Epicardial Coronary Arteries

Chapter 12 - The Heart

Frederick J. Schoen MD, PhD

The human heart is a remarkably efficient, durable, and reliable pump that propels over 6000 liters of blood through the body daily and beats more than 40 million times a year during an

individual's lifetime, thereby providing the tissues with a steady supply of vital nutrients and facilitating the excretion of waste products. As might be anticipated, cardiac dysfunction can

be associated with devastating physiologic consequences. Heart disease is the predominant cause of disability and death in industrialized nations. In the United States, it accounts for about

40% of all postnatal deaths, totaling about 750,000 individuals annually and nearly twice the number of deaths caused by all forms of cancer combined. The yearly economic burden of

ischemic heart disease, the most prevalent subgroup, is estimated to be in excess of $100 billion. The major categories of cardiac diseases considered in this chapter include congenital heart

abnormalities, ischemic heart disease, heart disease caused by systemic hypertension, heart disease caused by pulmonary diseases (cor pulmonale), diseases of the cardiac valves, and

primary myocardial diseases. A few comments about pericardial diseases and cardiac neoplasms as well as cardiac transplantation are also offered. Before considering details of specific

conditions, we will review salient features of normal anatomy and function as well as the principles of cardiac hypertrophy and failure, the common end points of many different types of

heart disease.

Normal

The normal heart weight varies with body height and weight; it averages approximately 250 to 300 g in females and 300 to 350 g in males. The usual thickness of the free wall of the right

ventricle is 0.3 to 0.5 cm and that of the left ventricle 1.3 to 1.5 cm. As will be seen, increases in cardiac size and weight accompany many forms of heart disease. Greater heart weight or

ventricular thickness indicates hypertrophy, and an enlarged chamber size implies dilation. An increase in cardiac weight or size (owing to hypertrophy and/or dilation) is termed

cardiomegaly.

Myocardium

Basic to the heart's function is the near-inexhaustible cardiac muscle, the myocardium, composed primarily of a collection of specialized muscle cells called cardiac myocytes ( Fig. 12-1 ).

They are arranged largely in a circumferential and

Figure 12-1Myocardium (cardiac muscle). A The histology of myocardium is shown, emphasizing the centrally-placed nuclei of the cardiac myocytes (arrowhead), intercalated discs

(representing specialized end-to-end junctions of adjoining cells; highlighted by a double arrow) and the sarcomeric structure visible as cross-striations within myocytes. A capillary

endothelial cell is indicated by an arrow. (Photomicrograph courtesy of Mark Flomenbaum, M.D., Ph.D., Office of the Chief Medical Examiner, New York City, NY.) B Electron

microscopy of myocardium, showing myofibrillar (my) and mitochondrial (mi) architecture and the sarcolemmal membrane (s). Z bands are indicated by arrows. Bar = 1 μm. (Reproduced

by permission from Vivaldi MT, et al. Triphenyltetrazolium staining of irreversible injury following coronary artery occlusion in rats. Am J Pathol 121:522, 1985. Copyright J.B.

Lippincott, 1985.)

Figure 12-2Aortic valve histology, shown as a low-magnification photomicrograph of cuspal cross-section in the systolic (nondistended) state, emphasizing three major layers

(ventricularis [v], spongiosa [s], and fibrosa [f]). Superficial endothelial cells (arrow) and diffusely distributed deep interstitial cells are noted. The strength of the valve is predominantly

derived from the fibrosa, with its dense collagen (yellow). This section highlights the dense, laminated elastic tissue in the ventricularis (double arrow). The outflow surface is at top.

(Reproduced by permission from Schoen FJ: Aortic valve structure-function correlations: Role of elastic fibers no longer a stretch of the imagination. J Heart Valve Dis 6:1, 1997.)

TABLE 12-1-- Changes in the Aging Heart

Chambers

Increased left atrial cavity size

Decreased left ventricular cavity size

Sigmoid-shaped ventricular septum

Valves

Aortic valve calcific deposits

Mitral valve annular calcific deposits

Fibrous thickening of leaflets

Buckling of mitral leaflets toward the left atrium

Lambl excrescences

Epicardial Coronary Arteries

Tortuosity

Increased cross-sectional luminal area

Calcific deposits

Atherosclerotic plaque

Myocardium

Increased mass

Increased subepicardial fat

Brown atrophy

Lipofuscin deposition

Basophilic degeneration

Amyloid deposits

Aorta

Dilated ascending aorta with rightward shift

Elongated (tortuous) thoracic aorta

Sinotubular junction calcific deposits

Elastic fragmentation and collagen accumulation

Atherosclerotic plaque

With advancing age, the amount of epicardial fat increases, particularly over the anterior surface of the right ventricle and in the atrial septum. A reduction in the size of the left ventricular

cavity, particularly in the base-to-apex dimension, is associated with increasing age and accentuated by systemic hypertension. Accompanied by a rightward shift and tortuosity of a dilated

ascending aorta, this chamber alteration causes the basal ventricular septum to bend leftward, bulging into the left ventricular outflow tract (termed sigmoid septum). Such reduction in the

size of the left ventricular cavity can simulate the obstruction to blood leaving the left ventricle that often occurs with hypertrophic cardiomyopathy, discussed later in this chapter.

Several changes of the valves are noted with aging, including calcification of the mitral annulus and aortic valve, the latter frequently leading to aortic stenosis. In addition, the valves can

develop fibrous thickening, and the mitral leaflets tend to buckle back toward the left atrium during ventricular systole, simulating a prolapsing (myxomatous) mitral valve (see later).

Moreover, many older persons develop small filiform processes (Lambl excrescences) on the closure lines of aortic and mitral valves, probably arising from the organization of small

thrombi on the valve contact margins.

Compared with younger myocardium, "elderly" myocardium also has fewer myocytes, increased collagenized connective tissue and, in some individuals, deposition of amyloid. In the

muscle cells, lipofuscin deposits ( Chapter 1 ), and basophilic degeneration, an accumulation within cardiac myocytes of a gray-blue byproduct of glycogen metabolism, may be present.

Extensive lipofuscin deposition in a small, atrophied heart is called brown atrophy; this change often accompanies cachectic weight loss, as seen in terminal cancer.

Although the morphologic changes described are common in elderly patients at necropsy, and they may mimic disease, in only a minority are they associated with clinical cardiac

dysfunction.

Pathology

Although many diseases can involve the heart and blood vessels, [6] [7] cardiovascular dysfunction results from one or more of five principal mechanisms:

• Failure of the pump. In the most common circumstance, the cardiac muscle contracts weakly or inadequately, and the chambers cannot empty properly. In some conditions,

however, the muscle cannot relax sufficiently to permit ventricular filling.

• An obstruction to flow, owing to a lesion preventing valve opening or otherwise causing increased ventricular chamber pressure (e.g., aortic valvular stenosis, systemic

hypertension, or aortic coarctation). The increased pressure overworks the chamber that pumps against the obstruction.

• Regurgitant flow causes some of the output from each contraction to flow backward, adding a volume workload to each of the chambers, which must pump the extra blood (e.g.,

left ventricle in aortic regurgitation; left atrium and left ventricle in mitral regurgitation).

• Disorders of cardiac conduction. Heart block or arrhythmias owing to uncoordinated generation of impulses (e.g., atrial or ventricular fibrillation) lead to nonuniform and

inefficient contractions of the muscular walls.

• Disruption of the continuity of the circulatory system that permits blood to escape (e.g., gunshot wound through the thoracic aorta).

Most cardiovascular disease arises from the interaction of environmental factors and genetic susceptibility. The contemporary view holds that most clinical cardiovascular diseases result

from a complex interplay of genetics and environmental factors that disrupt networks controlling morphogenesis, myocyte survival, biomechanical stress responses, contractility, and

electrical conduction. [8] For example, there is growing recognition that pathogenesis of congenital heart defects, in many cases, involves an underlying genetic abnormality whose

expression is strongly modified by external (environmental or maternal) factors. Moreover, since a diverse group of cytoskeletal protein mutations have been linked with cardiac muscle

cell dysfunction in the cardiomyopathies, perhaps subtle mutations or polymorphisms in these genes could confer an increased risk or more rapid onset of heart failure in response to

acquired cardiac injury. In these and other examples, the clinical expression of cardiac disease represents the end result of multiple internal and external cues for growth, death, and survival

of cardiac myocytes. These factors and pathways are shared with other normal tissues and pathological processes.[9]

Heart Failure

The abnormalities described above often culminate in heart failure, an extremely common result of many forms of heart disease. In heart failure, often called congestive heart failure

(CHF), the heart is unable to pump blood at a rate commensurate with the requirements of the metabolizing tissues or can do so only at an elevated filling pressure. Although usually

caused by a slowly developing intrinsic deficit in myocardial contraction, a similar clinical syndrome is present in some patients with heart failure caused by conditions in which the normal

heart is suddenly presented with a load that exceeds its capacity (e.g., fluid overload, acute myocardial infarction, acute valvular dysfunction) or in which ventricular filling is impaired (see

below). CHF is a common and often recurrent condition with a poor prognosis. The magnitude of the problem is exemplified by the impact of CHF in the United States, where each year it

affects nearly 5 million individuals, is the underlying or contributing cause of death of an estimated 300,000, and necessitates over 1 million hospitalizations.[10] Moreover, CHF is the

leading discharge diagnosis in hospitalized patients over age 65 and has an associated annual cost of $18 billion. In many pathologic states, the onset of heart failure is preceded by cardiac

hypertrophy, the compensatory response of the myocardium to increased mechanical work (see below).

The cardiovascular system maintains arterial pressure and perfusion of vital organs in the presence of excessive hemodynamic burden or disturbance in myocardial contractility by a

number of mechanisms.[11] The most important are:

• The Frank-Starling mechanism, in which the increased preload of dilation (thereby increasing cross-bridges within the sarcomeres) helps to sustain cardiac performance by

enhancing contractility

• Myocardial structural changes, including augmented muscle mass (hypertrophy) with or without cardiac chamber dilation, in which the mass of contractile tissue is augmented

• Activation of neurohumoral systems, especially (1) release of the neurotransmitter norepinephrine by adrenergic cardiac nerves (which increases heart rate and augments

myocardial contractility and vascular resistance), (2) activation of the renin-angiotensin-aldosterone system, and (3) release of atrial natriuretic peptide.

These adaptive mechanisms may be adequate to maintain the overall pumping performance of the heart at relatively normal levels, but their capacity to sustain cardiac performance may

ultimately be exceeded. Moreover, pathologic changes, such as apoptosis, cytoskeletal alterations, and extracellular matrix (particularly collagen) synthesis and remodeling, may also

occur, causing structural and functional disturbances. Most instances of heart failure are the consequence of progressive deterioration of myocardial contractile function (systolic

dysfunction), as often occurs with ischemic injury, pressure or volume overload, or dilated cardiomyopathy. The most frequent specific causes are ischemic heart disease and hypertension.

Sometimes, however, failure results from an inability of the heart chamber to relax, expand, and fill sufficiently during diastole to accommodate an adequate ventricular blood volume

(diastolic dysfunction), as can occur with massive left ventricular hypertrophy, myocardial fibrosis, deposition of amyloid, or constrictive pericarditis.[12] Whatever its basis, CHF is

characterized by diminished cardiac output (sometimes called forward failure) or damming back of blood in the venous system (so-called backward failure), or both.

The molecular, cellular, and structural changes in the heart that occur as a response to injury, and cause changes in size, shape, and function, are often called left ventricular remodeling.

Our discussion focuses on structural changes and considers heart failure to be a progressive disorder, which can culminate in a clinical syndrome characterized by impaired cardiac function

and circulatory congestion. Nevertheless, we recognize that the modern treatment of chronic heart failure emphasizes the neurohumoral hypothesis, in which neuroendocrine activation is

important in the progression of heart failure. Thus, inhibition of neurohormones may have long-term beneficial effects on morbidity and mortality.[13] In the future, patients with CHF may

be helped by implanted mechanical cardiac assist devices, an area in which considerable progress has recently been made.[14]

Date: 2016-04-22; view: 766