2505000623
  • Open Access
  • Review
Short QT Syndrome and Drug Treatment: A systematic Literature Review and PRISMA Analysis
  • Tingting You 1,   
  • Cunjin Luo 2, *,   
  • Kevin Zhang 3,   
  • Henggui Zhang 1, 4, 5, *

Received: 25 Jun 2024 | Revised: 26 Aug 2024 | Accepted: 26 Aug 2024 | Published: 12 May 2025

Abstract

Short QT Syndrome (SQTS) is a rare inherited myocardial ion channel disease characterized by abbreviated cardiac repolarization and shortened QT interval in ECGs, resulting to a high incidence of sudden death and malignant arrhythmias. While various gene mutations that encode subunits of K+, Ca2+, and Na+ channels, as well as the SLC4A3 gene mutation associated with plasma membrane anion exchange, have been implicated, targeted gene screening remains relatively low. In this review, we searched multiple databases, such as PubMed, ScienceDirect, Embase, Web of Science, and Medline, and followed the guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) to conduct a systematic review of literatures in SQTS. We first used VOSviewer to analyze the co-authorship, co-occurrence of countries, organizations, authors, and keywords in the published literatures of SQTs, and then surveyed evidences regarding the impact of single or polygenic gene mutations identified is SQT patients on the electrophysiological properties of IKr, IKs, IK1, ICa-L, INa, and the anion exchanger AE3. Additionally, this review also surveyed current progress in the understandings of potential mechanisms underlying arrhythmogenesis of the SQT gene mutations, and possible drug therapy, unraveled by both experimental and simulation studies.

References 

  • 1.
    Gollob, M.H. Short QT syndrome: Advancing our understanding of genetics and cardiac physiology. Heart Rhythm 2023, 20, 1144–1145. https://doi.org/10.1016/j.hrthm.2023.05.003.
  • 2.
    Gussak, I.; Brugada, P.; Brugada, J.; et al. Idiopathic short QT interval: A new clinical syndrome? Cardiology 2000, 94, 99–102. https://doi.org/10.1159/000047299.
  • 3.
    Mazzanti, A.; Kanthan, A.; Monteforte, N.; et al. Novel insight into the natural history of short QT syndrome. J. Am. Coll. Cardiol. 2014, 63, 1300–1308. https://doi.org/10.1016/j.jacc.2013.09.078.
  • 4.
    Al-Khatib, S.M.; Stevenson, W.G. Management of Ventricular Arrhythmias and Sudden Cardiac Death Risk Associated with Cardiac Channelopathies. JAMA Cardiol. 2018, 3, 775–776. https://doi.org/10.1001/jamacardio.2018.1116.
  • 5.
    Bjerregaard, P. Diagnosis and management of short QT syndrome. Heart Rhythm 2018, 15, 1261–1267. https://doi.org/10.1016/j.hrthm.2018.02.034.
  • 6.
    Lester, R.M.; Paglialunga, S.; Johnson, I.A. QT Assessment in Early Drug Development: The Long and the Short of It. Int. J. Mol. Sci. 2019, 20, 1324. https://doi.org/10.3390/ijms20061324.
  • 7.
    Providencia, R.; Karim, N.; Srinivasan, N.; et al. Impact of QTc formulae in the prevalence of short corrected QT interval and impact on probability and diagnosis of short QT syndrome. Heart 2018, 104, 502–508. https://doi.org/10.1136/heartjnl-2017-311673.
  • 8.
    Tülümen, E.; Giustetto, C.; Wolpert, C.; et al. PQ segment depression in patients with short QT syndrome: A novel marker for diagnosing short QT syndrome? Heart Rhythm 2014, 11, 1024–1030. https://doi.org/10.1016/j.hrthm.2014.02.024.
  • 9.
    Shiti, A.; Arbil, G.; Shaheen, N.; et al. Utilizing human induced pluripotent stem cells to study atrial arrhythmias in the short QT syndrome. J. Mol. Cell. Cardiol. 2023, 183, 42–53. https://doi.org/10.1016/j.yjmcc.2023.08.003.
  • 10.
    Suzuki, H.; Horie, M.; Ozawa, J.; et al. Novel electrocardiographic criteria for short QT syndrome in children and adolescents. Europace 2021, 23, 2029–2038. https://doi.org/10.1093/europace/euab097.
  • 11.
    Sedlak, T.; Shufelt, C.; Iribarren, C.; et al. Sex hormones and the QT interval: A review. J. Womens Health 2012, 21, 933–941. https://doi.org/10.1089/jwh.2011.3444.
  • 12.
    Giustetto, C.; Schimpf, R.; Mazzanti, A.; et al. Long-term follow-up of patients with short QT syndrome. J Am Coll Cardiol 2011, 58, 587–595. https://doi.org/10.1016/j.jacc.2011.03.038.
  • 13.
    Odening, K.E.; Bodi, I.; Rieke, R.; et al. Electro-mechanical remodeling in transgenig short QT syndrome rabbits. Heart Rhythm 2017, 14, S327.
  • 14.
    El-Battrawy, I.; Besler, J.; Liebe, V.; et al. Long-Term Follow-Up of Patients With Short QT Syndrome: Clinical Profile and Outcome. J Am. Heart Assoc. 2018, 7, e010073. https://doi.org/10.1161/jaha.118.010073.
  • 15.
    Priori, S.G.; 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, 36, 2793–2867. https://doi.org/10.1093/eurheartj/ehv316.
  • 16.
    Mazzanti, A.; Maragna, R.; Vacanti, G.; et al. Hydroquinidine Prevents Life-Threatening Arrhythmic Events in Patients With Short QT Syndrome. J. Am. Coll. Cardiol. 2017, 70, 3010–3015. https://doi.org/10.1016/j.jacc.2017.10.025.
  • 17.
    Walsh, R.; Adler, A.; Amin, A.S.; et al. Evaluation of gene validity for CPVT and short QT syndrome in sudden arrhythmic death. Eur. Heart J. 2022, 43, 1500–1510. https://doi.org/10.1093/eurheartj/ehab687.
  • 18.
    Brugada, R.; Hong, K.; Dumaine, R.; et al. Sudden death associated with short-QT syndrome linked to mutations in HERG. Circulation 2004, 109, 30–35. https://doi.org/10.1161/01.Cir.0000109482.92774.3a.
  • 19.
    Campuzano, O.; Sarquella-Brugada, G.; Cesar, S.; et al. Recent Advances in Short QT Syndrome. Front. Cardiovasc. Med. 2018, 5, 149. https://doi.org/10.3389/fcvm.2018.00149.
  • 20.
    Itoh, H.; Sakaguchi, T.; Ashihara, T.; et al. A novel KCNH2 mutation as a modifier for short QT interval. Int. J. Cardiol. 2009, 137, 83–85. https://doi.org/10.1016/j.ijcard.2008.05.050.
  • 21.
    Redpath, C.J.; Green, M.S.; Birnie, D.H.; et al. Rapid genetic testing facilitating the diagnosis of short QT syndrome. Can. J. Cardiol. 2009, 25, e133–e135.
  • 22.
    Hu, D.; Li, Y.; Zhang, J.; et al. The Phenotypic Spectrum of a Mutation Hotspot Responsible for the Short QT Syndrome. JACC Clin. Electrophysiol. 2017, 3, 727–743. https://doi.org/10.1016/j.jacep.2016.11.013.
  • 23.
    Sun, Y.; Quan, X.Q.; Fromme, S.; et al. A novel mutation in the KCNH2 gene associated with short QT syndrome. J. Mol. Cell. Cardiol. 2011, 50, 433–441. https://doi.org/10.1016/j.yjmcc.2010.11.017.
  • 24.
    Harrell, D.T.; Ashihara, T.; Ishikawa, T.; et al. Genotype-dependent differences in age of manifestation and arrhythmia complications in short QT syndrome. Int. J. Cardiol. 2015, 190, 393–402. https://doi.org/10.1016/j.ijcard.2015.04.090.
  • 25.
    Akdis, D.; Saguner, A.M.; Medeiros-Domingo, A.; et al. Multiple clinical profiles of families with the short QT syndrome. Europace 2018, 20, f113-f121. https://doi.org/10.1093/europace/eux186.
  • 26.
    Bellocq, C.; van Ginneken, A.C.; Bezzina, C.R.; et al. Mutation in the KCNQ1 gene leading to the short QT-interval syndrome. Circulation 2004, 109, 2394–2397. https://doi.org/10.1161/01.CIR.0000130409.72142.FE.
  • 27.
    Tamargo, J.; Caballero, R.; Gomez, R.; et al. Pharmacology of cardiac potassium channels. Cardiovasc. Res. 2004, 62, 9–33. https://doi.org/10.1016/j.cardiores.2003.12.026.
  • 28.
    Hong, K.; Piper, D.R.; Diaz-Valdecantos, A.; et al. De novo KCNQ1 mutation responsible for atrial fibrillation and short QT syndrome in utero. Cardiovasc. Res. 2005, 68, 433–440. https://doi.org/10.1016/j.cardiores.2005.06.023.
  • 29.
    Garcia Ordonez, G.; Reyes-Quintero, A.E.; Garcia, A.; et al. KCNQ1 V141M and Short QT Syndrome: Are we dealing with a different entity? Eur. Heart J. 2020, 41, 453. https://doi.org/10.1093/ehjci/ehaa946.0453.
  • 30.
    Wu, Z.J.; Huang, Y.; Fu, Y.C.; et al. Characterization of a Chinese KCNQ1 mutation (R259H) that shortens repolarization and causes short QT syndrome 2. J. Geriatr. Cardiol. 2015, 12, 394–401. https://doi.org/10.11909/j.issn.1671-5411.2015.04.002.
  • 31.
    Moreno, C.; Oliveras, A.; de la Cruz, A.; et al. A new KCNQ1 mutation at the S5 segment that impairs its association with KCNE1 is responsible for short QT syndrome. Cardiovasc. Res. 2015, 107, 613–623. https://doi.org/10.1093/cvr/cvv196.
  • 32.
    Rothenberg, I.; Piccini, I.; Wrobel, E.; et al. Structural interplay of KCNE1 and KV7.1 is crucial for both, SQT2 and LQT1. Acta Physiol. 2015, 213, 116. https://doi.org/10.1111/apha.12484.
  • 33.
    Hancox, J.C.; Whittaker, D.G.; Du, C.; et al. Emerging therapeutic targets in the short QT syndrome. Expert Opin. Ther. Targets 2018, 22, 439–451. https://doi.org/10.1080/14728222.2018.1470621.
  • 34.
    van der Schoor, L.; van Hattum, E.J.; de Wilde, S.M.; et al. Towards the development of agokirs: New pharmacological activators to study kir 2.x channel and target cardiac disease. Int. J. Mol. Sci. 2020, 21, 5746. https://doi.org/10.3390/ijms21165746.
  • 35.
    Priori, S.G.; Pandit, S.V.; 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, 800–807. https://doi.org/10.1161/01.RES.0000162101.76263.8c.
  • 36.
    Du, C.Y.; Rasmusson, R.L.; Bett, G.C.; et al. Investigation of the Effects of the Short QT Syndrome D172N Kir2.1 Mutation on Ventricular Action Potential Profile Using Dynamic Clamp. Front. Pharmacol. 2022, 12, 794620. https://doi.org/10.3389/fphar.2021.794620.
  • 37.
    Hattori, T.; Makiyama, T.; Akao, M.; et al. A novel gain-of-function KCNJ2 mutation associated with short-QT syndrome impairs inward rectification of Kir2.1 currents. Cardiovasc. Res. 2012, 93, 666–673. https://doi.org/10.1093/cvr/cvr329.
  • 38.
    Nagueh, S.F.; Zoghbi, W.A. Role of Imaging in the Evaluation of Patients at Risk for Sudden Cardiac Death: Genotype–Phenotype Intersection. JACC Cardiovasc. Imaging 2015, 8, 828–845. https://doi.org/10.1016/j.jcmg.2015.04.006.
  • 39.
    Ambrosini, E.; Sicca, F.; Brignone, M.S.; et al. Genetically induced dysfunctions of Kir2.1 channels: Implications for short QT3 syndrome and autism-epilepsy phenotype. Hum. Mol. Genet. 2014, 23, 4875–4886. https://doi.org/10.1093/hmg/ddu201.
  • 40.
    Hancox, J.C.; Du, C.Y.; Butler, A.; et al. Pro-arrhythmic effects of gain-of-function potassium channel mutations in the short QT syndrome. Philos. Trans. R. Soc. London. Ser. B Biol. Sci. 2023, 378, 20220165. https://doi.org/10.1098/rstb.2022.0165.
  • 41.
    Antzelevitch, C.; Pollevick, G.D.; Cordeiro, J.M.; 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, 442–449. https://doi.org/10.1161/CIRCULATIONAHA.106.668392.
  • 42.
    Endres, D.; Decher, N.; Röhr, I.; et al. New Cav1.2 Channelopathy with High-Functioning Autism, Affective Disorder, Severe Dental Enamel Defects, a Short QT Interval, and a Novel CACNA1C Loss-Of-Function Mutation. Int. J. Mol. Sci. 2020, 21, 8611. https://doi.org/10.3390/ijms21228611.
  • 43.
    Zhong, R.; Zhang, F.; Yang, Z.; et al. Epigenetic mechanism of L-type calcium channel beta-subunit downregulation in short QT human induced pluripotent stem cell-derived cardiomyocytes with CACNB2 mutation. Europace 2022, 24, 2028–2036. https://doi.org/10.1093/europace/euac091.
  • 44.
    Templin, C.; Ghadri, J.R.; Rougier, J.S.; et al. Identification of a novel loss-of-function calcium channel gene mutation in short QT syndrome (SQTS6). Eur. Heart J. 2011, 32, 1077–1088. https://doi.org/10.1093/eurheartj/ehr076.
  • 45.
    Ackerman, M.J.; Splawski, I.; Makielski, J.C.; et al. Spectrum and prevalence of cardiac sodium channel variants among black, white, Asian, and Hispanic individuals: Implications for arrhythmogenic susceptibility and Brugada/long QT syndrome genetic testing. Heart Rhythm 2004, 1, 600–607. https://doi.org/10.1016/j.hrthm.2004.07.013.
  • 46.
    Hong, K.; Hu, J.; Yu, J.; et al. Concomitant Brugada-like and short QT electrocardiogram linked to SCN5A mutation. Eur J. Hum. Genet. 2012, 20, 1189–1192. https://doi.org/10.1038/ejhg.2012.63.
  • 47.
    Tan, B.H.; Valdivia, C.R.; Rok, B.A.; et al. Common human SCN5A polymorphisms have altered electrophysiology when expressed in Q1077 splice variants. Heart Rhythm 2005, 2, 741–747. https://doi.org/10.1016/j.hrthm.2005.04.021.
  • 48.
    Gollob, M.H.; Redpath, C.J.; Roberts, J.D. The short QT syndrome: Proposed diagnostic criteria. J. Am. Coll. Cardiol. 2011, 57, 802–812. https://doi.org/10.1016/j.jacc.2010.09.048.
  • 49.
    Thorsen, K.; Dam, V.S.; Kjaer-Sorensen, K.; et al. Loss-of-activity-mutation in the cardiac chloride-bicarbonate exchanger AE3 causes short QT syndrome. Nat. Commun. 2017, 8, 1696. https://doi.org/10.1038/s41467-017-01630-0.
  • 50.
    Christiansen, M.K.; Kjaer-Sorensen, K.; Clavsen, N.C.; et al. Genetic analysis identifies the SLC4A3 anion exchanger as a major gene for short QT syndrome. Heart Rhythm 2023, 20, 1136–1143. https://doi.org/10.1016/j.hrthm.2023.02.010.
  • 51.
    Guo, F.F.; Sun, Y.X.; Wang, X.C.; et al. Patient-Specific and Gene-Corrected Induced Pluripotent Stem Cell-Derived Cardiomyocytes Elucidate Single-Cell Phenotype of Short QT Syndrome. Circ. Res. 2019, 124, 66–78. https://doi.org/10.1161/circresaha.118.313518.
  • 52.
    Giustetto, C.; Scrocco, C.; Giachino, D.; et al. The lack of effect of sotalol in short QT syndrome patients carrying the T618I mutation in the KCNH2 gene. Hear. Case Rep 2015, 1, 373–378. https://doi.org/10.1016/j.hrcr.2015.07.001.
  • 53.
    Hassel, D.; Scholz, E.P.; Trano, N.; et al. Deficient zebrafish ether-a-go-go-related gene channel gating causes short-QT syndrome in zebrafish reggae mutants. Circulation 2008, 117, 866–875. https://doi.org/10.1161/CIRCULATIONAHA.107.752220.
  • 54.
    Odening, K.E.; Bodi, I.; Franke, G.; et al. Transgenic short-QT syndrome 1 rabbits mimic the human disease phenotype with QT/action potential duration shortening in the atria and ventricles and increased ventricular tachycardia/ventricular fibrillation inducibility. Eur. Heart J. 2018, 40, 842–853. https://doi.org/10.1093/eurheartj/ehy761.
  • 55.
    El Harchi, A.; McPate, M.J.; Zhang, Y.H.; et al. Action potential clamp and mefloquine sensitivity of recombinant ‘I KS’ channels incorporating the V307L KCNQ1 mutation. J. Physiol. Pharmacol. 2010, 61, 123–131.
  • 56.
    El Harchi, A.; Melgari, D.; Zhang, Y.H.; et al. Action potential clamp and pharmacology of the variant 1 Short QT Syndrome T618I hERG K(+) channel. PLoS ONE 2012, 7, e52451. https://doi.org/10.1371/journal.pone.0052451.
  • 57.
    Patel, C.; Antzelevitch, C. Cellular basis for arrhythmogenesis in an experimental model of the SQT1 form of the short QT syndrome. Heart Rhythm 2008, 5, 585–590. https://doi.org/10.1016/j.hrthm.2008.01.022.
  • 58.
    El-Battrawy, I.; Lan, H.; Cyganek, L.; et al. Modeling Short QT Syndrome Using Human-Induced Pluripotent Stem Cell-Derived Cardiomyocytes. J. Am. Heart Assoc. 2018, 7, e007394. https://doi.org/10.1161/JAHA.117.007394.
  • 59.
    Huang, M.; Liao, Z.; Li, X.; et al. Effects of Antiarrhythmic Drugs on hERG Gating in Human-Induced Pluripotent Stem Cell-Derived Cardiomyocytes From a Patient With Short QT Syndrome Type 1. Front. Pharmacol. 2021, 12, 675003. https://doi.org/10.3389/fphar.2021.675003.
  • 60.
    Zhang, H.; Hancox, J.C. In silico study of action potential and QT interval shortening due to loss of inactivation of the cardiac rapid delayed rectifier potassium current. Biochem. Biophys. Res. Commun. 2004, 322, 693–699. https://doi.org/10.1016/j.bbrc.2004.07.176.
  • 61.
    Weiss, D.L.; Seemann, G.; Sachse, F.B.; et al. Modelling of short QT syndrome in a heterogeneous model of the human ventricular wall. Europace 2005, 7, 105–117. https://doi.org/10.1016/j.eupc.2005.04.008.
  • 62.
    Itoh, H.; Horie, M.; Ito, M.; et al. Arrhythmogenesis in the short-QT syndrome associated with combined HERG channel gating defects: A simulation study. Circ. J. 2006, 70, 502–508.
  • 63.
    Adeniran, I.; McPate, M.J.; Witchel, H.J.; et al. Increased vulnerability of human ventricle to re-entrant excitation in hERG-linked variant 1 short QT syndrome. PLoS Comput. Biol. 2011, 7, e1002313. https://doi.org/10.1371/journal.pcbi.1002313.
  • 64.
    Loewe, A.; Wilhelms, M.; Fischer, F.; et al. Arrhythmic potency of human ether-a-go-go-related gene mutations L532P and N588K in a computational model of human atrial myocytes. Europace 2014, 16, 435–443. https://doi.org/10.1093/europace/eut375.
  • 65.
    Zhang, H.; Kharche, S.; Holden, A.V.; Hancox, J.C. Repolarisation and vulnerability to re-entry in the human heart with short QT syndrome arising from KCNQ1 mutation--a simulation study. Prog. Biophys. Mol. Biol. 2008, 96, 112–131. https://doi.org/10.1016/j.pbiomolbio.2007.07.020.
  • 66.
    Adeniran, I.; Whittaker, D.G.; El Harchi, A.; et al. In silico investigation of a KCNQ1 mutation associated with short QT syndrome. Sci. Rep. 2017, 7, 8469. https://doi.org/10.1038/s41598-017-08367-2.
  • 67.
    Whittaker, D.G.; Colman, M.A.; Ni, H.; et al. Human Atrial Arrhythmogenesis and Sinus Bradycardia in KCNQ1-Linked Short QT Syndrome: Insights From Computational Modelling. Front. Physiol. 2018, 9, 1402. https://doi.org/10.3389/fphys.2018.01402.
  • 68.
    Adeniran, I.; El Harchi, A.; Hancox, J.C.; et al. Proarrhythmia in KCNJ2-linked short QT syndrome: Insights from modelling. Cardiovasc. Res. 2012, 94, 66–76. https://doi.org/10.1093/cvr/cvs082.
  • 69.
    Whittaker, D.G.; Ni, H.; El Harchi, A.; et al. Atrial arrhythmogenicity of KCNJ2 mutations in short QT syndrome: Insights from virtual human atria. PLoS Comput. Biol. 2017, 13, e1005593. https://doi.org/10.1371/journal.pcbi.1005593.
  • 70.
    Extramiana, F.; Antzelevitch, C. Amplified transmural dispersion of repolarization as the basis for arrhythmogenesis in a canine ventricular-wedge model of short-QT syndrome. Circulation 2004, 110, 3661–3666. https://doi.org/10.1161/01.Cir.0000143078.48699.0c.
  • 71.
    Deo, M.; Ruan, Y.; Pandit, S.V.; et al. KCNJ2 mutation in short QT syndrome 3 results in atrial fibrillation and ventricular proarrhythmia. Proc. Natl. Acad. Sci. USA 2013, 110, 4291–4296. https://doi.org/10.1073/pnas.1218154110.
  • 72.
    McPate, M.J.; Duncan, R.S.; Hancox, J.C.; et al. Pharmacology of the short QT syndrome N588K-hERG K(+) channel mutation: Differential impact on selected class I and class III antiarrhythmic drugs. Br. J. Pharmacol. 2008, 155, 957–966. https://doi.org/10.1038/bjp.2008.325.
  • 73.
    Fan, X.H.; Yang, G.Q.; Kowitz, J.; et al. Preclinical short QT syndrome models: Studying the phenotype and drug-screening. Europace 2022, 24, 481–493. https://doi.org/10.1093/europace/euab214.
  • 74.
    Zhang, S.; Lu, W.; Yang, F.; et al. Computational analysis of arrhythmogenesis in KCNH2 T618I mutation-associated short QT syndrome and the pharmacological effects of quinidine and sotalol. NPJ Syst. Biol. Appl. 2022, 8, 43. https://doi.org/10.1038/s41540-022-00254-5.
  • 75.
    Nof, E.; Burashnikov, A.; Antzelevitch, C. Cellular basis for atrial fibrillation in an experimental model of short QT1: Implications for a pharmacological approach to therapy. Heart Rhythm 2010, 7, 251–257. https://doi.org/10.1016/j.hrthm.2009.10.017.
  • 76.
    Giudicessi, J.R.; Ackerman, M.J. Potassium-channel mutations and cardiac arrhythmias—Diagnosis and therapy. Nat. Rev. Cardiol. 2012, 9, 319–332. https://doi.org/10.1038/nrcardio.2012.3.
  • 77.
    Zhao, Z.; Li, X.; El-Battrawy, I.; et al. Drug Testing in Human-Induced Pluripotent Stem Cell-Derived Cardiomyocytes From a Patient With Short QT Syndrome Type 1. Clin. Pharmacol. Ther. 2019, 106, 642–651. https://doi.org/10.1002/cpt.1449.
  • 78.
    Lan, H.; Xu, Q.; El-Battrawy, I.; et al. Ionic Mechanisms of Disopyramide Prolonging Action Potential Duration in Human-Induced Pluripotent Stem Cell-Derived Cardiomyocytes From a Patient With Short QT Syndrome Type 1. Front. Pharmacol. 2020, 11, 554422. https://doi.org/10.3389/fphar.2020.554422.
  • 79.
    Whittaker, D.G.; Hancox, J.C.; Zhang, H. In silico Assessment of Pharmacotherapy for Human Atrial Patho-Electrophysiology Associated With hERG-Linked Short QT Syndrome. Front. Physiol. 2018, 9, 1888. https://doi.org/10.3389/fphys.2018.01888.
  • 80.
    Lerche, C.; Bruhova, I.; Lerche, H.; et al. Chromanol 293B binding in KCNQ1 (Kv7.1) channels involves electrostatic interactions with a potassium ion in the selectivity filter. Mol. Pharmacol. 2007, 71, 1503–1511. https://doi.org/10.1124/mol.106.031682.
  • 81.
    Kang, J.; Chen, X.L.; Wang, L.; Rampe, D. Interactions of the antimalarial drug mefloquine with the human cardiac potassium channels KvLQT1/minK and HERG. J. Pharmacol. Exp. Ther. 2001, 299, 290–296.
  • 82.
    Campbell, C.M.; Campbell, J.D.; Thompson, C.H.; et al. Selective targeting of gain-of-function KCNQ1 mutations predisposing to atrial fibrillation. Circ. Arrhythmia Electrophysiol. 2013, 6, 960–966. https://doi.org/10.1161/CIRCEP.113.000439.
  • 83.
    An, M.Y.; Sun, K.; Li, Y.; et al. Therapeutic effects of a taurine-magnesium coordination compound on experimental models of type 2 short QT syndrome. Acta Pharmacol. Sin. 2018, 39, 382–392. https://doi.org/10.1038/aps.2017.86.
  • 84.
    Patel, C.; Yan, G.X.; Antzelevitch, C. Short QT syndrome: From bench to bedside. Circ. Arrhythmia Electrophysiol. 2010, 3, 401–408. https://doi.org/10.1161/CIRCEP.109.921056.
  • 85.
    Ren, S.; Pang, C.; Li, J.; et al. Styrax blocks inward and outward current of Kir2.1 channel. Channels 2017, 11, 46–54. https://doi.org/10.1080/19336950.2016.1207022.
  • 86.
    Ji, Y.; Veldhuis, M.G.; Zandvoort, J.; et al. PA-6 inhibits inward rectifier currents carried by V93I and D172N gain-of-function KIR2.1 channels, but increases channel protein expression. J Biomed. Sci. 2017, 24, 44. https://doi.org/10.1186/s12929-017-0352-x.
  • 87.
    Luo, C.; Wang, K.; Zhang, H. In silico assessment of the effects of quinidine, disopyramide and E-4031 on short QT syndrome variant 1 in the human ventricles. PLoS ONE 2017, 12, e0179515. https://doi.org/10.1371/journal.pone.0179515.
  • 88.
    Luo, C.; Wang, K.; Zhang, H. Modelling the effects of quinidine, disopyramide, and E-4031 on short QT syndrome variant 3 in the human ventricles. Physiol. Meas. 2017, 38, 1859–1873. https://doi.org/10.1088/1361-6579/aa8695.
  • 89.
    Schreibmayer, W.; Lindner, W. Stereoselective interactions of (R)- and (S)-propafenone with the cardiac sodium channel. J. Cardiovasc. Pharmacol. 1992, 20, 324–331.
  • 90.
    Monk, J.P.; Brogden, R.N. Mexiletine. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic use in the treatment of arrhythmias. Drugs 1990, 40, 374–411. https://doi.org/10.2165/00003495-199040030-00005.
  • 91.
    Singh, B.N. Antiarrhythmic actions of amiodarone: A profile of a paradoxical agent. Am. J. Cardiol. 1996, 78, 41–53.
  • 92.
    Bjerregaard, P.; Jahangir, A.; Gussak, I. Targeted therapy for short QT syndrome. Expert Opin. Ther. Targets 2006, 10, 393–400. https://doi.org/10.1517/14728222.10.3.393.
  • 93.
    Luo, C.; Wang, K.; Zhang, H. Effects of amiodarone on short QT syndrome variant 3 in human ventricles: A simulation study. Biomed. Eng. Online 2017, 16, 69. https://doi.org/10.1186/s12938-017-0369-0.
  • 94.
    Awamleh García, P.; Alonso Martín, J.J.; Graupner Abad, C.; et al. Prevalence of Electrocardiographic Patterns Associated With Sudden Cardiac Death in the Spanish Population Aged 40 Years or Older. Results of the OFRECE Study. Rev. Esp. Cardiol. 2017, 70, 801–807. https://doi.org/10.1016/j.rec.2016.11.039.
  • 95.
    Villafane, J.; Young, M.; Atallah, J.; et al. Long-term follow-up of a pediatric cohort with short QT syndrome. Heart Rhythm 2012, 9, 1920. https://doi.org/10.1016/j.hrthm.2012.09.019.
  • 96.
    Miyamoto, A.; Hayashi, H.; Yoshino, T.; et al. Clinical and electrocardiographic characteristics of patients with short QT interval in a large hospital-based population. Heart Rhythm 2012, 9, 66–74. https://doi.org/10.1016/j.hrthm.2011.08.016.
  • 97.
    Mariani, M.V.; Pierucci, N.; Fanisio, F.; et al. Inherited Arrhythmias in the Pediatric Population: An Updated Overview. Medicina 2024, 60, 94. https://doi.org/10.3390/medicina60010094.
  • 98.
    Guerrier, K.; Kwiatkowski, D.; Czosek, R.J.; et al. Short QT Interval Prevalence and Clinical Outcomes in a Pediatric Population. Circ. Arrhythmia Electrophysiol. 2015, 8, 1460–1464. https://doi.org/10.1161/circep.115.003256.
  • 99.
    Wang, B.; Ren, Q.; Cui, X.; et al. Generation of KCNH2 heterozygous knockout induced pluripotent stem cell (iPSC) line (Long and Short QT Syndrome). Stem Cell Res. 2024, 77, 103400. https://doi.org/10.1016/j.scr.2024.103400.
  • 100.
    Maurissen, T.L.; Kawatou, M.; Lopez-Davila, V.; et al. Modeling mutation-specific arrhythmogenic phenotypes in isogenic human iPSC-derived cardiac tissues. Sci. Rep. 2024, 14, 2586. https://doi.org/10.1038/s41598-024-52871-1.
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You, T.; Luo, C.; Zhang, K.; Zhang, H. Short QT Syndrome and Drug Treatment: A systematic Literature Review and PRISMA Analysis. International Journal of Drug Discovery and Pharmacology 2025, 4 (2), 100009. https://doi.org/10.53941/ijddp.2025.100009.
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