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Diagnosis and management of short QT syndrome

  • Preben Bjerregaard
    Correspondence
    Address reprint requests and correspondence: Dr. Preben Bjerregaard, Cardiovascular Division, Washington University in Saint Louis, 777 Knight Ln, El Dorado Hills, CA 95762-4300.
    Affiliations
    Division of Cardiology, Saint Louis University, Saint Louis, Missouri

    Cardiovascular Division, Washington University in Saint Louis, Saint Louis, Missouri
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      Establishing a definition of short QT syndrome (SQTS), including symptomatology and QT-interval duration, is still a work in progress. However, it is clear , that SQTS is a rare, life-threatening, inherited heart disease presenting as sudden cardiac death (SCD) or aborted SCD in 34% and a family history of SCD in 15%. Genetic testing is important in diagnosing the disease, but to date a causative mutation is found in <25%. A benign variety of the disease has been observed in children with atrial fibrillation and a KCNH2-V141M mutation, and recently a mutation in the cardiac Cl/HCO3 exchanger AE3 was found to cause SQTS. Issues related to measuring and correcting the QT interval for heart rate has made it difficult to rely entirely on QT duration for the diagnosis of SQTS. In order to establish the diagnosis on firmer grounds, symptoms, family history, and genetic testing need to be considered. Although the benefit of insertion of an implantable cardioverter–defibrillator as secondary prophylaxis against SCD in a patient with SQTS is well documented, the benefit as primary prophylaxis is controversial and not proven by solid data. In 2 recent similar studies involving 115 patients with approximately 5 years of follow-up, insertion of an implantable cardioverter–defibrillator in 40 patients saved the lives of 12, 11 who had presented with cardiac arrest and 1 with syncope. No appropriate shocks were delivered in any patients who did not have a history of either syncope or cardiac arrest. Currently quinidine is the only drug that has undergone any clinical testing.

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      References

        • Jervell A.L.
        • Lange-Nielsen F.
        Congenital deaf-mutism, functional heart disease with prolongation of the QT interval and sudden death.
        Am Heart J. 1957; 54: 59-68
        • Gussak I.
        • Brugada P.
        • Brugada J.
        • Wright S.
        • Kopecky S.L.
        • Chaitman B.R.
        • Bjerregaard P.
        Idiopathic short QT interval: a new clinical syndrome?.
        Cardiology. 2000; 94: 99-102
        • Gaita F.
        • Giustetto C.
        • Bianchi F.
        • Wolpert C.
        • Schimpf R.
        • Riccardi R.
        • Grossi S.
        • Richiardi E.
        • Borggrefe M.
        Short QT syndrome: a familial cause of sudden death.
        Circulation. 2003; 108: 965-970
        • 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
        • Bellocq C.
        • van Ginneken C.B.
        • Bezzina C.R.
        • Alders M.
        • Escande D.
        • Mannens M.M.A.M.
        • Baró I.
        • Wilde A.A.M.
        Mutation in the KCNQ1 gene leading to the short QT-interval syndrome.
        Circulation. 2004; 109: 2394-2397
        • Riera A.R.P.
        • Ferreira C.
        • Dubner S.J.
        • Schapachnik E.
        • Soares J.D.
        • Francis J.
        Brief review of the recently described short QT syndrome and other cardiac channelopathies.
        Ann Noninvasive Electrocardiol. 2005; 10: 371-377
        • Maury P.
        • Hollington L.
        • Duparc A.
        • Brugada R.
        Short QT syndrome: should we push the frontier forward?.
        Heart Rhythm. 2005; 2: 1135-1137
        • 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
        • Kirilmaz A.
        • Ulusoy R.E.
        • Kardesoglu E.
        • Ozmen N.
        • Demiralp E.
        Short QT interval: a case report.
        J Electrocardiol. 2005; 38: 371-374
        • 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
        • Giustetto C.
        • Di Monte F.
        • Wolpert C.
        • Borggrefe M.
        • Schimpf R.
        • Sbragia P.
        • Leone G.
        • Maury P.
        • Anttonen O.
        • Haïssaguerre M.
        • Gaita F.
        Short QT syndrome: clinical findings and diagnostic-therapeutic implications.
        Eur Heart J. 2006; 27: 2440-2447
        • Lu L.X.
        • Zhou W.
        • Zhang X.
        • Cao Q.
        • Yu K.
        • Zhu C.
        Short QT syndrome: a case report and review of literature.
        Resuscitation. 2006; 71: 115-121
        • Antzelevitch C.
        • Pollevick G.D.
        • Cordeiro J.
        • 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
        • Mizobuchi M.
        • Enjoji Y.
        • Yamamoto R.
        • Ono T.
        • Funatsu A.
        • Kambayashi D.
        • Kobayashi T.
        • Nakamura S.
        Nifekalant and disopyramide in a patient with short QT syndrome: evaluation of pharmacological effects and electrophysiological properties.
        Pacing Clin Electrophysiol. 2008; 31: 1229-1232
        • Fichet J.
        • Genee O.
        • Pierre B.
        • Babuty D.
        Fatal QT interval.
        Am J Emerg Med. 2008; 26: 739.e5-739.e6
        • Redpath C.J.
        • Green M.S.
        • Birnie D.H.
        • Gollop M.H.
        Rapid genetic testing facilitating the diagnosis of short QT syndrome.
        Can J Cardiol. 2009; 25: e133-e135
        • Villafane J.
        • Young M.L.
        • Maury P.
        • Wolpart C.
        • Anttonen O.
        • Hamilton R.
        • Kannankeril P.J.
        • Fischbach P.S.
        Short QT syndrome in a pediatric patient.
        Pediatr Cardiol. 2009; 30: 846-850
        • 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
        • Efremides M.
        • Letsas K.P.
        • Weber R.
        • Gavrielatos G.
        • Filippatos G.S.
        • Sideris A.
        • Kardaras F.
        Recurrent syncope associated with a distinct ECG pattern consisting of short QT interval, early repolarization and atrioventricular block.
        Clin Res Cardiol. 2009; 98: 807-810
        • Sun Y.
        • Zhang P.
        • Li X.
        • Guo J.
        Inappropriate ICD discharge due to T-wave oversensing in a patient with short QT syndrome.
        Pacing Clin Electrophysiol. 2010; 33: 113-116
        • Watanabe H.
        • Makiyama T.
        • Koyama T.
        • et al.
        High prevalence of early repolarization in short QT syndrome.
        Heart Rhythm. 2010; 7: 647-652
        • Sun Y.
        • Quan X.-Q.
        • Fromme S.
        • Cox R.H.
        • Zhang P.
        • Zhang L.
        • Guo D.
        • Guo J.
        • Patel C.
        • Kowey P.R.
        • Yan G.-X.
        A novel mutation in the KCNH2 gene associated with short QT syndrome.
        J Mol Cell Cardiol. 2011; 50: 433-441
        • Giustetto C.
        • Schimpf R.
        • Mazzanti A.
        • Scrocco C.
        • Maury P.
        • Anttonen O.
        • Probst V.
        • Blanc J.-J.
        • Sbragia P.
        • Dalmasso P.
        • Borggrefe M.
        • Gaita F.
        Long-term follow-up of patients with short QT syndrome.
        J Am Coll Cardiol. 2011; 58: 587-595
        • Templin C.
        • Ghadri J.-R.
        • Rougier J.-S.
        • et al.
        Identification of a novel loss-of-function calcium channel mutation in short QT syndrome (SQTS6).
        Eur Heart J. 2011; 32: 1077-1088
        • Chinushi M.
        • Sato A.
        • Izumi D.
        • Furushima H.
        Nifekalant enlarged the transmural activation-recovery interval difference as well as the peak-to-end interval on surface ECG in a patient with short-QT syndrome.
        J Cardiovasc Electrophysiol. 2012; 23: 877-880
        • Hattori T.
        • Makiyama T.
        • Akao M.
        • Ehara E.
        • Ohno S.
        • Iguchi M.
        • Nishis Y.
        • Sasaki K.
        • Itoh H.
        • Yokode M.
        • Kita T.
        • Horie M.
        • Kimura T.
        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
        • Bun S.-S.
        • Maury P.
        • Giustetto C.
        • Deharo J.-C.
        Electrical storm in short-QT syndrome successfully treated with isoproterenol.
        J Cardiovasc Electrophysiol. 2012; 23: 1028-1030
        • Hong K.
        • Hu J.
        • Yu J.
        • Brugada R.
        Concomitant Brugada-like and short QT electrocardiogram linked to SCN5A mutation.
        Eur J Hum Genet. 2012; 20: 1189-1192
        • Babaoğlu K.
        • Binnetoğlu K.
        • Altun G.
        • Tuzcu V.
        A 13-year-old boy with a short QT interval.
        Anadolu Kardiyol Derg. 2012; 12: 274-275
        • Villafane J.
        • Atallah J.
        • Gollob M.H.
        • et al.
        Long-term follow-up of a pediatric cohort with short QT syndrome.
        J Am Coll Cardiol. 2013; 61: 1183-1191
        • Deo M.
        • Ruan Y.
        • Pandit S.V.
        • Shah K.
        • Berenfeld O.
        • Blaufox A.
        • Cerrone M.
        • Noujaim S.F.
        • Denegri M.
        • Jalife J.
        • Priori S.G.
        KCNJ2 mutation in short QT syndrome 3 results in atrial fibrillation and ventricular proarrhythmia.
        Proc Natl Acad Sci U S A. 2013; 110: 4291-4296
        • Maltret A.
        • Wiever-Vacher S.
        • Denis C.
        • Extramiana F.
        • Morisseau-Durand M.P.
        • Fressart V.
        • Bobbet D.
        • Chabbert C.
        Type 2 short QT syndrome and ventricular dysfunction: mirror of the Jervell and Lange-Nielsen syndrome.
        Int J Cardiol. 2014; 171: 291-293
        • Villafane J.
        • Fischbach P.
        • Gebauer R.
        Short QT syndrome manifesting with neonatal atrial fibrillation and bradycardia.
        Cardiology. 2014; 128: 236-240
        • Sadeghian S.
        • Bozorgi A.
        • Safkhani Z.
        Short QT syndrome and idiopathic ventricular tachycardia in a 28-year-old young man: a potential disease-specific link?.
        Europace. 2014; 16: 1645
        • Portugal G.
        • Oliveira M.M.
        • Cunha P.S.
        • Ferreira F.
        • Lousinha A.
        • Fiarresga A.
        • Nogueira da Silva M.
        • Ferreira R.C.
        Short QT syndrome presenting as syncope: how short is too short?.
        Rev Port Cardiol. 2014; 33: 649.e1-649.e6
        • 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
        • Suzuki H.
        • Hoshina S.
        • Ozawa J.
        • Sato A.
        • Minamino T.
        • Aizawa Y.
        • Saitoh A.
        Short QT syndrome in a boy diagnosed on screening for heart disease.
        Pediatr Int. 2014; 56: 774-776
        • 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
        • Harrell D.T.
        • Ashihara T.
        • Ishikawa T.
        • Tominaga I.
        • Mazzanti A.
        • Takahashi K.
        • Oginosawa Y.
        • Abe H.
        • Maemura K.
        • et al.
        Genotype-dependent differences in age of manifestation and arrhythmia complications in short QT syndrome.
        Int J Cardiol. 2015; 190: 393-402
        • Moreno C.
        • Oliveras A.
        • de la Cruz A.
        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
        • Ergül Y.
        • Özyilmaz I.
        • Onan S.H.
        • Güzeltaş A.
        Short QT syndrome on a 14 year-old patient: the first pediatric case from Turkey.
        Anatol J Cardiol. 2015; 15: 586-591
        • Righi D.
        • Silvetti M.S.
        • Drago F.
        Sinus bradycardia, junctional rhythm, and low-rate atrial fibrillation in short QT syndrome during 20 years of follow-up: three faces of the same genetic problem.
        Cardiol Young. 2016; 26: 589-592
        • Sarguella-Brugada G.
        • Campuzano O.
        • Iglesias A.
        • Grueso J.
        • Bradley D.J.
        • Kerst G.
        • Shmorhun D.
        • Brugada J.
        • Brugada R.
        Short QT and atrial fibrillation: a KCNQ1 mutation-specific disease. Late follow-up in three unrelated children.
        HeartRhythm Case Rep. 2015; 1: 193-197
        • Rothenberg I.
        • Piccini I.
        • Wrobel E.
        • Stallmeyer B.
        • Müller J.
        • Greber B.
        • Strutz-Seebohm N.
        • Schulze-Bahr E.
        • Schmitt N.
        • Seebohm G.
        Structural interplay of Kv7.1 and KCNE1 is essential for normal repolarization and is compromised in short QT syndrome 2 (Kv7.1-A287T).
        HeartRhythm Case Rep. 2016; 2: 521-529
        • Thorsen K.
        • Dam V.S.
        • Kjær-Sørensen K.
        • et al.
        Loss-of-activity-mutation in the cardiac chloride-bicarbonate exchanger AE3 causes short QT syndrome.
        Nat Commun. 2017; 8: 1696
        • Rhodes T.E.
        • Abraham R.A.
        • Welch R.C.
        • et al.
        Cardiac potassium channel dysfunction in sudden infant death syndrome.
        J Moll Cell Cardiol. 2008; 44: 571-581
        • Priori S.G.
        • Wilde A.A.
        • Horie M.
        • et al.
        HRS/EHRA/APHRS expert consensus statement on the diagnosis and management of patients with inherited primary arrhythmia syndromes.
        Heart Rhythm. 2013; 10: 1933-1963
        • Giustetto C.
        • Scrocco C.
        • Schimpf R.
        • et al.
        Usefulness of exercise test in the diagnosis of short QT syndrome.
        Europace. 2015; 17: 628-634
        • Tülümen E.
        • Guistetto C.
        • Wolpert C.
        • et al.
        PQ depression in short QT syndrome patients: a novel marker for diagnosing short QT syndrome.
        Heart Rhythm. 2014; 11: 1024-1030
        • Pérez-Riera A.R.
        • Paixã-Almeida A.
        • Barbosa-Barros R.
        • Yanowitz F.G.
        • Baranchuk A.
        • Dubner S.
        • Chagas A.C.P.
        Congenital short QT syndrome: landmarks of the newest arrhythmogenic cardiac channelopathy.
        Cardiol J. 2013; 20: 464-471
        • Gollop M.H.
        • Redpath C.J.
        • Roberts J.D.
        The short QT syndrome: proposed diagnostic criteria.
        J Am Coll Cardiol. 2011; 57: 802-812
        • Anttonen O.
        • Junttila M.J.
        • Rissanen H.
        • Reunanen A.
        • Viitasalo M.
        • Huikuri H.V.
        Prevalence and prognostic significance of short QT interval in a middle-aged Finnish population.
        Circulation. 2007; 116: 714-720