The long QT interval is not only inherited but is also linked to cardiac hypertrophy

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Abstract
This review focuses on the molecular determinants of the duration of the QT interval as measured on by electrocardiography in normal subjects and during cardiac hypertrophy and failure. (a) In control conditions, on a single cell, the shape and duration of the action potential is the result of a balance between different ion currents which in turn were determined by the number of functional channels. On multicellular preparations the QT duration also represents the repolarization time; nevertheless it is modified by the transmural gradients. On body-surface electrocardiography the duration of the QT interval depends also of an additional factor: the spatial three-dimensional projection of the electrical waves vectors, which makes any determination of the epicardial dispersion by measuring QT interval dispersion questionable. (b) The enhanced action potential duration is well documented in cardiac hypertrophy and heart failure and is usually caused by a reduction in outward current densities in most of the species except mice. Among these currents ItO is the most frequently altered, especially in humans. Such an altered current density is caused by a diminished expression of the genes encoding either the ion channel subunits or regulatory proteins, such as KChIP2. In addition, hypertrophy modifies or even reverses the transmural gradient. In human and rats hypertensive cardiopathy is associated with a prolongation of the QT interval duration. The reduction in ItO is likely to be adaptive; it participates in the slowing of the cardiac cycle and reflects the fetal genetic reprogramming. Recent data also suggest that a reduction in the transient outward K+ current density triggers protein synthesis through an activation of the calcineurin pathways. Thus a prolongation of the QT interval is not only inherited or drug-induced; it is also an essential component of the adaptive process in chronic mechanical overload. It is fundamentally incorrect to measure QT dispersion on a surface electrocardiography, but the mean QT interval may provide information concerning the progression of the disease, just as, and with the same restrictions, in the case of the quantification of Vmax.