Any clinical syndrome is a combination of objective findings and symptoms that occur together and characterize a particular disease.
In this context, Short QT Syndrome, is an inheritable, electrical heart disease, that is characterized by:
- A short QT interval in the ECG (and)
- Symptoms like palpitations, syncope or cardiac arrest (due to)
- Paroxysmal atrial and/or ventricular fibrillation (due to)
- Accelerated cardiac (atrial and ventricular) repolarization (due to)
- Congenital (genetically heterogeneous) channelopathy.
QT interval in the ECG
The cornerstone in the diagnosis is a short QT interval, which, unfortunately, is difficult to define, because the QT interval can be difficult to measure and is not the same all the time. Before the discovery of Short QT Syndrome there was no universal agreement as to when a QT interval was short, and even though such an agreement still does not exist, approximate figures for the lower limit of a QT interval at a heart rate of 60 beats per minute are 360 milliseconds for men and 370 milliseconds for women.
The difficulties in measuring the QT interval has been dealt with in numerous publications, and centers around the different duration of a QT interval you can get depending upon the equipment you use for recording the ECG (digital or analog) the different resolution of the various techniques, and the use of single or multiple leads.
The other big difficulty in giving a specific number for the duration or length of the QT interval is the many things that can influence the QT interval such as age, gender, time of day and most of all the heart rate at the time the ECG is recorded. In order to compare two peoples QT intervals the most important thing is to record the QT intervals at the same heart rate. Since this is generally not possible, Henry Cuthbert Bazett (1885-1950) already in 1920 came up with a formula meant to alleviate this problem, and despite great inaccuracies in using this formula and because of lack of better formulas, it is still used extensively. Bazett’s formula is meant to correct a given QT interval taken at a heart rate other than 60 beats per minute to what the QT interval most likely would be, when measured at a heart rate of 60 beats per minute. The QT interval calculated by Bazett’s formula is called the corrected QT interval (QTc). The formula is based upon the assumption that the way the QT intervals varies with heart rate is the same in everybody, which is not true, and it is especially not true in patients with Short QT Syndrome, where the QT interval only changes very little with changes in heart rate and therefore needs no or very little correction. In other words, Bazett’s formula is not meant to be used in patients with Short QT Syndrome.
An example from the literature will help illustrate this latter problem:
In a recent article (Bun S-S et al. Electrical Storm in Short-QT Syndrome Successfully Treated with Isoproterenol. J Cardiovasc Electrophysiol 2012;23(9):1028-103) the authors describe a young patient who had been resuscitated after dying suddenly during his sleep. On arrival to the hospital his ECG showed a QT interval of 340 milliseconds at a heart rate of 75 beats per minute. The QTc using Bazetts formula calculated the QT to be 383 milliseconds, which is more than 360 milliseconds and therefore normal. There was, therefore, no immediate suspicion of Short QT Syndrome in this patient. When an ECG taken 6 years earlier showed up, the QT interval in his ECG at that time was slightly lower at 320 milliseconds at a heart rate of 60 beats per minute, and therefore much lower than 360 milliseconds and strongly suggesting Short QT Syndrome. This example shows that a patient with Short QT Syndrome can easily be misdiagnosed if the ECG looked at is taken at a heart rate faster than 60 beats per minute.
Therefore, in order to get a reliable assessment of the QT interval in a patient suspected of having a short QT interval and possibly Short QT Syndrome every effort should be made to get an ECG at a heart rate as close to 60 beats per minute as possible.
Despite the inappropriateness in using QTc when trying to make the diagnosis of Short QT Syndrome, it can at times be useful: if both the QT interval and the QTc in an ECG at a heart rate above 60 beats per minute is below normal, the patient will have a short QT interval, and, therefore, be under suspicion of having Short QT Syndrome.
QTc intervals calculated from QT intervals at heart rates below 60 beats per minute are often falsely shorter than the actual QT interval at 60 beats per minute, which can lead to over-diagnosing of Short QT in people with a slow heart rate as seen for instance in younger male persons, who often have a slow pulse.
In a study from 2008 of the first 49 patients diagnosed with Short QT Syndrome the QT intervals in these patients varied between 210 and 340 milliseconds with an average of 282 milliseconds. For all practical purposes a diagnosis of Short QT Syndrome is therefore unlikely if the QT interval is more than 340 milliseconds.
If a person is under suspicion of having a Short QT Syndrome it is important to make several ECG recordings, often a 24-hour ambulatory ECG recording or recordings during physical activity can be helpful.
The great majority of patients diagnosed with Short QT Syndrome have been males at the age from newborn to very old. Almost half of the patients have been diagnosed during screening for Short QT Syndrome after a family member had received the diagnosis, usually following cardiac arrest. Other more rare presentations have been passing out spells or palpitations. In only a couple of cases has Short QT Syndrome been discovered incidentally in an ECG taken as part of a general health screening.
Arrhythmias are heart rhythm disturbances causing a slow, fast or irregular pulse often appreciated by a person as what is called palpitations. At times such arrhythmias can become life-threatening, and that is more likely to happen in people having a short QT interval, which makes the heart especially irritable. The name of the arrhythmias most commonly associated with Short QT Syndrome are atrial fibrillation and ventricular fibrillation.
Accellerated cardiac repolarization
Accellerated cardiac repolarization is responsible for shortening of the QT interval and can be caused by either a gain-of-function in a potassium channel or loss-of-function in a sodium- or calcium channel, and all of the above have been related to either Short QT Syndrome or Brugada Syndrome with short QT interval.
Congenital (genetically heterogeneous) channelopathy
Congenital means that people are born with a short QT interval. Genetically heterogeneous means that it is hereditary and therefore due to a gene defect (a mutation) which stems from one of the parents. It also means that there are many different mutations, which can lead to a short QT interval. Channelopathy means that the genetic defect has changed the function of the so-called channels in the cells of the heart leading to accelerated cardiac repolarization described above.
Among families with Short QT Syndrome who has undergone genetic testing a mutation causing the disease has only been found in approximately 25 %, comprising 12 different Short QT Syndrome mutations in 3 different genes (KCNH2 (N588K, R1135H, T618I, E50D, p.Pro872fs), KCNQ1 (V307L, V141M, I274V) and KCNJ2 (D172N, K364T, E299V, M301K). In addition, a short QT interval has been found in some patients with another similar disease called Brugada Syndrome due to mutations in 4 other genes (CACNA1C, CACNB2, CACNA2D1 and SCN5A).
If a Short QT Syndrome mutation is found in a person with a short QT interval or in a person who has died suddenly, the diagnosis of Short QT Syndrome is established with a high degree of certainty. At the same time, knowing the mutation can help in diagnosing family members in whom the QT interval is difficult to assess because of either a fast heart rate, atrial fibrillation or bundle branch block, which can all make QT interval measurements difficult.
When should Short QT Syndrome especially be considered?
- Whenever an ECG has short QT interval as a diagnosis
- In family members of a patient with Short QT Syndrome
- In family members of a patient with Sudden Cardiac Death
- In a young patient with atrial fibrillation
- In a baby with persistently slow heart rate
In making the diagnosis of Short QT Syndrome a lot of factors have to be taken in account in addition to the ECG including family history, symptoms and result of genetic testing.
It is important to have in mind that Short QT Syndrome is an extremely rare diagnosis. Only approximately a hundred cases have been published since the first publication in 2000, but based upon information from around the world through this website there is probably at least another hundred cases which have not been published. An accurate measurement of the QT interval is crucial, and it is important to know that the way the QT interval varies with heart rate in patients with Short QT Interval is different from normal people.
A diagnosis of Short QT Syndrome should always be made by an electrophysiologist, preferably one with special knowledge of QT interval diseases.