Digitalis Administration: An Underappreciated but Common Cause of Short QT Interval

HomeCirculationVol. 109, No. 9Digitalis Administration: An Underappreciated but Common Cause of Short QT Interval Free AccessLetterPDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessLetterPDF/EPUBDigitalis Administration: An Underappreciated but Common Cause of Short QT Interval Tsung O. Cheng, MD Tsung O. ChengTsung O. Cheng Department of Medicine, George Washington University Medical Center, Washington, DC, Originally published9 Mar 2004https://doi.org/10.1161/01.CIR.0000118177.56908.5BCirculation. 2004;109:e152To the Editor:I read with interest the recent report by Gaita et al1 of short-QT syndrome as a familial cause of sudden death. The authors enumerated other factors that shorten QT interval, such as increased heart rate, hyperthermia, hypercalcemia, hyperkalemia, acidosis, and altered autonomic tone.1 I would like to add another important and common, but underappreciated, cause of short QT interval, that is, administration of digitalis preparations.Because digitalis administration is such a common everyday occurrence in the management of patients with congestive heart failure and in those with atrial fibrillation or paroxysmal atrial tachycardia, its effect on the QT interval should be kept in mind when evaluating ECG changes. Although PR prolongation is a commonly recognized ECG manifestation of digitalis administration, QT shortening is less well known. As a matter of fact, in several case reports in which ECGs were presented,2–5 the short QT interval was not mentioned even though it was present. The property of digitalis preparations to shorten the QT interval is useful clinically in the diifferential diagnosis of ST-T changes associated with left ventricular hypertrophy, myocardial ischemia, myocardial infarction, or bundle branch block, in all of which the QT-interval is prolonged. The shortened QT interval and the characteristic sagging, "coved," or "scooped" appearance of the asymmetric and downsloping ST depression, which resembles a reversed check mark, constitute the typical "digitalis effect" on ECG.The presence of a digitalis effect on ECG does not by itself connote digitalis intoxication. On the other hand, the same mechanism of sudden death in the familial short-QT syndrome as described by Gaita et al1 could play a role in fatal digitalis poisoning, either iatrogenic or suicidal, besides its association with hyperkalemia in patients with chronic renal insufficiency.1 Gaita F, Giustetto C, Bianchi F, et al. Short QT syndrome: a familial cause of sudden death. Circulation. 2003; 108: 965–970.LinkGoogle Scholar2 Hachimi-Idrissi S, Corne L, Maes V, et al. Gitaloxin poisoning in a child. Intensive Care Med. 1996; 22: 1442–1444.CrossrefMedlineGoogle Scholar3 Evans T. Diagnostic dilemma: digitalis toxicity with a preexisting bundle branch block. Am J Med. 2000; 108;504: 512–513.Google Scholar4 Jowett NI. Foxglove poisoning. Hosp Med. 2002; 63: 758–759.CrossrefMedlineGoogle Scholar5 Barrueto F Jr, Jortani SA, Valdes R Jr, et al. Cardioactive steroid poisoning from an herbal cleansing preparation. Ann Emerg Med. 2003; 41: 396–399.CrossrefMedlineGoogle ScholarcirculationahaCirculationCirculationCirculation0009-73221524-4539Lippincott Williams & WilkinsResponseGaita Fiorenzo, , MD, Giustetto Carla, , MD, Bianchi Francesca, , MD, Riccardi Riccardo, , MD, Grossi Stefano, , MD, Richiardi Elena, , MD, Wolpert Christian, , MD, Schimpf Rainer, , MD, and Borggrefe Martin, , MD09032004In the paper recently published in Circulation, we described a new genetic syndrome, in which a short QT interval on ECG was associated with a high incidence of sudden death.1 These subjects also had a high incidence of atrial arrhythmias; at electrophysiological study, effective refractory periods were very short at both the atrial and ventricular level, and ventricular fibrillation was inducible.2 In our families genetic screening has been performed and two different missense mutations have been found, which result in hyperfunction of IKr (human ether-a-go-go gene, HERG).3 The consequence is a heterogeneous abbreviation of action potential duration and refractoriness at both the atrial and the ventricular level. Short and inhomogeneous refractory periods favor reentry and thus arrhythmogenesis.There are also causes of acquired short QT interval. Some of them are cited in our report, and Dr Cheng is now adding another important one. Digitalis glycosides bind specifically to the Na+,K+-ATPase, decreasing the active transport of sodium. The increase in intracellular sodium causes an augmentation of the exchange of intracellular Na+ for extracellular Ca+. This can cause an increase in K permeability.4 An increased outward current during the plateau is probably the mechanism of the action potential duration and effective refractory period reduction. Digitalis shortens QT interval mainly at high plasma concentrations. Short-QT syndrome has a genetic basis, whereas the short QT of digitalis intoxication is acquired. However, the final mechanism of arrhythmogenesis in some cases of digitalis toxicity could be very similar to that of the genetic short-QT syndrome. Previous Back to top Next FiguresReferencesRelatedDetailsCited By Qu Y, Gao B, Arimura Z, Fang M and Vargas H (2021) Comprehensive in vitro pro‐arrhythmic assays demonstrate that omecamtiv mecarbil has low pro‐arrhythmic risk, Clinical and Translational Science, 10.1111/cts.13039, 14:4, (1600-1610), Online publication date: 1-Jul-2021. Ellermann C, Wolfes J, Eckardt L and Frommeyer G (2020) Role of the rabbit whole-heart model for electrophysiologic safety pharmacology of non-cardiovascular drugs, EP Europace, 10.1093/europace/euaa288, 23:6, (828-836), Online publication date: 7-Jun-2021. Saponara S, Fusi F, Iovinelli D, Ahmed A, Trezza A, Spiga O, Sgaragli G and Valoti M (2021) Flavonoids and hERG channels: Friends or foes?, European Journal of Pharmacology, 10.1016/j.ejphar.2021.174030, 899, (174030), Online publication date: 1-May-2021. Greenway S, Dallaire F, Hazari H, Patel D and Khan A (2018) Addition of Digoxin Improves Cardiac Function in Children With the Dilated Cardiomyopathy With Ataxia Syndrome: A Mitochondrial Cardiomyopathy, Canadian Journal of Cardiology, 10.1016/j.cjca.2018.02.019, 34:8, (972-977), Online publication date: 1-Aug-2018. Hancox J, Whittaker D, Du C, Stuart A and Zhang H (2018) Emerging therapeutic targets in the short QT syndrome, Expert Opinion on Therapeutic Targets, 10.1080/14728222.2018.1470621, 22:5, (439-451), Online publication date: 4-May-2018. Ramakrishna H, O'Hare M, Mookadam F, Gutsche J, Shah R and Augoustides J (2015) Sudden Cardiac Death and Disorders of the QT Interval: Anesthetic Implications and Focus on Perioperative Management, Journal of Cardiothoracic and Vascular Anesthesia, 10.1053/j.jvca.2015.07.026, 29:6, (1723-1733), Online publication date: 1-Dec-2015. Adeniran I (2014) The Short QT Syndrome Modelling the Short QT Syndrome Gene Mutations, 10.1007/978-3-319-07200-5_3, (51-64), . Tülümen E, Giustetto C, Wolpert C, Maury P, Anttonen O, Probst V, Blanc J, Sbragia P, Scrocco C, Rudic B, Veltmann C, Sun Y, Gaita F, Antzelevitch C, Borggrefe M and Schimpf R (2014) PQ segment depression in patients with short QT syndrome: A novel marker for diagnosing short QT syndrome?, Heart Rhythm, 10.1016/j.hrthm.2014.02.024, 11:6, (1024-1030), Online publication date: 1-Jun-2014. Lozano R, Bibian C, Quilez R, Gil J, Constante Y and Garcia-Arilla E (2014) Clinical relevance of the (S)-citalopram-omeprazole interaction in geriatric patients, British Journal of Clinical Pharmacology, 10.1111/bcp.12223, 77:6, (1086-1087), Online publication date: 1-Jun-2014. Wolpert C, Veltmann C, Schimpf R and Borggrefe M (2011) Short QT Syndrome Clinical Cardiogenetics, 10.1007/978-1-84996-471-5_11, (189-196), . Gollob M, Redpath C and Roberts J (2011) The Short QT Syndrome, Journal of the American College of Cardiology, 10.1016/j.jacc.2010.09.048, 57:7, (802-812), Online publication date: 1-Feb-2011. Fan X, Ma J, Wan W, Zhang P, Wang C and Wu L (2011) Increased intracellular calcium concentration causes electrical turbulence in guinea pig ventricular myocytes, Science China Life Sciences, 10.1007/s11427-011-4146-1, 54:3, (240-247), Online publication date: 1-Mar-2011. Himmel H and Hoffmann M (2010) QTc shortening with a new investigational cancer drug: A brief case study, Journal of Pharmacological and Toxicological Methods, 10.1016/j.vascn.2010.05.012, 62:1, (72-81), Online publication date: 1-Jul-2010. Wolpert C, Veltmann C, Schimpf R and Borggrefe M (2010) Short QT Syndrome Clinical Approach to Sudden Cardiac Death Syndromes, 10.1007/978-1-84882-927-5_11, (149-156), . Patel U and Pavri B (2009) Short QT Syndrome, Cardiology in Review, 10.1097/CRD.0b013e3181c07592, 17:6, (300-303), Online publication date: 1-Nov-2009. Hedley P, Jørgensen P, Schlamowitz S, Wangari R, Moolman-Smook J, Brink P, Kanters J, Corfield V and Christiansen M (2009) The genetic basis of long QT and short QT syndromes: A mutation update, Human Mutation, 10.1002/humu.21106, 30:11, (1486-1511), Online publication date: 1-Nov-2009. Schimpf R, Veltmann C, Wolpert C and Borggrefe M (2009) Channelopathies: Brugada syndrome, long QT syndrome, short QT syndrome, and CPVTIonenkanalerkrankungen: Brugada-Syndrom, Long-QT-Syndrom, Short-QT-Syndrom und CPVT, Herz, 10.1007/s00059-009-3238-1, 34:4, (281-288), Online publication date: 1-Jun-2009. Wang L, Wible B, Wan X and Ficker E (2006) Cardiac Glycosides as Novel Inhibitors of Human Ether-a-go-go -Related Gene Channel Trafficking , Journal of Pharmacology and Experimental Therapeutics, 10.1124/jpet.106.113043, 320:2, (525-534), Online publication date: 1-Feb-2007. McPate M, Witchel H and Hancox J (2006) Short QT syndrome, Future Cardiology, 10.2217/14796678.2.3.293, 2:3, (293-301), Online publication date: 1-May-2006. Kirilmaz A, Ulusoy R, Kardesoglu E, Ozmen N and Demiralp E (2005) Short QT interval syndrome: a case report, Journal of Electrocardiology, 10.1016/j.jelectrocard.2005.06.093, 38:4, (371-374), Online publication date: 1-Oct-2005. Wolpert C, Schimpf R, Veltmann C, Giustetto C, Gaita F and Borggrefe M (2014) Clinical characteristics and treatment of short QT syndrome, Expert Review of Cardiovascular Therapy, 10.1586/14779072.3.4.611, 3:4, (611-617), Online publication date: 1-Jul-2005. March 9, 2004Vol 109, Issue 9 Advertisement Article InformationMetrics https://doi.org/10.1161/01.CIR.0000118177.56908.5BPMID: 15007021 Originally publishedMarch 9, 2004 PDF download Advertisement