Cellular mechanisms leading to arrhythmias in<unk>  The various forms of<unk> , both congenital and acquired, produce abnormal heart rhythms (arrhythmias) by influencing the electrical signals used to coordinate individual heart cells. The common theme is a prolongation of the cardiac action potential – the characteristic pattern of voltage changes across the cell membrane that occur with each heart beat. Heart cells when relaxed normally have fewer positively charged ions on the inner side of their cell membrane than on the outer side, referred to as the membrane being polarised. When heart cells contract, positively charged ions such as sodium and calcium enter the cell, equalising or reversing this polarity, or depolarising the cell. After a contraction has taken place, the cell restores its polarity (or repolarises) by allowing positively charged ions such as potassium to leave the cell, restoring the membrane to its relaxed, polarised state. In<unk>  it takes<unk> er for this repolarisation to occur, shown in individual cells as a<unk> er action potential while being marked on the surface ECG as a<unk>  QT interval. The prolonged action potentials can lead to arrhythmias through several mechanisms. The arrhythmia characteristic of<unk> , Torsades de Pointes, starts when an initial action potential triggers further abnormal action potentials in the form of afterdepolarisations. Early afterdepolarisations, occurring before the cell has fully repolarised, are particularly likely to be seen when action potentials are prolonged, and arise due to reactivation of calcium and sodium channels that would normally switch off until the next heartbeat is due. Under the right conditions, reactivation of these currents, facilitated by the sodium-calcium exchanger, can cause further depolarisation of the cell. The early afterdepolarisations triggering arrhythmias in<unk>  tend to arise from the Purkinje fibres of the cardiac conduction system. Early afterdepolarisations may occur as single events, but may occur repeatedly leading to multiple rapid activations of the cell. Some research suggests that delayed afterdepolarisations, occurring after repolarisation has completed, may also play a role in<unk> . This form of afterdepolarisation originates from the spontaneous release of calcium from the intracellular calcium store known as the sarcoplasmic reticulum, forcing calcium out of cell through the sodium calcium exchanger in exchange for sodium, generating a net inward current. While there is strong evidence that the trigger for Torsades de Pointes comes from afterdepolarisations, it is less certain what sustains this arrhythmia. Some lines of evidence suggest that repeated afterdepolarisations from many sources contribute to the continuing arrhythmia. However, some suggest that the arrhythmia sustains through a mechanism known as re-entry. According to this model, the action potential prolongation occurs to a variable extent in different layers of the heart muscle with<unk> er action potentials in some layers than others. In response to a triggering impulse, the waves of depolarisation will spread through regions with shorter action potentials but block in regions with<unk> er action potentials. This allows the depolarising wavefront to bend around areas of block, potentially forming a complete loop and self-perpetuating. The twisting pattern on the ECG can be explained by movement of the core of the re-entrant circuit in the form of a meandering spiral wave.
Long QT syndrome
Brugada syndrome
Short QT syndrome
Arrhythmogenic cardiomyopathy
Catecholaminergic polymorphic ventricular tachycardia
Opitz G/BBB syndrome
Jervell and Lange-Nielsen syndrome
Familial atrial fibrillation