One of the most important discoveries in clinical electrophysiology has been the recognition of the importance of the pulmonary veins (PVs) in the initiation and maintenance of atrial fibrillation (AF). AF is the most common sustained cardiac arrhythmia seen in clinical practice and is associated with significant morbidity and mortality. Other atrial arrhythmias originating from the PVs include premature atrial contractions and ectopic atrial tachycardia. Because it is established that the PVs play a crucial role in the genesis and maintenance of AF, the electrical isolation of PVs has become the cornerstone for the treatment of this arrhythmia.

Over the past decade, the PV has been the focus of extensive research, and tremendous new insights have occurred with important clinical application. Morphologic studies have demonstrated the presence of complex anatomic and three-dimensional organization of myocardial clusters extending from the left atrium (LA) into the proximal PV.^1,2,3 Basic research studies have found the PVs to be the source of ectopic beats for the initiation of paroxysmal AF (PAF) and foci of ectopic atrial tachycardia.^4,5,6 Several studies have also suggested the role of PVs in maintenance of AF.^7,8 Experimental models have been developed to study the precipitating factors for enhancing PV arrhythmogenesis.^9,10 Electrophysiologic studies have shown that the underlying arrhythmogenic nature of PVs is caused by a combination of reentrant and nonreentrant mechanisms.^11,12,13 Studies using advanced imaging and mapping techniques have provided the road map for successful ablation therapy, both surgical and catheter based.^14,15

AF is the most common of all sustained abnormal heart rhythms and has the longest diagnostic history. William Einthoven published the first electrocardiogram (ECG) demonstrating AF in 1906. One hundred years later, we better understand the initiation and persistence of AF. The first Cox maze surgery for curative treatment of AF was performed in 1987. The cut-and-sew surgery included cutting the posterior LA and the attached PVs and then reattaching them to electrically isolate the PVs from the atrium. By 1992, improvements in the surgery led to the development of the Cox maze III, which is now considered the most effective surgical cure for AF. As the Cox maze procedure evolved, so did catheter-based approaches for the treatment of AF. In 1994, a trial of multiple linear burns with an ablation catheter by way of a transseptal puncture was undertaken. PV stenosis, a new and difficult-to-treat complication from catheter ablation, was unfortunately identified. This complication led to a complete abandonment of catheter-based ablation with long linear burns for the treatment of AF. Soon afterward, the association of frequent premature atrial contractions and the development of AF was noted. These focal atrial triggers were found to consistently originate from the PVs in most patients, which led to the return of catheter ablation for the treatment of AF. However, the approach was now limited to targeting only the focal triggers. The focal trigger approach promised a cure for many patients, but the recurrence rate was high, and new triggers commonly developed. Isolation of the PVs in patients with PAF reemerged as a treatment for AF but with care now exercised not to burn within the veins. Antral isolation of all PVs avoiding ablation inside the vein ostium is currently the foundation for both catheter-based treatment of AF as well as minimally invasive epicardial surgical ablation.

It is essential to have a good understanding of the PV architecture to both appreciate the electrical properties of the PVs and to direct therapies at successfully eliminating these atrial arrhythmias. The following sections describe the basics of gross anatomy, embryology, and histology.

Gross Description

Typical PV anatomy is defined as the presence of four PVs draining from the lungs into the LA (Figure 22-1). The four anatomically distinct ostia generally seen are the right and left superior and inferior ostia. Anatomic studies and also advanced imaging techniques using computed tomography (CT) and magnetic resonance imaging (MRI) have reported significant anatomic variability in the number, branching, shape, dimension, and orientation of the pulmonary ostia.^1,14,15,16 A frequent anatomical variant is the presence of a short or long common left trunk. Additional abnormalities include the presence of a right common trunk; a right middle PV; two right middle PVs; a right middle PV; and right “upper” PV, which is an anomalous vein distinct from the right superior PVs (Figure 22-2). Thus, it is apparent that the number of PV openings into the LA can vary between three to five in the normal population.

When there are four distinct PVs, the inferior veins are situated posteriorly relative to the superior veins. Both superior veins project forward and upward, and both the inferior PVs project backward and downward. Knowledge of the arrangement of the PVs affects the ease of intracardiac access during ablative therapy. Whereas the superior veins enter the LA at an angle of 45° to 60° to the horizontal, the inferior veins are at an angle of only 30° to 45°. These angulations may explain the difficulty in obtaining good contact of the catheter around the orifice of the inferior veins for effective ablation. The orifices of the left PVs are located more superiorly than those of the right PVs. The distance between the orifices of the right PVs range from 3 to 14 mm and between the left PVs from 2 to 16 mm apart. The average diameter of the PV ostia at the venoatrial junction ranges from 8 to 20 mm.¹⁷ Using MRI, Kato et al¹⁴ showed that PV ostia were more oblong than circular in shape, with a funnel-shaped morphology at the venoatrial junction in both AF patients and in control subjects. The orifice of the left atrial appendage lies in close proximity to the ostia of the left PVs and is separated by an endocardial ridge (Figure 22-3). This endocardial ridge may make stable catheter position during ablation more difficult in this anatomic region.¹⁸

Embryology

The location of the precursors of the conduction system is defined, during embryologic development of the heart, by the looping process of the heart tube. Specialized conduction tissue derived from the heart tube with pacemaker activity has been found within the myocardial sleeve of the PVs.^19,20 Perez-Lugones et al demonstrated the presence of P cells, Purkinje cells, and transition cells in the human PVs, which in subsequent studies were identified as the site of rapid electrical activity initiating AF. The presence of these cells also explains continued electrical activity seen within the PVs after disconnection from the atrium.²¹

Histologic Characteristics

Burch and Romney²² elucidated the functional anatomy of the PVs in 1954. Nathan and Iliacum¹ later described the presence of muscular sleeves of lengths varying 13 to 25 mm extending from the LA into all the PVs. The longest of these muscular sleeves extends over the left superior PV rather than the right superior PV. This anatomic arrangement coincides with the relative distribution of PV ectopy in the left superior PV as the most common trigger site for AF in a clinical series reported by Haissaguerre et al.⁵ These sleeves were better developed in the upper than lower veins and in the left more than the right PVs.^17,23 The thickness of the myocardial sleeves was not uniform on histologic sections. The greatest sleeve thickness occurs at the venoatrial junction, usually in the inferior walls of the superior veins and the superior walls of the inferior veins. The muscular sleeves tend to thin out distally, although significant variations can exist.

Over the years, investigators have focused on the arrangement of the muscle fibers around the proximal PVs. Histologic studies by Ho et al¹⁷ showed the walls of PVs to be composed of a thin endothelium surrounded by an irregular media of smooth muscle and fibrous tissue encased within thick outer fibrous adventitia. The transition from atrial to venous walls is gradual because the myocardial sleeves from the LA overlap with the smooth cells of the venous walls. Muscular fibers are found circumferentially around the entire left atrial–PV junction. However, there are gaps in the myocardial sleeves that are mainly composed of fibrous tissues, resulting in a complex meshlike arrangement of myocyte bundles. The sleeves in a circular or spiral orientation are interconnected with bundles that have longitudinal or oblique orientation, with frequent segmental disconnections and patchy areas of fibrosis. An abrupt change in fiber orientation acts as anatomical substrate for local reentry, which may be the basis for initiation of AF (Figure 22-4).

In addition, there are abundant adrenergic and cholinergic nerves in the ganglionated plexi (GP), preferentially in the left superior PV at the junction with the atrial roof, the posteroinferior junction of the inferior PVs, and the anterior border of the right superior PV. The presence of adrenergic and cholinergic nerves provide for the possibility of neurohumoral perpetuation of AF.^24,25 Some anatomical difference between the PVs of patients with and without atrial arrhythmia exist. Postmortem studies by Hassink et al²⁶ showed that PV myocardial sleeves were seen in only 85% of patients without a history of AF but were present in all patients with a history of AF. PV angiography has demonstrated a pattern of enlarged superior PV ostia compared with control subjects.²⁷ MRI studies measuring PV ostia have shown a similar pattern.¹⁴