Sandra L. Cassady & Lawrence P. Cahalin
INTRODUCTION
Despite the increased emphasis on health promotion and prevention, advances in technology, and the development of evidence-based treatment regimens, coronary atherosclerotic heart disease (ASHD) remains the leading cause of cardiovascular death and disability in the United States.1–3 All physical therapists, regardless of area of specialization or practice setting, treat patients with cardiovascular disease. Common symptoms of cardiovascular disease include dyspnea, chest pain, claudication, palpitations, syncope, and fatigue. None of these symptoms, however, are specific to a given system or cardiovascular disorder. By understanding the pathophysiology and clinical manifestations of common cardiovascular diseases, physical therapists are more likely to deliver safe interventions. The onset or change in symptoms detected during an examination may indicate the development or progression of a serious and potentially life-threatening disease.
This chapter presents the pathophysiology and clinical manifestations of most common cardiovascular diseases found in the adult. Medical care and therapeutic interventions are presented elsewhere in this text. Before discussing specific diseases, several important facts necessary to understand common pathologies of the cardiovascular system are presented. These facts provide a very brief introduction and rationale for the material presented in the remainder of the chapter.
OVERVIEW OF MAJOR CARDIOVASCULAR DISEASES
1.More than half of all deaths in industrialized countries are due to cardiovascular diseases. More than 50% of all adults in the United States and in other industrialized countries die of atherosclerosis and other major manifestations of this disease.4,5 Most of the related morbidity in this country can be accounted for by atherosclerosis of the coronary arteries, the cerebral blood vessels, and the aorta and its main branches. Hypertension, an important complication of atherosclerosis, contributes to the severity of the disease and aggravates its symptoms. Accounting for approximately 10% of all cases of heart disease,6 hypertension may occur independent of atherosclerosis or precede it. Clotting disturbances complicate atherosclerosis. Thrombosis of atherosclerotic coronary arteries is the main cause of myocardial infarction (MI).7–9 Thrombi may occur without preexisting atherosclerosis and are common in the venous system.
2.Abnormal cardiac development during fetal life is a significant cause of disease in newborns. Within the first 2 months after conception, the heart develops through several complex embryologic processes (see Chapter 4). The true incidence of cardiovascular malformations is difficult to determine accurately. It has been estimated that approximately 0.8% of livebirths are complicated by a cardiovascular malformation.10 Although many infants born with cardiac defects have anomalies that are not life-threatening and heal on their own, almost one-third (2.6 per 1,000 livebirths)11 have disease severe enough to result in a cardiac catherization, cardiac surgery, or death in the first year of life. Ventricular septal defects represent the most common congenital cardiac malformation in infants and children.5 In adults, the incidence of this defect and others is much lower due to spontaneous or surgical closure during infancy and death before adulthood. Further information about congenital cardiac abnormalities is found in Chapter 21.
3.Cardiac function is dependent on a constant supply of oxygen and nutrients. Reduction of the lumen secondary to narrowing or occlusion of the arteries affects blood supply to the myocardium and causes ischemia. Current theories for the pathogenesis of atherosclerosis will be presented. Other mechanisms (ie, vasospasm) will also be described in this chapter. Either sudden occlusion of arterial blood flow (MI) or chronic ischemia may lead to cardiac pump dysfunction or failure. Patients with ischemia may present with bouts of angina pectoris. Angina pectoris is one of the many causes of chest pain that physical therapists must be able to differentiate from other forms of chest discomfort.
4.Although regulated by hormones and biogenic amines, arterial blood pressure is dependent on both the action of the heart and elastic and contractile properties of the arteries and arterioles. Blood flow depends on pressure gradients generated by the action of the heart and the peripheral resistance of arteries and arterioles. Smooth muscle cells in the arteries and arterioles contract under the influence of adrenergic nerves, which release the catecholamines epinephrine and norepinephrine. These catecholamines are also produced by adrenal medullary cells and released into the circulation. Epinephrine and norepinephrine affect both the heart and the blood vessels. Blood pressure is also regulated by the hormones renin, angiotensin, and aldosterone. Abnormalities in the regulation of blood pressure may result in hypertension or hypotension. Both are commonly found in patients with cardiovascular disease.
5.Heart failure is a clinical syndrome, or a group of signs and symptoms, that results from abnormalities in the function of the heart. Heart (cardiac) failure is recognized as a pathophysiological state in which the heart is unable to pump blood at a rate commensurate with the requirements of metabolizing tissues. This results in elevated filling pressures due to loss of myocardial contractility.10 More than 6 million patients suffer from heart failure in the United States.12 This growth is not only due to the aging population but also due to the decrease in mortality from other cardiovascular diseases.
6.The heart is susceptible to blood-borne pathogens. A variety of inflammatory processes may be responsible for coronary artery abnormalities. Some of these mimic atherosclerotic disease and may predispose the individual to true atherosclerosis. Recent developments in our understanding of the inflammatory mechanisms and their direct and indirect effects on vascular wall cells have led to the consideration that chronic bacterial and viral infections may be potential initiating factors.13 Chlamydia pneumoniae,14,15 Helicobacter pylori,16 and cytomegalovirus17 are among the prominent potential infectious causes of atherosclerosis. Although there are several examples of positive associations between pathogens and disease, at present there is insufficient evidence18 to designate infection as a causal risk factor for coronary heart disease.
7.Bacteria and other pathogens found in blood-producing septicemia may invade the endothelium of blood vessels and the endocardium of the heart. Because the endocardium is in direct contact with blood, bacterial endocarditis is a common infectious lesion of the heart.19 With the exception of immunosuppressed persons, intramural bacterial abscesses of the myocardium and bacterial pericarditis are uncommon. Patients with preexisting lesions, as in congenital heart disease, valve deformities, or mural thrombi, are predisposed to cardiac infections. Blood clots provide a very suitable growth medium for bacteria. Clots within the ventricles and those attached to the valves often become infected. Emboli may result from infected thrombi, and embolization of peripheral arteries may result in infectious arteritis. Venous infections (eg, thrombophlebitis) are usually related to preexistent thrombosis.
8.Systemic metabolic diseases often affect the heart and the blood vessels. Diabetes mellitus is a very strong risk factor for the development of coronary artery disease (CAD) and stroke.20,21 Eighty percent of all deaths among patients with diabetes are due to atherosclerosis. Among all hospitalizations for diabetic complications, more than 75% are due to atherosclerosis.5 Caused by an absolute or relative deficiency of insulin or a resistance of tissues to insulin, this systemic disorder of intermediary metabolism primarily affects small blood vessels (microangiopathy). In all groups of patients, diabetes accelerates the natural course of atherosclerosis and involves a greater number of coronary vessels with more diffuse atherosclerotic lesions.22–25
9.Inflammatory and destructive cardiac lesions may result from immune complexes and immunoglobulins in the blood that may be deposited in the heart and blood vessels. Immunoglobulins are found in normal blood and have no adverse influences on the heart and blood vessels. However, when circulating immunoglobulins are complexed with antigen into immune complexes, they become pathogenic and cause vasculitis or endocarditis. Hypersensitivity reactions that elicit formation of antibodies to the body’s own tissues can damage the heart and blood vessels, as in rheumatic fever. Both fatal and nonfatal acute MIs and sudden coronary death may occur early in the course of autoimmune disorders. For example, patients with fatal systemic lupus erythematosus (SLE), who receive treatment with glucocorticoids for more than 2 years, demonstrate a high incidence of coronary atherosclerosis at the time of autopsy.26–28 Accelerated atherosclerosis is increasingly recognized as a leading cause of morbidity and mortality, especially among young women with systemic lupus erythematosus who receive long-term glucocorticoid administration.26,27
10.Malignant tumors of the cardiovascular system are rare. Primary tumors of the heart are less common (incidence of 0.002%–0.3%)29–35 than metastatic tumors of the heart.36 Benign tumors occur more frequently than malignant ones,37 and many tumors are curable by surgery. The most common cardiac tumor is the myxoma. Malignant tumors of the heart and blood vessels are classified as sarcomas and hemangiosarcomas, respectively. Small benign vascular tumors, hemangiomas, are very common and are of limited clinical significance.38,39
11.Within each form of cardiovascular disease, the level of impairment and limitation on activity may vary within and between patients. As a means of quantifying the activity limitations imposed by symptoms, the classification system of the New York Heart Association (NYHA)40 displayed in Box 6-1 is commonly used. Physical therapists are trained to address the needs of their patients and clients across all delivery settings, and they are encouraged to incorporate the principles of the disablement model as outlined in the Guide to Physical Therapist Practice.41 This resource guides therapists through the essential elements of patient/client management. Classifications such as that of the NYHA help facilitate communication among professionals about the functional limitations resulting from their active pathologies.
BOX 6-1
CARDIAC DISEASE
Atherosclerotic Heart Disease (Coronary Artery Disease)
As stated previously, coronary atherosclerotic heart disease is the most common cause of cardiovascular disability and death in the United States. Men are more often affected than women by an overall ratio of 4:1. Before age 40 this ratio is 8:1, but beyond age 70 it is 1:1. In men, the peak incidence of the clinical manifestations is in the fifth decade of life compared to the sixth decade for women.3
Atherosclerotic heart disease (ASHD), also known as coronary artery disease (CAD), is a progressive disease process characterized by irregularly distributed lipid deposits in the intimal layer of medium and large coronary arteries. Although the mechanisms of atherogenesis are still under investigation, epidemiological studies have identified several risk factors associated with an increased likelihood of developing premature CAD. Risk factors classified as modifiable characteristics, nonmodifiable characteristics, and lifestyle preferences are shown in Box 6-2. Alterable risk factors are the focus of interventional risk-factor reduction studies and cardiac rehabilitation. Blood homocysteine levels and hypoestrogenemia in women are two important risk factors under investigation. Several retrospective studies have identified mild-to-moderate increases in homocysteine, an amino acid, as a strong and independent risk factor for CAD, stroke, and peripheral vascular disease.42–45 However, some prospective studies46–48 have failed to show this association. In these patients, elevated plasma homocysteine appears to be more closely linked to thrombus-mediated coronary events (ie, MI) than to coronary atherosclerosis seen on angiography.49 Elevated homocysteine is also linked to venous thrombosis. The exact mechanisms remain unclear but may include endothelial toxicity, accelerated oxidation of cholesterol, an impairment of endothelial-derived relaxing factor, and a reduction in flow-mediated arterial vasodilation.50–53 As previously mentioned, chronic infections may also be involved and remain under investigation as causal risk factors for atherosclerosis.13
BOX 6-2
Characteristics and Lifestyles Associated with Increased Risk of Future Coronary Artery Disease
Personal Characteristics (Nonmodifiable)
Male gender
Age
Family history of CAD or other atherosclerotic vascular disease before age 55 in men, before age 65 in women
Personal history of CAD or other atherosclerotic vascular disease (eg, cerebrovascular or occlusive peripheral vascular disease)
Biochemical or Physiologic Characteristics (Modifiable)
Blood lipid abnormalities
Elevated blood total cholesterol
Elevated LDL cholesterol or VLDL cholesterol
Low HDL cholesterol
Elevated blood triglycerides
Hyperglycemia/diabetes mellitus
Obesity Hypertension
Lifestyles (Modifiable)
Tobacco smoking
Diet high in saturated fat, cholesterol, and calories
Excess alcohol consumption
Physical inactivity
LDL, low-density lipoprotein; HDL, high-density lipoprotein; CHD, coronary heart disease; VLDL, very low-density lipoprotein.
Adapted from Kasper EK, Agema WR, Hutchins GM, et al. The causes of dilated cardiomyopathy: a clinicopathologic review of 673 patients. J Am Coll Cardiol. 1994; 23:586.
Recent research has also focused on abnormalities of lipid metabolism. Risk increases progressively with higher levels of low-density lipoprotein (LDL) cholesterol and declines with higher levels of high-density lipoprotein (HDL) cholesterol. The ratio of LDL to HDL cholesterol provides a composite marker of risk. Ratios below 3:1 indicate lower risk, whereas ratios above 5:1 indicate a higher risk.54 There is further evidence that other abnormalities of lipid metabolism may also play a role in the pathogenesis of CAD. Patterns associated with increased atherosclerosis include elevated levels of apolipoprotein (A) and small, dense LDL lipoprotein particles. These lipoproteins and their accompanying lipids appear more likely to pass into the vessel wall and may be more difficult to clear. Although elevated triglyceride levels often occur in association with other lipid abnormalities, accumulating evidence suggests that hypertriglyceridemia is an independent risk factor for CAD.54–57 A more thorough review of the epidemiological evidence for the risk factors associated with cardiovascular disease can be found in Chapter 15.
The Atherosclerotic Lesion
Our knowledge of the pathophysiology of atherosclerosis and the clinical presentations of CAD continue to accumulate rapidly. Abnormal lipid metabolism and/or the excessive intake of cholesterol and saturated fats, especially when superimposed on genetic predisposition, initiate the atherosclerotic process and development of atherosclerotic plaque.5,10
Atherosclerotic plaque consists of accumulated intracellular and extracellular lipids, connective tissue, smooth muscle cells, and glycosaminoglycans (eg, several sulfates and hyaluronic acid). The earliest detectable lesion of atherosclerosis is the fatty streak. The fatty streak consists of lipid-laden foam cells, which are macrophages that have migrated as monocytes from the circulation into the subendothelial layer of the intima. Later, the fatty streak evolves into fibrous plaque that is made up of intimal smooth muscle cells surrounded by connective tissue and intra-cellular and extracellular lipids.
Pathogenic Mechanisms of Plaque Formation
Although the exact mechanism of plaque formation remains under study, many hypotheses have been developed. The most pervasive include the lipid hypothesis and the chronic endothelial injury hypothesis. Both are described in the following sections.
The lipid hypothesis—The lipid hypothesis states that elevation in plasma LDL levels results in penetration of LDL into the arterial wall, leading to lipid accumulation in smooth muscle cells and in macrophages (foam cells) (see Fig. 6-1). LDL also augments smooth muscle cell hyperplasia and migration of cells into the subintimal and intimal regions in response to growth factors. LDL is modified or oxidized in this environment and is rendered more atherogenic. Small, dense LDL cholesterol particles are also susceptible to modification and oxidation. The modified or oxidized LDL is chemotactic to monocytes, which promotes their migration into the intima, their early appearance in the fatty streak, and their transformation and retention in the subintimal compartment as macrophages. Scavenger receptors on the surface of macrophages facilitate the entry of oxidized LDL into these cells, transforming them into lipid-laden macrophages and foam cells. Oxidized LDL is also cytotoxic to endothelial cells and may be responsible for their dysfunction or loss from the more advanced lesion.58–60
FIGURE 6-1 Characteristics of “stable” and “vulnerable” coronary atherosclerotic lesions. Initially, vulnerable plaques grow outward. The vulnerable plaque has a substantial lipid core and thin fibrous cap separating the thrombogenic macrophages from the blood. At sites of lesion disruption, smooth muscle cells (SMC) are activated and detected by the presence of human leukocyte antigen-DR (HLADR). The stable plaque has a relatively thick fibrous cap protecting the lipid core from contact with the blood. Stable plaques often cause luminal narrowing.
An atherosclerosis model has been studied in monkeys fed a cholesterol-rich diet.61,62 This study demonstrated that within 1 to 2 weeks of inducing hypercholesterolemia, monocytes attached to the surface of the arterial endothelium through the induction of specific receptors, migrated into the subendothelium, and accumulated lipid in macrophages (ie, foam cells). Proliferating smooth muscle cells also accumulate lipid. As the fatty streak and fibrous plaque enlarge and bulge into the lumen, the subendothelium becomes exposed to the blood at sites of endothelial retraction or tear, and platelet aggregates and mural thrombi form. It is postulated that the release of growth factors from the aggregated platelets may increase smooth muscle proliferation in the intima. The organization and incorporation of the thrombus into the atherosclerotic plaque may contribute to its growth.63
The chronic endothelial injury hypothesis—The chronic endothelial injury hypothesis states that, through various mechanisms, endothelial injury produces loss of endothelium, adhesion of platelets to subendothelium, aggregation of platelets, chemotaxis of monocytes and T-cell lymphocytes, and release of platelet-derived and monocyte-derived growth factors. This induces migration of smooth muscle cells from the media into the intima, where they replicate, synthesize connective tissue and proteoglycans, and form a fibrous plaque (see Fig. 6-2). Other cells (eg, macrophages, endothelial cells, arterial smooth muscle cells) also produce growth factors that can contribute to smooth muscle hyperplasia and extracellular matrix production.5
FIGURE 6-2 The complex interaction of the endothelium, platelet aggregation, and coagulation. Vasorelaxation: nitric oxide (NO), nitric oxide synthase (NOS), C-type natriuretic peptide (CNP), prostaglandin I2 (PGI2), cyclooxygenase (COX). Anticoagulation: antithrombin (ATIII), tissue plasminogen factor (tPA), protein C, protein S (Pr C, Pr S), Coagulation: tissue factor (TF), von Willebrand factor (vWF). Platelet aggregation: serotonin (5-HT), adenosine diphosphate (ADP). Vasoconstriction and growth promotion: platelet-derived growth factor (PDGF), endothelin-converting enzyme (ECE), enthothelin-1 (ET-1), prostaglandin H2, thromboxane A2 (TXA2). (Reproduced with permission from Volta SD. Cardiology. Berkshire, UK: McGraw-Hill; © 1999.)
Modified LDL is cytotoxic to cultured endothelial cells and may induce endothelial injury, attract monocytes and macrophages, and stimulate smooth muscle growth. Modified LDL also inhibits the mobility of macrophages, so that once they transform into foam cells in the subendothelial space they may become trapped. In addition, regenerating endothelial cells (after injury) are functionally impaired and increase the absorbed LDL from plasma.
The atherosclerotic plaque may grow slowly and over several decades may result in severe arterial stenosis or may progress to total arterial occlusion. With time, the plaque becomes calcified. Some plaques are stable, but others, especially those rich in lipids and inflammatory cells (eg, macrophages) and covered by a thin fibrous cap, may undergo spontaneous fissure or rupture, exposing the plaque contents to flowing blood (see Fig. 6-2). These plaques are believed to be unstable or vulnerable and are more closely associated with the onset of an acute ischemic event.5 The ruptured plaque stimulates thrombosis; the thrombus may (1) embolize, (2) rapidly occlude the lumen to precipitate myocardial ischemia or infarction, or (3) gradually become incorporated into the plaque, contributing to its stepwise growth.
The two hypotheses just described are closely linked and not mutually exclusive. The lipid hypothesis suggests that remnants of triglyceride-rich lipoproteins or modified LDL of hyperlipidemic subjects are absorbed by macrophages to form the early atherosclerotic lesion and that chronic exposure of endothelium to these lipoproteins leads to cell injury. Cell necrosis in turn results in a deposition of lipid in the extracellular space. Injury to the endothelium and progression of atherosclerotic lesions by exposure to chronically elevated levels of remnants and/or modified LDL could be part of the sequence leading to the formation of occlusive plaques and to their clinical sequelae.64,65
As previously introduced, recent studies13,66,67 have validated an old theory that atherosclerosis progresses as the result of an inflammatory response in the vessel wall. The process may be initiated or worsened by an infectious agent as diverse as cytomegalovirus, C. pneumoniae, and H. pylori. A high circulating level of the nonspecific inflammatory marker, C-reactive protein, has been correlated with a higher rate of ischemic events.
Coronary Anastomosis (Collaterals)
Larger caliber collaterals develop below adjacent arteries on the epicardial surface. These are believed to be preexisting smaller arteries altered by flow-induced pressure differentials between different coronary beds. Functionally, these have been considered very important for maintaining blood supply to myocardial cells supplied by stenotic vessels.5 Angiographical evidence indicates that coronary artery collaterals form locally at sites of high-grade lesions in response to chronic ischemia.5
Progression and Regression of Atherosclerosis
With sequential angiographical studies, the progression of atherosclerosis is known to be phasic and unpredictable. High-grade lesions do not necessarily appear where low-grade lesions were once found. New lesions of more than 50% can occur between repeated angiograms. Sites of future lesions cannot be identified and the progression cannot be predicted.68–71 Individual plaques may progress at accelerated rates unrelated to their degree of stenosis. We do know that high-grade lesions tend to progress. Chronic total occlusions result from high-grade lesions three times more frequently than in cases of less severe lesions but frequently do not result in infarction because of collateral development.72 Stenotic regression can also be demonstrated angiographically in some but not all cases after either aggressive pharmacologic treatment with statins or very low-fat diets.
Manifestations of Atherosclerotic Heart Disease
The clinical manifestations of ASHD typically evolve after many decades of progressive atherosclerosis and include myocardial ischemia, infarction, congestive heart failure, and sudden death. Each of the possible manifestations and related pathophysiology are presented.
Myocardial Ischemia
Myocardial ischemia results when there is an imbalance between myocardial oxygen supply and myocardial oxygen demand. It is a reversible phenomenon, which typically comes on with exertion and goes away with rest. The factors affecting the balance between myocardial oxygen supply and demand are illustrated in Fig. 6-3. Increased myocardial oxygen requirements may be provoked by a number of factors including exercise, mental stress, or even spontaneous fluctuations in heart rate and blood pressure. Decreased oxygen supply may result from a reduction in coronary blood flow. (The reader may recall the already-high extraction of oxygen from blood flowing through myocardial tissue, with the resultant dependence on coronary blood flow to meet myocardial demand. See Chapters 3 and 5.) Decreased blood flow may be due to decreased aortic driving pressure or increased coronary vascular resistance, which may be due to coronary vasospasm, platelet aggregation, or partial thrombosis.
FIGURE 6-3 Factors influencing myocardial oxygen supply and demand.
It is a commonly held belief that coronary artery occlusion greater than 70% produces myocardial ischemia, which in turn provokes the symptoms that bring the patient to the doctor’s office. The patient at this stage of atherosclerotic progression is comfortable at rest but will complain of chest pressure during mild-to-moderate exercise, which is relieved by rest. The diagnosis of ischemic heart disease is usually made on the basis of a formal exercise stress test.
Coronary atherosclerosis and coronary arterial spasm both reduce coronary blood flow and thus reduce myocardial oxygen supply. When this happens, myocardial ischemia and irritability occur, which may produce arrhythmias, impaired myocardial contractility (systolic dysfunction), and impaired myocardial relaxation (diastolic dysfunction). This diastolic dysfunction prolongs systole and reduces ventricular filling time. Ventricular compliance decreases and the ventricular end-diastolic pressure rises, causing aortic driving pressure to be further reduced. Myocardial ischemia often manifests itself on an electrocardiogram (ECG) as ST-segment displacement (see Chapter 11).
The threshold for myocardial ischemia can be either predictable or unpredictable. Abnormal endothelial function appears to play a role in the unpredictable, fluctuating threshold for ischemia. The majority of studies suggest that endothelium-dependent vasodilator mechanisms predominate in nondiseased epicardial coronary arteries. During interventions that normally induce increases in myocardial oxygen consumption and blood flow (eg, exercise, stress, induced tachycardia), epicardial vascular dilation occurs. This dilation is at least partially endothelial dependent. However, the presence of even nonocclusive, early atherosclerosis appears to impair the release of endotheliumrelived relaxing factor (nitrous oxide), attenuating this vasodilator mechanism, which results in prevailing, unop-posed vasoconstriction. Moderate vasoconstriction in an area of minimal occlusion may be of little hemodynamic consequence; however, the same degree of vasoconstriction in an area of greater occlusion may markedly decrease blood flow and induce ischemia.73–75
Stable angina—The classical symptom of myocardial ischemia is angina pectoris. This discomfort is described as pressure, heaviness, or tightness that may be located in the middle of the chest (substernal); over the heart (precordial); or in the shoulder, arm, throat, or jaw. Angina may be precipitated by exertion, stress, emotions, and heavy meals. Stable angina usually lasts for several minutes and is usually relieved by rest and/or nitroglycerin. The patient is pain free at rest.
Anginal pain arises within the myocardium and is thought to stimulate free nerve endings in or near small coronary vessels. Impulses travel in afferent unmyelinated or small myelinated cardiac sympathetic nerves through the upper thoracic ganglia to dorsal horn cells and through the spinothalamic tract of the thalamus to the cortex.5,76 The cerebral cortex integrates and modifies these impulses. This modulation may contribute to the variability in the perception of angina across patients. Psychosocial and cultural factors may also influence the perception of pain at the cortical level.
Unstable angina—The term unstable angina is usually used to denote either a change in the anginal pattern or angina at rest. Unstable angina may occur with less exertion than previously described, may last longer, or become less responsive to medication. Angiography has shown that a high proportion of patients with unstable angina have complex coronary stenoses characterized by plaque rupture, ulceration, or hemorrhage with subsequent thrombus formation. This inherently unstable situation may progress to complete occlusion and infarction, or may heal, with reendothelialization and return to a stable though possibly more severe pattern of ischemia. New-onset angina is sometimes considered unstable, but if it presents in response to exertion and responds to rest and medication, it does not carry the same poor prognosis.
Prinzmetal (variant) angina—Prinzmetal angina, also called atypical or variant angina, is an unusual type of cardiac pain due to myocardial ischemia that occurs almost exclusively at rest. Prinzmetal and colleagues77 hypothesized that variant angina was the result of transient increases in vasomotor tone or vasospasm. Vasospasm causes a transient, abrupt, marked decrease in the diameter of the coronary artery that results in myocardial ischemia. In such cases, no preceding increases in myocardial oxygen demand occur. Vasospasm can occur in both normal and diseased coronary arteries. Often the decrease in the diameter can be reversed by nitroglycerin.10 Variant angina is usually not associated with physical exertion or emotional stress and is associated with ST-segment elevation, rather than with depression on ECG.78 This form of angina is often severe and characteristically occurs in the early morning, awakening patients from sleep. It tends to involve the right coronary artery and is likely to be associated with arrhythmias or conduction defects.5 Prinzmetal angina may be associated with acute MIs and severe cardiac arrhythmias, including ventricular tachycardia and fibrillation (see Fig. 6-4).79
FIGURE 6-4 Clinical presentation, electrocardiographic, chemical, and arterial changes associated with coronary artery spasm. Note the ST-segment elevation above baseline.
Asymptomatic (silent) myocardial ischemia—Many individuals have some episodes of “silent” ischemia (ischemia without symptoms); some patients have only silent ischemia. Asymptomatic ischemic episodes may be present in patients with any of the aforementioned ischemic coronary syndromes or after an MI. Some patients never complain of chest pain with episodes of ischemia; others inconsistently report chest pain with episodes of ischemia. The true prevalence of silent ischemia is undetermined, but it is believed to be high. Important factors include age, the presence and extent of CAD, and other disease processes that include peripheral neuropathy as a component (eg, diabetes mellitus, alcoholic neuropathy).
Some clinicians have attempted to explain silent ischemia as angina that is less noxious than reported angina. The correlation between ECG evidence of ischemia and the report of anginal pain in patients with chronic stable angina is only fair.80,81 Therefore, the most likely explanation is neurologic. Neuropathy with defective sensory efferent nerves occurs commonly in persons with diabetes. The variable expression of ischemic pain may be explained by modification of pain stimuli in the central nervous system. Patients with diabetes have a relatively high incidence of painless MIs and definite silent ischemic episodes as documented by ambulatory ECG recordings and exercise testing.82–85
Anginal equivalents—These include dyspnea, fatigue, light-headedness, and belching brought on by exercise or stress and relieved by rest or nitroglycerin. We have said that some patients with diabetes may not complain of chest discomfort due to impaired peripheral sensation (eg, silent ischemia). Alterations in neural processing can, by extension, also give rise to anginal equivalents. Ischemic episodes in this group can present as a fullness in the throat and jaw, a desire to cough, or dyspnea. Elderly patients and patients with peripheral neuropathies may also present with anginal equivalents.
The rich variety of radiation patterns associated with angina pectoris is determined by the levels of the spinal cord, which share sensory inputs with somatic structures (eg, gut) and the heart. The precise mechanisms causing angina and anginal equivalents are yet to be defined.
Myocardial Infarction
Pathogenesis—MI results from prolonged myocardial ischemia and is precipitated in most cases by an occlusive coronary thrombus at the site of a preexisting atherosclerotic plaque. Less frequently,3,65,86 infarction may result from prolonged vasospasm, inadequate myocardial blood flow (eg, hypotension), or excessive metabolic demand. Very rarely, MI may be caused by embolic occlusion, aortitis, vasculitis, or coronary artery dissection. Cocaine87 and other similar types of drugs can induce coronary artery vasoconstriction and may lead to myocardial ischemia as well as to infarction.
Regardless of the etiology, an MI results in the complete interruption of blood supply to an area of myocardium, almost always in the left ventricle, and more rarely in the right ventricle. Cells die and tissues become necrotic in an area referred to as the zone of infarction. Within 18 to 24 hours after MI, an inflammatory response occurs in response to necrosis. Leukocytes aid in the removal of dead cells, and fibroblasts form a connective tissue scar within the area of infarction. Visible necrosis is present in 2 to 4 days. During this time, proteolytic enzymes remove debris while catecholamines, lipolysis, and glycogenolysis elevate plasma glucose and increase free fatty acids to assist depleted myocardium recovery from an anaerobic state. By 4 to 10 days the debris is cleared and a collagen matrix is laid down. Between 10 and 14 days, weak, fibrotic scar tissue with beginning revascularization is present. This area remains vulnerable to stress. Usually, the formation of fibrous scar tissue is complete within 6 to 8 weeks.88,89 Inelastic scar tissue replaces the necrotic tissue and the region is unable to contract and relax like healthy myocardial tissue. When a transmural MI occurs with full-thickness necrosis, wall motion may be reduced (hypokinetic), abnormal (dyskinetic), or absent (akinetic). When necrosis is limited to the innermost layer of the heart (ie, subendocardial MI), wall motion will usually appear to be normal.
CLINICAL CORRELATE
The completed scar is tough, usually thick, and fibrous and serves to protect the heart from further damage. Current best practice calls for the implementation of low-level exercises designed to maintain function and prevent the deleterious effects of prolonged inactivity during this initial 6- to 8-week period.
Adjacent to the zone of infarction is a less seriously damaged area of injury called the zone of hypoxic injury. This zone is able to return to normal, but may become necrotic if blood flow is not restored. With adequate collateral circulation, this area may regain function within 2 to 3 weeks. Immediately surrounding the zone of injury is another reversible zone known as the zone of ischemia (see Fig. 6-5).
FIGURE 6-5 ECG changes associated with the three zones of infarction.
The location and extent of infarction depend on the anatomic distribution of the occluded vessel, the presence of additional stenotic lesions, and the adequacy of collateral circulation. Occlusion in the anterior descending branch of the left coronary artery results in infarction of the anterior left ventricle and the interventricular septum. Occlusion of the left circumflex artery produces anterolateral or posterolateral infarction. Right coronary thrombosis leads to infarction of the posteroinferior portion of the left ventricle and may involve the right ventricular myocardium and interventricular septum. The arteries supplying the atrioventricular node and the sinus node more commonly arise from the right coronary; thus, atrioventricular blocks at the nodal level and sinus node dysfunction occur more frequently during inferior infarctions. A general rule is that the more proximal the lesion, the greater the extent of the infarct. Individual variation in coronary anatomy and the presence of collateral vessels can make it difficult to locate the precise site of the lesion responsible for infarction. The gold standard for identification of the blockage and infarct site remains that of coronary angiography rather than that of ECG. The necrotic, ischemic, and injured myocardial tissue cause characteristic ECG changes as the myocardium heals. These changes are described in the following sections.
As mentioned previously, MIs are classified as either trans-mural (full-thickness) or subendocardial (partial-thickness) infarctions. Transmural MIs are characterized by electrocardiographic evolution of ST-segment elevation with significant Q waves. Subendocardial MIs are characterized by ST-T wave changes but without the development of significant Q waves (see Chapter 11). On pathologic examination, however, most infarctions involve the subendocardium initially, and some transmural extension is common even in the absence of Q waves. Thus, some cardiologists prefer the classification of Q wave or non–Q-wave infarction. The non–Q-wave infarction generally results from incomplete occlusion or spontaneous lysis of the thrombus and signifies the presence of additional jeopardized myocardium; non–Q-wave infarctions are associated with a higher incidence of reinfarction and recurrent ischemia.90,91
CLINICAL CORRELATE
Because of this high incidence of reinfarction, patients with subendocardial MIs are considered less stable than those with transmural MIs. Indeed, many of these patients will be referred to surgery for surgical management. For this reason, physical therapy interventions tend to be more conservative than those directed toward patients with full-thickness MIs.
The size and anatomic location of the infarction strongly influence the acute course, the early complications, and the long-term prognosis. Hemodynamic stability is related to the extent of necrosis. In small infarctions, cardiac function may be normal, whereas with more extensive damage, early heart failure and cardiogenic shock92 may appear. Prevention of infarct extension by reducing both the zones of injury and ischemia is a major goal of early intensive care unit management.
Diagnosis of an MI relies upon the presentation of classical symptoms, elevation of specific enzymes, and an acute injury pattern on ECG with evolutionary ECG changes over time.93–95 Because of the multiple neural innervation levels, pain presentation with MI may vary (see CD-ROM). It has been estimated that up to 25% of MIs occur without any symptoms.96 These silent MIs present a challenge to the clinician who must utilize other monitoring techniques and instruct patients about symptom recognition and provide activity guidelines. These alternative methods of therapeutic intervention are described in Chapter 10.
Diagnosis and laboratory findings—Diagnosis of an acute MI requires that at least two of the following three elements be present: (1) a history of ischemic-type chest discomfort, (2) evolutionary changes on serially obtained ECG tracings, and (3) a rise and fall in serum cardiac enzymes.97 With respect to these three elements, there is considerable variation in presentation.
Clinical presentation of myocardial infarction—The most notable symptom of an MI is the sudden sensation or onset of chest discomfort that is often described as “crushing chest pain or pressure,” which occasionally radiates to the arms, neck, throat, and back. This pain is usually constant, lasts for 30 minutes or more, and may be associated with pallor and shortness of breath. The pain of MI is qualitatively different from the pain of angina. The former is usually more severe and prolonged and unrelieved by rest. Patients who are prescribed nitroglycerin are instructed to report to the hospital if their angina is unrelieved after three doses, because of the likelihood of an evolving MI.
The chest pain of an MI is accompanied by a dramatic surge in sympathetic nervous system activity. The release of catecholamines results in sympathetic stimulation, which may produce diaphoresis and peripheral vasoconstriction that may cause the skin to become cool and clammy to touch. Reflex stimulation of vomiting centers may cause nausea and vomiting. In the first 24 hours, fever may develop and persist for up to a week because of the inflammatory responses within the myocardium. If cardiac output is compromised, the patient may complain of lightheadedness due to a reduction in blood pressure. The patient experiencing an acute MI may also be in denial and not seek care for several days following the event. It should be noted that patient denial of symptoms will result in the delay of medical care. This delay does not only affect diagnosis and treatment—it can also have tragic consequences. Indeed, the sooner the patient presents to the hospital, the better the chances of survival. “Time is muscle” is a phrase that can save a patient’s life!
Electrocardiography—Electrocardiographic changes are almost always present in patients experiencing acute infarctions. A normal tracing obtained during an MI is rare. The extent of the electrocardiographic abnormalities provides only a rough estimate of the magnitude of infarction. The earliest signs are usually peaked or “hyperacute” T waves, followed by ST-segment elevation, Q-wave development, and finally T-wave inversion. This sequence of events may develop over a few hours or over several days. The evolution of new Q waves (>30 ms in duration and one-third the height of the R wave) is diagnostic for transmural MI. Q waves do not develop in 30% to 50% of acute infarctions, representing subendocardial MI. If these patients have a typical clinical presentation (ie, elevated cardiac enzymes and ST-segment changes, usually depression or T-wave inversion lasting at least 48 hours), they are classified as having non–Q-wave infarctions.93,94 Some of these changes are shown in acute and subacute tracings for an anterior and lateral wall infarction (Fig. 6-6). Further discussion of electrocardiography can be found in Chapter 11.
FIGURE 6-6 Twelve-lead electrocardiogram showing an acute anterolateral wall myocardial infarction. Note the ST-segment elevations in V2–V6, coupled with deep Q waves in V1–V5, representing areas of myocardial injury and necrosis, respectively.
Cardiac enzymes—As myocytes become necrotic, the integrity of the sarcolemmal membrane is compromised and serum cardiac markers diffuse into the cardiac interstitium. These markers eventually reach the microvasculature and lymphatics in the region of the infarct.98 Intracellular location, molecular weight, local blood and lymphatic flow, and the rate of elimination from the blood are all factors that determine the rate of appearance of the markers.99–101 Markers currently monitored include creatine kinase (CK), myoglobin, and the cardiac-specific troponins (troponin T, and troponin I). Lactic dehydrogenase (LDH) and serum glutamic–oxaloacetic transaminase (SGOT) are also enzymes that are frequently used to rule in an MI.
CK is released when cells die. Three isoenzymes of CK have been identified by electrophoresis: The MM band is specific to skeletal muscle death, the BB band is specific to brain cell death, and the MB band is specific to myocardial cell death. Rapid assays are now available for CK-MB isoforms. A ratio of CK-MB2/CK-MB1 greater than 2.5 has a sensitivity for the presence of myocardial cell necrosis of 46.4% at 4 hours and 91.5% at 6 hours.62Serum CK levels exceed the normal range within 4 to 8 hours after the onset of an acute MI and returns to normal within 2 to 3 days.10 Peak CK occurs on average at approximately 24 hours. Although the elevation of CK is considered a sensitive detector of an acute infarction, false positives are found in many patients including those with muscle disease, diabetes mellitus, skeletal muscle trauma, pulmonary embolism, and alcohol intoxication.99,101,102
Myoglobin is a protein released into circulation from injured myocardial cells and can be detected within a few hours after the onset of infarction. Peak levels of myoglobin are reached within 1 to 4 hours. Myoglobin is excreted into the urine. Its measurement has been suggested as a useful index of successful reperfusion.103 Patients presenting with ST-segment elevation less than 6 hours from symptoms and a diagnosis of MI are at increased risk of mortality when myoglobin is elevated.
The cardiac troponins are the newest markers. The troponin complex consists of three subunits that regulate the calcium-mediated contractile processes of striated muscle. Troponin C binds Ca2+[H11001]; troponin I binds to actin and inhibits actin–myosin interactions; and troponin T binds to tropomyosin. Troponin T and troponin I are highly cardiac selective and are released into the blood during an MI. These regulatory proteins rise within 4 to 6 hours of the onset of cell necrosis and remain elevated for several days after the infarction.10
CLINICAL CORRELATE
Because of the rapid elevation and decline in CK-MB assays, patients who are in denial and who delay presentation to the emergency room may show normal CK-MB values. However, troponin levels remain elevated for a longer period of time and may “salvage” a diagnosis (see Fig. 6-7).
FIGURE 6-7 Evolution of three major serum markers (CK-MB, myoglobin, and troponin T) after myocardial infarctions in patients in whom (A) reperfusion with thrombolytics was successful and (B) not achieved. (Reprinted with permissions of Chapelle JP. Diagnosticum. 1993;93(1):8-15).
Treatments and complications—Management of patients with MI can be divided into medical and surgical interventions. Medical interventions include the use of pharmacological agents aimed at reducing myocardial oxygen demand (eg, β-blockade, calcium channel blockade), increasing myocar-dial oxygen supply (eg, coronary artery vasodilators), and improving/maintaining myocardial function (eg, digitalis glycosides). These medical interventions are covered in some detail in Chapter 8. Current surgical interventions for patients with MI include thrombolysis, intra-aortic balloon pump, angioplasty, and stent placement104–106 (see Table 6-1).
Some of the surgical interventions in Table 6-1 deserve comment. Drugs that have the potential to dissolve (“lyse”) a thrombus within a coronary artery are called thrombolytic agents and are introduced surgically by way of a catheter whose tip is placed in the coronary artery at the site of the blockage. Thrombolytic agents such as streptokinase and tissue plasminogen activator (tPA) are then administered, usually within a few hours of an acute MI in hope of dissolving a thrombus and improving blood flow to areas of myocardium in the zones of injury and ischemia.
Coronary artery stents were first introduced into clinical practice in the mid-1980s. These are cylindrical wire-mesh devices that are placed at the site of vascular occlusion via balloon angioplasty. Stents are now used in 80% of all percutaneous cardiac interventions.107 However, their propensity to restenosis has led to the recent development in drug-eluting “coated stents.” These devices are coated with antiproliferative substances, most notably rapamycin. Early results show extremely low restenosis rates averaging between 0% and 9% after 6 and 12 months,107 respectively.
The use of intracoronary radiation therapy (brachytherapy) is a relatively recent addition to management options of patients with MI and/or residual ischemia. It was developed to address the relatively high rate of restenosis in patients following stent placement.108–110 This technique involves the use of radiation delivered either via a stent or a catheter-based system. It is believed that this radiation inhibits smooth muscle cell mitosis and proliferation of adventitial myofibroblasts.111
BOX 6-3
Complications Following Myocardial Infarction
Infarct extension and postinfarction ischemia
Arrhythmias
Sinus bradycardia
Supraventricular tachyarrhythmias
Ventricular arrhythmias
Conduction disturbances
Myocardial dysfunction
Acute left ventricular failure
Hypotension and shock
Right ventricular infarction
Mechanical defects (partial or complete rupture of a papillary muscle or interventricular septum)
Myocardial rupture
Left ventricular aneurysm
Pericarditis
Mural thrombus
The use of enhanced external counterpulsation (EECP) devices demonstrates early promise in the treatment of ischemia.112–116 It is a noninvasive outpatient series of treatment sessions that consists of total 35 hours, divided into one or two 60-minute treatment sessions 5 days a week. A series of pneumatic compressive cuffs is wrapped around the calves and thighs. Inflation of the cuffs is synchronized with the cardiac cycle such that inflation occurs during diastole and deflation occurs during systole (see Table 6-1). The benefits of enhanced external counterpulsation have been shown to last up to 5 years following initial treatment.
TABLE 6-1 Current Treatment of Myocardial Infarction
With all these interventions, it is important to remember that early recognition and prompt intervention provide the most options and increased chance of salvaging injured myocardium.
Even when treatment is initiated promptly, a variety of complications can occur following an MI (Box 6-3). Approximately 10% of patients experience a recurrent infarction in the first 10 to 14 days.3 Infarct extension is at least twice as common in non–Q-wave infarcts when compared to Q-wave infarcts. The recurrent infarct may be relatively silent or associated with prolonged or intermittent chest pain. Abnormalities of rhythm and conduction are common. Myocardial dysfunction is proportionate to the extent of necrosis. A large MI will destroy a large portion of myocardium and likely result in extensive myocardial dysfunction. Extensive myocardial dysfunction is likely to produce acute heart failure, hypotension, and possibly shock, all of which are indicative of a poor prognosis after an acute MI.95
Heart Failure
In this chapter, heart failure is presented as one of the possible manifestations of ASHD. Further information about heart failure can be found in Chapter 18. Heart failure exists when the heart is unable to pump sufficient cardiac output to meet the body’s metabolic demands. Clinically, heart failure is defined as a syndrome with a variety of interrelated pathophysiologic phenomena, of which impaired ventricular function is the most important. This results in a reduction of exercise capacity and other characteristic clinical manifestations.64 Many of the signs and symptoms are related to systolic dysfunction.
Systolic function of the heart is determined by four major determinants: (1) the end-diastolic volume and the resultant fiber length of the ventricles prior to onset of the contraction (preload), (2) the impedance to left ventricular ejection (after-load), (3) the contractile state of the myocardium (contractility), and (4) the rate of contraction, or heart rate (chronotropy).3
Heart function may be impaired as a result of alterations in any of these four determinants. The most common problem is depression of myocardial contractility, caused either by a loss of functional muscle due to infarction or by processes diffusely affecting the myocardium. The heart may fail as a pump because of excessive preload (eg, valvular regurgitation) or when afterload is excessively elevated, as occurs in severe hypertension. Pump function may also be inadequate when the heart rate is too slow or too rapid. The normal heart is capable of handling considerable variation in preload, after-load, and heart rate; however, the diseased heart often has limited reserve for handling such challenges.
Cardiac pump function may be normal or even supranormal at rest, but inadequate when metabolic demands or requirements for blood flow are in excess. This situation is termed high-output heart failure. Hyperthyroidism, beriberi, severe anemia, arteriovenous shunting, osteitis deformans (Paget disease), and sepsis may result in high-output heart failure.117
Cardiac failure may also occur as a result of isolated or predominant diastolic dysfunction of the heart. In these cases, filling of the left or right ventricle is impaired because of excessive hypertrophy or changes in the composition of the myocardium. Contractility may be preserved; however, diastolic pressures are elevated and cardiac output may be reduced.10,118
A number of cardiac and systemic adaptations occur when the heart fails. If the stroke volume of either ventricle is reduced by depressed contractility or excessive afterload, end-diastolic volume and pressure in that chamber will rise. This increases end-diastolic myocardial fiber length, resulting in a greater systolic shortening in the normal heart; but in the failing heart, Starling’s law is less applicable. If the condition is chronic, ventricular dilatation will occur. Although this may restore resting cardiac output, the resulting chronic elevation of diastolic pressures will be transmitted back up to the atria and to the pulmonary and systemic venous circulation. Ultimately, increased pulmonary capillary pressure may lead to transudation of fluid, with resulting pulmonary or systemic edema. Reduced cardiac output will also activate several neural and humoral systems. Increased activity of the sympathetic nervous system will stimulate myocardial contractility, heart rate, and venous tone. This change results in a rise in central blood volume, which serves to further elevate preload. Although these adaptations are designed to increase cardiac output, tachycardia and increased contractility may result and cause ischemia in patients with underlying CAD. The rise in preload may worsen pulmonary congestion. Sympathetic nervous system activation also increases peripheral vascular resistance. Because peripheral vascular resistance is also a major determinant of left ventricular afterload, excessive sympathetic activity may further depress cardiac function. Lower cardiac output causes a reduction in renal blood flow and glomerular filtration rate, which leads to sodium and fluid retention. The renin–angiotensin–aldosterone system is also activated, leading to further increases in peripheral vascular resistance and left ventricular afterload as well as sodium and fluid retention. Heart failure is also associated with increased circulating levels of arginine vasopressin, a vasoconstrictor and inhibitor of water excretion.118,119
Myocardial failure is characterized by two hemodynamic alterations. The first is a reduction in the ability to increase cardiac output in response to increased demands imposed by activity or exercise (cardiac reserve). The second major abnormality is the elevation of ventricular diastolic pressure. This is considered a result of compensatory processes.
Heart failure may be left sided or right sided, or involve both sides of the heart (biventricular failure). Patients with left heart failure have symptoms of low cardiac output and elevated pulmonary and venous pressures. In right-sided heart failure, signs of fluid retention predominate. Many patients exhibit signs and symptoms of both right- and left-sided failure. Left ventricular failure is the most common cause of right-sided failure. The pathophysiology and manifestations for left- and right-sided heart failure are listed in Table 6-2.
TABLE 6-2 Clinical Manifestations of Heart Failure
Left ventricular failure (congestive heart failure)—Intrinsic myocardial disease (eg, ASHD, cardiomyopathy), excessive workload on the heart (eg, hypertension, valvular disease, congenital defects), and cardiac arrhythmias or iatrogenic damage (eg, drug toxicity, irradiation) can result in the development of left ventricular failure. Systolic ventricular dysfunction results in a reduced stroke volume and increased end-diastolic volume with a resultant drop in the ejection fraction (stroke volume/end-diastolic volume). Increased left ventricular end-diastolic volume (LVEDV) decreases left ventricular compliance and causes the left atrial volume to expand, which results in left atrial dilatation. The elevated end-diastolic volume will produce higher end-diastolic pressure, which will be reflected back to the left atria, and pulmonary vessels and their pressures will be elevated. If pulmonary pressures rise high enough to cause transudation of intravascular fluid from the pulmonary capillaries (and if the rate of transudation exceeds the rate of lymphatic drainage), then dyspnea and possibly pulmonary edema will develop. In addition, the diastolic dysfunction or delayed ventricular relaxation resulting from left ventricular hypertrophy causes an even greater left ventricular end-diastolic pressure (LVEDP). Elevated LVEDP inhibits diastolic coronary blood flow to the endocardium and thus increases the risk of subendocardial ischemia. Finally, marked left ventricular dilatation can stretch the mitral valve annulus, resulting in functional mitral regurgitation.
Left heart failure may cause a reduction in physical exercise capacity. Systolic dysfunction may result in a marked decrease in stroke volume and ejection fraction, producing an elevated end-diastolic pressure, which causes blood to be reflected backward into the lung fields. The lungs become soggy and difficult to move, resulting in premature exercise-induced shortness of breath. Redistribution of blood flow due to reduced cardiac output during exercise will also cause a reduction of blood flow to the kidneys and skin initially and later to the brain, gut, and skeletal muscle. However, during exercise, peripheral arteriovenous oxygen extraction will increase, which may compensate for reduced blood flow.
Right ventricular failure—Elevated pulmonary artery pressures caused by left ventricular failure, mitral valve regurgitation, or chronic or acute pulmonary disease can result in an increased pressure load on the right ventricle, with resultant right ventricular dilatation. Right ventricular hypertrophy may or may not develop, depending on the acuteness and severity of the pressure load. If the pressure rises acutely (eg, massive pulmonary embolism or acute mitral regurgitation), there will be right ventricular dilatation and failure without right ventricular hypertrophy. If pulmonary hypertension is a chronic problem (eg, COPD), the right ventricle will undergo hypertrophy in response to chronically increased right ventricular afterload.
Prolonged pulmonary hypertension causes irreversible anatomic changes in the walls of the small pulmonary arteries so that the hypertension becomes chronic, with resultant right ventricular dilatation and right ventricular hypertrophy. Hypoxia, hypercapnia, and/or acidosis cause further pulmonary vasoconstriction, resulting in an even greater degree of pulmonary hypertension. The workload on the right ventricle is subsequently increased. Eventually the right ventricular end-diastolic pressure increases, which will be reflected back to the right atrium and the venous system with resultant jugular venous distension, liver engorgement, ascites, and peripheral edema. Also, right ventricular hypertrophy reduces right ventricular compliance that may interfere with right ventricular filling and further reduce cardiac output. If there is a reduction in blood flow to the pulmonary vascular bed, or an increase in cardiac output, heart rate, or blood volume, then pulmonary hypertension will worsen, producing increased signs and symptoms of right ventricular failure. The manifestations of left- and right-sided heart failure are summarized in Table 6-2.
When possible, the treatment of heart failure targets the underlying cause (eg, ischemia, hypertension, valvular disease, arrhythmias).120,121 Pharmacologic therapy includes a wide variety of agents that attempt to improve contractility, reduce preload, promote vasodilation, impede the stimulation of the sympathetic nervous system, or relieve hypoxia. See Chapter 8. Nonpharmacologic, surgical, and therapeutic interventions for the management of heart failure are presented in Chapter 18.
Sudden Death
Sudden death is characterized by a loss of consciousness and absence of an arterial pulse without prior circulatory collapse. It is the result of a fatal cardiac arrhythmia, which is typically due to CAD in the middle-aged and elderly adult. In as many as 25% of patients, sudden death may be the first clinical manifestation of coronary disease.122 Sudden death is a multi-factorial problem and is more likely to occur in patients with prior infarct and moderate to severe left ventricular dysfunction. Ischemic heart disease is most often the underlying cause, but cardiomyopathy, valvular heart disease, electro-physiologic abnormalities, and idiopathic ventricular fibrillation may also cause sudden death. Triggering factors include physical or mental stress, ionic or metabolic disorders, an acceleration of sinus rhythm, or the appearance of a supraventricular arrhythmia. Other factors are the arrhythmogenic effect of certain drugs and the interaction of electrical instability with ischemia and/or left ventricular dysfunction due to multiple causes.64 Approximately 20% of patients with acute MI die before reaching a hospital.3 Most of these deaths are caused by ventricular fibrillation. Transient ischemia is rarely the cause of sudden death. Most patients who die suddenly have a vulnerable myocardium. The risk of sudden death in postinfarction patients is strongly related to the presence of electrical instability and its interaction with left ventricular dysfunction and residual ischemia. Patients at high risk of sudden death are those with a history of malignant ventricular arrhythmias (sustained ventricular tachycardia or out-of-hospital arrest), heart disease with markers of a vulnerable myocardium for malignant ventricular arrhythmias (depressed contractility, ischemia, electrical instability), and severe bradyarrhythmias.64
VALVULAR HEART DISEASE
Cardiovascular problems secondary to impaired valves may be caused by congenital deformities, infection, or disease (eg, coronary thrombosis or rheumatic fever). Any of the valves within the heart may become stenotic, insufficient, or pro-lapsed (Fig. 6-8).
FIGURE 6-8 Valves of the heart. (A) The pulmonic, aortic, mitral, and tricuspid valves are shown here as they appear during diastole (ventricular filling) and systole (ventricular contraction). (B) Normal position of the valve leaflets, or cusps, when the valve is open and closed; fully open position of stenosed valve; closed regurgitant valve showing abnormal opening for blood and flow back into the heart chamber. (Reprinted from Goodman CC, Boissonnault WG. Pathology: Implications for the Physical Therapist. Philadelphia, PA: WB Saunders; Copyright 1998, with permission from Elsevier.)
Stenosis is a narrowing or constriction that prevents the valve from fully opening. Scars and abnormal deposits on the valve leaflets are often the cause. Valvular stenosis obstructs blood flow, and the chamber behind the narrowed valve must contract more forcefully in order to sustain cardiac output. Insufficiency refers to regurgitation or a leakage of blood back into the heart chamber through a valve whose leaflets fail to close completely. As a result of the leaky valve, the chamber behind (retrograde to) the valve initially dilates, and then ultimately hypertrophies, in response to the increased volume of work. Severe degrees of incompetence are possible in the absence of symptoms. Prolapse of the mitral valve occurs as enlarged leaflets bulge backward into the left atrium.
The mitral and tricuspid valves have larger cross-sectional areas than the semilunar valves and are subject to less mechanical force during valve opening and closure. Higher pressures generated during systole lead to greater valve dysfunction on the left side of the heart than on the right side, and often more than one valve is involved.10,123 Valvular dysfunction increases the work of the heart, requiring the chamber to pump harder to force blood through a stenosed valve or to maintain adequate flow if blood is seeping back. Patients with valvular disease are often asymptomatic for many years, or may present with easy fatigue. However, abnormal valve structure results in turbulent blood flow, which increases the hemodynamic stress on these structures and leads to progressive damage and dysfunction. Compensatory mechanisms including ventricular hypertrophy, chamber dilation, and peripheral processes can help maintain the overall performance of the heart for many years, even when there is malfunction of more than one valve. Eventually, these compensatory mechanisms fail or the stenosis or insufficiency progresses. Patients may become exhausted and symptoms of heart failure may develop (eg, breathlessness, dyspnea). The etiology,124 pathophysiology, and clinical manifestations125,126 of common valvular abnormalities are described in Table 6-3. Medical and therapeutic interventions including valvuloplasty and valve replacement are described elsewhere in this chapter and in related references.
TABLE 6-3 Etiology, Pathophysiology, and Clinical Manifestations of Valvular Heart Disease
CARDIOMYOPATHIES
The cardiomyopathies consist of a diverse group of diseases involving a primary disorder of the myocardial cells with resultant myocardial dysfunction. Current classification is based on the presentation, pathophysiology, and type of abnormal myocardial structure and function. Dilated cardiomyopathies, hypertrophic cardiomyopathies, and restrictive cardiomyopathies represent the three main categories.127 The pathophysiology and common signs and symptoms for each group of cardiomyopathies are found in Table 6-4. A brief description of each group follows.
TABLE 6-4 Classifications of the Cardiomyopathies
Primary Dilated Cardiomyopathy
Dilated cardiomyopathies are characterized by an increased cardiac mass, dilatation of all four cardiac chambers with little or no wall thickening and systolic dysfunction.128 Patients with dilated cardiomyopathies often present with dyspnea as well as with the other signs and symptoms of heart failure. In some patients, the presenting event is a symptomatic ventricular arrhythmia (ie, palpitations). Dilated cardiomyopathy may be idiopathic or may result from infectious and noninfectious inflammatory processes; toxins such as alcohol and drugs; pregnancy; a variety of metabolic disorders including endocrine, nutritional, altered metabolism, and myocardial ischemia; or hereditary diseases such as glycogen storage diseases and muscular dystrophies.129 Chronic alcohol abuse and myocarditis are also frequent causes of dilated cardiomyopathy.
Dilated cardiomyopathy results in a decreased stroke volume, which is compensated at rest by an increase in heart rate. These patients have an impaired ability to increase cardiac output during exercise, which results in an increase in LVEDP and reduced exercise tolerance. The patient’s cardiac reserve depends on preservation of right ventricular function and systemic vasodilator reserve during exercise. Eventually, the patient develops left ventricular failure and right ventricular failure. Oxygen desaturation occurs, which results in an increased arteriovenous oxygen difference. Increased left ventricular filling pressure increases the risk of subendocardial ischemia. Without clinical heart failure, the prognosis of dilated cardiomyopathy is good but usually worsens. The natural history resembles that of other causes of heart failure once heart failure becomes manifest.
Hypertrophic Cardiomyopathy
Hypertrophic cardiomyopathy is characterized by a considerable increase in cardiac mass (hypertrophy), which may be symmetrical or asymmetrical, without cavity dilatation, accompanied by normal or increased systolic function.130 In addition, there may be a left ventricular outflow obstruction, known as hypertrophic obstructive cardiomyopathy and formerly referred to as idiopathic hypertrophic subaortic stenosis (IHSS). In IHSS, impaired systolic anterior motion of the mitral valve apparatus can bring the leaflet into contact with the interventricular septum and cause outflow tract obstruction. In hypertrophic cardiomyopathy, left ventricular hyper-trophy results in diastolic dysfunction due to abnormal left ventricular relaxation and distensibility, which leads to decreased left ventricular compliance and increased left ventricular filling pressures. Decreased left ventricular compliance causes an increased dependence on left ventricular filling from atrial systole. Hyperdynamic left ventricular function produces rapid ejection. Myocardial ischemia is common and may result from impaired vasodilator reserve, increased oxygen demands, especially if hypertrophic obstructive cardiomyopathy develops. Increased filling pressures cause subendocardial ischemia.
Restrictive Cardiomyopathy
Restrictive cardiomyopathy is characterized by a restriction of ventricular filling caused by endocardial or myocardial disease or both. The ventricular walls lose compliance and become excessively rigid. In the presence of endocardial or myocardial disease, decreased left ventricular compliance causes a reduction in ventricular filling. This creates a back pressure that leads to atrial enlargement and increased atrial pressures, which are reflected back to filling vessels. Distortion of the ventricular cavity and involvement of the papillary muscles and chordae tendineae can cause mitral and/or tricuspid regurgitation.131 Partial obliteration of the fibrous tissue and thrombus results in reduced stroke volume and often compensatory tachycardia. Eventually systolic function becomes impaired. If there is left ventricular involvement, pulmonary hypertension is common.
OTHER CARDIAC DISORDERS
Acute Myocarditis
Inflammation of the myocardial wall most frequently results from streptococcal infection leading to rheumatic fever or viral infections, such as coxsackie B virus, but can also be caused by other bacterial, rickettsial, fungal, or parasitic infections as well as by immunologic reactions, pharmacologic agents, toxins, and some systemic diseases. Myocarditis can be an acute or chronic process, may involve a limited area of myocardium, or may be diffuse. Many patients have nonspecific cardiovascular complaints, including fatigue, dyspnea, palpitations, and precordial discomfort.132
Infectious myocarditis often follows an upper respiratory infection. The patient may present with chest pain or signs of heart failure. Myocarditis is often accompanied by pericarditis.
Pericarditis
Acute inflammation of the pericardium may be either infectious in origin or caused by a wide variety of systemic diseases. Viral infections represent the most common cause of acute pericarditis. Other causes include bacterial infections, uremia, acute MI, and pericardiotomy associated with cardiac surgery, tuberculosis, malignancy, and trauma. Systemic diseases, which may lead to pericarditis, include autoimmune disorders (ie, connective tissue diseases), other inflammatory disorders (eg, sarcoidosis, amyloidosis, inflammatory bowel disease), drug toxicity, chest irradiation, and hypothyroidism. Pericarditis presents with a wide range of signs and symptoms as it progresses from a simple inflammatory response with no cardiovascular compromise to pulmonary effusions and cardiac tamponade, which may limit ventricular filling, stroke volume, and cardiac output.133
Initially, patients with pericarditis may present without signs or symptoms. When present, symptoms of acute pericarditis include chest pain, dyspnea, a higher resting heart rate, and an elevated temperature. Over time, the chest pain associated with pericarditis may mimic that of an MI. Position, breathing, and movement rarely affect the pain associated with an MI. The pain associated with pericarditis may be relieved with leaning forward, kneeling on all fours, or sitting upright.
Pericardial Effusion
Pericardial effusion may develop during pericarditis. The speed with which the fluid accumulates within the pericardial sac determines the physiological significance of the effusion. Because the pericardium stretches, a large effusion (<1000 mL) that develops slowly may produce no hemodynamic effects and the patient may remain asymptomatic. However, smaller effusions that appear rapidly can cause tamponade. Cardiac tamponade is characterized by elevated intrapericardial pressure (<15 mm Hg), which restricts venous return and ventricular filling.134,135 As a result, stroke volume and pulse pressure fall and the heart rate and venous pressure rise. If left untreated, tamponade may result in shock and death.
Pericardial effusions may be painful, most commonly as the result of an acute inflammatory process, or painless as is often the case with uremic or neoplastic effusion. Dyspnea and cough are common. A pericardial friction rub may be present with large effusions. Tachycardia, tachypnea, and a narrow pulse pressure with a relatively preserved systolic blood pressure are characteristic of cardiac tamponade. Pulsus paradoxus (more than 10 mm Hg decline in systolic pressure during inspiration) is the classic finding. Central venous pressure is elevated in patients with pericardial effusion. Edema and ascites may also be present. When tamponade is present, urgent pericardiocentesis is required. Although significant improvements in cardiac hemodynamics may be noted when a small amount of fluid is removed from the pericardium, continued drainage with a catheter is often required.
Rheumatic Heart Disease
Rheumatic fever is a systemic immune process that may result subsequent to a hemolytic streptococcal infection of the pharynx, for example, “strep throat,” and leads to infection of the endocardium, usually the mitral valve leaflets. Acute rheumatic fever most commonly affects children 5 to 15 years of age, whereas chronic rheumatic heart disease may develop in older patients, especially those with more severe carditis. The mitral valve is attacked in 75% to 80% of the cases, the aortic valve is affected in 30% of the cases, and the tricuspid and pulmonary valves are affected in less than 5% of the cases.3,136 Often more than one valve is affected. There appear to be two different clinical groups. One group shows evidence of significant valvular disease with a higher percentage of death within the first 5 years after onset. The other group has relatively mild valve disease that slowly develops progressive dysfunction due to gradual wear and tear on the valve caused by turbulent flow through its defective structures. The pathophysiology and clinical manifestations of rheumatic heart disease are incorporated into Table 6-3.
Infective Endocarditis
Bacterial or fungal infection of the heart valves causes vegetations to form along the cusps, which may interfere with proper opening and closing. Any abnormality of either a heart valve or the blood flow through a heart valve increases the risk of infective endocarditis. The degree of risk varies substantially according to the specific abnormality. The development of infective endocarditis is associated with situations where infective organisms may be introduced directly into the bloodstream (eg, dental, urinary, or intestinal procedures; intravenous drug abuse; central venous catheter placement). The clinical manifestations of infective endocarditis are highly variable and depend on the involvement of other organ systems because of embolization of valvular vegetation fragments, bacterial seeding of distant foci, or the development of immune complex–associated disease. Generally, there are symptoms suggestive of a flulike illness and possibly the clinical manifestations of specific valvular lesions and/or congestive heart failure.
Intracardiac infection can result in perforation of valve leaflets; rupture of the chordae tendineae, intraventricular septum, or papillary muscle; valve ring abscesses; occlusion of a valve orifice; coronary emboli; burrowing abscesses of the myocardium; and purulent pericardial effusions. Treatment is directed toward the specific infective organism with high serum levels of an effective antibiotic. Surgical intervention (eg, valve replacement or resection) is indicated if medical treatment is unsuccessful or for an unusual pathogen, myocar-dial abscess formation, refractory heart failure, serious embolic complications, or refractory prosthetic valve disease. Antibiotic prophylaxis is indicated for all patients with congenital or acquired valvular dysfunction, prosthetic heart valves, obstructive hypertrophic cardiomyopathy, a number of other congenital cardiac defects or shunt repairs, and for patients with previous endocarditis. Antibiotics are recommended before all dental, respiratory, and surgical procedures.
VASCULAR DISEASE
Atherosclerosis is a systemic disease that affects all major arteries. It represents the most common form of arterial wall disease. Clinical manifestations result most often from the narrowing and occlusion of a limited number of arteries, usually at the bifurcation of larger arteries. Additionally, with a reduction in elastin and collagen, the arterial wall weakens and may result in aneurysmal dilation. It is beyond the scope of this chapter to present every form of vascular disease. Common forms of arterial vascular disease include hypertension, aneurysms, and peripheral arterial occlusive disease.
This section begins with a description of hypertension. Although a disorder of vascular system, hypertension is a risk factor of coronary heart disease. If untreated, hypertension may result in many of the common cardiac disorders presented earlier in this chapter. Hypertension is also a risk factor for peripheral arterial occlusive disease, which is briefly discussed following a review of the common diseases found in the aorta and in other large vessels. For a description of the less common forms of vascular disease (ie, vasculitis, thromboangiitis obliterans, syphilitic aortitis, fibrodysplasia of visceral arteries, and radiation arteritis) the reader may refer to other comprehensive references.3,64 This section ends with a description of metabolic syndrome, an increasing problem for adults, children, and adolescents.
Hypertension
Definition and Classification
Systemic hypertension is defined as a persistent elevation in systolic blood pressure above 140 mm Hg and/or diastolic pressure above 90 mm Hg measured on at least two separate occasions at least 2 weeks apart. An estimated 50 million Americans have elevated arterial blood pressure; of these, 68% are aware of their diagnosis, 53% are receiving treatment, and 27% are under control by the 140/90 threshold.137 Table 6-5 provides the current (2003) classification for blood pressure measurements. Morbidity and mortality increase as both systolic and diastolic blood pressure rise. Therefore, both systolic hypertension and diastolic hypertension are clinically significant. When systolic and diastolic pressures fall into different categories, the higher category should be selected to classify the individual’s blood pressure. Isolated systolic hypertension refers to the case where systolic blood pressure is 140 mm Hg or more and diastolic blood pressure is less than 90 mm Hg (see Table 6-5).
TABLE 6-5 Classification of Blood Pressure
When hypertension is the result of an unidentifiable cause, it is called primary or essential hypertension. In approximately 95% of the cases, no cause can be established.3 Essential hypertension123 is relatively uncommon before the age of 20 and usually presents between the ages of 25 and 55. When hypertension results from an identifiable cause such as renal insufficiency, renal artery stenosis, or coarctation of the aorta, it is referred to as secondary hypertension.
The fact that hypertension and its sequela appear to “run in families” was observed in sibling pair studies, twin studies, and family studies and has led to some inaccurate assumptions that hypertension was inherited as a simple, autosomal dominant trait. In the 1950s, a research team showed that primary hypertension was a complex genetic condition where 5 to 20 or more genes were involved. Further research has demonstrated that some unusual forms of inherited hypertension are indeed inherited as a simple monogenic trait.138
Blood pressure is a function of two main determinants: (1) the amount of blood flow (cardiac output) and (2) the peripheral vascular resistance. The pathogenesis of primary hypertension involves a series of feedback loops and interrelated regulatory systems. Disturbances within any of these systems can increase blood pressure. In the past 10 years, the vascular endothelium has been identified as a major blood pressure regulatory organ. Endothelial cells produce potent vasodilator substances. The most important may be the endothelial-derived relaxing factor nitric oxide. Other substances secreted by the endothelium are the vasodilator prostaglandins. The endothelium also produces potent vasoconstrictors, such as endothelin, which is the most potent constrictor known and may contribute to increased peripheral vascular resistance in advanced hypertension. Through these substances, the endothelium responds to sheer stress and a variety of circulating factors; modulates underlying vascular smooth muscle cell tone; and facilitates growth, differentiation, and angiogenesis.
Changes in blood pressure are sensed by baroreceptors located primarily in the aortic arch and the carotid sinus. These receptors relay information to the central nervous system via the vagus and glossopharyngeal nerves. When blood pressure is low, sympathetic output produces vasoconstriction and a reflex increase in heart rate. When blood pressure is high, sympathetic tone should be reduced and the heart rate should reflexively decrease through parasympathetically mediated mechanisms. However, in patients with primary or secondary hypertension, these baroreceptor mechanisms are altered or reset and their sensitivity to a given pressure level is decreased.
Hypertension is an important risk factor for heart disease. Over time, elevated blood pressure causes an increased pressure load on the left ventricle, which responds by developing compensatory left ventricular hypertrophy in order to maintain forward flow. Over time, however, diastolic dysfunction develops while normal left ventricular systolic function is maintained. The left ventricular hypertrophy and the resultant prolonged relaxation time produce a stiffer and less compliant left ventricle, causing a higher LVEDP at any volume. This in turn increases the load on the left atrium, which slows ventricular filling rate and reduces the passive filling volume. The stiffer left ventricle becomes more dependent on active atrial contraction for adequate filling. If there is inadequate filling volume, stroke volume will decrease and symptoms of inadequate cardiac output and pulmonary congestion may develop. Higher filling pressures exert pressure on the left ventricular wall. This inhibits coronary blood flow and increases the risk of subendocardial ischemia, as the demand for oxygen exceeds the supply.
As hypertension becomes more severe and more prolonged, systolic dysfunction develops. With the progression of left ventricular hypertrophy, the metabolic demand of the hypertrophied left ventricle will exceed the supply of blood to the heart muscle, causing myocardial ischemia. As a result, stroke volume will fall, causing a further elevation in left ventricular end-diastolic volume and LVEDP. The rise in enddiastolic pressure will be reflected back to the left atrium and pulmonary vessels. If the pulmonary pressures rise high enough to cause transudation of intravascular fluid from the capillaries, pulmonary edema will result. This systolic dysfunction will initially manifest itself as reduced left ventricular functional reserve during exercise. Later, the signs and symptoms of systolic dysfunction may develop even at rest.
The longer the hypertension is present, the greater the tendency of resistance vessels to adapt to the elevated blood pressure by way of media hypertrophy and increased wall-to-lumen ratio (vessel remodeling), which makes the vessels even more susceptible to vasoconstrictors. Thus, the original mechanism (ie, primary or secondary) eventually becomes less relevant, because the altered vascular structures themselves serve to perpetuate the condition. Renal blood flow declines and renal vascular resistance rises. Consequently, the sodium-excreting capacity of the kidneys further declines, making the hypertension more volume dependent over time. Compliance of large vessels, including the aorta, declines, produces a stiffer arterial wall, and impairs the ability of the arterial wall to contribute to pulsatile blood flow (Windkessel effect). This creates more work for the heart and leads to further increases in systolic blood pressure.138
Patient Presentation
The patient with hypertension, known as the “silent killer,” is generally asymptomatic. Untreated or poorly managed hyper-tension results in multiple complications including cerebral vascular accidents, congestive heart failure, ASHD, renal failure or nephrosclerosis, simple or dissecting aortic aneurysms, peripheral vascular disease, and retinopathy. Pharmacologic therapy is addressed in Chapter 8 and incorporates many groups of cardiovascular drugs including β-blockers, diuretics, α-adrenergic blockers, central acting α-adrenergic agonists, angiotensin-converting enzyme (ACE) inhibitors, and calcium channel blockers. Nonpharmacologic treatment includes weight reduction, alcohol moderation, sodium restriction, relaxation training, and exercise training. Although nonpharmacologic interventions may not eliminate the need for antihypertensive medications, they often permit lower dosages with fewer side effects.
Aneurysms
An aneurysm is a localized dilatation of the wall of a blood vessel, usually caused by atherosclerosis and hypertension, or less frequently by trauma, infection, or a congenital weakness in the vessel wall. Aneurysms are common in the aorta but can occur in any peripheral vessel.5,10 They are common in the popliteal arteries of the elderly. The sign of an aneurysm is a pulsating swelling that produces a blowing murmur on auscultation. An aneurysm may rupture, causing hemorrhage, or thrombi may form in the dilated pouch and give rise to emboli that may obstruct smaller vessels.
Aortic Aneurysm
More than 90% of abdominal atherosclerotic aneurysms originate below the renal arteries and many are located at the bifurcation of the aorta.3 The infrarenal aorta is normally 2 cm in diameter; an aneurysm at this site is diagnosed when the diameter exceeds 4 cm. Aneurysms are typically asymptomatic and usually are discovered on routine physical examination in men over 50 years of age. Severe back or abdominal pain indicates rupture. Aortic aneurysms are not necessarily associated with atherosclerotic occlusive disease.
Patients may be asymptomatic or symptomatic. In those who are symptomatic, chronic midabdominal and/or low back pain may be present. Symptoms often occur as a result of an inflammatory process. Peripheral emboli may occur, and symptomatic arterial insufficiency may result. A ruptured aortic aneurysm typically results in death before the patient can be hospitalized or before the patient reaches the operating room. Patients with bleeding confined to the retroperitoneal area may have severe pain in the abdomen, flank, or back and a pulsating abdominal mass. Abdominal ultrasonography is the preferred diagnostic study. Surgical excision and grafting is the treatment of choice for most aneurysms of the infrarenal abdominal aorta. The complication rate following repair is 5% to 10% and includes MI, bleeding, respiratory insufficiency, limb ischemia, ischemic colitis, renal insufficiency, and stroke.139,140
Aneurysms of the Thoracic Aorta
Thoracic aneurysms are most commonly due to atherosclerosis. Other causes of thoracic aneurysms include Marfan syndrome, cystic medial necrosis, and vasculitis. Traumatic aneurysms may result from rapid deceleration accidents and may occur at the ligamentum arteriosis just beyond the left subclavian artery. Most thoracic aneurysms are asymptomatic. Manifestations depend on the size and position of the aneurysm and its rate of growth. When symptomatic, substernal, back or neck pain may occur. Pressure on the trachea, esophagus, left recurrent laryngeal nerve, and the superior vena cava may result in dyspnea, stridor, dysphagia, hoarseness, and edema in the cervical and upper extremities and jugular venous distention.
Thoracic aneurysms are most commonly detected by imaging techniques (ie, CT scan and MRI). Aortography may be used to confirm the diagnosis and delineate the location and extent of the aneurysm. In total, less than 10% of aortic aneurysms are thoracic.3
Aortic Dissection
Aortic dissection is the most common aortic catastrophe requiring admission to the hospital. It originates at the site of an intimal tear and then propagates distally. More than 95% of the intimal tears occur either in the ascending aorta just distal to the aortic valve or just distal to the left subclavian artery.141 The initial intimal tear probably results from the constant torque applied to the ascending and proximal descending aorta occurring at these two points associated with the pulsatile blood flow from the heart, usually under hypertensive conditions.142 Dissection occurs on rare occasions in an aorta without an apparent intimal tear. Invariably, these aortas show histological abnormalities of the media. Proximal dissections occur more often in aortas143 with abnormalities of the smooth muscle, elastic tissue, or collagen. Distal dissections occur more commonly in patients with hypertension. When undiagnosed and untreated, aortic dissection is a lethal disease. Death is usually due to rupture of the aorta into the pericardial sac or pleural space or to acute aortic regurgitation with left ventricular failure.5
Aortic dissection is most commonly confused with MI and other causes of chest pain. It may simulate numerous neurologic lesions and various abdominal conditions related to renal–visceral ischemia. Aggressive medical measures are taken to lower hypertension when aortic dissection is present using a fast-acting antihypertensive agent with continuous blood pressure monitoring. Emergent surgical repair is necessary for patients with tears in the ascending aorta just distal to the aortic valve. Tears distal to the left subclavian artery may be managed successfully with aggressive drug therapy unless the patient has severe pain, aortic rupture, ischemia, or a progression of the dissection. Without treatment, the mortality rate of aortic dissection at 3 months exceeds 90%.3
Popliteal and Femoral Aneurysms (Peripheral Artery Aneurysms)
Popliteal aneurysms account for approximately 85% of all peripheral artery aneurysms.3 Peripheral aneurysms occur almost exclusively in men, and about half are symptomatic at the time of diagnosis. Symptoms result from thrombosis, peripheral embolization, or compression of adjacent structures with resultant venous thrombosis or neuropathy. Ultra-sound is used to diagnose and measure the diameter of the aneurysm. Arteriography is needed to define the anatomy of the outflow arteries in preparation for the operative repair. A reversed saphenous vein bypass graft with proximal and distal ligation is generally used.
A femoral aneurysm manifests itself as a pulsatile mass on one or both sides of the thigh. Potential complications are the same as described for popliteal aneurysms. Complications occur less frequently, and asymptomatic aneurysms are typically not repaired. Pseduoaneurysms often develop at distal anastomotic sites from previous aortic surgery and may require repair.144
Peripheral Arterial Occlusive Disease
Occlusive disease of the aorta and the iliac arteries begins most frequently just proximal to or just distal to the bifurcation of the aorta. Atherosclerotic changes occur in the media and intima, often with perivascular inflammation and calcified plaques in the media. Progression involves the complete occlusion of one or both common iliac arteries and then the abdominal aorta up to the segment just below the renal vessels. Although a generalized disease, occlusion tends to be segmental in distribution, and when the involvement is in the aorto–iliac vessels there may be minimal atherosclerosis in the more distal external iliac and femoral arteries. Patients with localized occlusion beyond the aortic bifurcation are good candidates for angioplasty, atherectomy, and stenting.
The classic symptom of peripheral arterial occlusive disease is intermittent claudication. This condition is initially manifested as cramp-like pains in the calves during walking and is relieved by rest.145,146 Patients with multisegmental disease usually have more symptoms and are at greater risk of losing a limb. Abrupt worsening of claudication may be associated with plaque rupture (crescendo claudication) as with myocardial ischemia.
Clinical Findings
As indicated previously, patients with occlusive arterial disease present with pain or weakness in the lower extremities, which is brought on by walking, and relieved after a few minutes of rest. It is almost always present in the calf muscles and often in the thighs and buttocks as well. Resting pain is infrequent but a serious symptom when present. Resting pain usually presents as a nocturnal pain located in the region of the heads of the metatarsal bones of the feet. It is relieved by placing the legs in the dependent position such as hanging them over the side of the bed.
TABLE 6-6 Diagnostic Criteria for Metabolic
Metabolic Syndrome
Definition and Categorization
Metabolic syndrome has been loosely described as a constellation of metabolic risk factors that is strongly associated with type 2 diabetes and the promotion of atherosclerotic cardiovascular disease.147 In 2001, the National Cholesterol Education Program (NCEP)—Adult Treatment Panel III (ATP III) proposed that metabolic syndrome be based on several common clinical measures including waist circumference, triglycerides, HDL-C, blood pressure, and fasting glucose level.147 Abnormalities in any three of the above five measures result in a diagnosis of metabolic syndrome.147 The presence of an abnormality in the above five measures is defined in Table 6-6 by using the categorical cut points for each of the five areas.
The threshold cut points listed in Table 6-6 identify levels that have been observed to confer greater risk of type 2 diabetes and atherosclerotic cardiovascular disease.147 The individual and interrelated methods by which each of the five factors contributes to the development of these diseases is shown in Fig. 6-9.148,149 As shown in Fig. 6-9, the major components of metabolic syndrome and subsequent effects on the development of diabetes and atherosclerotic cardiovascular disease include the presence of vascular abnormalities, oxidative stress, visceral fat, inflammation, adipocytokines, and cortisol.147,148 The separate and interrelated characteristics of these factors promote the development of diabetes and atherosclerotic cardiovascular disease, which are both interrelated (and overlapping as shown in Fig. 6-9). In fact, prospective population studies reveal that presence of metabolic syndrome is associated with a twofold increase in atherosclerotic cardiovascular events and a fivefold increase in the risk of developing diabetes in persons without established type 2 diabetes.147,148
FIGURE 6-9 Schematic of the components of metabolic syndrome. (Reprinted with permission from Steinberger J, Daniels SR, Eckel RH, et al. Progress and challenges in metabolic syndrome in children and adolescents: a scientific statement from the American Heart Association Atherosclerosis, Hypertension, and Obesity in the Young Committee of the Council on Cardiovascular Disease in the Young; Council on Cardiovascular Nursing; and Council on Nutrition, Physical Activity, and Metabolism. Circulation. 2009;119:628-647.)
Also, as shown in Fig. 6-9, ethnic and genetic factors are also related to metabolic syndrome, which highlights the importance of examining the presence of metabolic syndrome in children and adolescents.147,148 White, black, and Hispanic individuals (both adults and children), as opposed to Asian individuals, have been observed to have greater propensity for metabolic syndrome, but with different predisposing factors. For example, black children and adults have lower total cholesterol and triglyceride levels and higher HDL-C levels than white children, but black and Hispanic children are more insulin resistant than white children.147,148 Although ethnic differences are poorly understood, they are important to consider in the examination and management of persons with metabolic syndrome.147,148
The clinical management of metabolic syndrome has centered on reducing the risk factors identified in Table 6-6 and in Fig. 6-9.147,148 Thus, the management of metabolic syndrome involves both lifestyle treatment and appropriate pharmacologic therapy for metabolic risk factors. Lifestyle recommendations include weight maintenance/reduction, increased physical activity, and a healthy diet (reduction of saturated fat, trans fat, and cholesterol). Optimal pharmacologic therapy for metabolic syndrome risk factors may include lipid-lowering drugs, antihypertensive drugs, aspirin therapy, and drug therapy to control elevated plasma glucose for individuals with diabetes. Currently, drug therapy to reduce plasma glucose or insulin resistance is not recommended for individuals with impaired fasting glucose.147,148
SUMMARY
This chapter reviewed the pathophysiology of the common forms of cardiovascular disease including CAD, heart failure, valve disease, and cardiomyopathies. Special emphasis was placed on the pathogenesis of atherosclerosis, the most common cause of CAD. The discussion of peripheral vascular disorders focused on hypertension, aneurysms, and arterial occlusive disease. Finally, the chapter ended with a description of metabolic syndrome. The interested reader may seek additional information in other excellent, comprehensive cardiology references.5,10
Heads Up!
This chapter includes a CD-ROM activity.
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