Short QT Syndrome Patients

Short QT interval in situations other than SQTS

Deceleration-Dependent Shortening of the QT Interval: A New Electrocardiographic Phenomenon? Gussak I, Liebl N, Nouri S, Bjerregaard P, Zimmerman F, Chaitman BR. Clin Cardiol 1999;22:124-126

Case report describing a 4-year-old African-American girl with complications related to premature birth, developmental delay and recurrent episodes of cardiac arrest with brady-arrhythmias. An episode documented electrocardiographically showed QT-interval shortening during severe bradycardia.Activation of the IkACh channel due to high vagal discharge was proposed as a possible mechanism responsible for both slowing of the heart rate and shortening of the QT interval.The question was raised whether deceleration-dependent shortening of the QT interval has arrhythmogenic potential?

ECG Phenomenon of Idiopathic and Paradoxical Short QT Intervals. Gussak I, Brugada P, Brugada J, Antzelevich C, Osbakken M, Bjerregaard, P. Cardiac Electrophysiology Review 2002;6:49-53

Discussion of clinical scenarios where a short QT interval may occur followed by a description of possible electrophysiologic consequences of a short QT interval.

Is idiopathic ventricular fibrillation a short QT syndrome? Comparison of QT intervals of patients with idiopathic ventricular fibrillation and healthy controls. Viskin S, Zeltser D, Ish-Shalom M, Katz A, Glikson M, Justo D, Tekes-Manova D, Belhassen B.. Heart Rhythm 2004;1(5):587-591

ECGs of 28 patients with idiopathic VF (17 men and 11 women, age 31 +/- 17 years) were compared to those of 270 age- and gender- matched healthy controls. The QTc of males with idiopathic VF was shorter than the QTc of healthy males (371 +/- 22 ms vs 385 +/- 19 ms, P = 0.034), and 35% of the male patients had QTc < 360 msec (range 326 – 350 msec) compared to only 10 % of male controls (345-360 msec). No such differences were found among women.The findings suggest, but does not prove, that QTc intervals shorter than 360 msec may entail some arrhythmic risk.

The study also emphasizes that QTc </= 360 msec (for males) or QTc </= 370 msec (for females) are not exceptional in healthy adults, especially during bradycardia. This could lead to overdiagnosis of SQTS in patients with syncope and no documented arrhythmias who have QTc values ranging from 340 to 360 msec.

Idiopathic VF and short repolarization: Intriguing new concept**.** Zareba W. Heart Rhythm 2004:1(5);592-593 Editorial comment to ref. # 18

It is pointed out that the difference in QTc between controls and patients with idiopathic ventricular fibrillation is very small (14 msec on average) and could be an incidental finding.Problems in using a much larger control group than patient group for comparison is pointed out, and the lack of a difference between the female groups is puzzling.

The short QT syndrome and sudden infant death syndrome Morphet JAM.. Can J Cardiol 2007;23(2):105

Three week-old neonate was admitted with episodes of apnea. The ECG showed QT-interval of 210 msec. During ECG monitoring sinus node dysfunction in terms of sinus bradycardia, sinus arrest and atrial and ventricular standstill was observed.

The case was interpreted as SIDS with SQTS in which sinus node dysfunction was an important aspect of the pathophysiology.

Loss-of-Function Mutations in the Cardiac Calcium Channel Underlie a New Clinical Entity Characterized by ST-Segment Elevation, Short OT Intervals, and Sudden Cardiac Death Antzelevitch C, Pollevick GD, Cordeiro JM, Casis O, Sanguinetti MC, Aizawa Y, Guerchicoff A, Pfeiffer R, Oliva A, Wollnik B, Gelber P, Bonaros EP, Burashnikov E, Wu Y, Sargent JD, Schickel S, Oberheiden R, Bhatia A, Hsu L-F, Jaissaguerre M, Schrimpf R, Borggrefe M, Wolpert C.. Circulation 2007;115:442-449

By screening of 82 consecutive probands with clinically robust diagnosis of Brugade Syndrome for ion channel gene mutations, they found 3 probands displaying ST-segment elevation in V1 through V3 and QTc </= 360msec among 7 who had mutations in genes encoding the cardiac L-type calcium channel. Rate adaptation of QT interval was reduced and Quinidine normalized the QT intervals and prevented stimulation-induced VT.Genetic and heterologous expression studies revealed loss-of-function missense mutations in CACNA1C (A39V and G490R) and CACNB2 (S481L) encoding the α1 and β2b –subunits of the L-type calcium channel.This is the first report of loss-of-function mutations in genes encoding the cardiac L-type calcium channel to be associated with a familial sudden cardiac death syndrome in which a Brugada Syndrome phenotype is combined with shorter-than-normal QT intervals.

A novel KCNH2 mutation as a modifier for short QT interval. Itoh H, Sakaguchi T, Ashihara T, Ding W-G, Nagaoka I, Oka Y, Nakazawa Y, Yao T, Jo H, Ito M, Nakamura K, Ohe T, Matsuura H, Horie M. Int J Cardiol 2008

This study using voltage clamp experiments describes a novel C-terminal KCNH2 mutation, R1135H, which was found to explain both the marked QT shortening (QTc 329 msec) and the Brugada-type ECG in a 34 year-old man. (Wilders R, Verkerk AO. Role of the R1135H KCNH2 mutation in Brugada syndrome. Int J Cardiol 2010;144:149-51 computer simulation studies later confirmed the findings.)

Short QT Interval: A Novel Predictor of Androgen Abuse in Strength Trained. Bigi MAB, Aslani A, Aslani A. Ann Noninvasive Electrocardiol 2009;14(1):35-39

The QTc was measured in 90 sedentary men (418 +/- 24 msec), 86 drug-free bodybuilders (422 +/- 25 msec) and in 79 bodybuilders using anabolic androgenic steroids (367 +/- 17 msec). The heart rate was the same in the two groups of bodybuilders.

Drug induced shortening of the QT/QTc interval: An emergence safety issue warranting further modeling and evaluation in drug research and development.

Holbrook M, Malik M, Shah RR, Valentin J-P J Pharmacology and Toxicology Methods 2009;59:21-28

Drug-induced QT interval shortening: an emerging component in integrated assessment of cardiac safety of drugs

Shah RR, Bjerregaard P, Gussak I.. J Electrocardiol 2010;

Short QT interval in clinical practice. Bjerregaard P, Nallapaneni H, Gussak I.. J Electrocardiol 2010;43:390-395

Dilated Cardiomyopathy with Short QT Interval: Is It a New Clinical Entity? Bohora S, Namboodiri N, Tharakan J, Kumura A, Nayyar S. PACE 2009;32:688-690

Review of clinical settings with short QT interval, including SQTS, idiopathic VF, Brugada syndrome, early repolarization, hypercalcemia, chronic fatigue syndrome and hyperthermia.

27 year-old male presents with an eight-year history of dyspnea on exertion. ECG shows Atrial fibrillation with narrow QRS and QT 260 msec (QTc always < 320 msec). Echocardiography showed severe dilated cardiomyopathy (LVEF 36%).

Evaluation of his brother and only younger sibling also showed dilated cardiomopathy (LVEF 48%) with atrial fibrillation with narrow QRS and QT 312 msec (average QTc 302 msec).

No other family members with known heart disease. Genetic testing not performed.

Recurrent syncope associated with a distinct ECG pattern consisting of short QT interval, early repolarization and atrioventricular block Efremidis M, Letsas KP, Weber R, Gavrielatos G, Filippatos GS, Sideris A, Kardaras F.. Clin Res Cardiol 2009;98:807-810

17-year-old individual with recurrent syncope and ECG showing prominent J-waves, ST-elevation and short QT interval of 320 msec (QTc 283 msec). Early repolarization disappeared during stress test. Positive late potentials.

Holter monitoring showed several episodes of abrupt advanced AV block with longest RR of 4.2 sec’s (apparently during sinus bradycardia).

Procainamide challenge did not induce Brugada sign. Quinidine normalized the QT interval.

EP study showed AH 110 msec, HV 49 msec. AERP 190 msec, VERP 200 msec. No atrial or ventricular arrhythmias and no AV block induced during EP study.

Genetic testing negative

Because of the combination of a short QT interval and positive late potentials the patient was found to be at a high risk for ventricular tachy-arrhythmias and received an ICD.

High prevalence of early repolarization in short QT syndrome Watanabe H, Makiyama T, Koyama T, Kannankeril PJ, Seto S, Okamura K, Oda H, Itoh H, Okada M, Tanabe N, Yagihara N, Kamakura S, Horie M, Aizawa Y, Shimizu W.. Heart Rhythm 2010;7:647-652

This study consisted of 3 cohorts: 1) 37 SQTS patients (12 new patients with QTc </= 330 msec plus an arrhythmic event and/or genetic mutation, and 25 patients with SQTS from the literature)

  1. 44 control cohort with QTc</= 330 msec and no symptoms, and 3) 185 control cohort with normal QTc and no sign or symptoms of heart disease.

The prevalence of early repolarization was 65% in cohort 1, 30% in cohort 2 and only 10% in cohort 3.

In a multivariable model early repolarization was associated with arrhythmic events in the SQTS cohort whereas neither QT nor QTc duration were associated with arrhythmic events.

Conclusion: There is a high prevalence of early repolarization in patients with SQTS. Early repolarization may be useful in identifying risk of cardiac events in patients with SQTS.

Early repolarisation and short QT interval in healthy subjects.

Panicker GK, Manohar D, Karnad DR, Salvi V, Kothari S, Lokhandwala Y Heart Rhythm 2012;9:1265-1271

Out of 1886 healthy subjects early repolarization (ER) was found in 514 or 27 %. 35% of males had ER compared to only 2% of females. Highest prevalence was seen in 18- to 29-y-o. The ER group had slightly shorter QTcF (11 +/- 22 ms) than the non-ER group. Only 4 subjects has QTcF < 350 ms and none < 340 ms..

Conclusion: Although ER may be common in SQTS, the converse does not appear to be true.

Drug-induced QT-interval shortening following antiepileptic treatment with oral rufinamide

Schimpf R, Veltman C, Papavassiliu T, Rudic B, Göksu T, Kuschyk J, Wolpert C. Antzelevitch C, Ebner A, Borggrefe M, Brandt C.. Heart Rhythm 2012;9(5):776-781

A 13-year-old boy with a short QT interval.

Babao─člu K, Binneto─člu K, Altun G, Tuzcu V. Anadolu Kardiyol Derg 2012;12(3):

13 y.o. child with recurrent chest pain, but otherwise asymptomatic. His ECG typical for Short QT syndrome with QT of 280 msec at 62 bpm and tall peaked T-waves in lateral precordial leads. His mother had a QT interval of 320 msec (HR?). His maternal uncle died suddenly at 28 years of age of possible myocardial infarction. An electrophysiologic study showed AERP of 230 ms and VERP of 170 msec, and no inducible arrhythmias. Genetic testing not performed.

Only long term follow-up will be able to tell whether this patient has SQTS, but because of the very short QT interval and relatively short VERP close follow up is warranted.

Exercise-Related QT Interval Shortening with a Peaked T Wave in a Healthy Boy with a Family History of Sudden Cardiac Death. Chinushi M, Sato A, Iijima K, Suzuki K, Hiroshi F, Izumi D, Watanabe H, Kanae H, Aizawa Y. PACE 2012;35:e239-e24215 y.o. asymptomatic boy underwent extensive electrophysiologic examination due to sudden unexplained death in two older siblings, who had normal QT intervals ( 284 ms at 112 beats/min and 378 msec at 55 bpm respectively). The boy had a normal ECG with QT interval of 320 msec at 73 beats per minute (QTc(B) of 388 msec). During a stress test the QT interval shortened to 200 msec while peaking of the T waves were noticed. During an EP study polymorph non-sustained VT episodes were induced and a peculiar hump became apparent on the T wave of the first post-pacing beat. Also VERPs less than 170 msec were found in both the atria and the ventricles. A genetic test revealed only a single nucleotide polymorphism (C5457T) in the SCN5A gene. The authers suggest that the patient might be in the intermediate range of probability of SQTS.

The only borderline short QT at rest and significant shortening of the QT with an increase in heart rate makes in my opinion a diagnosis of SQTS very unlikely.

Short QT in a Cohort of 1.7 Million Persons: Prevalence, Correlates, and Prognosis. Carlos Iribarren, Alfred D. Round, Jonathan A. Peng, Meng Lu, Arthur L. Klatsky, Jonathan G. Zaroff, Taylor J. Holve, Amit Prasad and Paul Stang, Ann Noninvasive Eleectrocardiol 2014;19(5);490-500.