Atrial Fibrillation

Atrial fibrillation is a common impulse generation and conduction abnormality in which disorganized and irregular electrical activation of the atrial myocardium results in ineffective atrial systole. In this setting, the heart rate is typically irregular because activation of the AV node occurs by random synergistic confluence of atrial signals. Tachycardia invariably occurs if AV nodal function is normal. For this reason, negatively chronotropic medications, such as β receptor–blocking agents or calcium channel–blocking agents, are typically given to patients with atrial fibrillation to depress AV nodal conduction. A ventricular rate of less than 100 beats/min in patients with atrial fibrillation in the absence of negatively chronotropic medications implies CS disease. The irregularly irregular ventricular rate in atrial fibrillation is a common problem for gating cardiac CT and MRI studies.

Left Bundle Branch Block

Left bundle branch block, another common abnormality of electrical impulse generation and conduction that is relevant to cardiac imaging, can be idiopathic, but it often occurs in the setting of myocardial disease. In this condition, the left bundle branch conducts transmitted impulses with delay or not at all. Instead, ventricular depolarization begins via the right bundle branch only, and left ventricular myocardium depolarizes without the help of the CS, causing the left ventricle to contract later than the right ventricle. As a result, the interventricular septum moves and contracts in atypical, “paradoxical” fashion. This common abnormality of ventricular septal contractility must (and can) be differentiated from other causes of abnormal septal motion.

Vascular Biology of Atherosclerosis

The normal blood vessel wall consists of three distinct layers—intima, tunica media, and tunica adventitia. The innermost layer, the intima, is the site where atherosclerosis first manifests (Fig. 4-5). The intima consists mainly of endothelial cells, whereas the media contains smooth muscle cells, macrophages, mast cells, and extracellular matrix (primarily collagen and proteoglycans). The adventitia is composed primarily of extracellular connective tissue, but it also contains the vasa vasorum (vascular supply to the blood vessel wall itself) and nerve fibers involved in vasoregulation.

FIGURE 4-5 Atherosclerosis. A, Normal vessel. B, Atherosclerotic plaque, with lipid-laden macrophages (white arrow), smooth muscle proliferation (black arrowhead), and extracellular matrix (asterisk). C, Marked luminal narrowing from plaque growth. Variable amounts of collagen (black asterisk) and intraplaque hemorrhage (white asterisk) are present within the plaque. D, Plaque rupture (arrowheads) resulting in intravascular thrombosis (asterisk).

(Images courtesy of Dr. Amir Lerman, Mayo Clinic, Rochester, MN.)

In areas of low shear stress (e.g., at vessel bifurcations or near the ostia of side branches), the endothelial layer may thicken (often eccentrically). These areas of thickened endothelium often show early findings of atherosclerosis.⁴ The earliest atherosclerotic manifestation is the “fatty streak,” characterized by intimal deposition of lipid-laden macrophages and T lymphocytes.⁵ Fatty streaks occur in areas of intimal thickening because of multifactorial endothelial dysfunction and denudation, allowing intraintimal deposition of serum lipoproteins. Toxic damage from tobacco smoking and oxidative damage from very-low-density lipoproteins can be contributory factors. This initial endothelial injury incites an inflammatory response mediated by vascular cell adhesion molecules, selectins, and cytokines. The inflammatory response leads to ingestion of the lipoproteins by monocytes and macrophages, producing characteristic lipid-laden macrophages (“foam cells”) on histology.⁶

Over time, demise and disintegration of lipid-laden macrophages and further deposition of serum lipoproteins lead to accumulation of extracellular lipid in the growing “plaque.” Connective tissue, with varying portions of smooth muscle, collagen, and other extracellular proteins, also proliferates. As the plaque grows in size, the lumen of the vessel can become narrowed, although adaptive, positive remodeling of the vessel lumen by outward expansion of the vessel wall with an increase of vessel cross-section area (see Fig. 4-5) may initially prevent stenosis.⁷ Paradoxically, positive remodeling may occur in an effort to resist endothelial shear stress, but the lower shear stress created by positive remodeling may lead to further lipid accumulation.⁴ Vascular remodeling can be examined well with cross-sectional imaging modalities that show lumen and vessel wall (Fig. 4-6). On invasive, selective coronary angiography, the vessel wall is not imaged, and plaque “hidden” by positive remodeling may not be recognized.

FIGURE 4-6 Correlation of coronary CT angiography (upper left), selective coronary angiography (upper right), and intravascular ultrasound (lower panel). Caliber of the proximal left anterior descending artery on selective coronary angiography is normal at two locations (A, B) where CT and intravascular ultrasound show presence of noncalcified atherosclerotic plaque.

(From Schoenhagen P, Tuzcu EM, Stillman AE, et al. Non-invasive assessment of plaque morphology and remodeling in mildly stenotic coronary segments: comparison of 16-slice computed tomography and intravascular ultrasound. Coron Artery Dis 2003; 14:459-462.)

Calcification frequently occurs in atherosclerotic plaque, and can occur in lipid-rich and predominantly fibrotic plaques. The quantity of coronary calcification is nonlinearly proportional to overall atherosclerotic burden. Coronary calcification represents approximately 20% of plaque volume.⁸ The location of calcification does not predict the location of high-grade stenosis or plaque prone to rupture. The relationship between coronary calcification and overall atherosclerotic burden provides the rationale for the practice of coronary artery calcium screening for risk stratification.⁹

The plaque core eventually becomes hypoxic as it outstrips the nutrient supply by the vascular network within the blood vessel wall, the vasa vasorum. Subsequent hypoxia-induced cellular death within the plaque core and recruitment of fragile, immature neovasculature predisposes to intraplaque hemorrhage. Necrosis of the plaque core and intraplaque hemorrhage are the key contributors to plaque growth at later stages and eventually to rupture of the “unstable” plaque. When the plaque ruptures, the exposed lipid-rich core triggers platelet aggregation and intravascular thrombosis.¹⁰

Plaque Rupture and Acute Coronary Syndromes

Counterintuitively, plaque rupture leading to acute cardiac events is more likely to occur in coronary segments with low-grade stenoses than in segments with high-grade coronary stenoses. An analysis of factors associated with progression of CAD in 2938 coronary segments in 298 patients who had not undergone coronary bypass from the Coronary Artery Surgery Study (CASS) showed that although individual segments with high-grade stenoses were more likely to become occluded than individual segments with low-grade stenoses, occlusion was overall much more likely to occur in segments with low-grade stenoses because low-grade stenoses are much more common.¹¹

The acute interruption of coronary blood flow, typically by plaque rupture, without adequate compensatory mechanisms to maintain oxygen supply to the myocardium results in myocardial infarction, defined as myocyte necrosis. The diagnostic criteria for myocardial infarction include prolonged severe chest discomfort of acute onset; elevation of the ST segment on the ECG; and elevated blood concentrations of enzymes specific for myocyte demise, such as the MB-fraction of creatine kinase or the troponins.¹² Infarction occurs within minutes to hours from the inciting event. Because myocardial oxygen is supplied from the epicardial vessels toward the subendocardial perforators, the subendocardial myocardium is the layer affected first as the end-vessel territory. With prolonged severe ischemia, myocyte necrosis spreads transmurally from the endocardium toward the mesocardial and epicardial layers. The treatment of choice is revascularization by percutaneous coronary intervention within 4 to 6 hours of symptom onset if available. Intravenous administration of thrombolytic agents, such as recombinant tissue plasminogen activator (rTPA), is an acceptable alternative.¹³

Chronic Coronary Artery Disease

In the setting of chronic CAD with progressive narrowing of the coronary lumen but without sudden complete occlusion, the typical clinical feature is chronic stable angina. “Typical” angina is defined as retrosternal discomfort that is provoked by exertion and relieved by rest or administration of nitroglycerin. Episodes of typical angina last less than 30 minutes. It can be difficult to determine with anatomic imaging modalities such as coronary CT or MRI whether a stenosis caused by plaque is “significant”—severe enough to limit oxygen delivery and be the cause of angina or myocardial dysfunction (see later section on myocardial viability) or both. At rest, the myocardial oxygen extraction rate is approximately 60%.¹⁴ An increase in oxygen consumption, such as occurs with physical activity, requires an increase in oxygen delivery, which is accomplished by vasodilation under normal circumstances. The ability of the coronary vasculature to increase coronary blood flow, expressed as the ratio of maximal coronary flow to resting flow, is referred to as coronary flow reserve.¹⁵ In the presence of coronary stenosis, vasodilation to improve blood flow distal to the narrowed segment occurs at rest. This vasodilation decreases coronary flow reserve because the compensatory mechanism is already employed at baseline. The ability to elicit and document abnormal coronary flow reserve is the basic principle underlying stress testing as a functional means for assessing CAD.¹⁶

Although numerous studies have shown a correlation between percent stenosis and decrease in coronary flow reserve, the correlation is nonlinear. Functional severity of a given percent stenosis may vary among patients, depending on many factors, including coronary perfusion pressure, narrowest lumen diameter, and number and length of stenoses. Although it is generally accepted that stenoses greater than 70% reduce coronary flow reserve to a clinically relevant degree, the clinical “significance” of stenoses of intermediate severity (50% to 70%) can be difficult to ascertain. Qualitative or quantitative assessment of myocardial perfusion during stress and at rest using nuclear medicine techniques or MRI can provide information that is complementary to arterial illustration using conventional x-ray or CT angiography, and has important implications for patient management.^17,18

When chronic ischemia occurs in the presence of a coronary stenosis, numerous compensatory mechanisms are activated in addition to chronic vasodilation. Among these is the development of collaterals from other coronary artery perfusion territories. The precise mechanism of collateral development is unclear, but probably involves recruitment and enlargement of existing coronary anastomoses and generation of new connections by neovascularization.

Myocardial infarction in the setting of chronic CAD with preexisting high-grade coronary stenoses can occur (1) as a consequence of plaque rupture, or (2) in situations where myocardial oxygen demand exceeds the oxygen supply that is limited by coronary stenosis, such as during unusual physical exertion or other physiologic stress, including high-risk surgery or severe systemic illness. The latter scenario often results in so-called non–ST segment elevation myocardial infarction.^19,20

Ischemic Cardiomyopathy

The most prevalent and important form of secondary cardiomyopathy is ischemic in origin. The key imaging feature distinguishing primary from ischemic cardiomyopathy is the presence of global hypokinesis in the former and of regional wall motion abnormalities in the latter. The regionality of myocardial dysfunction in ischemic cardiomyopathy reflects the fact that coronary arteries are end arteries, each of which, with large variability, supplies a specific myocardial perfusion territory. Chronic severe, diffuse CAD can cause global left ventricular dysfunction, however, which is indistinguishable from primary cardiomyopathy by imaging of myocardial contractile function alone.

Information on the degree of left ventricular dysfunction is crucial for patient management. Poor left ventricular function predicts poor outcome. At an EF of less than 20%, the average 1-year survival is less than 50%. In these patients, ventricular dysrhythmia is at least as important a cause of death as is heart failure. Placement of implantable cardioverter defibrillators can improve survival, and is recommended for prevention of sudden cardiac death in patients with EF less than 30% to 40% and New York Heart Association (NYHA) class II-III heart failure or EF less than 30% to 35% and NYHA class I heart failure.²¹

Myocardial Viability, Stunning, and Hibernation

Assessing the status of the coronary arteries is a key step in the management of newly recognized left ventricular dysfunction. If CAD is present and believed to be the main cause of left ventricular dysfunction, it is important to establish whether coronary revascularization can improve the cardiomyopathy.

In chronic CAD, compensatory changes occur at the myocardial level, such as decreased oxygen demand and increased myocardial oxygen extraction, cell loss, and increased glycogen storage. With more severe chronic ischemia, hemodynamic and functional adaptations, including elevation of end-diastolic pressure, decreased stroke volume, and delayed myocardial contraction and relaxation, help cope further with reduced oxygen delivery. The net effect of these mechanisms representing “myocardial hibernation” decreased systolic function, which may be reversible if adequate oxygen supply is restored by revascularization.²² Reversible myocardial dysfunction may also result from “stunning” in the setting of acute but transient ischemic events. Stunning may be the only consequence of an acute coronary syndrome or may coexist with irreversible myocyte damage.

The concept of viability imaging is important for decision making in these situations. If dysfunctional myocardium can be shown to have retained metabolic activity, or does not show evidence for fibrosis typical of repair of irreversible myocardial damage, improvement of systolic function after revascularization may reasonably be expected.

Pressure and Volume Overload

The response of the heart to increased work demand is hypertrophy—an increase in myocardial mass accomplished by enlargement of individual myocytes. Hypertrophy can represent a physiologic response to repetitive exercise, and probably plays a role in the normal enlargement of the heart through childhood and adolescence as well as in physiologic states such as pregnancy. The hypertrophic response can result in decompensated hypertrophy, however, in the setting of pressure or volume overload, or when it occurs as a compensatory mechanism after infarction of another coronary perfusion territory. The relationship between pressure and volume can be quite complex, and although the classification into pressure and volume overload is a useful conceptual construct, many patients have elements of both processes and may not fit neatly into one category or the other.²³

Pressure overload (e.g., as seen in hypertension, left ventricular outflow obstruction, or aortic coarctation) causes increased systolic wall stress, stimulating concentric hypertrophy of the myocardium. Pressure overload causes not only myocyte hypertrophy, but also upregulation of extracellular matrix production, with the effect of increasing the thickness and the stiffness of the myocardium. These patients are prone to have diastolic dysfunction (see later).

A similar pattern is seen in genetically determined hypertrophic cardiomyopathies. These diseases, which are associated with a large variety of mutations in genes that encode for sarcomeric and nonsarcomeric proteins, are characterized phenotypically by myocyte hypertrophy and disarray, and extracellular fibrosis. Hypertrophic cardiomyopathy is one of the most frequent causes of death in young individuals, particularly young athletes. Death may result from the hemodynamic abnormalities in the left ventricular outflow tract or from ventricular arrhythmia, or both.

Volume overload, which may result from valvular disease or intracardiac or extracardiac shunting of blood, typically results in dilative, eccentric hypertrophy. There are also genetically determined primary forms of dilated cardiomyopathy that respond poorly to treatment other than pharmacologic management of heart failure or, eventually, may require heart transplantation. In pure dilated cardiomyopathies of all types, the common gross morphologic feature is a characteristic dilated, thin-walled chamber.

Tamponade

Tamponade is a pathophysiologic state in which pericardial effusion alters the filling pressures of the heart. Because of its stiff fibrous makeup, the pericardium cannot accommodate rapid increases in pericardial fluid. Even with small but rapidly accumulating pericardial effusions, intrapericardial pressure may increase sufficiently to equal the pressures in the cardiac chambers, and any further increase in volume of pericardial fluid occurs at the expense of the chamber volumes. As a result of decreased chamber volumes and diastolic compliance, venous return is first shifted from systole and early diastole to systole only. Eventually, venous return may decrease sufficiently that the decrease in ventricular preload affects cardiac output and results in profound systemic hypotension, often resulting in exacerbated pulse weakening during inspiration (a phenomenon known as pulsus paradoxus). Pulsus paradoxus occurs because the increased venous return during inspiration expands the right ventricle at the expense of the left ventricle.

Acute cardiac tamponade is a medical emergency. The treatment of choice is emergent pericardiocentesis, preferably under echocardiographic guidance if available. Chronic tamponade can have numerous causes (Table 4-1). Because the pericardium can gradually expand to accommodate slowly growing effusions, however, the volume of pericardial effusion can be large (2 L), and is generally less important than the rate of increase for determining the physiologic consequences (Fig. 4-8). In this situation, removal of even small amounts of fluid can result in impressive improvement of diastolic filling and cardiac output.

TABLE 4-1 Causes of Cardiac Tamponade and Constrictive Pericarditis

FIGURE 4-8 Large effusion without tamponade. CT shows large pericardial effusion (arrowheads) in a patient who had undergone total thyroidectomy and had not received thyroid hormone replacement therapy. Despite the large size of the effusion, Doppler echocardiography showed no evidence of tamponade.

Constrictive Pericarditis

Constrictive pericarditis results from pericardial scarring, which often has a nodular and calcified appearance on imaging (Fig. 4-9). Constrictive pericarditis can occur secondary to many causes, all of which functionally eliminate the pericardial space and “constrict” the volume of the heart (Table 4-2). In contrast to tamponade, early diastolic filling not only is unimpeded by pressure equalization, but also is even more rapid than usual. Mid-diastolic and late diastolic filling is decreased, however, when the volume of the heart approaches the fixed volume of the constricting pericardium.

FIGURE 4-9 Constrictive pericarditis. A, Posteroanterior chest radiograph shows pericardial calcifications (arrowheads) in a patient with constrictive pericarditis after coronary artery bypass graft surgery. B, MRI horizontal long-axis steady-state free precession sequence shows bowing of the septum into the left ventricular cavity during diastole (arrowhead). C, Double inversion recovery fast spin-echo sequence shows nodular pericardial thickening, compatible with constrictive pericarditis (arrowheads).

TABLE 4-2 Normal Ventricular Values

As a feature distinguishing the physiologies of tamponade and constrictive pericarditis, systemic venous return does not increase during inspiration in the latter. Clinically, patients often present with findings of venous congestion and severe right heart failure, which can mimic hepatic failure. As might be expected, the clinical presentation is similar to restrictive cardiomyopathy. In contrast to restrictive cardiomyopathy, constrictive pericarditis can generally be treated successfully with a pericardial resection. It is important to distinguish constrictive from merely restrictive physiology when diastolic dysfunction is present. Imaging can be useful to confirm the presence of pericardial thickening or calcifications to support a diagnosis of pericardial constriction. The most compelling data for the clinician are determined by cardiac catheterization; specific patterns of the left ventricular pressure curve, equalization of diastolic pressure in all chambers, and greatly increased “ventricular interdependence” during respiration are features diagnostic of constrictive pericarditis.²⁶

Mitral Valve Disease

The principal causes of mitral insufficiency are abnormalities of the mitral valve (e.g., mitral valve prolapse) or the mitral valve annulus, defective tensor apparatus (papillary muscles and chordae), and altered left atrial or ventricular size or geometry (dilative or hypertrophic cardiomyopathies). In addition, chronic elevation of end-systolic pressure from hypertension and obesity may contribute to mild, asymptomatic valvular regurgitation in many patients. Physical examination shows a systolic murmur, often holosystolic or preceded by a “mid-systolic click,” depending on the mechanism of mitral insufficiency. Because of the chronic volume overload resulting from continuous back-and-forth flow of blood across the insufficient valve, the left atrium and left ventricle enlarge, and stroke volume and EF are supranormal. The treatment of choice is valve repair (where possible) or valve replacement. Optimal timing of surgery is when mitral regurgitation is “severe” (stage 4) while the patient is still asymptomatic.²⁸ Acute mitral regurgitation can occur as a complication of myocardial infarction, endocarditis, or trauma, and often causes severe hemodynamic instability and congestive heart failure. This group of patients requires aggressive management and early surgery.

Mitral stenosis is currently rare in the Western world. The principal cause is rheumatic fever. Dyspnea and exercise intolerance are initial symptoms. Classic findings on cardiac auscultation are an “opening snap” followed by a “diastolic rumble.” Left atrial enlargement and atrial fibrillation are common. Pulmonary hypertension and right ventricular failure are irreversible late consequences of mitral stenosis. Timing of surgery depends on severity symptoms and the diastolic gradient across the mitral valve. In many scenarios, clinical guidelines now favor transcutaneous balloon valvotomy over surgical management.

Aortic Valve Disease

Aortic stenosis can be subvalvular (which is different from the dynamic outflow tract obstruction in hypertrophic cardiomyopathy), valvular, or supravalvular. The valvular form is most common, and the most common cause is senile degeneration. Rarer causes of aortic stenosis include congenitally bicuspid valve and rheumatic fever. Physical examination is remarkable for a systolic murmur, the characteristics of which vary and can provide important clues to distinguishing aortic stenosis from hypertrophic cardiomyopathy. The increased afterload leads to compensatory left ventricular hypertrophy (which serves to normalize wall stress.) Chamber size is typically normal until compensatory mechanisms are exhausted, and left ventricular dilation and dysfunction occur. The proximal aorta may show typical “poststenotic” dilation. The treatment of choice is valve replacement. Valve replacement is indicated for all patients with “critical” aortic stenosis (pressure gradient between left ventricular outflow tract and thoracic aorta >80 mm Hg or aortic valve area <0.7 cm²). Traditionally, severe aortic stenosis (pressure gradient >40 mm Hg or aortic valve area <1 cm²) was an indication only for patients symptomatic with dyspnea, chest pain, or syncope. More recent studies of the natural history of severe aortic stenosis suggest, however, that asymptomatic patients with severe aortic stenosis should also undergo valve replacement.²⁹

Imaging Assessment of Valve Disease

Echocardiography is the mainstay of assessing heart valve disease noninvasively. Physiologic and hemodynamic measurements obtained by Doppler sonography are at least as important as visualization of the diseased valve or assessing heart chamber size. Invasive, catheter-based hemodynamic assessment of valvular disease is reserved for patients in whom symptoms and physical examination are inconsistent with echocardiographic findings, or if hemodynamic assessment can be combined with therapy (balloon valvulotomy for mitral stenosis).

Clinically, MRI is increasingly used to evaluate valvular function in various clinical scenarios.³⁰ These examinations classically are performed using phase-contrast sequences that allow quantification of flow (Fig. 4-10). Even in the absence of such dedicated sequences, many “bright blood” gradient-echo sequences show intravoxel dephasing from turbulent flow. These findings can provide important clues to valvular abnormalities on conventional MRI examinations, on which the valve leaflets themselves are often seen only partially or not at all (Fig. 4-11). Assessment of valvular disease by CT is currently not part of routine clinical practice.

FIGURE 4-10 MRI of bicuspid aortic valve. A-C, Steady-state free precession (SSFP) images of the left ventricular outflow tract, perpendicular (A) and parallel (B) to the aortic valve plane, and phase contrast image parallel to the valve plane (C), showing the flow through a bicuspid aortic valve that appears like a “lens” or open “fish mouth.” Note dephasing from the turbulent flow across the valve leaflets on the SSFP sequences and retrograde flow lateral to the valve leaflets on the phase contrast sequence (arrows).

FIGURE 4-11 Patient with hypertrophic cardiomyopathy and systolic anterior motion of the anterior mitral valve leaflet on MRI, causing subaortic stenosis (arrow) on bright blood imaging.