The artificial pacemaker is one of the great medical inventions of the 20th century. Cardiac pacing has evolved from a hazardous experiment in the 1930s, to a routine, safe, and sophisticated treatment used worldwide. Artificial pacemakers have benefitted immensely from advances in engineering, notably with the advent of transistors, programmable circuits, lithium batteries, and Internet-connected devices. Additional breakthroughs have been achieved in recent years, with the leadless pacemaker being the most promising improvement.¹

Given the wide use of pacemakers and the trend towards increased use of cardiac devices in general, it is crucial to be familiar with these devices. This section is devoted to artificial pacemakers. More advanced devices (ICD, implantable cardioverter defibrillator; CRT, cardiac resynchronization therapy) are discussed in subsequent chapters. The first part consists of a brief rehearsal of the basics of cardiac automaticity, action potentials, and pacemaker cells.

Principles of myocardial excitability and the conduction system

Achieving an effective pumping mechanism requires the atria and the ventricles to be activated rapidly and sequentially. Rapid activation is important in order to activate as much myocardium simultaneously as possible; the more myocardium contracting at the same time, the more efficient the pumping mechanism. Sequential activation means that the atria activate first, filling the ventricles with adequate volumes of blood before the ventricles begin contracting. To coordinate these two tasks, the heart has an intrinsic pacemaker–i.e. the sinus node–and an electrical conduction system composed of specialized myocardial cells. Conduction cells form bundles of fibers that spread the action potential rapidly and sequentially to the contractile myocardium. When the contractile myocardium receives the action potential, it is activated and contracts. Figure 1 illustrates the sinus node and the components of the conduction system.

The AV system consists of the AV node, the bundle of His and the Purkinje fibers. These structures transmit the atrial pulse to the ventricles. Impulse transmission is rapid through the bundle of His and the Purkinje fibers, such that virtually all ventricular myocardium is activated (depolarized) simultaneously. The rapid activation of the ventricles yields a narrow QRS complex (defined as QRS duration <120 ms).

The cardiac action potential

The action potential includes a depolarization (activation) followed by repolarization (recovery). The cardiac cycle starts when the sinus node discharges the first action potential, which then spreads through the myocardium like a wave front in water. Figure 2 shows the appearance of the action potential in contractile myocardial cells.

Cardiac electromechanical coupling

Depolarization activates the myocardial cells and induces cellular processes that lead to cell contraction. The spread of an electrical impulse is therefore directly coupled to a mechanical event; this is referred to as electromechanical coupling.

The electrical conduction system of the heart

The sinus node (sinoatrial node) and intrinsic automaticity

The sinus node is a small oval structure located near the entrance of the superior vena cava in the right atrium (Figure 1). The sinus node is composed of highly specialized cells that have a unique ability to spontaneously depolarize. Thus, the cells of the sinus node are capable of spontaneously discharging an action potential. This ability is referred to as automaticity. The cells of the sinus node have an intrinsic rate of depolarization at approximately 70 times per minute, which results in 70 contractions per minute. The sinus node is the primary pacemaker of the heart.

Secondary (latent) pacemakers

There are additional structures that possess automaticity and thus the ability to serve as the heart’s pacemaker. These structures are as follows:

• Parts of the atrial myocardium: There are clusters of atrial myocardial cells located around the crista terminalis, the entrance of the coronary sinus and the inferior vena cava, as well as cells around the mitral and tricuspid valves, which possess automaticity. These cells are not conduction cells per se; they are actually contractile cells that possess automaticity. Thus, automaticity is not exclusive to cells of the conduction system.
• Cells surrounding the atrioventricular (AV) node: It is a common misconception that the atrioventricular (AV) node possesses automaticity because there is no compelling evidence for that. There is, however, evidence that cell clusters surrounding the AV node possess automaticity.
• The His-Purkinje network: The bundle of His and the entire Purkinje network possess automaticity.

Thus, the heart has four pacemakers (the sinus node; parts of atrial myocardium; myocardium around the AV node; the His-Purkinje network). The reason that the sinus node is the primary pacemaker is simply that it has the highest intrinsic rate of spontaneous depolarization (i.e the fastest automaticity). The heart rhythm is governed by the fastest pacemaker because that pacemaker will depolarize before the competing pacemakers, and reset them.

The intrinsic rate of depolarization of all pacemaker cells is depicted in Figure 3.

Artificial pacemakers

Failure of the sinus node to generate impulses, or failure of the electrical conduction system to transmit impulses, may lead to bradycardia or even asystole. Latent pacemakers typically prevent asystole by establishing an escape rhythm. Although such escape rhythms may be life-saving, they have two fundamental shortcomings:

• Escape rhythms established by latent pacemakers have a lower frequency than the sinus node, which means that cardiac output is reduced.
• Escape rhythms established by latent pacemakers are unreliable in the long term because their activity may cease completely, which results in asystole.

Artificial pacemakers are indicated if impulse formation or impulse conduction is defective, such that bradycardia develops. The most common cause of defective impulse formation is sinus node dysfunction, and the most common cause of defective impulse conduction is AV blocks.

Although stroke volume increases slightly during bradycardia (due to increased filling time), it results in diminished cardiac output. If cardiac output decreases substantially, symptoms such as dizziness, presyncope or even syncope occur. If cardiac output is diminished, but cerebral perfusion is sufficient, dyspnea, fatigue, exercise intolerance, chest discomfort or heart failure may develop.

From a clinical perspective, management is more urgent if bradycardia is due to AV block, which is explained by the fact that high-degree AV blocks (second-degree AV block, third-degree AV block) can cause asystole.

Intrinsic cardiac automaticity: Pacemaker potential

The automaticity of the cells in the sinus node is explained by the fact that these cells start leaking sodium (Na+) into the cell as soon as they return to their resting state (Figure 4). As sodium leaks into the cell, the cell membrane gradually becomes more positive. When the membrane potential reaches its threshold –40 mV, the action potential is triggered and the cell depolarizes. At –40 mV voltage-gated calcium (Ca2+) channels open so that calcium flows into the cell and causes depolarization. Subsequently, outward-directed potassium (K+) channels open which results in repolarization of the cell. The cycle then repeats itself. The leakage of sodium during the resting phase is referred to as pacemaker potential.

The depolarization spreads from the sinoatrial node to the atrial and ventricular myocardium. Propagation of the action potential is possible because all cardiac cells are electrically interconnected by gap junctions (Figure 4). The density of gap junctions within the Purkinje network is very high, which explains the rapid impulse transmission in the network. Cells of the atrioventricular node, on the other hand, have a very low density of gap junctions, which explains the slow impulse conduction through the atrioventricular node. Transmission of the action potential between contractile myocardial cells is also slow, owing to the scarcity of gap junctions between them.

The contractile cells, unlike cells of the sinoatrial node, display a true resting potential (phase 4), which is around –90 mV. These cells must be stimulated in order to evoke an action potential. Upon stimulation, sodium (Na+) channels open which causes a rapid influx of sodium and depolarizes the cell. Contractile cells start to contract a few milliseconds after the start of the depolarization and they start relaxing a few milliseconds after the repolarization is completed. The duration of the action potential is approximately 0.20 seconds in the atrial myocardium and 0.3 seconds in the ventricular myocardium (Figure 4).

Read more: Cardiac electrophysiology: action potential, automaticity and vectors

Absolute and relative refractory periods during the action potential

During the greater part of the action potential, the myocardial cell is absolutely refractory to stimulation, meaning that an additional stimulus cannot trigger a new action potential, regardless of the intensity of the stimulus. The absolute refractory period is followed by a relative refractory period, during which a strong stimulation may trigger a new action potential. The absolute and relative refractory periods are displayed in Figure 5.

Principles of artificial pacemakers

Modern pacemakers are extremely sophisticated. They can replace both impulse formation and impulse conduction. They can also adapt their function to the heart’s own activity (by sensing) as well as the needs of the body (through rate responsiveness). Modern pacemakers can also detect and treat tachyarrhythmias, both supraventricular and ventricular. These topics, and much more, will be discussed in subsequent chapters.

References

Reynolds et al. A Leadless Intracardiac Transcatheter Pacing System List of authors. The New England Journal of Medicine.

Mulpuru et al. Cardiac Pacemakers: Function, Troubleshooting, and Management. JACC.