Short QT syndrome

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. 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. ==Cause==

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. 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. 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. ==Diagnosis==

Short QT syndrome is diagnosed primarily using an electrocardiogram (ECG), but may also take into account the clinical history, family history, and possibly genetic testing. Whilst a diagnostic scoring system has been proposed that incorporate all of these factors (the Gollob score), it is uncertain whether this score is useful for diagnosis or risk stratification, and the Gollob score has not been universally accepted by international consensus guidelines. 12-lead ECG The mainstay of diagnosis of short QT syndrome is the 12-lead ECG. The precise QT duration used to diagnose the condition remains controversial with consensus guidelines giving cutoffs varying from 330 ms, 340 ms or even 360 ms when other clinical, familial, or genetic factors are present. The QT interval normally varies with heart rate, but this variation occurs to a lesser extent in those with short QT syndrome. It is therefore recommended that the QT interval is assessed at heart rates close to 60 beats per minute. Other features that may be seen on the ECG in short QT syndrome include tall, peaked T-waves and PR segment depression. Other features supporting diagnosis Other features that support a diagnosis of short QT syndrome include: a history of ventricular fibrillation or ventricular tachycardia despite an apparently structurally normal heart; a family history of confirmed short QT syndrome; a family history of sudden cardiac death aged <40 years; and identification of a genetic mutation consistent with short QT syndrome. Invasive electrophysiological studies, in which wires are passed into the heart to stimulate and record the heart's electrical impulses, are not currently recommended for diagnosing short QT syndrome or predicting the risk of sudden cardiac death. ==Treatment==

The treatment for short QT syndrome is aimed at preventing abnormal heart rhythms and reducing the risk of sudden cardiac death. It has been difficult to experimentally test potential treatments as the condition is very rare, so the evidence for treatment effectiveness comes largely from consensus opinion. Medication Medication aimed at correcting the ECG abnormality – the shortened QT interval – has been tried. Quinidine, a class Ia antiarrhythmic agent, has been shown to partially correct the QT interval and make the heart more resilient to artificially-induced abnormal heart rhythms, although it is still uncertain at present whether this translates to a lower risk of sudden death. Sotalol, another antiarrhythmic, may prolong the QT in some subtypes of short QT syndrome. == Epidemiology ==

Short QT syndrome is a very rare condition with, as of 2018, fewer than 300 cases described in the medical literature. Males and females are equally likely to be affected, and have a similar risk of sudden cardiac death. == Prognosis ==

The rarity of short QT syndrome makes calculating prognosis accurately difficult. The risk of sudden cardiac death has been estimated at 0.8% per year, leading to a cumulative risk of sudden cardiac death of 41% by the age of 40. A previous history of cardiac arrest predicts a higher likelihood of further dangerous arrhythmias. Some have suggested that those with the shortest QT intervals may have a higher risk of arrhythmias, but this view has not been supported by all. The findings from invasive electrophysiological studies do not predict an individual with short QT syndrome's risk of cardiac arrest. == History ==

The first report of short QT syndrome to be published was in 2000, describing a family with short QT intervals on the 12-lead ECG, atrial fibrillation occurring at a young age, and an unrelated patient who had a sudden cardiac death associated with a short QT interval. The association between short QT and sudden cardiac death was described in 2003, and the first gene associated with the condition was identified in 2004. Criteria for diagnosing Short QT syndrome were proposed in 2011. Using this animal model, in vivo gene therapy for short QT syndrome was successfully demonstrated for the first time using adenoviral suppression and replacement (Sup-Rep) gene transfer. == See also ==