Molecular biology and the prolonged QT syndromes

Fifteen-lead surface electrocardiogram of a 12-year-old female with long QT syndrome. Apparent in lead II is a deformation in the T wave. This is an example of “pseudo” 2:1 atrioventricular block in a patient with a QTc of 500 milliseconds.

One-day-old female infant with Romano-Ward long QT syndrome and a QTc of 560 milliseconds. A zoomed view of lead V6 shows classic T-wave alternans with a change in T-wave axis on alternating beats.

Two-day-old male infant with long QT syndrome. Polymorphic ventricular tachycardia with a more classic appearance of torsades de pointes is seen. Note the obvious rapid changing axis over one beat in the first three strips. Again, the arrhythmia self terminates.

Genetics of ventricular arrhythmias. Chromosomal location and ion channel topology, as well as some of the original mutations identified in each channel, are demonstrated.

Cardiac action potential. Note that the time course of the cardiac action potential can be divided into five phases: upstroke of rapid depolarization (phase 0), which is mostly the result of rapid inflow of sodium (SCN5A); rapid repolarization after the peak (phase 1) is primarily the result of an outward repolarizing chloride current; the plateau (phase 2) where there is a balance of the inward currents caused by calcium and sodium and outward currents caused by chloride and potassium (I_Kr); rapid repolarization after the plateau (phase 3), predominantly caused by outward potassium current (I_Ks); and the period between the maximum negativity (maximum diastolic potential) and the upstroke of the next action potential (phase 4) caused by the balance between slow inward sodium current and outward potassium current.

Electrocardiograms from patients with mutations in KVLQT1, HERG, and SCN5A, respectively. Note the broad T waves associated with KVLQT1 mutations, whereas the electrocardiogram from a HERG-mutated patient has low amplitude T waves. The SCN5A-associated electrocardiogram shows high amplitude and long delay in the onset of the T wave. (Reprinted with permission from reference 100.)