Short QT syndrome

Short QT syndrome (SQT) is a very rare genetic disease of the electrical system of the heart, and is associated with an increased risk of abnormal heart rhythms and sudden cardiac death. The syndrome gets its name from a characteristic feature seen on an electrocardiogram (ECG) – a shortening of the QT interval. It is caused by mutations in genes encoding ion channels that shorten the cardiac action potential, and appears to be inherited in an autosomal dominant pattern. The condition is diagnosed using a 12-lead ECG. Short QT syndrome can be treated using an implantable cardioverter-defibrillator or medications including quinidine. Short QT syndrome was first described in 2000, and the first genetic mutation associated with the condition was identified in 2004. Those affected by short QT syndrome (SQT) have an increased risk of developing abnormal heart rhythms. These abnormal heart rhythms often occur at a young age. They may take relatively benign forms such as atrial fibrillation, leading to symptoms of palpitations, breathlessness, or fatigue. Accordingly, atrial fibrillation presenting in a newborn should raise the suspicion of short QT syndrome. In addition, far more dangerous heart rhythm disturbances such as ventricular fibrillation can also occur in those with short QT syndrome, leading to blackouts or even sudden death. More than a third of those with short QT present with ventricular arrhythmias or sudden cardiac death, while one in five cases are detected during family screening, and one in five cases are found incidentally after an electrocardiogram (ECG) has been recorded for another reason. If someone with short QT syndrome is examined while their heart is beating in an abnormal rhythm such as atrial fibrillation, this can be detected by feeling their pulse. No abnormal signs will usually be found when examining someone with short QT syndrome while their heart is beating in its normal or sinus rhythm. Short QT syndrome is a genetic disorder caused by mutations in genes responsible for producing certain ion channels within heart cells. It appears to be inherited in an autosomal dominant pattern. Some genetic variants cause an increased flow of potassium out of the cell, while others reduce the flow of calcium into the cell. The common effect of all these variants is to shorten the cardiac action potential, reflected on the surface ECG as a shortening of the QT interval. A list of genes in which variants have been associated with short QT syndrome can be found in the table below. The overall effect of each of the genetic variants associated with short QT syndrome is to shorten the cardiac action potential, which in turn increases the risk of developing abnormal heart rhythms including atrial fibrillation and ventricular fibrillation. During the normal rhythm of the heart, or sinus rhythm, smooth waves of electrical activity pass regularly through the cardiac muscle. In contrast, during atrial or ventricular fibrillation, waves of electrical activation spiral through the cardiac muscle chaotically in a mass of disorganised, broken wavelets. The consequence of fibrillation is that the chambers of the heart affected by the disorganised electrical activation lose their pumping ability – fibrillation of the cardiac atria in atrial fibrillation leads to an irregular pulse, and fibrillation of the cardiac ventricles in ventricular fibrillation renders the heart unable to pump blood at all. There are several possible mechanisms by which short action potentials might promote fibrillation. The link between these mechanisms is how the duration of the action potential influences how frequently a heart muscle cell can be excited. A shorter action potential generally allow a heart muscle cell to be excited more frequently – the refractory period is shorter. The first mechanism, referred to as the dispersion of repolarisation, occurs because the action potential shortening seen in this condition occurs to a greater extent in some layers of the heart wall than in others. This means that at certain points in the cardiac cycle, some layers of the heart wall will have fully repolarised, and are therefore ready to contract again, while other regions are only partially repolarised and therefore are still within their refractory period and not yet able to be re-excited. If a triggering impulse arrives at this critical point in the cardiac cycle, the wavefront of electrical activation will conduct in some regions but block in others, potentially leading to wavebreak and re-entrant arrhythmias. The second mechanism relates to the increased number of fibrillatory wavelets that can simultaneously exist if the action potential decreases, in a concept known as the arrhythmia wavelength. During fibrillation, the chaotic wavelets rotate, or re-enter, within the muscle of the heart, continually extinguishing and reforming. The volume of tissue in which each wavelet can complete a re-entrant circuit is dependent on the refractory period of the tissue and the speed at which the waves of depolarisation traverse move – the conduction velocity. The product of the conduction velocity and refractory period is known as the wavelength. In tissue with a lower wavelength a wavelet can re-enter within a smaller volume of tissue. A shorter refractory period therefore allows more wavelets to exist within a given volume of tissue, reducing the chance of all wavelets simultaneously extinguishing and terminating the arrhythmia.