Short QT syndrome
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor-In-Chief: Cafer Zorkun, M.D., Ph.D. [2]
Synonyms and keywords: SQTS; short QT; short QTc; QT interval shortening
Overview
Short QT syndrome is a genetic disease of the electrical system of the heart. It consists of a constellation of signs and symptoms, consisting of a short QT interval on an EKG (≤ 300 ms) that does not significantly change with heart rate, tall and peaked T waves, and a structurally normal heart. Short QT syndrome appears to be inherited in an autosomal dominant pattern, and a few affected families have been identified. It is associated with an increased risk of atrial fibrillation, syncope and sudden death.
Historical Perspective
The syndrome was first described by Dr. Prebe Bjerregaard MD, DMSc in 1999.
First Patient with Short QT Syndrome
Shalon Hill, a 17 year old white female, underwent laparoscopic cholecystectomy at Anderson Hospital, Maryville, Illinois in 1999 which was complicated by atrial fibrillation with a rapid ventricular response (RVR) at 150-200 beats/min along with acute pulmonary edema[1]. The atrial fbrillation with RVR was treated with DC cardioversion and she was discharged to home in normal sinus rhythm on digoxin. The atrial fibrillation recurred 6 weeks later and she was found at that time to have a short QT interval of 225 mseconds which was treated with prophylactic therapy with propafenone. She then remained asymptomatic for 6 months and the propafenone was discontinued. However, the atrial fibrillation recurred 2 months after the propafenone was discontinued, and it was therefore resumed. She remained asymptomatic on propafenone, but an AICD was implanted given reports from around the world of sudden cardiac death.
First Family with Short QT Syndrome
EKGs of the first patient's family members were analyzed. The QT interval of her 21 year old brother was 240 msec, the QT interval of her 84 year old maternal grandfather was 240 msec, and the QT interval of her 51 year old mother was 230 msec. The EKG of here father was normal.
He brother was asymptomatic, and on August 13, 2003 was found to have inducible ventricular fibrillation on programmed electrical stimulation. This was treated with implantation of an implantable cardioverter defibrillator. Subsequently he complained of occasional palpitations and paroxysmal atrial fibrillation with a rapid ventricular response was noted on interrogation of the ICD.
Her mother is a 51 year old healthy white female with a history of 3 episodes of sustained palpitations and paroxysmal atrial fibrillation. She has remained asymptomatic on propafenone since April, 2003. Programmed electrical stimulation on September 29, 2003 induced both atrial and ventricular fibrillation and an AICD was implanted.
Her maternal grandfather was an 84 year old white male who had chronic atrial fibrillation, coronary artery disease and hypertension who died following an embolic stroke.
Classification
Pathophysiology
It has been hypothesized that short QT syndrome is due to increased activity of outward potassium currents in phase 2 and 3 of the cardiac action potential. This would cause a shortening of the plateau phase of the action potential (phase 2), causing a shortening of the overall action potential, leading to an overall shortening of refractory periods and the QT interval. In the families afflicted by short QT syndrome, two different missense mutations have been described in the human ether-a-go-go gene (HERG). These mutations result in expression of the same amino acid change in the cardiac IKr ion channel. This mutated IKr has increased activity compared to the normal ion channel, and would theoretically explain the above hypothesis.
Genetics
In the families afflicted by short QT syndrome, mutations have been described in three genes, KvLQT1, the human ether-a-go-go gene (HERG), and KCNJ2. Mutations in the KCNH2, KCNJ2, and KCNQ1 genes cause short QT syndrome. These genes provide instructions for making proteins that act as channels across the cell membrane. These channels transport positively charged atoms (ions) of potassium into and out of cells. In cardiac muscle, these ion channels play critical roles in maintaining the heart's normal rhythm. Mutations in the KCNH2, KCNJ2, or KCNQ1 gene increase the activity of the channels, which changes the flow of potassium ions between cells. This disruption in ion transport alters the way the heart beats, leading to the abnormal heart rhythm characteristic of short QT syndrome. Short QT syndrome appears to have an autosomal dominant pattern of inheritance.
Due to the autosomal dominant inheritance pattern, individuals may have family members with a history of unexplained or sudden death at a young age (even in infancy), palpitations, or atrial fibrillation.
Causes
Common Causes
Causes in Alphabetical Order
- Digoxin
- Hypercalcaemia
- Lanatoside C
- Rufinamide
- Short QT syndrome type 1
- Short QT syndrome type 2
- Short QT syndrome type 3
Epidemiology and Demographics
Since the syndrome was first described in 2000, < 30 cases have been identified.
Natural History, Complications, Prognosis
Short QT syndrome is associated with an increased risk of atrial fibrillation, syncope and sudden death due to ventricular fibrillation.
Diagnosis
Diagnostic Criteria
Recent diagnostic criteria have been published out of the Arrhythmia Research Laboratory at the University of Ottawa Heart Institute from Drs. Michael H Gollob and Jason D Roberts.[2]
The Short QT Syndrome diagnostic criteria is based on a point system as follows:
- QTc in milliseconds
- <370 = 1 point
- <350 = 2 points
- <330 = 3 points
- J point - T peak interval in milliseconds
- <120 = 1 point
- Clinical History
- Sudden cardiac arrest = 2 points
- Polymorphic VT or VF = 2 points
- Unexplained syncope = 1 point
- Atrial fibrillation = 1 point
- Family History
- 1st or 2nd degree relative with SQTS = 2 points
- 1st or 2nd degree relative with sudden death = 1 point
- Sudden infant death syndrome = 1 point
- Genotype
- Genotype positive = 2 points
- Mutation of undetermined significance in a culprit gene = 1 point
The points are summed and interpreted as follows:
- > or equal to 4 points: High-probability of SQTS
- 3 Points: Intermediate probability of SQTS
- 2 points or less: Low probability of SQTS
Symptoms
Some individuals with short QT syndrome complain of frequent palpitations and may experience unexplained syncope (loss of consciousness).
Electrocardiogam
The characteristic findings of short QT syndrome on EKG are a short QT interval, typically ≤ 300 ms, that doesn't significantly change with the heart rate. Tall, peaked T waves may also be noted. Individuals may also have an underlying atrial rhythm of atrial fibrillation.
Electrophysiologic Studies
In the electrophysiology lab, individuals with short QT syndrome are noted to have short refractory periods, both in the atria as well as in the ventricles. Also, ventricular fibrillation is frequently induced on programmed stimulation.
Genetic Testing
Mutations in the KCNH2, KCNJ2, and KCNQ1 genes cause short QT syndrome. These genes provide instructions for making proteins that act as channels across the cell membrane. These channels transport positively charged atoms (ions) of potassium into and out of cells. In cardiac muscle, these ion channels play critical roles in maintaining the heart's normal rhythm. Mutations in the KCNH2, KCNJ2, or KCNQ1 gene increase the activity of the channels, which changes the flow of potassium ions between cells. This disruption in ion transport alters the way the heart beats, leading to the abnormal heart rhythm characteristic of short QT syndrome. Short QT syndrome appears to have an autosomal dominant pattern of inheritance.
Centers Performing Genetic Testing for Short QT Syndrome
Treatment
Given the increased risk of sudden death, it is not unreasonable for patients with short QT syndrome to undergo implantation of an implantable cardioverter-defibrillator (ICD). This is true even if the patient is asymptomatic.
Quinidine may prolong the QT interval in patients with short QT syndrome due to its effects on prolonging the action potential and by virtue of its action on the IK channels.[3] It is unclear if the prolongation of the QT interval by quinidine would reduce the risk of sudden cardiac death.
See also
References
- ↑ http://www.shortqtsyndrome.org/short_qt_history.htm
- ↑ Gollob M, Redpath C, Roberts J. (2011). "The Short QT syndrome: Proposed Diagnostic Criteria". J Am Coll Cardiol. 57 (7): 802–812. doi:10.1016/j.jacc.2010.09.048. PMID 21310316.
- ↑ Gaita F, Giustetto C, Bianchi F, Schimpf R, Haissaguerre M, Calo L, Brugada R, Antzelevitch C, Borggrefe M, Wolpert C. (2004). "Short QT syndrome: pharmacological treatment". J Am Coll Cardiol. 43 (8): 1494–1499. doi:10.1016/j.jacc.2004.02.034. PMID 15093889.