Potential application of late sodium current blockade in the treatment of heart failure and atrial fibrillation.

The cardiac action potential consists of the sequential activation of various ion channels in a precisely orchestrated manner. Pathologic alterations of ion channel currents disrupt this coordinated behavior and have been linked to arrhythmias, such as atrial fibrillation, as well as to heart failure. The late sodium current is increased in the ventricular myocytes in patients with heart failure and can result in contractile dysfunction. The most likely mechanism whereby elevated intracellular Na+ levels may lead to heart failure is through calcium overload. Sodium channel blockade is a proven strategy in the treatment of atrial fibrillation. Although all class I antiarrhythmic drugs inhibit the sodium current, ranolazine has been shown to be a more specific and potent blocker of the late sodium current. In clinical trials, ranolazine has significantly decreased episodes of nonsustained ventricular tachycardia and supraventricular tachycardia as compared with placebo.