by Dr Jay Lu

In this blog, we will explore the concept of proarrhythmia, a serious adverse effect of certain medications that can disrupt the normal electrical activity of the heart and lead to life-threatening arrhythmias, such as early afterdepolarizations (EADs) and Torsade de Pointes (TdP). The normal electrical activity of the heart is regulated by complex mechanisms involving ion channels and other proteins that determine the shape and duration of the cardiac action potential.

What is the mechanism behind it?
Action potential triangulation leads to proarrhythmia by altering the normal shape and duration of the action potential of heart cells. Normally, the action potential of heart cells has a rounded, upward slope, which allows for efficient electrical conduction throughout the heart. However, in action potential triangulation, the slope of the action potential becomes steeper and more triangular, causing the action potential to last longer. This increased duration of the action potential can lead to an increased refractory period, which is the time during which the heart cell cannot be re-stimulated by another electrical impulse.

The increased refractory period can result in decreased excitability of the heart cells, making it more difficult for electrical impulses to travel through the heart. This can lead to the development of arrhythmias and increase the risk of cardiac events such as ventricular fibrillation and sudden cardiac death. In addition, the prolonged refractory period can increase the likelihood of re-entry, a phenomenon in which an electrical impulse circulates in a loop, causing the heart to beat irregularly. These effects of action potential triangulation can be potentiated by certain anti-arrhythmic drugs, further increasing the risk of proarrhythmia.

How do we calculate the triangulation ratio?
The triangulation ratio (APD30/APD80) can be calculated using OMapScope software, which uses optical mapping data to provide a visual representation of the electrical activity of the heart (Fig.1). This software allows researchers to easily and accurately compute the triangulation ratio, providing insights into the underlying causes of proarrhythmia and helping to improve patient safety and prevent life-threatening arrhythmias.

Fig.1 OMapScope provides users with one-click action potential triangulation analysis. Red arrow indicates the action potential triangulation calculation function.