Mechanisms of Arrhythmogenesis
Tachyarrhythmias
A tachyarrhythmia is an abnormally fast rhythm, with a rate > 100 bpm.
As there are many different tachyarrhythmias, to aid in diagnosis and management, clinicians categorize them based on the origin of the rhythm:
supraventricular tachyarrhythmias: the rhythm originates or involves the structures above the level of the ventricles, namely the atria and AV junction
ventricular tachyarrhythmias: the rhythm originates in the ventricles
More info about where this info is obtained from can be found here.
Mechanisms of Arrhythmogenesis
Every arrhythmia needs two things:
a trigger - something to initiate the arrhythmia. This is typically a premature beat (a.k.a. an extrasystole), which is discussed later.
a substrate - something to keep the arrhythmia going so it doesn't falter out.
There are a few different mechanisms by which arrhythmias can be triggered or maintained. These can be organized into disordered impulse generation or disordered impulse conduction.
Abnormal impulse generation refers to one of two mechanisms: increased automaticity or triggered afterdepolarizations. Abnormal impulse conduction, as a mechanism of arrhythmogenesis, usually refers to re-entry.
Usually, arrhythmias result from multiple mechanisms interacting. For example, an arrhythmia can be triggered by an afterdepolarization but subsist through re-entry.
This module will discuss these mechanisms further below.
Increased Automaticity
Automaticity is the intrinsic rate at which cardiac cells spontaneously ("automatically") generate action potentials.
Increased automaticity involves something either raising the intrinsic firing rate of a cardiac pacemaker, or a non-pacemaking cell abnormally acquiring automaticity.
When the sinus node fires faster because of sympathetic stimulation (i.e. exercise, fear, pain, hypovolemia, and so on), increased automaticity occurs physiologically and is called enhanced normal automaticity.
When the sinus node fires faster aberrantly, outside of normal physiologic responses, it is known as abnormal automaticity. Potential causes of this include:
Parasympathetic inhibition: with medications or disruptions of the vagus nerve.
Pathologic states: outside of adrenergic stimulation, sinus automaticity can be enhanced by hypokalemia, digoxin toxicity, and hypoxia/ischemia. These pathologies reduce Na/K pump activity, thereby reducing the hyperpolarizing current, and leading to sinus nodal hyperexcitability.
You may also get abnormal automaticity in non-pacemaker cells. Various factors (i.e. hypokalemia, digoxin, hypoxemia, mechanical stretch) can provoke automaticity in cells other than the dominant pacemaker, leading to something known as a ectopic focus (also known as a driver). With enough automaticity, these ectopic foci can cause overdrive suppression of the sinus node and take over as the dominant pacemaker, leading to a tachyarrhythmia.
Triggered Activity
In the normal cardiac action potential:
An initial inward surge of sodium ions causes rapid membrane depolarization (Phase 0).
Then, a slow inward trickle of potassium initiates repolarization (Phase 1).
Soon after, an influx of calcium ions that balances out the flow of charges, leading to a "plateau" membrane voltage (Phase 2). These intracellular calcium ions allow myocardial contraction.
Calcium channels eventually close, and a dominant outward potassium current completes repolarization (Phase 3).
The cell returns to resting membrane potential (Phase 4), while the NCX and Na-K pump restore the gradients.
In triggered afterdepolarization (also known as "triggered activity"), a cardiomyocyte that has already depolarized gets depolarized again (hence the afterdepolarization) while in Phase 2, 3, or 4 of its action potential. If this occurs during Phases 2 or 3 (i.e. during the refractory period), it's known as an early afterdepolarization (EAD), whereas if it occurs during Phase 4 (i.e. after full repolarization), it's known as a delayed afterdepolarization (DAD).
Afterdepolarizations occur under conditions involving an excess of intracellular calcium, which can be seen in conditions involving excess catecholamines, digitalis, hypokalemia, hypercalcemia, hypertrophy, and heart failure. The intracellular calcium overload increases the activity of the sodium-calcium exchanger (NCX). The depolarizing current generated by the NCX (which displaces 1 intracellular calcium ion for 3 extracellular sodium ions) causes afterdepolarization.
Re-Entry
Normally, the entirety of the myocardium is uniformly depolarized, and repolarizes in relative unison. At this point, the electrical activity in the heart terminates before the next cardiac cycle begins (corresponding to the TP segment on the ECG).
Re-entry is a phenomenon whereby an electrical impulse is allowed to recirculate within myocardial tissue that has already been activated, perpetuating itself and forming a "loop" of activation that doesn't terminate. This loop is referred to as a re-entrant circuit. Re-entry relies on a heterogeneous dispersion of conduction velocities and refractoriness throughout a region of myocardium.
Obstacles in myocardium can facilitate something known as circus-type re-entry. The obstacles can be anatomical (i.e. non-conducting scar tissue) or functional (i.e. a region of refractory myocardium). The obstacles here form the substrate to allow for re-entry to perpetuate.
Re-entry can occur without obstacles as well. These are known as reflection-type re-entry and phase 2 re-entry, which you can read about in further detail in the article linked below.