CHAPTER 1
Indications for permanent cardiac pacing

Roy M. John

Center for Advanced Management of Ventricular Arrhythmias, Northshore University Hospital, Manhasset, NY, USA

Introduction

Defects of cardiac impulse generation and conduction can occur at various levels in the cardiac conduction system. In general, intrinsic disease of the conduction system is often diffuse. For example, normal atrioventricular (AV) conduction cannot necessarily be assumed when a pacemaker is implanted for a disorder seemingly localized to the sinus node. Similarly, normal sinus node function cannot be assumed when a pacemaker is implanted in a patient with AV block. Conduction disorders that lead to important bradycardia or asystole may result from reversible or irreversible causes. Recognition of reversible causes is critical to avoid unnecessary commitment to long-term pacemaker therapy. This chapter reviews the common disorders that warrant cardiac pacing and lists the recommended indications set out by published guidelines.

Anatomy and physiology of the conduction system

For a complete understanding of rhythm generation and intracardiac conduction, and of their pathology, a brief review of the anatomy and physiology of the specialized conduction system is warranted.

Sinus node

The sinus node or sinoatrial (SA) node is a crescent-shaped subepicardial structure located at the junction of the right atrium and superior vena cava along the terminal crest. It measures 10-20 mm (with larger extension in some studies) and has abundant autonomic innervation and blood supply, with the sinus node artery commonly coursing through the body of the node. Endocardially, the crista terminalis overlies the nodal tissue, although the inferior aspect of the node has a more subendocardial course. Histologically, the sinus node comprises specialized nodal cells (P cells) packed within a dense matrix of connective tissue. At the periphery, these nodal cells intermingle with transitional cells and the atrial working myocardium, with radiations extending toward the superior vena cava, the crista terminalis, and the intercaval regions [1,2]. The absence of a distinct border and the presence of distal fragmentation explain the lack of a single breakthrough of the sinus node excitatory wavefront. The radiations of the node, although histologically distinct, are not insulated from the atrial myocardium. Hence, a clear anatomical SA junction is absent. The sinus node is protected from the hyperpolarizing effect of the surrounding atria, probably by its unique structure wherein electrical coupling between cells and expression of ion channels vary from the center of the node to the periphery. The pacemaker cells at the center of the node are more loosely coupled, while those at the periphery are more tightly coupled with higher density If (funny current, a mixed sodium and potassium current carried by the HCN channels) and INa currents [2].

The SA node has the highest rate of spontaneous depolarization (automaticity) in the specialized conduction system and is responsible for the generation of the cardiac impulse under normal circumstances, although normal human pacemaker activity may be widely distributed in the atrium. The unique location of the sinus node astride the large SA nodal artery provides an ideal milieu for continuous monitoring and instantaneous adjustment of heart rate to meet the body's changing metabolic needs.

Impulse generation in the sinus node remains incompletely understood. Sinus nodal cells have a low resting membrane potential of -50 to -60 mV. Spontaneous diastolic (phase 4) depolarizations are probably triggered by several currents, including If. The predominant inward current in the center of the node is ICaL that generates a "slow" action potential. The action potentials spread peripherally into the musculature of the terminal crest. In the periphery of the node, INa is operative and necessary for providing sufficient inward current to depolarize the larger mass of atrial tissue. Defects of a number of molecular and biophysical factors that govern the ionic channels of the sinus node can lead to sinus node dysfunction (Figure 1.1).

Differential sensitivity to adrenergic and vagal inputs exists along the nodal pacemaker cells, such that superior sites tend to dominate during adrenergic drive while the inferior sites predominate during vagal stimulation [3]. Interventions including premature stimulation, autonomic stimulation, and drugs have been shown to induce pacemaker shifts (due to multicentric origins) with variable exit locations [4].

Figure 1.1 Summary of factors contributing to sinus node (SN) dysfunction. The central node (CN) shown in red is surrounded by the peripheral nodal (PN) structure in blue. RAA, right atrial appendage; SVC, superior vena cava; IVC, inferior vena cava.

Source: modified from Monfredi O, Boyett MR. Sinus sinus syndrome and atrial fibrillation in older persons: a view from the sinoatrial nodal myocyte. J Mol Cell Cardiol 2015;83:88-100. Reproduced with permission of Elsevier.

Atrioventricular node

The compact AV node is a subendocardial structure situated within the triangle of Koch and measuring 5-7 mm in length and 2-5 mm in width [5,6]. On the atrial side, the node is an integral part of the atrial musculature, in contrast to the AV bundle which is insulated within the central fibrous body and merges with the His bundle. Based on action potential morphology in rabbit hearts, atrial (A), nodal (N), and His (H) cells have been defined. Intermediate cell types such as AN and NH define areas toward the atrial and His bundle ends of the compact node, respectively. Histologically, the mid nodal part has densely packed cells in a basket-like structure interposed between the His bundle and the loose atrial approaches to the node. The AN cells are composed primarily of transitional cells. Distinct electrical and morphological specialization is seen only in the progressively distal His fibers. Rightward and leftward posterior extensions of the AV node were described by Inoue and Becker [7]. These extensions have clinical implications for defining reentrant circuits that act as a substrate of AV nodal reentrant tachycardia.

The AV node has extensive autonomic innervation and an abundant blood supply from the large AV nodal artery, a branch of the right coronary artery, in 90% of patients, and from the left circumflex artery in 10% (Figure 1.2). AV nodal conduction is mediated via "slow" calcium-mediated action potential and demonstrates decremental conduction due to post-repolarization refractoriness as a result of delayed recovery of the slow inward currents. AV nodal tissue closer to the His bundle (NH and proximal His bundle area) generates junctional escape rhythms (Figure 1.3). Escape rates are dependent on the site of dominant pacemaker activity. Isoproterenol stimulation, for example, accelerates junctional escape and shifts the dominant activity to the transitional cells in the AN region and posterior extensions of the node [8-10].

His-Purkinje system

Purkinje fibers emerging from the area of the distal AV node converge gradually to form the His bundle, a narrow tubular structure that runs through or around the membranous septum to the crest of the muscular septum, where it divides into the bundle branches. The bulk of the His bundle cells contribute to the left bundle branch with a smaller contribution to the right bundle. Longitudinal strands of Purkinje fibers, divided into separate parallel compartments by a collagenous skeleton, can be discerned by histological examination of the His bundle [11]. The collagen sheathing minimizes lateral spread of impulses from the main body of the bundle branches. The rapid conduction of electrical impulses across the His-Purkinje system is responsible for the almost simultaneous activation of the right and left ventricles. The His bundle has relatively sparse autonomic innervation, although its blood supply is quite ample, emanating from both the AV nodal artery and the septal branches of the left anterior descending artery (Figure 1.2).

The bundle branch system is a complex network of interlaced Purkinje fibers that varies greatly among individuals. It generally starts as one or more large fiber bands that split and fan out across the ventricles until they finally terminate in a Purkinje network that interfaces with the myocardium (Figure 1.2). In some cases, the bundle branches clearly conform to a tri- or quadri-fascicular system. In other cases, however, detailed dissection of the conduction system has failed to delineate separate fascicles. The right bundle is usually a single discrete structure that extends down the right side of the interventricular septum to the base of the anterior papillary muscle, where it divides into three or more branches. The left bundle more commonly originates as a very broad band of interlaced fibers that spread out over the left ventricle, sometimes in two or three distinct fiber tracts. There is relatively little autonomic innervation of the bundle branch system, but the blood supply is extensive, with most areas receiving branches from both the right and left coronary systems.

Figure 1.2 Schematic of the conduction...