved in sudden cardiac death and their associations and interactions. Heart Fail Rev 2016; 21:401. Topic 1019 Version 26.0 https://www.uptodate.com/contents/approach-to-sudden-cardiac-arrest-in-the-absence-of-apparent-structural-heart-disease/print 12/21 7/6/23, 11:24 AM Approach to sudden cardiac arrest in the absence of apparent structural heart disease - UpToDate GRAPHICS Risk of SCD is related to clinical manifestations of CHD During a 38-year follow-up of subjects in the Framingham Heart Study, the annual incidence of sudden cardiac death (SCD) in both men and women was related to the clinical manifestations of coronary heart disease (CHD). It was highest in those with a myocardial infarction, intermediate in those with angina and no prior infarction, and lowest in those without overt CHD. Data from: Kannel WB, Wilson PWF, D'Agostino RB, et al. Am Heart J 1998; 136:205. Graphic 52309 Version 2.0 https://www.uptodate.com/contents/approach-to-sudden-cardiac-arrest-in-the-absence-of-apparent-structural-heart-disease/print 13/21 7/6/23, 11:24 AM Approach to sudden cardiac arrest in the absence of apparent structural heart disease - UpToDate Incidence of sudden death in men and women increases with age During a 38-year follow-up of subjects in the Framingham Heart Study, the annual incidence of sudden death increased with age in both men and women. However, at each age, the incidence of sudden death is higher in men than women. Data from Kannel WB, Wilson PWF, D'Agostino RB, et al. Am Heart J 1998; 136:205. Graphic 59028 Version 4.0 https://www.uptodate.com/contents/approach-to-sudden-cardiac-arrest-in-the-absence-of-apparent-structural-heart-disease/print 14/21 7/6/23, 11:24 AM Approach to sudden cardiac arrest in the absence of apparent structural heart disease - 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 ozogamacin Propafenone Azithromycin Encorafenib Propofol Isoflurane Capecitabine Entrectinib Quetiapine Carbetocin Erythromycin Ribociclib https://www.uptodate.com/contents/approach-to-sudden-cardiac-arrest-in-the-absence-of-apparent-structural-heart-disease/print 15/21 7/6/23, 11:24 AM Approach to sudden cardiac arrest in the absence of apparent structural heart disease - 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 (systemic) Romidepsin Anagrelide Foscarnet Roxithromycin Apomorphine Fostemsavir Mifepristone Salmeterol Arformoterol Gadofosveset Mirtazapine Sertraline Artemether- lumefantrine Glasdegib Mizolastine 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/approach-to-sudden-cardiac-arrest-in-the-absence-of-apparent-structural-heart-disease/print 16/21 7/6/23, 11:24 AM Approach to sudden cardiac arrest in the absence of apparent structural heart disease - 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 overdose in Eliglustat Primaquine Vorinostat 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 073161.pdf with additional data from CredibleMeds QT drugs list criteria may lead to some agents being classified differently by other sources. [1,2] . 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/approach-to-sudden-cardiac-arrest-in-the-absence-of-apparent-structural-heart-disease/print 17/21 7/6/23, 11:24 AM Approach to sudden cardiac arrest in the absence of apparent structural heart disease - 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/approach-to-sudden-cardiac-arrest-in-the-absence-of-apparent-structural-heart-disease/print 18/21 7/6/23, 11:24 AM Approach to sudden cardiac arrest in the absence of apparent structural heart disease - UpToDate Single lead electrocardiogram (ECG) showing polymorphic ventricular tachycardia (VT) This is an atypical, rapid, and bizarre form of ventricular tachycardia that is characterized by a continuously changing axis of polymorphic QRS morphologies. Graphic 53891 Version 5.0 https://www.uptodate.com/contents/approach-to-sudden-cardiac-arrest-in-the-absence-of-apparent-structural-heart-disease/print 19/21 7/6/23, 11:24 AM Approach to sudden cardiac arrest in the absence of apparent structural heart disease - UpToDate 12-lead electrocardiogram (ECG) from a patient with the Brugada syndrome shows downsloping ST elevation ST segment elevation and T wave inversion in the right precordial leads V1 and V2 (arrows); the QRS is normal. The widened S wave in the left lateral leads (V5 and V6) that is characteristic of right bundle branch block is absent. Courtesy of Rory Childers, MD, University of Chicago. Graphic 64510 Version 10.0 https://www.uptodate.com/contents/approach-to-sudden-cardiac-arrest-in-the-absence-of-apparent-structural-heart-disease/print 20/21 7/6/23, 11:24 AM Approach to sudden cardiac arrest in the absence of apparent structural heart disease - UpToDate Contributor Disclosures Mark S Link, MD No relevant financial relationship(s) with ineligible companies to disclose. Peter J Zimetbaum, MD Consultant/Advisory Boards: Abbott Medical [Lead extraction]. All of the relevant financial relationships listed have been mitigated. Scott Manaker, MD, PhD Other Financial Interest: Expert witness in workers' compensation and in medical negligence matters [General pulmonary and critical care medicine]; National Board for Respiratory Care [Director]. 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/approach-to-sudden-cardiac-arrest-in-the-absence-of-apparent-structural-heart-disease/print 21/21