correlates, and prognosis. Ann Noninvasive Electrocardiol 2014; 19:490. Topic 16697 Version 32.0 https://www.uptodate.com/contents/short-qt-syndrome/print 24/34 7/6/23, 1:45 PM Short QT syndrome - UpToDate GRAPHICS Ventricular action potential and QRS-T cycle The QRS-T cycle on the electrocardiogram corresponds to different phases of the ventricular action potential. Graphic 78354 Version 1.0 https://www.uptodate.com/contents/short-qt-syndrome/print 25/34 7/6/23, 1:45 PM Short QT syndrome - UpToDate Genetic basis of SQTS QTc (milliseconds) Gene (cardiac ion channel) [1] ) SQT1 286 6 KCNH2 (I Kr [2] ) SQT2 302 KCNQ1 (I Ks [3] ) SQT3 315-330 KCNJ2 (I K1 [4] ) SQT4 331-370 CACNB2b (I Ca [4] ) SQT5 346-360 CACNA1C (I Ca [5] ) SQT6 330 CACNA2D1 (I Ca [6] SLC22A5 ( carnitine - I SQT7 282-340 ) Kr [7] SQT8 340 18 SLC4A3 (pHi-[Cl-]) References: 1. Brugada R, Hong K, Dumaine R, et al. Sudden death associated with short-QT syndrome linked to mutations in HERG. Circulation 2004; 109:30. 2. Bellocq C, van Ginneken AC, Bezzina CR, et al. Mutation in the KCNQ1 gene leading to the short QT-interval syndrome. Circulation 2004; 109:2394. 3. Priori SG, Pandit SV, Rivolta I, et al. A novel form of short QT syndrome (SQT3) is caused by a mutation in the KCNJ2 gene. Circ Res 2005; 96:800. 4. Antzelevitch C, Pollevick GD, Cordeiro JM, et al. Loss-of-function mutations in the cardiac calcium channel underlie a new clinical entity characterized by ST-segment elevation, short QT intervals, and sudden cardiac death. Circulation 2007; 115:442. 5. Templin C, Ghadri JR, Rougier JS, et al. Identi cation of a novel loss-of-function calcium channel gene mutation in short QT syndrome (SQTS6). Eur Heart J 2011; 32:1077. 6. Roussel J, Labarthe F, Thireau J, et al. Carnitine de ciency induces a short QT syndrome. Heart Rhythm 2016; 13:165. 7. Thorsen K, Dam VS, Kjaer-Sorensen K, et al. Loss-of-activity-mutation in the cardiac chloride-bicarbonate exchanger AE3 causes short QT syndrome. Nature communications 2017; 8:1696. Graphic 72304 Version 6.0 https://www.uptodate.com/contents/short-qt-syndrome/print 26/34 7/6/23, 1:45 PM Short QT syndrome - UpToDate Action potential currents Major cardiac ion currents and channels responsible for a ventricular action potential are shown with their common name, abbreviation, and the gene and protein for the alpha subunit that forms the pore or transporter. The diagram on the left shows the time course of amplitude of each current during the action potential, but does not accurately reflect amplitudes relative to each of the other currents. This summary represents a ventricular myocyte, and lists only the major ion channels. The currents and their molecular nature vary within regions of the ventricles, and in atria, and other specialized cells such as nodal and Purkinje. Ion channels exist as part of multi-molecular complexes including beta subunits and other associated regulatory proteins which are also not shown. Courtesy of Jonathan C Makielski, MD, FACC. Graphic 70771 Version 4.0 https://www.uptodate.com/contents/short-qt-syndrome/print 27/34 7/6/23, 1:45 PM Short QT syndrome - UpToDate Electrocardiographic characteristics of the short QT syndrome (A) A 12-lead ECG showing ECG characteristic of SQT1. (B) A 12-lead ECG showing ECG characteristic of SQT4 displaying combined ECG phenotype of Brugada and short QT syndromes. Note that ECG shows Brugada type ST elevation in V1 and V2 after administration of ajmaline in addition to short QT intervals. Reproduced with permission from: Patel C, Yan GX, Antzelevitch C. Short QT syndrome: from bench to bedside. Circ Arrhythm Electrophysiol 2010; 3:401. Copyright 2010 Lippincott Williams & Wilkins. Graphic 51616 Version 6.0 https://www.uptodate.com/contents/short-qt-syndrome/print 28/34 7/6/23, 1:45 PM Short QT syndrome - UpToDate Proposed diagnostic criteria for short QT syndrome Criteria Points QTc, milliseconds <370 1 <350 2 <330 3 J T point peak interval <120 milliseconds 1 Clinical history* History of sudden cardiac arrest 2 Documented polymorphic VT or VF 2 Unexplained syncope 1 Atrial fibrillation 1 Family history* First- or second-degree relative with high probability of SQTS 2 First- or second-degree relative with autopsy-negative sudden cardiac death 1 Sudden infant death syndrome 1 Genotype* Genotype positive 2 Mutation of undetermined significance in a culprit gene 1 Total High-probability SQTS: 4 points. Intermediate-probability SQTS: 3 points. Low-probability SQTS: 2 points. VF: ventricular fibrillation; VT: ventricular tachycardia; SQTS: short QT syndrome; QT: Bazett corrected QT interval. A minimum of 1 point must be obtained in the electrocardiographic section in order to obtain additional points. Original table modi ed for this publication. Gollob MH, Redpath CJ, Roberts JD: The short QT syndrome: proposed diagnostic criteria. J Am Coll Cardiol 2011; 57:802. Table used with the permission of Elsevier Inc. All rights reserved. https://www.uptodate.com/contents/short-qt-syndrome/print 29/34 7/6/23, 1:45 PM Short QT syndrome - UpToDate Graphic 65743 Version 5.0 https://www.uptodate.com/contents/short-qt-syndrome/print 30/34 7/6/23, 1:45 PM Short QT syndrome - UpToDate Secondary causes of short QT interval on ECG Hyperkalemia Hypercalcemia Hyperthermia Acidosis Effect of catecholamine Activation of ATP-sensitive potassium current Activation of acetylcholine-sensitive potassium current Effects of drugs like digitalis Myocardial ischemia Increased vagal tone Bufatolin (toad extract and antineoplastic, traditional Chinese medicine) Graphic 59159 Version 2.0 https://www.uptodate.com/contents/short-qt-syndrome/print 31/34 7/6/23, 1:45 PM Short QT syndrome - UpToDate Revised (2018) Vaughan Williams classification of antiarrhythmic drugs abridged table Class 0 (HCN channel blockers) Ivabradine Class I (voltage-gated Na+ channel blockers) Class Ia (intermediate dissociation): Quinidine, ajmaline, disopyramide, procainamide Class Ib (rapid dissociation): Lidocaine, mexilitine Class Ic (slow dissociation): Propafenone, flecainide Class Id (late current): Ranolazine Class II (autonomic inhibitors and activators) Class IIa (beta blockers): Nonselective: carvedilol, propranolol, nadolol Selective: atenolol, bisoprolol, betaxolol, celiprolol, esmolol, metoprolol Class IIb (nonselective beta agonists): Isoproterenol Class IIc (muscarinic M2 receptor inhibitors): Atropine, anisodamine, hyoscine, scopolamine Class IId (muscarinic M2 receptor activators): Carbachol, pilocarpine, methacholine, digoxin Class IIe (adenosine A1 receptor activators): Adenosine Class III (K+ channel blockers and openers) Class IIIa (voltage dependent K+ channel blockers): Ambasilide, amiodarone, dronedarone, dofetilide, ibutilide, sotalol, vernakalant Class IIIb (metabolically dependent K+ channel openers): https://www.uptodate.com/contents/short-qt-syndrome/print 32/34 7/6/23, 1:45 PM Short QT syndrome - UpToDate Nicorandil, pinacidil Class IV (Ca++ handling modulators) Class IVa (surface membrane Ca++ channel blockers): Bepridil, diltiazem, verapamil Class IVb (intracellular Ca++ channel blockers): Flecainide, propafenone Class V (mechanosensitive channel blockers): No approved medications Class VI (gap junction channel blockers) No approved medications Class VII (upstream target modulators) Angiotensin converting enzyme inhibitors Angiotensin receptor blockers Omega-3 fatty acids Statins HCN: hyperpolarization-activated cyclic nucleotide-gated; Na: sodium; K: potassium; Ca: calcium. Graphic 120433 Version 3.0 https://www.uptodate.com/contents/short-qt-syndrome/print 33/34 7/6/23, 1:45 PM Short QT syndrome - UpToDate Contributor Disclosures Charles Antzelevitch, PhD, FACC, FAHA, FHRS Grant/Research/Clinical Trial Support: InCarda Pharmaceuticals [Atrial fibrillation]; Kymera Pharmaceuticals [Safety pharmacology]; NHLBI of the NIH [WW Smith Trust]; Novartis [Atrial fibrillation]; Trevena Inc [Electrophysiology of oliceridine]. Consultant/Advisory Boards: Novartis [Atrial fibrillation]; Trevena Inc [Electrophysiology of oliceridine]. Speaker's Bureau: Invitae [Mechanisms underlying the J wave syndromes as a cause of SCD]. All of the relevant financial relationships listed have been mitigated. Mark S Link, MD No relevant financial relationship(s) with ineligible companies to disclose. 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/short-qt-syndrome/print 34/34