Anatomic considerations and examination of cardiovascular specimens (excluding devices)

Great vessels

The relationship between the great vessels and the investing pericardium is best understood when their roots are viewed after removal of the heart ( Fig. 2.4 ). An investment of serous pericardium encloses the great arteries, and a second contains all the veins. Thus the pericardium encloses the distal half of the superior vena cava, most of the ascending aorta, and pulmonary trunk. Compromise of any portion of the vascular wall, within the encased area, may result in hemopericardium.

The main pulmonary trunk/artery arises from the right ventricle and travels to the left of the ascending aorta, directed toward the left shoulder. At its bifurcation, the left pulmonary artery continues over the left bronchus, whereas the right pulmonary artery courses beneath the aortic arch and posterior to the superior vena cava.

The aorta arises at the level of the aortic valve annulus and terminates at its bifurcation into the common iliac arteries. It can be divided into four distinct regions: the ascending aorta (beginning at the aortic annulus and extending to the origin of the brachiocephalic artery), aortic arch (extending to the ligamentum arteriosum), descending thoracic aorta (extending to the diaphragm), and the abdominal aorta (extending to the iliac bifurcation). The ascending aorta includes both a bulbous sinus portion at its proximal end and a more tubular portion extending toward the arch. The regions of the aorta are differentiated not only by their location but also by their embryologic derivation. The aortic root is derived from the second heart field (lateral plate mesoderm), the ascending aorta and arch from the neural crest, and the descending aorta from the paraxial mesoderm .

Coronary vessels

The epicardial coronary arteries are examined before incising the heart chambers. The right and left coronary arteries arise from their respective aortic sinuses (of Valsalva) ( Fig. 2.4 ). Their ostia arise midway between the aortic valve commissures, just below the sinotubular junction (the ridge within the ascending aorta formed by the virtual ring connecting the tips of the aortic valve commissures). The right coronary artery (RCA) usually arises perpendicular to the aortic sinus, whereas the left main coronary artery will often arise at an acute angle and travel downward, before branching to become the left anterior descending (LAD) and circumflex (LCX) coronary arteries. The LCX and RCA travel in their respective atrioventricular grooves, defining the plane of the cardiac base. The anterior and posterior descending arteries travel in their respective interventricular grooves and will indicate the plane of the ventricular septum. The RCA will supply the posterior descending coronary artery in 70% of individuals, so-called right-sided coronary dominance . The LCX will supply the posterior descending coronary artery in 10% of individuals (left-sided coronary dominance), with the remaining individuals (20%) having shared coronary dominance (codominance).

Epicardial branches include diagonals arising from the LAD and marginals arising from the RCA and LCX (acute and obtuse, respectively). In 60% of individuals, the first branch of the RCA is the conus coronary artery, which supplies the right ventricular outflow tract (conus or infundibulum); in the remaining 40%, the artery arises independently from the right aortic sinus, when a separate ostium will be noted . The sinoatrial nodal artery arises from the RCA in approximately 60% of hearts and from the LCX in the balance. The aortic valve (AV) nodal artery, in contrast, will arise from the dominant coronary artery, with the RCA supplying it in approximately 90% of hearts.

If the prosector has ready access to postmortem radiography, dissection can be complemented by postmortem angiography, which can indicate the presence of calcific coronary artery disease as well as assess the disease burden. Otherwise, palpation of the coronary arteries should be performed to evaluate for calcification. If identified, the entire epicardial arterial tree must be dissected from the heart and decalcified ( Table 2.1 ). Each artery should be removed and placed in a separate container. Decalcification prevents artifactual damage caused by cutting through a calcified arterial wall, crushing the lumen and plaque disruption. Performing decalcification is the best way to prepare calcified coronary arterial tissue for histologic examination. In the absence of any suspicion of coronary artery disease, especially if the patient is young and vessels are apparently noncalcified, they may be opened in situ, by cross sectioning at 0.2–0.5 cm intervals. Opening the vessels longitudinally is not optimal as it becomes difficult to assess disease severity and luminal narrowing. Diseased areas should be submitted for histology (4–6 cross sections per cassette), to include both hematoxylin-eosin staining and an elastic stain (e.g., Verhoeff-van Gieson, Movat pentachrome, etc.). Dividing each of the coronary arteries into thirds (proximal, middle, and distal) and designating as such can facilitate interpretation and reporting.

The presence of coronary artery stents presents a unique challenge in the evaluation of coronary artery disease. Methods that involve cutting the stented vessel with a diamond microtome, electrolytic stent dissolution, and physical stent removal have all been described . Regardless of the method chosen, effort should be made to evaluate these regions of the vessel to evaluate for disease progression as well as device failure.

Coronary veins follow, in an antiparallel fashion, the course of the arteries. They are more superficial in the epicardial fat and eventually join the coronary sinus, which passes from left to right in the posterior atrioventricular groove to open into the posterior wall of the right atrium just anterior to the inferior vena cava. Some small (accessory) coronary veins drain the free wall of the right ventricle and open directly into the anterior wall of the right atrium. The smallest veins, Thebesian or luminal veins, form within the myocardium and drain directly into each of the heart chambers . They are remnants of sinusoidal intramyocardial blood vessels present in the embryonic heart, at the stage of the noncompacted (spongy) myocardium.

The coronary sinus ( Fig. 2.4 ) is the most easily evaluated cardiac vein and is guarded by the valve of the coronary sinus (Thebesian valve) at its opening into the right atrium. It may be larger than normal if it drains anomalous vessels (e.g., a persistent left superior vena cava via an oblique vein of Marshall or vessels from the lung—anomalous pulmonary venous drainage) or in the presence of severe right heart failure. Alternatively, the coronary sinus opening may be smaller than normal or even atretic if coronary sinus blood is passing from the heart through a persistent left superior vena cava to the innominate vein and, hence, via a right superior vena cava to the right atrium. The coronary sinus may be absent, as in those conditions in which a left superior vena cava connects directly to the left atrium (an unroofed sinus). Such variations in the size of the coronary sinus may be isolated and incidental, but they often accompany serious cardiac malformations.

A cardiac lymphatic system has been well described . Lymphatic plexi within the subendocardium, myocardium, subepicardium, and pericardium have all been demonstrated. When engorged, these can grossly manifest as white streaking in the heart.

Right atrium

The right atrium serves as the receiving chamber for blood returning from the systemic veins and lies posterior to the right ventricle and anterior to the left atrium in a right lateral position ( Fig. 2.5 ) . Its basic anatomic components are that of the free wall and the septum. It has variable thickness, measuring 2–6 mm in some regions and <1 mm in others.

The free wall, internally, has a smooth-walled posterior portion, derived from the embryological sinus venosus that receives blood from the vena cavae and the coronary sinus. The remaining free wall is derived from the primitive atrium and contains prominent small muscular ridges arranged in parallel, called pectinate muscles. The crista terminalis, corresponding internally to the external sulcus terminalis, serves as the dividing line between these two portions.

Pectinate muscles arise from the crista terminalis, which is a prominent C-shaped ridge of muscle that separates the smooth-walled portion of the atrium from the trabeculated portion. The inferior aspect of the right atrium, between the ostium of the coronary sinus, posteriorly, and the tricuspid annulus, anteriorly, is a region referred to as the cavotricuspid isthmus. It is in this region of the heart where atrial flutter is frequently thought to arise . The midportion of the isthmus containing a shallow pouch with trabeculated lining is called the sub-Eustachian sinus of Keith .

Three distinct valves can be visualized inside the right atrium: the valve of the inferior vena cava (Eustachian), the valve of the coronary sinus (Thebesian), and the valve of the fossa ovalis. The first two valves, remnants of the right venous valve, vary greatly in size and may be fenestrated or absent, but the Eustachian valve is well developed in approximately 90% of normally formed hearts . The Thebesian valve is generally less well developed, covering the ostium of the coronary sinus in approximately 40% of subjects with normal heart weight . A Chiari network, usually a web or lace-like sheet of tissue, may span the atrial cavity from the region of the Thebesian or the Eustachian valve to insert into the crista terminalis ( Fig. 2.6 ) . The left venous valve is usually absorbed into the atrial septum, but remnants may be found as bands of tissue bridging the posteroinferior margin of the fossa ovalis.

The most prominent feature of the septal portion of the right atrium is that of the fossa ovalis ( Fig. 2.5 ). This structure can be as large as 3.5 cm in diameter and is usually well defined superiorly and anteriorly by the raised limbus of the fossa ovalis . The horseshoe-shaped limbus surrounds a relatively thin membrane, the valve of the fossa ovalis. This valve is thin and translucent early in life, but progressively thickens throughout life . Probing under the limbus anteriorly shows whether the foramen ovale is obliterated or patent; the latter may be seen in a third of people beyond the first year of life .

An aneurysmal bulge of the septum primum may occur through the fossa ovalis into either atrium . The association in adults of aneurysms of the fossa ovalis with increased frequency of embolic stroke has been attributed to its significant association with mitral valve prolapse, dilated atria, intracardiac thrombi, and patent foramen ovale; the latter condition is present in 70% of such subjects . An aneurysm of the fossa ovalis bulging to the left atrium is also seen during fetal life and is associated with fetal arrhythmia and other causes of fetal heart failure .

By transillumination, part of the membranous interventricular septum is seen in the right atrium just proximal to the tricuspid annulus where it joins the base of the septal leaflet of the tricuspid valve. A defect in this area permits communication between the left ventricle and the right atrium, whereas a defect distal to the septal leaflet is a membranous ventricular septal defect at its most common location. Usually, the anterior and septal leaflets of the tricuspid valve cross the membrane to meet at their commissure. Rarely, they insert at the edge of the membrane without forming a commissure. This does not produce valvular regurgitation. The right aortic sinus is also closely related to the right atrium and may cause a smooth protuberance of the right side of the anterosuperior atrial septum, the torus aorticus . The interventionalist should be mindful of this anatomic relationship during procedures such as transseptal puncture or placement of a septal occluder device.

The tendon of Todaro is a ligament attached to the fibrous skeleton of the heart. It may represent the commissure of the Eustachian and Thebesian valves. This tendon probably functions during fetal life to strengthen the free edge of the Eustachian valve and helps to direct venous return from the inferior vena cava across the foramen ovale . The tendon of Todaro is sometimes seen in adult hearts, but it is more obvious in children. The tendon is a white cord deep to the right atrial endocardium, passing from the sinus septum, which separates the ostia of the inferior vena cava and the coronary sinus, toward the membranous septum. When this tendon is visible, it is a useful landmark for the atrioventricular node, which lies within an anatomic triangle (the triangle of Koch, described below).

Tricuspid valve

The tricuspid valve is a three-leaflet valve with a saddle-shaped annulus and its valvular plane facing toward the right ventricular apex . Its normal annular circumference is 10–11.1 cm in women and 11.2–11.8 cm in men . The three leaflets hang from the valve ring like a veil, with the septal and posterior leaflets against the septal and inferior walls of the right ventricle, respectively ( Fig. 2.7 ). The anterior leaflet forms a diagonal curtain separating the inflow and outflow tracts of the right ventricle. A papillary muscle is located directly beneath each commissure, sending tendinous cords up to the adjacent leaflets (roughly half to each) . Each leaflet has a distal rough zone and a proximal basal zone into which the cords insert, as well as a clear zone free of cord insertion that lies between the rough and the basal zones.

The annulus of the tricuspid valve is more apically positioned than that of the mitral valve annulus ( Fig. 2.8 ). This nonplanar arrangement of the atrioventricular valves allows for three distinct regions to be defined in the septum that divide the right and left heart: the interatrial component (atrial septum), separating the right and left atria; the atrioventricular component (atrioventricular septum), separating the right atrium from the left ventricle; and the interventricular component (ventricular septum), separating right and left ventricles.

The anterior leaflet is usually the longest (average 2.2 cm). It is semicircular or quadrangular and is 3.7 cm in average width at its base. Rarely, it has a distinct scallop in its medial side near the anteroseptal commissure. The septal leaflet is semioval and is 1.6 cm long by 3.6 cm wide on average. It shows a characteristic fold on its atrial surface in the angle where its base passes from the posterior ventricular free wall to the membranous area. The posterior leaflet, which averages 2.0 cm long by 3.6 cm wide at its base, has a variable number of scallops, usually two or three, produced by indentations in its free edge. The cords are of varying length (0.3–2.2 cm) and thickness (0.05–0.15 cm) .

Of the three papillary muscles, the anterior is the largest and most well formed. It may be single or bifid and provides cordal insertions to the anterior and posterior leaflets. The posterior papillary muscle arises from the inferior wall sending cords to the septal and posterior leaflets. The medial papillary muscle (also called the papillary muscle of the conus or the muscle of Lancisi) arises along the superior aspect of the septal band, at the level of the membranous septum and has cordal attachments to both the septal and anterior leaflets. It is important to note that in addition to cords to the papillary muscles, the tricuspid valve characteristically has cords to trabeculations of the septum. These septal cord attachments serve to help differentiate the tricuspid from the mitral valve in the setting of congenital heart disease.

Right ventricle

The right ventricle lies anterior to the other heart chambers . Posteriorly and to the left, it is related to the left ventricle from which it is separated by the interventricular septum, which is vertically oriented and lies at a 45° angle to the median plane of the body. The right ventricle is crescentic in shape in short-axis (transverse) section ( Fig. 2.9 ), with its free wall forming an acute angle often referred to as the acute margin of the heart.

The anatomic right ventricle has an inflow portion, an apical trabeculated portion and an outflow portion, the latter of which is often referenced as the infundibulum or conus. The infundibulum is separated anatomically from the sinus by a muscular crest or arch, the crista supraventricularis. This crest, which separates tricuspid and pulmonary valves, merges medially where it meets the septum, with muscular ridges of variable prominence called the septal and parietal bands that course in those walls of the right ventricle. The site of insertion of the crest between these trabeculations may be smooth or marked by either a vertical ridge or a groove. The papillary muscle of the conus arises from the septal wall just proximal to the crista; it is an important surgical landmark for the conduction system .

The junction of the inflow tract with the infundibulum is defined anteriorly by the upper edge of another smooth arch of muscle formed by the junction of the septal band, the moderator band, and the anterior papillary muscle. The apex of the papillary muscle often points toward the commissure between the anterior and posterior tricuspid valve leaflets. The moderator band is not always as distinct in human hearts as in those of animals. The entire luminal surface of the right ventricle, with the exception of the septal and parietal bands and the posterior wall of the infundibulum above the crest (conus muscle), is coarsely trabeculated and, on section, the trabeculations form the inner two-thirds or three-fourths of the ventricular wall. Aberrant ventricular bands, usually muscular rather than fibrotic, are common in the distal part of the right ventricle and may be congenital or acquired . The conus muscle separates the pulmonary valve ring from the aortic valve ring and is responsible for the higher position by approximately 1.5 cm of the former structure ( Fig. 2.7 ). Within this muscle is a variable fibrous attachment between the rings of the two semilunar valves; the conus ligament.

Ventricular septal defects or the sites of patch repair may be seen proximal to, or, rarely, distal to the crest. If there are defects between the inflow portions of the ventricles, they will open among the trabeculations on the interventricular septum . Such defects may be multiple, small, and tortuous. Small ones often close spontaneously, being obliterated either by adherent tricuspid leaflet tissue or by endocardial proliferation about their edges and sometimes small aneurysms result.

Pulmonary valve

The pulmonary valve lies between the infundibulum and the pulmonary artery and is attached to the pulmonary annulus, which points posteriorly, superiorly, and to the left (pointing toward the left shoulder) . Its ring circumference is 5.7–7.4 cm in women and 6.0–7.5 cm in men . The pulmonary infundibulum winds across the anterior aspect of the aortic root, with the annulus approximately 1.5 cm higher than the aortic annulus. The three cusps are named the anterior, the right (closest to the right aortic cusp), and the left (closest to the left aortic cusp).

Both the aortic and pulmonary semilunar valves consist of an annulus, cusps, and commissures. Semilunar valves lack tendinous cords and papillary muscles; hence their opening and closing are a passive function of hemodynamics. The annuli of the semilunar valves are shaped like a triradiate crown, with the three points representing the three commissures where adjacent cusps meet.

The three pulmonary cusps are half-moon (semilunar) shaped structures made of fibroelastic tissue. The distal edge is referred to as the free edge, beneath which lies a biscalloped ridge, the closing edge or margin, along the ventricular aspect of the cusp. A fibrous nodule, named for both Arantius and Morgagni, is located centrally on the free edge of each cusp. Extending away from the nodule, on either side, is a crescent-shaped area, referred to as the lunula, which represent the closing surfaces of each cusp.

Left atrium

The left atrium, with a wall 0.3 cm in average thickness, lies in a midline-posterior position immediately anterior to the lower esophagus . The descending thoracic aorta lies immediately to the left and the bifurcated pulmonary artery and left bronchus, superiorly.

As with the right atrium, the left atrium can be divided into its septal and free walls. The left side of the atrial septum contains the valve of the fossa ovalis, the remnant of septum primum. Most of the free wall consists of a dome-shaped, smooth-walled portion that receives the four pulmonary veins. Like the sinus venosus of the right atrium, this smooth-walled portion of the left atrium is of venous origin (arising from the common pulmonary vein, embryologically). Anteriorly is the base of the left atrial appendage.

Unlike the pyramidal right atrial appendage ( Fig. 2.10 ), the left atrial appendage has a more variable morphology that has been typed into four major categories: cauliflower, cactus, windsock, and chicken wing. Of note, the latter is thought to be somewhat protective of thromboembolic events . The atrial appendage is lined by pectinate muscles like those in the right atrial appendage, but unlike the right atrium, those in the left are fine, radially arranged, and do not exist outside of the appendage. There may be tiny ostia of Thebesian veins in the left atrium as there are in the right; the largest, the ostia of Lannelongue, are central in the wall. The endocardial lining of the left atrium is thicker and more opaque than that of the right atrium, in keeping with the higher pressure within the left side of the heart.

Mitral valve

The mitral valve is a two-leaflet valve with a saddle-shaped annulus and its valvular plane facing anteriorly, inferiorly, and to the left ( Fig. 2.11 ) . The valve’s normal annular circumference is between 8.2 and 9.1 cm in women and 9.2 and 9.9 cm in men . The two leaflets, anterior and posterior, are attached around the annulus, meeting at the commissures.

The anterior mitral leaflet is in fibrous continuity with the aortic valve proximal to its posterior (noncoronary) and left aortic cusps ( Fig. 2.12 ) . Although the entire annular circumference connects to the atrium because of this fibrous continuity, only a C-shaped portion attaches to the underlying left ventricular free wall. The anterior mitral leaflet forms a curtain that, like the anterior tricuspid leaflet, separates the inflow and outflow portions of its respective ventricle. The anterior leaflet is long (average 3 cm) and triangular, or almost sail-like, having an average width of 3.3 cm at its base. A ridge on its atrial aspect, 0.8–1.0 cm from the free edge, defines the line of valve closure. The rough zone of cordal attachment on the ventricular surface lies between the line of closure and the free edge.

The posterior mitral leaflet attaches to the parietal part of the mitral annulus. Although more shallow than the anterior leaflet, it occupies approximately two-thirds of the mitral annular circumference . It is divided into scallops, usually three: P1, P2, and P3. The posterior leaflet has an average width of 4.8 cm, and the longest scallop, usually the middle one, has an average length of 1.3 cm. Unlike the anterior leaflet, the posterior leaflet has a basal zone of cord attachment that is separated from the rough zone near the free edge by a narrow clear zone. The line of valve closure, located on the atrial surface of the leaflet, lies approximately 0.2 cm from the free edge.

The mitral valve cords vary in number, length, and thickness . So-called primary cords attach to the free edge of the valve and are responsible for leaflet coaptation, while secondary cords attach to the ventricular surface and serve to help maintain ventricular geometry . A large, thick cord can usually be seen arising from each papillary muscle and inserting on the anterior mitral leaflet. These specialized secondary cords are often referred to as strut cords. Commissural cords are also recognized.

The two papillary muscles of the left ventricle are the anterolateral and posteromedial. They are of approximately equal size and are often double throughout or bifid at their tips, the posterior muscle showing subdivision into two or more columns more often than the anterior muscle . The papillary muscles have broad bases in the apical trabecular muscle, and their tips give attachment to cords that tether the adjacent halves of each mitral leaflet. The cords from the anterior papillary muscle attach to the anterior halves of each leaflet.

Left ventricular pseudotendons (also termed false cords) arise from a papillary muscle and insert onto either the septum or the opposite papillary muscle. These ventricular bands may be seen in upwards of 50% of subjects . Their lack of attachment to valves helps to distinguish them from congenital bands (like that seen in straddling valves associated with atrioventricular canal defects) .

Left ventricle

The left ventricle forms the posterior and left lateral surfaces of the heart . It is circular in short-axis cross section, but somewhat triangular when viewed along the long axis. Its shape approximates that of a truncated ellipsoid. Trabeculations are present in the left ventricular myocardium, but are finer and more numerous than in the right ventricle. They make up less than the inner one-fourth of the wall; the outer three-fourths are composed of compact muscle, spirally arranged, from apex to base.

Like the right ventricle, the left ventricle has three distinct regions: an inflow portion, apical portion, and an outflow portion. Blood flowing through the left ventricle changes direction by nearly 180° in passing the free edge of the anterior mitral leaflet. The inflow portion contains two papillary muscles, as described previously; in a contracted heart, they abut on each other and the interventricular septum to virtually obliterate the ventricular cavity. The apical portion contains trabeculations that are both finer and more numerous than the apical trabeculations of the right ventricle. The outflow portion has a smooth septal wall formed by the upper third of the interventricular septum anteriorly and to the right, and by the ventricular surface of the anterior mitral leaflet posteriorly and to the left ( Fig. 2.12 ). The smooth muscular interventricular septum bulges somewhat into the left ventricular outflow tract and may become more prominent with increasing age, producing a “sigmoid” septum (see Chapter 3 ) .

The triangular membranous septum lies proximal to and between the posterior and right aortic valve cusps and can be transilluminated. A ventricular septal defect may occur in the membranous septum, but commonly involves the muscular septum immediately proximal and anterior to this region. Small muscular ventricular septal defects often heal spontaneously and may be marked by gray–white endocardial dimples or small septal aneurysms.

Aortic valve

The aortic valve lies between the left ventricular outflow tract and the aorta . Its normal annular circumference is 5.7–7.9 cm in women and 6.0–8.5 cm in men . The valve annulus is a midline structure and occupies a central position in the cardiac base. The plane of the valve points posteriorly, superiorly, and to the right (directed toward the right shoulder) ( Fig. 2.4 ). The annulus and cusps are very similar to those of the pulmonary valve, as previously described. The higher, left-sided pressures typically make the closing edge and midline cusp nodule (nodule of Arantius) more evident than in that of the pulmonary valve ( Fig. 2.13 ). Lambl excrescences are frequently found on the nodules and along the line of valve closure ( Fig. 2.14 ) (see Chapter 3 ).

The posterior noncoronary cusp is posterior in position, and the right and left coronary cusps are anterior ( Fig. 2.4 ). The valve cusps are similar in size, though are usually not equal. In some instances, this may hasten calcification . The aortic and mitral valve rings are fused (intervalvular fibrosa) over the length of attachment of the anterior mitral leaflet, which has a variable degree of fibrous continuity with the adjacent halves of the posterior and left aortic valve cusps ( Fig. 2.15 ) .

The sinus (of Valsalva) of each aortic cusp is the pocket enclosed by the cusp attachment proximally and a ridge encircling the aortic lining at the level of the commissures. An imaginary line connecting the tips of the commissures (prongs of the triradiate annulus) forms the sinotubular junction where the aortic sinus becomes the tubular portion of the ascending aorta. The sinus is 1.5 times wider than the proximal tubular ascending aorta, but this is better appreciated in angiograms taken during life than in gross specimens.

The coronary arterial ostia may be variable in number, position, and size. The mean diameter of the right vessel is 0.32 cm, and of the left, 0.40 cm. They are usually single, centrally located within the wall of the aortic sinus, and approximately equal in size. If unequal, the left is more often larger, but the right is often double, with one ostium representing the conus artery ostium.

Normal variations of coronary ostia are distinguished from anomalies (e.g., both the LAD artery and the LCX coronary artery may arise from the same coronary sinus) . Nevertheless, a solitary coronary ostium, stenosis of an ostium, acute angulation or arterial takeoff, or an intussusception of an ostium may be associated with sudden death (see Chapter 10: Myocardial Ischemia and Its Complications ) .

Conduction system

The cardiac conduction system consists of the sinus node, internodal pathways, and atrioventricular conduction tissues. Its function is influenced by the innervation of the heart (described below). The sinus and atrioventricular nodes are both right atrial structures. It is important to note that all structures of the conduction system are specialized cardiac myocytes (not nerves) whose primary function is impulse propagation rather than contraction and relaxation.

The sinus node is located subepicardially, along the superior aspect of the sulcus terminalis, near the confluence of the superior vena cava, sinus venosus, and muscular right atrial free wall. These latter two structures are the reason the sinus node is sometimes referred to as the sinoatrial node. It is elliptical in shape with the sinoatrial nodal artery, which is often grossly identifiable, running centrally through the nodal tissue.

The internodal pathways serve as preferential tracts by which impulse propagation is transmitted from the sinus node to the atrioventricular node. They have been described in the atrial septum, right atrial free wall, and the crista terminalis. While electrophysiologically identifiable, these structures have not been definitively teased out morphologically, except for the Bachman bundle between the atria .

The atrioventricular node is located subendocardially (rather than subepicardially, like the sinus node) within the triangle of Koch. The triangle of Koch is the anatomic region bordered by the tricuspid annulus (of the septal tricuspid leaflet), the ostium of the coronary sinus, and the tendon of Todaro (described above). The apex of the triangle is adjacent to the central fibrous body. The atrioventricular nodal artery does not necessarily travel intranodally, like that of the sinus nodal artery.

The atrioventricular bundle (bundle of His) extends from the node, traveling through the central fibrous body, to the basal ventricular septum, adjacent to the membranous septum. It then splits into both its right and left bundle branches. The right bundle branch is a cord-like structure that travels subendocardially to the moderator band and then out to the free wall of the right ventricle. The broaderleft bundle branch also travels subendocardially toward the left ventricular apex, while fanning out into fascicles of Purkinje cells.

Cardiac innervation

The nerve supply to the heart is autonomic, including both sympathetic and parasympathetic innervation via both efferent and afferent fibers . It is conveyed to the cardiac plexus in branches from the vagus and phrenic nerves and also from the cervical and thoracic cardiac nerves. The cardiac plexus is a group of nerve ganglia located between the arch of the aorta and the bifurcation of the trachea. The largest ganglion, the ganglion of Wrisberg, lies below the arch of the aorta. Nerve ganglia are seen frequently in microscopic sections of the subendocardial muscle of the right atrium, particularly in the interatrial septum and in the epicardium near the roots of the great vessels. Both sympathetic and parasympathetic nerves innervate the nodes, myocardium, and coronary arteries.

General

When handling specimens, universal safety precautions should always be employed. Appropriate protective clothing and personal protective items should be worn. No tissue, even fixed material, should ever be handled with bare hands. It must be kept in mind that noxious agents are present in the laboratory. They must be treated with respect and appropriate precautions. Formaldehyde solution soon irritates nasal mucosa, making its presence known, but long exposure can lead to debilitating corneal ulceration, respiratory problems, dermatitis, or other pathology. Other agents are flammable and still others toxic. Potential untoward actions must be recognized and prevented. Knowledge of safety regulations is essential, and the location of safety features in the laboratory should be known by all. It is especially important to be cognizant of the procedures to be followed by individuals and staff if a toxic spill occurs or a fire starts.

Receipt/accession of specimens

Specimens, irrespective of their nature, are received with a consultation request or requisition bearing demographic details about the patient, as well as clinical data. All this information is vital and is incorporated into generating the final pathology report. Surgeons and/or clinicians should realize that a final pathology report may be delayed unless this information is provided. The pathologist must ensure that specimen containers are correctly labeled and must not accept tissue from more than one anatomic site in a container. Errors at this stage are best dealt with by promptly contacting the clinical team. The tissue may be in a saline fixative solution, or fresh, and is given a laboratory accession number; correct identification must be maintained at all subsequent stages of the process. However, in some cases, before collection is made, and in many others, before dissection and blocking for histology are performed, the pathologist must consider the need for any other action. For example, should an individual specimen be collected fresh or should it be placed in a special fixative? Communication between the pathologist and the clinician may be invaluable in choice of specimen collection and triage.

In many instances, photography can add depth to the gross report and may help when reviewing histology or in subsequent conferences. Edwards provides guidance for this type of activity . Radiography can assist in determining the degree of calcification of the valves and coronary arteries. Also, radiography can locate stents or other prostheses ( Fig. 2.16 ). Microbiologic cultures or use of electron microscopy may be indicated, and frozen tissue is required for some examinations.

Gross examination

Economically responsible practice is good practice. Therefore consideration must be given as to whether to perform histologic sections on all specimens. For medicolegal purposes, pathologists must practice according to the standards established in their communities. In other words, if all cardiovascular pathologists in a city or region submit every specimen for histology, it would be prudent to do so. Useful recommendations have come from the Society for Cardiovascular Pathology and the Association of European Cardiovascular Pathology . For example, some groups do not perform routine histologic examinations of heart valves, incidentally removed right atrial appendages, varicose veins, and aortic buttons removed during bypass grafting. However, one must have a low threshold to perform histologic analysis should a suspicious gross finding be encountered. If gross examination alone is performed, the report should reflect such. Retaining the gross specimen for a period of time after case sign-out is strongly encouraged, particularly if only gross analysis was done. If additional information comes to light that would prompt histological evaluation, it will then be available for such.

Cleanliness and organization at the workbench are essential to prevent contamination of the area and to prevent the spread of tissue contamination from one case to another. Copious use of water and handling each specimen on a clean surface helps to maintain a clean workspace. No more than one specimen container should be open at a time.

In examination, the description must be exact and detailed. The description must include information about the source of the specimen, the number and size of fragments included in the container, measurements, and (if appropriate) the specimen weight. The specimen should also be described in terms of shape, surface, edge, color, consistency, and relationships. With the widespread use of digital photography, a relatively low threshold should be maintained for deciding whether or not to photograph gross specimens.

Histologic sampling must be representative. In some instances, all of a specimen, especially if it is small, is embedded, with that fact noted in the report. Very small specimens may be wrapped in tissue paper and stained grossly with 10% eosin to help in identification when the paper is unwrapped. Tissue blocks must be no thicker than 3 mm and should not overfill the cassette in which they are placed. Histopathology cannot be expected to deliver good sections if the material supplied to them is less than ideal. Tissue should always be decalcified if the blade grates during sectioning; rapid decalcification does not delay processing. Only rarely, when calcification is very extensive (e.g., calcification that affects the posterior mitral annulus), need processing be prolonged and done before sections are cut. Metal staples should be removed. Also, if blocks must include suture, cloth, or other unusual material, the histopathology laboratory should be advised of their presence. Processing may be completed overnight or by more rapid methods.

Of the routine stains available, hematoxylin and eosin (H&E) and Verhoeff-van Gieson stains are the most commonly employed (an elastic stain being essential for assessment of vascular specimens). In examining cardiovascular lesions, a pathologist employs the full barrage of other histochemical, immunohistochemical, and molecular diagnostic techniques available and may employ morphometry or other techniques in examination.

For some specimens, protocol examinations and templates may be appropriate. Protocols help to teach, and ensure consistency, whereas templates speed report preparation and help consistency. Again, time can be saved by predetermining the type of special stains that are required for certain gross findings and by ordering stains when blocks are submitted.

Handling particular specimens

While it is not possible to account for each and every cardiovascular specimen that may be encountered in clinical practice, we will attempt to address the most commonly encountered types and present general approaches to the handling and processing of such. No mention is made in this chapter of certain devices used to treat or ameliorate cardiovascular disease (such as ventricular assist devices or artificial hearts). Additionally, the handling of native or donor hearts from patients who have received a transplant or of endomyocardial biopsies is also not discussed. That information is presented in Chapter 8, Chapter 14, Chapter 17 , respectively.

Vascular specimens

Vascular specimens include a wide variety of sample types, including (but not limited to) aortic resections, temporal artery biopsies, endarterectomy specimens, and varicose veins. The one commonality among these specimens is the necessity for the pathologist to evaluate the specimens with a standard H&E stain as well as some type of elastic stain (e.g., Verhoeff-van Gieson, Movat pentachrome, Elastic-van Gieson). The latter is essential for proper examination of the vessel wall. In general, vascular specimens are typically evaluated in cross section. One exception to this rule is when the clinical concern is fibromuscular dysplasia, where longitudinal evaluation can help to see the segmental nature of the disease over the course of the vessel .

Aortic specimens are generally procured during the course of surgical repair of aortic aneurysms, dissections, or congenital forms of aortic disease (e.g., coarctation, vascular rings). The type of resection should be noted as either segmental or partial, with the former typically consisting of a complete circumference of aorta, the latter representing an opened specimen. Overall (aggregate) size, thickness, and any gross pathology (atherosclerosis, dissection, fibrosis) should be documented. Generally, examination of between six and eight full-thickness sections of aortic wall sampled from various areas of the specimen is sufficient for evaluation.

Temporal arteries, biopsied to evaluate for vasculitis, should be serially cross-sectioned following documentation of the size and character of the sample. Sectioning is best done after processing at the time of embedding. It is imperative to evaluate complete cross sections of the vessel, so proper orientation is paramount. In general, each section should be evaluated at multiple levels (20–40). Several levels may be put on a single slide. Findings may be focal and examination of levels may be evaluated for features of healed arteritis or prior traumatic injury.

Endarterectomy specimens are procured during the course of the therapeutic removal of a luminal obstruction, usually by atherosclerosis or intimal fibroplasia. Not all institutions routinely process these specimens for gross or histologic examination. However, vascular pathology can be identified by the pathologist when the vessel wall is examined. The specimens should be measured and the remaining description should include degree of luminal obstruction (stenosis).

Native heart valves

Both atrioventricular (mitral and tricuspid) and semilunar (aortic and pulmonary) valves may be resected for stenosis or regurgitation. Of these, aortic and mitral valves are the most frequently encountered, with the former typically being resected for stenosis and the latter typically being resected for regurgitation. Regardless of which valve is being evaluated, knowing the reason for resection as well as whether there is a clinical suspicion of endocarditis is essential at the time of grossing. Occasionally, the entire valve will have been resected, but part of the tissue will have been sent to the microbiology laboratory for culture. Correlating with these microbiologic reports and incorporating the culture results creates a more complete pathology report .

Atrioventricular valves should be measured, both in terms of the size of resected leaflet(s) and the length of the attached cords and whether papillary muscle is included. The presence and location of calcification should be noted as well as the thickness of the leaflet and cord tissue. A good rule of thumb is if the valve is translucent and color can be seen through the tissue, it is probably not appreciably thickened. Myxomatous degeneration (which often causes prolapse and regurgitation) will often impart a thickened and rubbery appearance to the valve, which should be spelled out in the gross description. Both the cords and the commissures (if present) should be evaluated for fusion. The former is usually only evident with complete valvular resection. The leaflets should be evaluated for the presence of perforation (which may indicate active or healed endocarditis) and the entire specimen should be evaluated for thrombus or vegetation.

Valves are best examined, histologically, with an H&E stain and an elastic stain. Stains for microorganisms (Gram, silver stains, Giemsa, periodic acid Schiff with diastase digestion) should be ordered if vegetation is found or if there is clinical concern for endocarditis . If papillary muscle is received, it too should be evaluated histologically, usually by sectioning it longitudinally.

In the case of semilunar valves, the cusps should be quantified and measured. Lining the cusps up and measuring the total annular circumference and then the average cusp width is often adequate. If one cusp is remarkably larger or smaller than the others, it also should be indicated. The presence and size of Lambl excrescences (arising on the closing surface of the valve) should also be noted. As in the case of the atrioventricular valves, the specimen should be examined for calcification, vegetation, commissural fusion, and perforation. In terms of commissural fusion, some attempt should be made to decipher whether the fusion appears to be congenital or acquired.

Congenital fusion typically produces an obtuse angle between adjacent cusps, and the ventricular aspect of the conjoined cusps appears relatively smooth. Acquired fusion typically results in an acute angle between the fused cusps and a small cleavage plane between them that can be seen on their ventricular aspects. Congenitally bicuspid valves will also often have a raphe at the point of fusion on the arterial aspect of the valve. The raphe may be either fenestrated (atypical bicuspid variant) or nonfenestrated.

Routine histologic evaluation of semilunar valves, particularly those resected for degenerative stenosis or congenitally bicuspid valvular stenosis, may not be seen as necessary in all institutions. However, if any vegetation or suspicious lesion is present on the cusp tissue, microscopic evaluation is mandatory. As with atrioventricular valves, H&E and an elastic stain is sufficient to evaluate the valve structure and special stains for microorganisms can be added at the dissection of the pathologist.

Prosthetic heart valves

Prosthetic heart valves can be either of the mechanical or bioprosthetic variety. Bioprosthetic valves can be further subdivided into bovine pericardial, porcine bioprosthetic, and homograft valves. New generation transcatheter valves (deployed percutaneously) may also be encountered by the pathologist . Like native valves, close correlation with the hemodynamic profile that prompted removal is paramount. Importantly, prosthetic valves removed in the setting of periprosthetic leak may have no gross pathology whatsoever. Radiography is useful for valve type identification, assessment of integrity of the prosthesis, and assessment of calcifications.

The mechanical or bioprosthetic leaflets/cusps should move freely at the time of grossing. The valves should be examined for the presence of thrombus, obstructive fibrous ingrowth (pannus), and vegetation. Careful evaluation of the sewing ring for vegetation is also necessary. Histologic evaluation of vegetation and thrombus is mandatory.

Myocardium

Myocardial specimens are typically produced during septal myomectomy (for either hypertrophic cardiomyopathy or with aortic stenosis), ventricular assist device implantation, atrial appendectomy, and endomyocardial biopsy. The amount of tissue received varies based not only by the type of procedure, but can be highly variable within each procedure. The gross report should include the size and number of specimens received. It should also document the character and consistency of the samples. Sample weight is also a useful indicator of size (particularly for septal myomectomies). Samples should be cut to include all layers of the sample wall (from endocardium to epicardium). The presence of mural thrombus should always be documented, both grossly (if apparent) and histologically.

In addition to H&E staining, special stains for amyloid (Congo red, sulfated Alcian blue) may be helpful. Generally, if the clinical history is suspicious for amyloidosis or the patient is >65 years old, amyloid stains ordered up front can be helpful. Other special histochemical and immunohistochemical stains can be added as needed.

Pericardium

Pericardial tissue, procured most commonly during pericardiectomy for recurrent effusion or pericardial constriction, is usually sectioned easily but may be heavily calcified. After describing the specimen, 4–6 full-thickness samples should be evaluated histologically. Sampling of the heavily calcified areas is not often informative. In trying to determine the cause of pericarditis, it is better to see H&E sections before ordering special stains that may define pathogenesis.

Tumor and tumor-like conditions

Cardiac masses are the most likely cardiovascular specimen to prompt a surgeon to ask for an intraoperative diagnosis, necessitating frozen section analysis by the pathologist. Cardiac masses are typically handled like masses in other locations. They are described in terms of size and character (color, consistency, etc.). Additionally, whether or not they appear infiltrative or well circumscribed should be noted as well as whether or not they are sessile or polypoid. Ink may be useful to help keep the sample oriented and in the evaluation of resection margins. In general, the adage of one section of tumor examined histologically for each centimeter of greatest tumor size serves as a good starting point for evaluation if the diagnosis is not well defined at the time of grossing. Communication with the surgeon is essential as the specimen location and correlation with preoperative imaging may be helpful.