(BQ) Part 2 book Pathophysiology of heart disease presents the following contents: Heart failure, the cardiomyopathies, mechanisms of cardiac arrhythmias, clinical aspects of cardiac arrhythmias, hypertension, diseases of the pericardium, diseases of the peripheral vasculature, congenital heart disease.
CHAPTER Heart Failure Neal Anjan Chatterjee Michael A Fifer PHYSIOLOGY Determinants of Contractile Function in the Intact Heart Pressure–Volume Loops PATHOPHYSIOLOGY Heart Failure with Reduced EF Heart Failure with Preserved EF Right-Sided Heart Failure COMPENSATORY MECHANISMS Frank–Starling Mechanism Neurohormonal Alterations Ventricular Hypertrophy and Remodeling MYOCYTE LOSS AND CELLULAR DYSFUNCTION PRECIPITATING FACTORS CLINICAL MANIFESTATIONS Symptoms Physical Signs Diagnostic Studies PROGNOSIS TREATMENT OF HEART FAILURE WITH REDUCED EJECTION FRACTION Diuretics Vasodilators Inotropic Drugs -Blockers Aldosterone Antagonist Therapy Additional Therapies TREATMENT OF HEART FAILURE WITH PRESERVED EJECTION FRACTION ACUTE HEART FAILURE Acute Pulmonary Edema T severe hemorrhage) or increased metabolic demands (e.g., hyperthyroidism), in this chapter, only cardiac causes of heart failure are considered Heart failure may be the final and most severe manifestation of nearly every form of cardiac disease, including coronary atherosclerosis, myocardial infarction, valvular diseases, hypertension, congenital heart disease, and the cardiomyopathies More than 500,000 new cases are diagnosed each year in the United States, where the current prevalence he heart normally accepts blood at low filling pressures during diastole and then propels it forward at higher pressures in systole Heart failure is present when the heart is unable to pump blood forward at a sufficient rate to meet the metabolic demands of the body (forward failure), or is able to so only if the cardiac filling pressures are abnormally high (backward failure), or both Although conditions outside the heart may cause this definition to be met through inadequate tissue perfusion (e.g., 216 77237_ch09.indd 216 8/11/10 8:13:42 AM Heart Failure is approximately million The number of patients with heart failure is increasing, not only because the population is aging, but also because of interventions that prolong survival after damaging cardiac insults such as myocardial infarction As a result, heart failure now accounts for more than 12 million medical office visits annually and is the most common diagnosis of hospitalized patients aged 65 and older Heart failure most commonly results from conditions of impaired left ventricular function Thus, this chapter begins by reviewing the physiology of normal myocardial contraction and relaxation PHYSIOLOGY Experimental studies of isolated cardiac muscle segments have revealed several important principles that can be applied to the intact heart As a muscle segment is stretched apart, the relation between its length and the tension it passively develops is curvilinear, reflecting its intrinsic elastic properties (Fig 9.1A, lower curve) If the muscle is first passively stretched and then stimulated to contract while its ends are held at fixed positions (termed an isometric contraction), the total tension (the sum of active plus passive tension) generated by the fibers is proportional to the length of the muscle at the time of stimulation (see Fig 9.1A, upper curve) That is, stretching the muscle before stimulation optimizes the overlap and interaction of myosin and actin filaments, increasing the number of cross bridges and the force of contraction Stretching cardiac muscle fibers also increases the sensitivity of the myofilaments to calcium, which further augments force development This relationship between the initial fiber length and force development is of great importance in the intact heart: within a physiologic range, the larger the ventricular volume during diastole, the more the fibers are stretched before stimulation and the greater the force of the next contraction This is the basis of the Frank–Starling relationship, the observation that ventricular output increases in relation to the preload (the stretch on the myocardial fibers before contraction) A second observation from isolated muscle experiments arises when the fibers are not tethered at a fixed length but are allowed to shorten during stimulation against a fixed load (termed the afterload) In this situation (termed an isotonic contraction), the final length of the muscle at the end of contraction is determined by the magnitude of the load but is independent of the length of the muscle before stimulation (see Fig 9.1B) That is, (1) the tension generated by the fiber is equal to the fixed load; (2) the greater the load opposing contraction, the less the muscle fiber can shorten; (3) if the fiber is stretched to a longer length before stimulation but the afterload is kept constant, the muscle will shorten a greater distance to attain the same final length at the end of contraction; and (4) the maximum tension that can be produced during isotonic contraction (i.e., using a load sufficiently great such that the muscle is just unable to shorten) is the same as the force produced by an isometric contraction at that initial fiber length This concept of afterload is also relevant to the intact heart: the pressure generated by the ventricle, and the size of the chamber at the end of each contraction depend on the load against which the ventricle contracts, but are independent of the stretch on the myocardial fibers before contraction A third key experimental observation relates to myocardial contractility, which accounts for changes in the force of contraction independent of the initial fiber length and afterload Contractility reflects chemical and hormonal influences on cardiac contraction, such as exposure to catecholamines When contractility is enhanced pharmacologically (e.g., by a norepinephrine infusion), the relation between initial fiber length and force developed during contraction is shifted upward (see Fig 9.1C) such that a greater total tension develops with isometric contraction at any given preload Similarly, when contractility is augmented and the cardiac muscle is allowed to shorten against a fixed afterload, the fiber contracts to a greater extent and achieves a shorter 217 77237_ch09.indd 217 8/11/10 8:13:43 AM Chapter d b e a c a c f b g e a Figure 9.1 Physiology of normal cardiac muscle segments A Passive (lower curve) and total (upper curve) length–tension relations for isolated cat papillary muscle Lines ab and cd represent the force developed during isometric contractions Initial passive muscle length c is longer (i.e., has been stretched more) than length a and therefore has a greater passive tension When the muscle segments are stimulated to contract, the muscle with the longer initial length generates greater total tension (point d vs point b) B If the muscle fiber preparation is allowed to shorten against a fixed load, the length at the end of the contraction is dependent on the load but not the initial fiber length; stimulation at point a or c results in the same final fiber length (e) Thus, the muscle that starts at length c shortens a greater distance (⌬Lc) than the muscle at length a (⌬La) C The uppermost curve is the length–tension relation in the presence of the positive inotropic agent norepinephrine For any given initial length, an isometric contraction in the presence of norepinephrine generates greater force (point f ) than one in the absence of norepinephrine (point b) When contracting against a fixed load, the presence of norepinephrine causes greater muscle fiber shortening and a smaller final muscle length (point g) compared with contraction in the absence of the inotropic agent (point e) (Adapted from Downing SE, Sonnenblick EH Cardiac muscle mechanics and ventricular performance: force and time parameters Am J Physiol 1964;207:705–715.) 218 77237_ch09.indd 218 8/11/10 8:13:43 AM Heart Failure final fiber length compared with the baseline state At the molecular level, enhanced contractility is likely related to an increased cycling rate of actin–myosin cross-bridge formation Determinants of Contractile Function in the Intact Heart In a healthy person, cardiac output is matched to the body’s total metabolic need Cardiac output (CO) is equal to the product of stroke volume (SV, the volume of blood ejected with each contraction) and the heart rate (HR): CO ϭ SV ϫ HR The three major determinants of stroke volume are preload, afterload, and myocardial contractility, as shown in Figure 9.2 Preload The concept of preload (Table 9.1) in the intact heart was described by physiologists Frank and Starling a century ago In experimental preparations, they showed that within physiologic limits, the more a normal ventricle is Contractility + + Heart rate Afterload Preload – Stroke volume + + CARDIAC OUTPUT Figure 9.2 Key mediators of cardiac output Determinants of the stroke volume include contractility, preload, and afterload Cardiac output ϭ Heart rate ϫ Stroke volume distended (i.e., filled with blood) during diastole, the greater the volume that is ejected during the next systolic contraction This relationship is illustrated graphically by the Frank– Starling curve, also known as the ventricular function curve (Fig 9.3) The graph relates a measurement of cardiac performance (such as cardiac output or stroke volume) on the vertical axis as a function of preload on the horizontal axis As described earlier, the Table 9.1 Terms Related to Cardiac Performance Term Definition Preload The ventricular wall tension at the end of diastole In clinical terms, it is the stretch on the ventricular fibers just before contraction, often approximated by the end-diastolic volume or end-diastolic pressure Afterload The ventricular wall tension during contraction; the resistance that must be overcome for the ventricle to eject its content Often approximated by the systolic ventricular (or arterial) pressure Contractility (inotropic state) Property of heart muscle that accounts for changes in the strength of contraction, independent of the preload and afterload Reflects chemical or hormonal influences (e.g., catecholamines) on the force of contraction Stroke volume (SV) Volume of blood ejected from the ventricle during systole SV ϭ End-diastolic volume ᎐ End-systolic volume Ejection fraction (EF) The fraction of end-diastolic volume ejected from the ventricle during each systolic contraction (normal range ϭ 55% to 75%) EF ϭ Stroke volume Ϭ End-diastolic volume Cardiac output (CO) Volume of blood ejected from the ventricle per minute CO ϭ SV ϫ Heart rate Compliance Intrinsic property of a chamber that describes its pressure–volume relationship during filling Reflects the ease or difficulty with which the chamber can be filled Strict definition: Compliance ϭ ⌬ Volume Ϭ ⌬ Pressure 219 77237_ch09.indd 219 8/11/10 8:13:43 AM Stroke volume (or cardiac output) Chapter Increased contractility Normal a c Heart failure Hypotension b Pulmonary congestion Left ventricular end-diastolic pressure (or end-diastolic volume) Figure 9.3 Left ventricular (LV) performance (Frank–Starling) curves relate preload, measured as LV end-diastolic volume (EDV) or pressure (EDP), to cardiac performance, measured as ventricular stroke volume or cardiac output On the curve of a normal heart (middle line), cardiac performance continuously increases as a function of preload States of increased contractility (e.g., norepinephrine infusion) are characterized by an augmented stroke volume at any level of preload (upper line) Conversely, decreased LV contractility (commonly associated with heart failure) is characterized by a curve that is shifted downward (lower line) Point a is an example of a normal person at rest Point b represents the same person after developing systolic dysfunction and heart failure (e.g., after a large myocardial infarction): stroke volume has fallen, and the decreased LV emptying results in elevation of the EDV Because point b is on the ascending portion of the curve, the elevated EDV serves a compensatory role because it results in an increase in subsequent stroke volume, albeit much less than if operating on the normal curve Further augmentation of LV filling (e.g., increased circulating volume) in the heart failure patient is represented by point c, which resides on the relatively flat part of the curve: stroke volume is only slightly augmented, but the significantly increased EDP results in pulmonary congestion preload can be thought of as the amount of myocardial stretch at the end of diastole, just before contraction Measurements that correlate with myocardial stretch, and that are often used to indicate the preload on the horizontal axis, are the ventricular end-diastolic volume (EDV) or end-diastolic pressure (EDP) Conditions that decrease intravascular volume, and thereby reduce ventricular preload (e.g., dehydration or severe hemorrhage), result in a smaller EDV and hence a reduced stroke volume during contraction Conversely, an increased volume within the left ventricle during diastole (e.g., a large intravenous fluid infusion) results in a greater-than-normal stroke volume Afterload Afterload (see Table 9.1) in the intact heart reflects the resistance that the ventricle must overcome to empty its contents It is more formally defined as the ventricular wall stress that develops during systolic ejection Wall stress (), like pressure, is expressed as force per unit area, and for the left ventricle, may be 220 77237_ch09.indd 220 8/11/10 8:13:43 AM Heart Failure Pϫr ϭ _ 2h where P is ventricular pressure, r is ventricular chamber radius, and h is ventricular wall thickness Thus, ventricular wall stress rises in response to a higher pressure load (e.g., hypertension) or an increased chamber size (e.g., a dilated left ventricle) Conversely, as would be expected from LaPlace’s relationship, an increase in wall thickness (h) serves a compensatory role in reducing wall stress, because the force is distributed over a greater mass per unit surface area of ventricular muscle Contractility (also termed “Inotropic State”) In the intact heart, as in the isolated muscle preparation, contractility accounts for changes in myocardial force for a given set of preload and afterload conditions, resulting from chemical and hormonal influences By relating a measure of ventricular performance (stroke volume or cardiac output) to preload (left ventricular end-diastolic pressure or volume), each Frank–Starling curve is a reflection of the heart’s current inotropic state (see Fig 9.3) The effect on stroke volume by an alteration in preload is reflected by a change in position along a particular Frank–Starling curve Conversely, a change in contractility actually shifts the entire curve in an upward or downward direction Thus, when contractility is enhanced pharmacologically (e.g., by an infusion of norepinephrine), the ventricular performance curve is displaced upward such that at any given preload, the stroke volume is increased Conversely, when a drug that reduces contractility is administered, or the ventricle’s contractile function is impaired (as in certain types of heart failure), the curve shifts in a downward direction, leading to reductions in stroke volume and cardiac output at any given preload Pressure–Volume Loops Another useful graphic display to illustrate the determinants of cardiac function is the Pressure (mm Hg) estimated from Laplace’s relationship: d c Stroke volume b a Volume (mL) Figure 9.4 Example of a normal left ventricular (LV) pressure– volume loop At point a, the mitral valve opens During diastolic filling of the LV (line ab), the volume increases in association with a gradual rise in pressure When ventricular contraction commences and its pressure exceeds that of the left atrium, the mitral valve (MV) closes (point b) and isovolumetric contraction of the LV ensues (the aortic valve is not yet open, and no blood leaves the chamber), as shown by line bc When LV pressure rises to that in the aorta, the aortic valve (AV) opens (point c) and ejection begins The volume within the LV declines during ejection (line cd), but LV pressure continues to rise until ventricular relaxation commences, then it begins to lessen At point d, the LV pressure during relaxation falls below that in the aorta, and the AV closes, leading to isovolumetric relaxation (line da) As the LV pressure falls further, the mitral valve reopens (point a) Point b represents the end-diastolic volume (EDV) and pressure, and point d is the end-systolic volume (ESV) and pressure Stroke volume is the difference between the EDV and ESV ventricular pressure–volume loop, which relates changes in ventricular volume to corresponding changes in pressure throughout the cardiac cycle (Fig 9.4) In the left ventricle, filling of the chamber begins after the mitral valve opens in early diastole (point a) The curve between points a and b represents diastolic filling As the volume increases during diastole, it is associated with a small rise in pressure, in accordance with the passive length–tension properties or compliance (see 221 77237_ch09.indd 221 8/11/10 8:13:43 AM Chapter Table 9.1) of the myocardium, analogous to the lower curve in Figure 9.1A for an isolated muscle preparation Next, the onset of left ventricular systolic contraction causes the ventricular pressure to rise When the pressure in the left ventricle (LV) exceeds that of the left atrium (point b), the mitral valve is forced to close As the pressure continues to increase, the ventricular volume does not immediately change, because the aortic valve has not yet opened; therefore, this phase is called isovolumetric contraction When the rise in ventricular pressure reaches the aortic diastolic pressure, the aortic valve is forced to open (point c) and ejection of blood into the aorta commences During ejection, the volume within the ventricle decreases, but its pressure continues to rise until ventricular relaxation begins The pressure against which the ventricle ejects (afterload) is represented by the curve cd Ejection ends during the relaxation phase, when the ventricular pressure falls below that of the aorta and the aortic valve closes (point d) As the ventricle continues to relax, its pressure declines while its volume remains constant because the mitral valve has not yet opened (this phase is known as isovolumetric relaxation) When the ventricular pressure falls below that of the left atrium, the mitral valve opens again (point a) and the cycle repeats Note that point b represents the pressure and volume at the end of diastole, whereas point d represents the pressure and volume at the end of systole The difference between the EDV and end-systolic volume (ESV) represents the quantity of blood ejected during contraction (i.e., the stroke volume) Changes in any of the determinants of cardiac function are reflected by alterations in the pressure–volume loop By analyzing the effects of a change in an individual parameter (preload, afterload, or contractility) on the pressure–volume relationship, the resulting modifications in ventricular pressure and stroke volume can be predicted (Fig 9.5) Alterations in Preload If afterload and contractility are held constant but preload is caused to increase (e.g., by administration of intravenous fluid), left ventricular EDV rises This increase in preload augments the stroke volume via the Frank–Starling mechanism such that the ESV achieved is the same as it was before increasing the preload This means that the normal left ventricle is able to adjust its stroke volume and effectively empty its contents to match its diastolic filling volume, as long as contractility and afterload are kept constant Although end-diastolic volume and enddiastolic pressure are often used interchangeably as markers of preload, the relationship between filling volume and pressure (i.e., ventricular compliance; see Table 9.1) largely governs the extent of ventricular filling If ventricular compliance is reduced (e.g., in severe LV hypertrophy), the slope of the diastolic filling curve (segment ab in Fig 9.4) becomes steeper A “stiff” or poorly compliant ventricle reduces the ability of the chamber to fill during diastole, resulting in a lowerthan-normal ventricular end-diastolic volume In this circumstance, the stroke volume will be reduced while the end-systolic volume remains unchanged Alterations in Afterload If preload and contractility are held constant and afterload is augmented (e.g., in highimpedance states such as hypertension or aortic stenosis), the pressure generated by the left ventricle during ejection increases In this situation, more ventricular work is expended in overcoming the resistance to ejection and less fiber shortening takes place As shown in Figure 9.5B, an increase in afterload results in a higher ventricular systolic pressure and a greater-than-normal LV end-systolic volume Thus, in the setting of increased afterload, the ventricular stroke volume (EDV–ESV) is reduced The dependence of the end-systolic volume on afterload is approximately linear: the greater the afterload, the higher the endsystolic volume This relationship is depicted in Figure 9.5 as the end-systolic pressure– volume relation (ESPVR) and is analogous to the total tension curve in the isolated muscle experiments described earlier 222 77237_ch09.indd 222 8/11/10 8:13:44 AM Pressure (mm Hg) Pressure (mm Hg) Heart Failure Volume (mL) Pressure (mm Hg) Volume (mL) Volume (mL) Figure 9.5 The effect of varying preload, afterload, and contractility on the pressure–volume loop A When arterial pressure (afterload) and contractility are held constant, sequential increases (lines 1, 2, and 3) in preload (measured in this case as end-diastolic volume [EDV]) are associated with loops that have progressively higher stroke volumes but a constant end-systolic volume (ESV) B When the preload (EDV) and contractility are held constant, sequential increases (points 1, 2, and 3) in arterial pressure (afterload) are associated with loops that have progressively lower stroke volumes and higher endsystolic volume end-systolic volume There is a nearly linear relationship between the afterload and ESV, termed the end-systolic pressure–volume relation (ESPVR) C A positive inotropic intervention shifts the end-systolic pressure–volume relation upward and leftward from ESPVR-1 to ESPVR-2, resulting in loop 2, which has a larger stroke volume and a smaller end-systolic volume than the original loop Alterations in Contractility The slope of the ESPVR line on the pressurevolume loop graph is a function of cardiac contractility In conditions of increased contractility, the ESPVR slope becomes steeper; that is, it shifts upward and toward the left Hence, at any given preload or afterload, the ventricle empties more completely (the stroke volume increases) and results in a smaller-than-normal end-systolic volume (see Fig 9.5C) Conversely, in situations of reduced contractility, the ESPVR line shifts downward, consistent with a decline in stroke volume and a higher end-systolic volume Thus, the end-systolic volume is dependent on the afterload against which the ventricle contracts and the inotropic state, but is independent of the end-diastolic volume prior to contraction The important physiologic concepts in this section are summarized here: Ventricular stroke volume is a function of preload, afterload, and contractility SV 223 77237_ch09.indd 223 8/11/10 8:13:44 AM Chapter rises when there is an increase in preload, a decrease in afterload, or augmented contractility Ventricular end-diastolic volume (or enddiastolic pressure) is used as a representation of preload The end-diastolic volume is influenced by the chamber’s compliance Ventricular end-systolic volume depends on the afterload and contractility but not on the preload PATHOPHYSIOLOGY Chronic heart failure may result from a wide variety of cardiovascular insults The etiologies can be grouped into those that (1) impair ventricular contractility, (2) increase afterload, or (3) impair ventricular relaxation and filling (Fig 9.6) Heart failure that results from an abnormality of ventricular emptying (due to impaired contractility or ↑↑Afterload Impaired Contractility (Chronic Pressure Overloada) Coronary artery disease • Myocardial infarction • Transient myocardial ischemia Chronic volume overload • Mitral regurgitation • Aortic regurgitation Dilated cardiomyopathies Advanced aortic stenosis Uncontrolled severe hypertension Reduced Ejection Fraction (Systolic Dysfunction) Heart Failure Preserved Ejection Fraction (Diastolic Dysfunction) Impaired Diastolic Filling Left ventricular hypertrophy Restrictive cardiomyopathy Myocardial fibrosis Transient myocardial ischemia Pericardial constriction or tamponade Figure 9.6 Conditions that cause left-sided heart failure through impairment of ventricular systolic or diastolic function aNote that in chronic stable stages the conditions in this box may instead result in heart failure with preserved EF, due to compensatory ventricular hypertrophy and increased diastolic stiffness (diastolic dysfunction) 224 77237_ch09.indd 224 8/11/10 8:13:44 AM Heart Failure Heart Failure with Reduced EF Pressure (mm Hg) In states of systolic dysfunction, the affected ventricle has a diminished capacity to eject blood because of impaired myocardial contractility or pressure overload (i.e., excessive afterload) Loss of contractility may result from destruction of myocytes, abnormal myocyte function, or fibrosis Pressure overload Volume (mL) impairs ventricular ejection by significantly increasing resistance to flow Figure 9.7A depicts the effects of systolic dysfunction due to impaired contractility on the pressure–volume loop The ESPVR is shifted downward such that systolic emptying ceases at a higher-than-normal endsystolic volume As a result, the stroke volume falls When normal pulmonary venous return is added to the increased end-systolic volume that has remained in the ventricle because of incomplete emptying, the diastolic chamber volume increases, resulting in a higher-than-normal end-diastolic volume and pressure While that increase in preload induces a compensatory rise in stroke volume (via the Frank–Starling mechanism), impaired contractility and the reduced ejection fraction cause the end-systolic volume to remain elevated During diastole, the persistently elevated LV pressure is transmitted to the left atrium (through the open mitral valve) and to the pulmonary veins and capillaries An elevated pulmonary capillary hydrostatic pressure, when sufficiently high (usually Ͼ20 mm Hg), results in the transudation of fluid into the pulmonary Pressure (mm Hg) greatly excessive afterload) is termed systolic dysfunction, whereas heart failure caused by abnormalities of diastolic relaxation or ventricular filling is termed diastolic dysfunction However, there is much overlap, and many patients demonstrate both systolic and diastolic abnormalities As a result, it is now common to categorize heart failure patients into two general categories, based on the left ventricular ejection fraction (EF), a measure of cardiac performance (see Table 9.1): (1) heart failure with reduced EF (i.e., primarily systolic dysfunction) and (2) heart failure with preserved EF (i.e., primarily diastolic dysfunction) In the United States, approximately one half of patients with heart failure fall into each of these categories Volume (mL) Figure 9.7 The pressure–volume loop in systolic and diastolic dysfunction A The normal pressure–volume loop (solid line) is compared with one demonstrating systolic dysfunction (dashed line) In systolic dysfunction caused by decreased cardiac contractility, the end-systolic pressure–volume relation is shifted downward and rightward (from line to line 2) As a result, the end-systolic volume (ESV) is increased (arrow) As normal venous return is added to that greater-than-normal ESV, there is an obligatory increase in the end-diastolic volume (EDV) and pressure (preload), which serves a compensatory function by partially elevating stroke volume toward normal via the Frank–Starling mechanism B The pressure–volume loop of diastolic dysfunction resulting from increased stiffness of the ventricle (dashed line) The passive diastolic pressure–volume curve is shifted upward (from line to line 2) such that at any diastolic volume, the ventricular pressure is higher than normal The result is a decreased EDV (arrow) because of reduced filling of the stiffened ventricle at a higher-than-normal end-diastolic pressure 225 77237_ch09.indd 225 8/11/10 8:13:44 AM Index Heart failure (contd.) compensatory mechanisms adrenergic nervous system, 228–229 antidiuretic hormone, 229 description of, 226–227 Frank–Starling mechanism, 227, 227 natriuretic peptides, 229–230 neurohormonal alterations, 227–230, 228 renin–angiotensin–aldosterone system, 229 ventricular hypertrophy and remodeling, 230 definition of, 216 description of, 216 laboratory tests and findings, 234–235 left-sided acute pulmonary edema associated with, 242 characteristics of, 226 mitral regurgitation associated with, 234 myocyte loss and cellular dysfunction secondary to, 230–231 New York Heart Association classification of, 233t orthopnea associated with, 232 pathophysiology of description of, 224–225 diastolic dysfunction, 225, 226 systolic dysfunction, 225, 225–226, 238 physiology of, 217–224 precipitating factors, 231, 231t with preserved EF, 225, 226 prevalence of, 216–217 prognosis, 235 radiographic findings, 48, 49t with reduced EF, 225, 225–226 right-sided, 226, 226t signs and symptoms of, 232–234, 232t sinus tachycardia findings, 234 stages of, 233t tachyarrhythmias effect, 231 treatment of, 241 aldosterone antagonist therapy, 239–240 angiotensin-converting enzyme inhibitors, 237–238 -adrenergic agonists, 238–239 biventricular pacing, 240 cardiac transplantation, 240 digitalis, 239 diuretics, 236–237 goals of, 235–236 inotropic drugs, 238–239 nitrates, 237 phosphodiesterase inhibitors, 239 resynchronization therapy, 240 spironolactone, 239 vasodilators, 237–238 tricuspid regurgitation associated with, 234 wall stress increases, 220–221 Heart loop, 362–363, 363 Heart murmurs (see Murmurs) Heart rate electrocardiogram assessments of, 87, 88, 103t myocardial oxygen demand and, 140 parasympathetic nervous system effects, 266 Heart sounds extra diastolic, 35–36, 42t extra systolic, 34–35, 42t first (see First heart sounds) fourth, 36 “gallops,” 36 myocardial infarction, 173 pericardial knock, 36 second (see Second heart sounds) third, 35–36 Heart transplantation dilated cardiomyopathy treated using, 250 heart failure treated using, 240 Heart valves aortic (see Aortic valve) embryologic development of, 366 mitral (see Mitral valve) prosthetic, 51, 208, 208–209 pulmonary (see Pulmonary valve) Hemiblocks, 95 Hemorrhagic pericarditis, 327 Hemostasis, 162 Heparan sulfate, 162 Heparin deep venous thrombosis treated with, 358 low molecular weight, 179, 428–429 myocardial infarction treated using, 179 ST- segment elevation myocardial infarction treated using, 180 unfractionated, 178, 428 unstable angina treated using, 180 Heparin-induced thrombocytopenia (HIT), 428 Hereditary amyloidosis, 257 (see also Amyloidosis) Hibernating myocardium, 144 nuclear imaging findings, 65, 67t High-density lipoprotein (HDL), 120b Hill sign, 206t His–Purkinje system, 7–8 HIT (see Heparin-induced thrombocytopenia (HIT)) HMG-CoA reductase, 121b, 128 HMG-CoA reductase inhibitors (see also Statins) description of, 128, 431 mechanisms of action, 431–433 types of, 431, 431t Holosystolic murmurs (see Pansystolic murmurs) Holt–Oram syndrome, 381b Homocysteine, 132 Hormone replacement therapy, 131 Hydralazine, 238, 321, 326, 398, 398t Hydrochlorothiazide, 420t, 421 Hypercoagulability, 356, 356t Hyperglycemia, 422 Hyperkalemia, 397 Hyperpolarization, 265 Hyperpolarizing current, 265 Hypertension accelerated-malignant, 317 antihypertensive therapy, 130 arterial narrowing associated with, 315 atherosclerosis risk and, 130 448 77237_ind.indd 448 8/11/10 8:26:38 AM Index consequences of, 313 coronary artery disease caused by, 315 definition of, 301–302 essential abnormalities in, 305 definition of, 301 epidemiology of, 304–305 experimental findings in, 305 genetics of, 304–305 insulin and, 305–306 natural history of, 306–308 obesity and, 306 prevalence of, 306 severity of, 317 incidence of, 301 mild, 318 nephrosclerosis, induced by, 316 organ damage caused by aorta, 315 cerebrovascular system, 315 description of, 314–315 diastolic dysfunction, 314–315 heart, 314 kidneys, 316–317 left ventricular hypertrophy, 314–315 overview of, 314t retina, 317 systolic dysfunction, 315 vasculature abnormalities, 313–314 pulmonary, 47, 404 renovascular, 310–311 secondary adrenocortical hormone excess, 312–313 coarctation of the aorta, 311 definition of, 301–302 description of, 308t evaluation of, 309 laboratory tests, 309 medications, 309 pheochromocytoma, 312 renal parenchymal disease, 310 thyroid hormone abnormalities, 313 signs and symptoms of, 313 stroke caused by, 314–315 treatment of ACE inhibitors, 321 alcohol reduction, 319 angiotensin II receptor blockers, 322 antihypertensive medications, 319–323, 322t -blockers, 321, 407 calcium channel blockers, 321 centrally acting ␣2-adrenergic agonists, 321 dietary changes, 318 diuretics, 319 exercise, 318 hydralazine, 398, 398t nonpharmacologic treatment, 318–319 pharmacologic treatment, 319–323 potassium levels, 318–319 relaxation therapy, 319 salt restriction for, 318 smoking cessation, 319 sympatholytic agents, 321 vasodilators, 321 weight reduction, 318 Hypertensive crisis, 317 Hypertensive encephalopathy, 317 Hypertensive retinopathy, 317 Hypertrophic cardiomyopathy (HCM), 244 anatomic appearance of, 245 angina pectoris associated with, 254 atrial fibrillation associated with, 253, 254, 256 clinical findings, 254 diagnostic studies, 255 echocardiographic findings, 56t etiology, 250–251 genetic counseling for patients with, 256 genetic testing in, 255 murmurs, 255 effects of maneuvers on, 254t mutations in genes coding for, 247t pathology, 251 pathophysiology, 252, 253 HCM with outflow obstruction, 252–254 HCM without outflow tract obstruction, 252 physical examination, 254–255 postmortem heart specimen, 251 prognosis, 256–257 risk factors for sudden death due to, 254 surgical therapy in, 256 treatment, 255–256 two-dimensional echocardiographic findings, 53 ventricular fibrillation in, 254 Hypertrophic myocardium, light microscopy of, 251 Hypertrophy, ventricular concentric, 230 eccentric, 230 hypertension and, 314–315 left, 92–93, 93 QRS complex abnormalities associated with, 92–93, 93, 109, 111 radiographic findings, 45 right, 92, 93 wall stress effects, 140, 230 Hyperuricemia, 422 Hypokalemia, 390, 420, 421 Hyponatremia, 421–422 Hypotension, 396 I Ibutilide, 416 ICAM-1 (see Intercellular adhesion molecule (ICAM-1)) ICD therapy, in hypertrophic cardiomyopathy, 256 IDL (see Intermediate-density lipoprotein (IDL)) IL-6 (see Interleukin-6 (IL-6)) Imaging cardiac catheterization (see Cardiac catheterization) computed tomography, 67–69, 68, 69, 70, 73t, 336 echocardiography (see Echocardiography) 449 77237_ind.indd 449 8/11/10 8:26:38 AM Index Imaging (contd.) magnetic resonance angiography, 69 magnetic resonance imaging applications of, 69–70 characteristics of, 73t contrast-enhanced, 70–71, 72 principles of, 69–71 nuclear characteristics of, 73t description of, 62 myocardial metabolism assessments, 66–67 myocardial perfusion assessments, 62–63, 65–66 pharmacologic agents, 66 positron emission tomography, 66–67, 73t radioisotopes, 62–63, 65 radionuclide ventriculography, 66 stress studies, 65–66 Immune response endothelial cell role in, 114 Implantable cardioverter-defibrillator (ICD), 249 tachyarrhythmias treated using, 277 Impulse blockade of, 269–272 conduction of accessory tracts, 272–273 altered, 269–273 process of, 22 reentry, 270–273, 271 system for, 7–8 formation of abnormal automaticity, 268 automaticity, 262–263 description of, 262 escape rhythms, 267 latent pacemakers assumption of, 267–268 overdrive suppression, 264–265 pacemakers, 263–264 triggered activity, 268–269 Indapamide, 420t, 421 Infective endocarditis (IE), 256 acute, 211 causes of, 210t classification of, 209–210 description of, 209–210 echocardiographic findings, 212–213 electrocardiographic findings, 212–213 inflammatory response to, 212 microorganisms associated with, 211t, 213, 213t mortality rates, 209 murmur associated with, 211 pathogenesis of, 210–211 prophylaxis, 213, 213t prosthetic valves and, 209 skin manifestations of, 212 subacute, 211 treatment of, 213, 213t Inferior vena cava, 367–368 Inflammatory mediators, 119 Inotropic drugs, 253 description of, 386–387 digitalis (see Digitalis) heart failure treated using, 238–239 mechanism of action, 387–389 phosphodiesterase-3 inhibitors, 393 pulmonary edema treated using, 242 sympathomimetic amines (see Sympathomimetic amines) vasopressin, 393 Inotropic state (see Contractility) Insulin, 305 Insulin resistance, 305 Intercalated disk, 11 Intercellular adhesion molecule (ICAM-1), 118 Interleukin-6 (IL-6), 115 Intermediate-density lipoprotein (IDL), 120b, 128 Internal jugular (IJ) veins, 30b Internal mammary artery grafts, 158 Interventricular septum (IVS), 5–7, 251 Intima anatomy of, 113, 114, 340 functions of, 113 leukocyte adherence to, 118 lipoprotein retention in, 118 Intra-aortic balloon pump, 186 Intracardiac pressure tracings, 58b Inward rectifier potassium channels, 17 Ion channels description, 13 energetics of, 13 fast sodium, 13–14, 16, 17b gating, 13 permeability of, 13–16 selectivity, 13 structure of, 14, 15 voltage sensitive, 13 Iron chelation therapy, 258 Ischemic heart disease adaptations, 347 chest pain associated with, 149t cholesterol levels and, 128 consequences of, 144–147 electrocardiographic findings, 149–150 exercise stress test for, 150–151 factors contributing to, 254 myocardial effects, 143–144 nuclear imaging findings, 67t pathophysiology of, 141–143 endothelial cell dysfunction, 142–143 fixed vessel narrowing, 141–142 myocardial oxygen alterations, 144 prevention of, 156–157 recurrent, 154–156 silent characteristics of, 146–147 defined, 136t description of, 135 treatment of acute episodes, 153–154, 154t coronary artery bypass graft surgery, 158, 158–159, 159t percutaneous coronary interventions, 157–158, 159t 450 77237_ind.indd 450 8/11/10 8:26:38 AM Index percutaneous transluminal coronary angioplasty, 157–158 pharmacologic agents, 153–156 revascularization, 157–159 Ischemic preconditioning, 170–171 Isoelectric complex, 91 Isometric contraction, 217 Isoproterenol, 391t, 392–393 Isosorbide dinitrate, 238, 398, 403 Isosorbide mononitrate, 403 Isovolumetric contraction, 222 Isovolumetric relaxation, 222 J Janeway lesions, 212 Jones criteria for rheumatic fever, 191, 192t Jugular venous pulsations, 30b Junctional escape rhythms, 281, 281–282 JUPITER trial, 132 K Kerley B lines, 49, 235 Kidneys glomerular filtration rate, 418 hypertension effects, 316–317 tubules of, 419, 419 Kussmaul sign, 258, 335 L Lactate dehydrogenase, 334 LAFB (see Left anterior fascicular block (LAFB)) Laplace’s relationship, 140 Latent pacemaker, 264 Late systolic murmurs, 38, 40, 42t LBBB (see Left bundle branch block (LBBB)) LCAT (see Lecithin cholesterol acyltransferase (LCAT)) Lecithin cholesterol acyltransferase (LCAT), 121b Left anterior descending coronary artery, 8, Left anterior fascicular block (LAFB), 95, 96 Left atrial pressure (LAP), 61 Left atrium anatomy of, compliance of, 198, 219t interior structures of, mitral stenosis pathophysiology, 194 pressure measurement, 198 pressure measurements, 57 Left bundle branch, Left bundle branch block (LBBB) description of, 34 electrocardiographic findings, 94, 95 QRS complex abnormalities associated with, 95 Left main coronary artery, Left posterior fascicular block (LPFB), 96, 97 Left-to-right shunting, 370 Left ventricle anatomy of, aneurysm of, 187 depolarization of, 83, 85 diastolic dysfunction, 170 dilatation of, 205 enlargement of, 197, 200 interior structures of, Lepirudin, 429 Leukocytes pericarditis and, 327 recruitment of, 118–119 Levine sign, 147 Lidocaine, 412–413 Lipid-regulating drugs bile acid-binding agents, 431t, 433–434 cholesterol absorption inhibitors, 431t, 434 fibrates, 431t, 435 HMG-CoA reductase inhibitors (see HMG-CoA reductase inhibitors) niacin, 431t, 434–435 sites of action, 432 Lipoprotein (a), 132 Lipoprotein lipase, 120b–121b Lipoprotein(s) atherosclerosis and, 118, 127–130 classification of, 118 high-density, 120b intermediate-density, 120b, 128 low-density (see Low-density lipoproteins (LDL)) lowering of, 128–130, 129 oxidation of, 118 reduction methods diet, 128 exercise, 128 lipid-regulating drugs (see Lipid-regulating drugs) statins, 128–130, 129 transport of, 120b–121b very low density atherosclerosis risks and, 128 characteristics of, 120b LMWH (see Low molecular weight heparin (LMWH)) Local metabolites, 142 Lovastatin, 431, 431t, 433 Low-density lipoproteins (LDL) atherosclerosis risks and, 127–128 characteristics of, 118 familial hypercholesterolemia, 128 serum levels of, 128 subclasses of, 128 Low molecular weight heparin (LMWH), 178 (see also Heparin) Lown–Ganong–Levine syndrome, 293 LPFB (see Left posterior fascicular block (LPFB)) Lymphatic vessels, 10 M Magnetic resonance angiography (MRA), 69 Magnetic resonance imaging (MRI) applications of, 69–70 characteristics of, 73t contrast-enhanced, 70–71, 72 principles of, 69–71 451 77237_ind.indd 451 8/11/10 8:26:38 AM Index Magnetic resonance venography, 357 MAT (see Multifocal atrial tachycardia (MAT)) MCP-1 (see Monocyte chemotactic protein (MCP-1)) Mean arterial pressure (MAP), 61 Mean pulmonary artery pressure (MPAP), 61 Mean QRS axis, 87–92, 89–91 Media anatomy of, 113, 114, 340 degeneration of, 341 Membrane potential, 263, 268 Mesenchymal tissue, 367 Metabolic acidosis, 400 Metabolic syndrome, 131 Metolazone, 420t, 421 Metoprolol, 239 Mexiletine, 413 MIBI (see 99mTc-sestamibi) Milrinone, 393, 394t Mineralocorticoids, 312 Minoxidil, 321, 398–399, 398t Mitral regurgitation acute, 197, 198–199 cardiac catheterization findings, 64t characteristics of, 214t chronic, 197, 199 clinical manifestations of, 199–200 description of, 32 Doppler color flow mapping of, 51 echocardiographic findings, 56t, 200 electrocardiographic findings, 200 etiology of, 196–197 in heart failure, 234 hemodynamic profile of, 198 left ventricle enlargement and, 197 natural history of, 200–201 pansystolic murmur caused by, 39 pathophysiology of, 197, 197–199 physical examination findings, 199–200 pulmonary capillary wedge pressure associated with, 60 radiographic findings, 49t, 200 regurgitant fraction in, 198 rheumatic fever and, 197 treatment of, 200–201 Mitral stenosis acute rheumatic fever and, 192 cardiac catheterization findings, 64t, 195 characteristics of, 214t clinical manifestations of, 194–195 complications of, 194 description of, 32 diagnostic findings, 194 diastolic murmurs caused by, 40–41 dyspnea associated with, 194 echocardiographic findings, 56t, 195 electrocardiographic findings, 195 etiology of, 192 evaluation of, 194–195 hemodynamic profile of, 193 left atrium effects, 192 murmurs associated with, 195 natural history of, 194 opening snap associated with, 35, 195 open mitral commissurotomy, 196 pathology of, 192 pathophysiology of, 192–194, 193 percutaneous balloon mitral valvuloplasty, 196 pulmonary artery pressure in, 192, 194 pulmonary capillary wedge pressure associated with, 60 radiographic findings, 46, 49t, 195 treatment of, 195–196 Mitral valve anatomy of, development of, 367 echocardiographic evaluation of, 195 opening of, 35 prolapse, 201–202 regurgitation of (see Mitral regurgitation) replacement of, 201 M-mode echocardiography, 49 Möbitz block type I, 282, 282–283 type II, 283, 283 Moderator band, Monocyte chemotactic protein (MCP-1), 118 MRA (see Magnetic resonance angiography (MRA)) MRI (see Magnetic resonance imaging (MRI)) 99m Tc-sestamibi, 65 Müller sign, 206t Multidetector computed tomography, 68, 70 Multifocal atrial tachycardia (MAT), 293–294, 294 Murmurs (see also Hypertrophic cardiomyopathy (HCM), murmurs) continuous, 41, 42t definition of, 36 descriptive terms for, 36–37 diastolic (see Diastolic murmurs) infective endocarditis, 211 location of, 37 of LV outflow obstruction, 254 maximum intensity locations for, 43 mechanisms of, 36 in mitral stenosis, 195 of mitral valve regurgitation, 248 pitch of, 37 shape of, 37 squatting position and, 255 standing position and, 255 systolic (see Systolic murmurs) timing of, 36 of tricuspid valve regurgitation, 248 Myocardial biopsy, 255 Myocardial cells depolarization of, 265, 266 gap junctions, 263–264 repolarization of, 265 Myocardial infarction angiotensin-converting enzyme inhibitors, 157 -Blockers for, 155 catecholamine release secondary to, 172 cell death mechanisms, 168 452 77237_ind.indd 452 8/11/10 8:26:38 AM Index chest pain associated with, 173 clinical features of, 174t complications of arrhythmias, 184–185 description of, 183, 183 Dressler syndrome, 187 myocardial dysfunction, 185–186 papillary muscle rupture, 186 pericarditis, 187, 326 recurrent ischemia, 183, 184 right ventricular infarction, 186 thromboembolism, 187 ventricular aneurysm, 187 ventricular free wall rupture, 186 ventricular septal rupture, 186–187 defined, 136t diagnosis of creatine kinase levels, 176 echocardiography, 176 electrocardiographic findings, 97–98, 100–102 electrocardiography, 175 serum markers, 175 troponin levels, 175–176 echocardiographic findings, 56t heart sounds, 173 localization of, 97t non–Q-wave, 162, 171 nuclear imaging findings, 67t pain associated with, 172 prevention of, 156–157 Q-wave, 98, 100, 162, 171 risk stratification and management, 187–188 signs and symptoms of, 172–173, 172t subendocardial, 167 transmural, 167, 170t treatment of anti-ischemic agents, 177–178 antithrombotic agents, 178–179, 182 aspirin, 178, 180 -blockers, 177–178, 180 calcium channel blockers, 178 clopidogrel, 178 conservative vs early invasive approaches, 179–180 description of, 177 fibrinolytic agents, 180–182, 181 heparin, 179, 180 nitrates, 178 percutaneous coronary intervention, 182 statins, 182–183 ventricular remodeling, 171 Myocardial ischemia (see Ischemic heart disease) Myocardial oxygen supply and demand alterations in, 143–144 descriptions of, 136 determinants of, 137, 140–141 Myocardial perfusion, assessment of, 66 Myocarditis, viral, 245 Myocardium blood vessels of, 167 coagulative necrosis of, 167 contractility of, 140, 217, 219, 219t, 221 edema of, 168 hibernating, 65, 67t, 144 ischemia effects, 143–144 metabolism, 66–67 necrosis, 173, 175 perfusion, 62–63, 65–66 stunned, 144, 170 viability assessments, 66 Myocytes action potential of, 19 active transporters of, 12 calcium levels in, 168 contractile proteins, 23, 23–25, 25 cotransporters of, 12 description of, 10 destruction of, 230–231 injured, 168 ion channels of, 12, 24 loss of, 230–231 permeability of, 18 potassium channels of, 17–18 refractory period, 21, 21–22 relaxation of, 26 repolarization of, 77, 77–78 resting potential of, 18, 22 tubular systems of, 11 ultrastructure of, 10 Myofibrils, 10 Myomectomy, 256 Myopathy, 433 Myosin, 23 Myosin-binding protein C, 250 -Myosin heavy chain (-MHC), 250 gene, mutations in, 251 N National Cholesterol Education Program, 128 Native pacemakers, 264 Natriuretic peptides, 229–230, 403–404 NBTE (see Nonbacterial thrombotic endocarditis (NBTE)) Neoplastic pericarditis, 326 Nephrosclerosis, hypertension-induced, 316 Nesiritide, 238, 394, 403–404 New York Heart Association (NYHA) heart failure classification of, 233t Niacin, 431t, 434–435 Niemann-Pick C1–like protein, 434 Nifedipine, 155 Nitrates, 256 adverse effects, 403 agents, 403 heart failure, 237 hemodynamic effects, 402–403 indications angina pectoris, 154, 155, 178 coronary artery disease, 154, 155 myocardial infarction, 178 mechanism of action, 402, 402 453 77237_ind.indd 453 8/11/10 8:26:38 AM Index Nitrates (contd.) nitroglycerin (see Nitroglycerin) pharmacokinetics, 403 vascular smooth muscle effects, 402 Nitric oxide (NO) actions of, 138b, 139 description of, 117 platelet effects, 164 relaxation effects of, 142 Nitric oxide synthase, 138b Nitroglycerin intravenous, 403 sublingual angina pectoris managed using, 148, 154 description of, 138b hemodynamic effects, 402–403 pharmacokinetics, 403 transdermal, 403 Nkx2.5, 381b NO (see Nitric oxide (NO)) Nocturnal cough, 232 Nonbacterial thrombotic endocarditis (NBTE), 210 Non-Q-wave myocardial infarction, 162, 171 Non-ST-segment elevation myocardial infarction (NSTEMI) description of, 161, 166, 172 electrocardiography findings, 174 treatment of angiotensin-converting enzyme inhibitors, 182 anti-ischemic agents, 177–178 antithrombotic agents, 178–179 -blockers, 177–178 calcium channel blockers, 178 clopidogrel, 178 conservative vs early invasive approaches, 179–180 heparin, 179 nitrates, 178 statins, 182–183 Nontuberculous bacterial pericarditis, 325 Norepinephrine, 391t, 392 NSTEMI (see Non-ST-segment elevation myocardial infarction (NSTEMI)) Nuclear imaging angina pectoris evaluations, 151 characteristics of, 73t description of, 62 ischemic heart disease evaluations, 151 myocardial assessments metabolism, 66–67 perfusion, 62–63, 65–66 pharmacologic agents, 66 positron emission tomography, 66–67, 73t radioisotopes, 62–63, 65 radionuclide ventriculography, 66 stress studies, 65–66 NYHA (see New York Heart Association (NYHA)) O Occlusive arterial diseases acute arterial occlusion, 349–350 peripheral artery disease (see Peripheral artery disease) vasculitic syndromes (see Vasculitic syndromes) Ohm’s law, 141 Opening snap, associated with mitral stenosis, 195 Open mitral commissurotomy, 196 Oral anticoagulation therapy, 250 Orthopnea, 232 Orthostatic hypotension in restrictive cardiomyopathy, 257 Orthostatic lightheadedness, 254 Osler nodes, 212 Ostium primum, 364 Ostium secundum, 364, 370 Overdrive suppression, 264–265 P Pacemaker, 249 latent, 264, 267–268 native, 264 permanent, 275 temporary, 275 Pacemaker cells action potential of, 20, 263 anatomic connections, 265 description of, 262 electrical coupling of, 265 membrane potential of, 263 repolarization phase, 263 sinoatrial node, 262 voltage gated, 267 Pacemaker current alterations in, 263, 264 definition of, 262 Pacing, 240 Pansystolic murmurs, 38, 39, 42t Papillary muscle anatomy of, rupture of, 186 Papilledema, 317 Paradoxical embolism, 349 Paradoxical splitting, 33, 34 Parietal pericardium, 2, 2, 324 Paroxysmal nocturnal dyspnea (PND), 232 Paroxysmal supraventricular tachycardias (PSVT) characteristics of, 288–293 Wolff–Parkinson–White syndrome and, 291–292, 291–293 Partially occlusive thrombus, 162 Parvovirus B19, 245 Patch-clamp recordings, 12 Patent ductus arteriosus diagnostic studies, 375 incidence of, 374 pathophysiology of, 374–375 physical examination, 375 454 77237_ind.indd 454 8/11/10 8:26:38 AM Index symptoms of, 375 treatment of, 375 PCW (see Pulmonary capillary wedge pressure (PCW)) PDGF (see Platelet-derived growth factor (PDGF); Platelet-derived growth factor (PDGF)) Peptic ulcer disease, 149t Percutaneous balloon mitral valvuloplasty, 196 Percutaneous coronary intervention (PCI) angina pectoris treated using, 157–158, 159t ischemic heart disease treated using, 157–158, 159t ST- segment elevation myocardial infarction treated using, 182 Percutaneous septal ablation, 256 Percutaneous transluminal coronary angioplasty, 157–158 Perfusion pressure, 137 Pericardial effusion clinical features of, 330, 330t diagnostic studies of, 330–331 echocardiographic evaluations, 55 etiology of, 329 pathophysiology of, 329 treatment of, 331 Pericardial friction rub, 327–328 Pericardial knock, 36 Pericardiocentesis, 328, 334 Pericarditis causes of, 325t chest pain associated with, 149t clinical features of, 327–328, 327t connective tissue diseases associated with, 326 diagnostic studies of, 328 differential diagnosis of, 173t drug-induced, 326, 326t echocardiographic evaluations, 55–56 electrocardiogram in, 328, 328 etiology of, 325–326 hemorrhagic, 327 idiopathic, 325 myocardial infarction related, 325–326 myocardial infarction-related, 187 neoplastic, 326 nontuberculous bacterial, 325 pathogenesis of, 327 pathology of, 327 purulent, 325 radiation-induced, 326 serofibrinous, 327 serous, 327 suppurative, 327 treatment of, 329 tuberculous, 325 uremic, 326 viral, 325 Pericardium anatomy of, 1–2, 2, 324 functions of, 324–325 parietal, 324 visceral, 324 volume–pressure relationship of, 330 Peripartum cardiomyopathy, 246 Peripheral ␣-adrenergic receptor antagonists, 404–406, 406t Peripheral artery disease claudication associated with, 348, 348t clinical presentation of, 347–349 description of, 346 diagnosis of, 347–349 etiology of, 346–347 exercise capacity reduction, 346–347 ischemic ulcers caused by, 346, 348 pathogenesis of, 346–347 physical examination of, 348 treatment of, 349 Peripheral edema, 233 Peripheral pruning, 47, 49 Peripheral vascular diseases definition of, 339 occlusive arterial diseases (see Occlusive arterial diseases) Raynaud phenomenon, 352–353, 353 Permanent pacemaker, 275 Peroxisomal proliferation activating receptor-␣ (PPAR-␣), 128 PET (see Positron emission tomography (PET)) Phenoxybenzamine, 406, 406t Phentolamine, 406, 406t Pheochromocytoma, 312 Phlebotomy, 258 Phosphodiesterase inhibitors, 239 type 3, 393, 394t type 5, 404 Phospholamban, 26 Phospholipase A2, 423 Physiologic splitting, 32, 33 PISA (see Proximal isovelocity surface area (PISA)) Plateau, 19 Platelet-derived growth factor (PDGF), 122 Platelet(s) activation of, 165 aggregation of, 142, 165 endogenous inhibition of, 164 endothelial cells and, interaction between, 143 nitric oxide effects, 164 vasoconstricting actions of, 142 Pleural effusions, 46, 48, 49 PND (see Paroxysmal nocturnal dyspnea (PND)) Pneumonia, 173t Pneumothorax, 173t Poiseuille’s law, 141, 346 Polymorphic ventricular tachycardia, 269, 272, 276, 296b Positron emission tomography (PET), 66, 73t Posteroanterior radiographs cardiac silhouette, 46 description of, 45, 46 Postpericardiotomy pericarditis, 326 Postphlebitic syndrome, 356 455 77237_ind.indd 455 8/11/10 8:26:39 AM Index Potassium equilibrium potential, 18 PPAR-␣ (see Peroxisomal proliferation activating receptor-␣ (PPAR-␣)) Pravastatin, 431, 431t, 433 Prazosin, 405, 406t Preganglionic parasympathetic fibers, Pregnancy, peripartum cardiomyopathy during, 246 Preload alterations in, 222 definition of, 219t description of, 217, 219–220 reduction method, 242 Pressure natriuresis, 303 Pressure–volume loops, 221, 221–224 Primary aldosteronism, 312 Primary pulmonary hypertension, 404 PR interval description of, 87, 89t, 103t first-degree atrioventricular block, 282 Proarrhythmia, 276 Procainamide, 326, 326t, 410–412 Propafenone, 413 Prostacyclin, 139, 164 Prosthetic heart valves, 51, 208, 208–209 Protamine sulfate, 428 Protein C, 163 Protein S, 163 Proximal isovelocity surface area (PISA), 54 Pseudoaneurysm, 186, 341 Pulmonary artery, 46, 46 catheter, 60 pressure, 59–60, 59t, 194 wedge pressure, 59t, 60 Pulmonary blood flow, 46 Pulmonary capillary hydrostatic pressure, 225 Pulmonary capillary wedge pressure (PCW), 60 Pulmonary edema, 242 Pulmonary embolism, 173t, 231, 355, 356t Pulmonary hypertension primary, 404 radiographic findings, 47 Pulmonary valve anatomy, 4–5 development of, 366 regurgitation of, 40, 208 stenosis of (see Pulmonic stenosis) Pulmonary vascular resistance (PVR) calculation of, 61 perinatal, 373 postnatal changes, 374 Pulmonary vasculature, 46, 47, 369 Pulmonary venous pressure, 46 Pulmonic ejection click, 35 Pulmonic regurgitation, 208 Pulmonic stenosis, 208 diagnostic studies of, 378 pathophysiology of, 377–378 physical examination of, 378 radiographic findings, 49t radiographic findings of, 378 symptoms of, 378 systolic ejection murmur caused by, 38–39 treatment of, 378 Pulse pressure, 206, 206t Pulsus alternans, 234 Pulsus paradoxus, 333, 335 Purkinje fibers, 7–8, 23 Purulent pericarditis, 325, 329 PVR (see Pulmonary vascular resistance (PVR)) Q QRS interval, 87, 89t, 103t, 250 QT interval congenital long-QT syndromes, 296b–297b description of, 87, 89t, 103t Quadruple rhythm, 36 Quincke sign, 206t Quinidine, 410 Q-wave myocardial infarction, 162, 171 Q waves, 255 R Radiography cardiac silhouette, 45–46 characteristics of, 73t frontal view, 45, 45 indications aortic regurgitation, 207 atrial septal defect, 371 coarctation of the aorta, 379 constrictive pericarditis, 336 mitral stenosis, 195 lateral view, 45, 45 posteroanterior view of, 45–46, 46 principles of, 44–45 pulmonary manifestations, 46, 49 Radionuclide ventriculography (RVG), 66 Ranolazine, 156 RAP (see Right atrial pressure (RAP)) Raynaud phenomenon, 352–353, 353 RBBB (see Right bundle branch block (RBBB)) Reactive oxygen species, 117, 118 Reentry interruption of, 276 mechanisms of, 270–272, 271 Renal insufficiency, 396, 412 Renal parenchymal disease, 310 Renin–angiotensin–aldosterone system drug interactions, 396t heart failure-related compensatory response, 229 inhibition of, 237 schematic diagram of, 310, 395 Renovascular hypertension, 310–311 Repolarization in congenital long-QT syndromes, 296b delayed afterdepolarizations, 268–269, 269 description of, 77, 77–78, 102 Resting state, 75 456 77237_ind.indd 456 8/11/10 8:26:39 AM Index Restrictive cardiomyopathy, 244 anatomic appearance of, 245 clinical findings, 257–258 constrictive pericarditis vs., 337t diagnostic studies, 258 echocardiographic findings, 56t examples of, 257t pathophysiology, 257, 258 physical examination, 258 treatment, 258 Retinopathy, hypertensive, 317 Rheumatic fever, 190–192, 192t mitral regurgitation and, 197 Right atrial pressure (RAP), 61 Right atrium anatomy of, 2, 4–5, pressure measurements, 57, 57–59, 58b, 59t Right bundle branch, Right bundle branch block (RBBB) electrocardiographic findings, 94, 95 QRS complex abnormalities associated with, 93, 94, 95 Right-to-left shunting, 371 Right ventricle anatomy of, 4–5, 226 failure of, 226 infarction of, 186–187 pressure measurements, 57, 58b, 59, 59t Right ventricular heave, 234 Rosuvastatin, 431, 431t, 433 Roth spots, 212 RVG (see Radionuclide ventriculography (RVG)) Ryanodine receptors, 24 S Salt restriction, 258 Sarco(endo)plasmic reticulum Caϩϩ ATPase (SERCA), 25 Sarcolemma, 11, 12–13 Sarcomeres, 10–11 Sarcoplasmic reticulum (SR), 11–12 SBE (see Subacute bacterial endocarditis (SBE)) Secondary aldosteronism, 312 Second-degree atrioventricular block, 282–283, 282–283 Second heart sound abnormalities of, 32–33 in atrial septal defect, 371 characteristics of, 42t description of, 29, 31 production of, 32 splitting of, 32–34, 33, 377 Semilunar valves, 366 Senile amyloidosis, 257 (see also Amyloidosis) Septum primum, 363, 364 Septum secundum, 364 Serofibrinous pericarditis, 327 Serous pericarditis, 327 Serum electrolytes, 249 Shunting, 370 Sick sinus syndrome (SSS), 280, 281 Sildenafil, 404 Silent ischemia, 135, 136t, 146–147 Simvastatin, 431, 431t Single photon emission computed tomography (SPECT), 63, 64, 73t Sinoatrial node anatomy, automaticity alterations, 266–267 pacemaker cells of, 262 suppression of, 267 Sinus, definition of, 87 Sinus bradycardia definition of, 87, 279 etiology of, 279 management of, 280 myocardial infarction-related, 185 Sinus rhythm, 87, 250, 258 Sinus tachycardia characteristics of, 284–285 definition of, 87 electrocardiographic findings, 284–285, 285 in heart failure, 234 myocardial infarction-related, 185 Sinus venosus, 362, 363 Sinus venosus defect, 370–371 Smoking atherosclerosis and, 130 hypertension and, 319 Smooth muscle cells, vascular atherosclerotic role of, 119, 122 description of, 115 Sodium nitroprusside, 138b, 398t, 399, 399–400 Sotalol, 416 SPECT (see Single photon emission computed tomography (SPECT)) Spiral CT, 67–68, 69 Spironolactone, 249, 422 Splitting of second heart sound fixed, 33, 34 paradoxical, 33, 34 physiologic, 32, 33 widened, 33, 33–34 Squatting position and murmurs, 255 (see also Murmurs) SREBP (see Sterol regulatory element binding protein (SREBP)) SSS (see Sick sinus syndrome (SSS)) Stable angina causes of, 144, 145 coronary angiography evaluations, 152 definition of, 136t diagnostic studies for, 149–153 differential diagnosis of, 148, 149t electrocardiographic findings, 149, 150 exercise echocardiography evaluations, 151–152 exercise stress test for, 150, 151 frequency of, 148 history-taking findings, 147–149 location of, 147 457 77237_ind.indd 457 8/11/10 8:26:39 AM Index Stable angina (contd.) natural history of, 153 nitroglycerin for, 148 nuclear studies for, 151 oxygen supply inadequacies associated with, 146 pathophysiologic findings, 145 physical examination findings, 148, 149 precipitants of, 148 quality of, 147 risk factors, 148 signs and symptoms of, 147–148 treatment of, 153, 154t Standing position and murmurs, 255 (see also Murmurs) Staphylococcus aureus endocarditis, 209 Statins, 128–130, 129, 156, 182–183 (see also HMGCoA reductase inhibitors) “Steal” phenomenon, 66 Stents, coronary, 157, 158 Sterol regulatory element binding protein (SREBP), 121b Stethoscopes, 31, 31 Streptokinase, 180 Stress echocardiography, 55, 151–152 Stress nuclear imaging studies, 65 Stress tests, 150–153 Stroke volume afterload, 217, 219t, 220–221 contractility, 219t, 221 definition of, 219t preload, 217, 219–220, 219t ST-segment elevation myocardial infarction (STEMI) description of, 162, 172 electrocardiography findings, 174 treatment of angiotensin-converting enzyme inhibitors, 182 antithrombotic agents, 182 -blockers, 180 description of, 180 fibrinolytic agents, 180–182, 181 heparin, 180 percutaneous coronary intervention, 182 statins, 182–183 Stunned myocardium, 144, 170 Subacute bacterial endocarditis (SBE), 209 Subendocardial infarcts, 167 Sudden death, 250, 254, 256 implantable cardioverter defibrillators for, 277 Summation gallop, 36 Superoxide anion, 118 Suppurative pericarditis, 327 Supraventricular arrhythmias, 185 Surgical therapy in hypertrophic cardiomyopathy, 256 SVR (see Systemic vascular resistance (SVR)) Swan–Ganz catheter, 57 Sympatholytic agents, 321 Sympathomimetic amines cAMP formation, 390 definition, 390 dobutamine, 391t, 392, 394t dopamine, 391–392, 391t, 394t epinephrine, 391t, 392 isoproterenol, 391t, 392–393 norepinephrine, 391t, 392 Syncope, 254 Syndrome X, 147 Systemic vascular resistance (SVR), 61 Systole blood flow during, 136–137 description of, 28–29, 29, 31 Systolic dysfunction description of, 170 heart failure caused by, 225, 225–226 hypertension and, 315 treatment of (see Heart failure, treatment of) Systolic murmurs classification of, 37, 38 grading of, 37 late, 38, 40, 42t pansystolic, 38, 39, 42t systolic ejection murmurs, 38, 39, 42t T Tachyarrhythmias (see also Arrhythmias) atrial fibrillation (see Atrial fibrillation) atrial flutter, 285–287 atrial premature beats, 185, 285, 285 definition of, 284 differential diagnosis, 284 impulse formation and conduction alterations, 262 mechanisms of, 274t tachycardia (see Tachycardia) treatment of cardioversion, 277 catheter ablation, 277 defibrillation, 277 implantable cardioverter defibrillators, 277 pharmacologic, 276 vagotonic maneuvers, 276 types of, 280t Tachycardia atrioventricular nodal reentrant, 289–291 atrioventricular reentrant, 291 concealed accessory pathways, 293 ectopic trial, 293 multifocal atrial, 293–294, 294 paroxysmal supraventricular, 288–293 sinus characteristics of, 284–285 definition of, 87 electrocardiographic findings, 284–285, 285 in heart failure, 234 myocardial infarction-related, 185 ventricular, 295, 295–298, 297b Tachypnea, 234, 242 Takayasu arteritis, 342, 342t, 350 TBX1, 381b T cells, 118, 164 Technetium-99m, 63 TEE (see Transesophageal echocardiography (TEE)) Temporary pacemaker, 275 458 77237_ind.indd 458 8/11/10 8:26:39 AM Index Terazosin, 405, 406t Terminal cisternae, 11 Tetralogy of Fallot, 380–382 TFPI (see Tissue factor pathway inhibitor (TFPI)) Thallium-201 (201Tl) imaging, 62, 65 Thermodilution method, 60–61 Thiazide diuretics, 237 Thienopyridines, 178 Third-degree atrioventricular block, 283–284, 284 Third heart sound, 35–36 Three-dimensional (3-D) echocardiography, 53 (see also Echocardiography) Thrombin, 163, 165 Thromboembolism, 187 Thrombogenic potential, 123, 124, 125 Thrombolysis in Myocardial Infarction (TIMI) risk score, 179–180 Thrombolytic therapy, 178–179, 182 (see also Fibrinolytic therapy) Thrombomodulin, 163 Thrombophlebitis, superficial, 359 Thrombosis antithrombotic agents, 162–164 consequences of, 166 formation of, 165–166 partially occlusive, 162 pathogenesis of, 164–166, 166 significance of, 165–166, 166 Thromboxane (TXA2), 178, 423 Ticlopidine, 426 TIMI risk score (see Thrombolysis in Myocardial Infarction (TIMI) risk score) Tirofiban, 427 Tissue factor pathway inhibitor (TFPI), 162 Tissue plasminogen activator (tPA), 163, 180, 181, 182 Titin, 23 TNF-␣ (see Tumor necrosis factor-␣ (TNF-␣)) Torsades de pointes, 295, 298, 298–299 Torsemide, 420t, 421 Total peripheral resistance (TPR), 227 TPA (see Tissue plasminogen activator (tPA)) TPR (see Total peripheral resistance (TPR)) Trabeculae carneae, Transesophageal echocardiography (TEE), 51–53, 52, 213 Transmural infarcts, 167, 170t Transposition of the great arteries, 382–384 Transthoracic echocardiography (TTE), 50, 50–51, 212 Traube sign, 206t Triamterene, 422 Tricuspid regurgitation, 39, 234 Tricuspid regurgitation (TR), 207–208 Tricuspid stenosis (TS), 207 Tricuspid valve anatomy of, development of, 366 insufficiency of, 64t opening of, 35 stenosis of, 58, 207 Triggered activity description of, 268–269 treatment of, 409–410 Triglycerides, 120b Tropomyosin, 23 Troponins (Tn), 23 defined, 175 I, 175 myocardial necrosis detection by, 176 myocardial necrosis diagnosed by, 175–176 T, 175 Truncus arteriosus, 363 TS (see Tricuspid stenosis (TS)) TTE (see Transthoracic echocardiography (TTE)) T tubules, 11 Tuberculous pericarditis, 325 Tumor necrosis factor-␣ (TNF-␣), 115 Turner syndrome, 378, 381b Two-dimensional (2-D) echocardiography apical views, 50, 51 description of, 49–50, 50 indications coronary artery disease, 55 pericardial disease, 55–60 ventricular assessments, 53, 53–54 parasternal view, 50, 51 subcostal view, 50, 51 U Unfractionated heparin, 178, 428 (see also Heparin) Unidirectional block, 270–272 Unstable angina characteristics of, 146 clinical features of, 174t clinical presentation of, 171–172 complications of, 183 definition of, 136t diagnosis of, 174 pathophysiologic findings, 145 treatment of anti-ischemic agents, 177–178 antithrombotic agents, 178–179 -blockers, 177–178 calcium channel blockers, 178 clopidogrel, 178 conservative vs early invasive approaches, 179–180 heparin, 179 nitrates, 178 Uremic pericarditis, 326 V Valsalva maneuver, 254–255 (see also Hypertrophic cardiomyopathy (HCM)) Valvular heart disease mitral valve prolapse, 201–202 pulmonic regurgitation, 40, 208 459 77237_ind.indd 459 8/11/10 8:26:39 AM Index Valvular heart disease (contd.) pulmonic stenosis, 208 tricuspid regurgitation, 39, 207–208 tricuspid stenosis, 58, 207 Valvular lesions, echocardiographic findings, 54 Variant angina characteristics of, 146 definition of, 136t pathophysiologic findings, 145 Varicose veins, 353–355, 354 Vascular cell adhesion molecule (VCAM-1), 118 Vascular endothelial growth factor, 349 Vascular smooth muscle cells atherosclerotic role of, 119, 122 description of, 115 Vasculitic syndromes characteristics of, 351t description of, 350 giant cell arteritis, 351, 351t Takayasu arteritis, 350 thromboangiitis obliterans, 351–352, 351t Vasoconstriction description of, 138b, 140 inappropriate, 142 platelet, 142 torsional stress caused by, 165 Vasodilatation, 142, 164 Vasodilators, 256 angiotensin-converting enzyme inhibitors (see Angiotensin-converting enzyme (ACE) inhibitors) angiotensin II receptor blockers (see Angiotensin II receptor blockers (ARB)) description of, 138b, 139–140, 142, 143 direct-acting, 398–400, 398t fenoldopam, 398t, 400 heart failure treated using, 237–238 hydralazine, 321, 326, 398, 398t mechanism of action, 393–394 minoxidil, 321, 398–399, 398t nesiritide, 238, 394, 403–404 nitrates (see Nitrates) sites of action, 395 sodium nitroprusside, 138b, 398t, 399, 399–400 Vasopressin, 393 VCAM-1 (see Vascular cell adhesion molecule (VCAM-1)) Veins, 353–355, 354 Venography, 357 Venous compression duplex ultrasonography, 357 Venous insufficiency, 348 Venous thrombosis (see Deep venous thrombosis) Venous vasodilators, 237 Ventricles of heart contraction of, 29 depolarization, 82–86, 84–85, 90 description of, 4–5 free wall rupture, 186 gallop of, 36 heart failure-related compensatory response, 230 nuclear imaging assessments, 67t outflow tracts septation of, 365 remodeling, 171 right (see Right ventricle) septal rupture, 186–187 septation of, 365 two-dimensional echocardiography assessments, 53, 53–54 wall stress, 140, 220–221, 230 Ventricular ectopic beats myocardial infarction-related, 185 Ventricular end-diastolic volume, 224 Ventricular escape rhythms, 281, 281–282 Ventricular fibrillation characteristic of, 299, 299 in hypertrophic cardiomyopathy, 254, 255 Ventricular filling in dilated cardiomyopathy, 248 in hypertrophic cardiomyopathy, 255 in restrictive cardiomyopathy, 257, 258 Ventricular free wall rupture, 186 Ventricular hypertrophy concentric, 230 eccentric, 230 hypertension and, 314–315 left, 92–93, 93 QRS complex abnormalities associated with, 92–93, 93, 109, 111 radiographic findings, 45 right, 92, 93 wall stress effects, 140, 230 Ventricular myocardial cells histology of, 10–11 Ventricular premature beats (VPB), 294, 294–295 Ventricular septal defect clinical features of, 372, 372–373 diagnostic studies of, 373 left-to-right shunting associated with, 373 pansystolic murmurs caused by, 39 pathophysiology of, 373 physical examination of, 373 symptoms of, 373 treatment of, 373–374 Ventricular septal rupture, 186–187 Ventricular stroke volume, 223–224 Ventricular tachycardia, 295, 295–298, 297b Venturi forces, 252–253 Verapamil, 155, 253 Very low density lipoproteins (VLDL) atherosclerosis risks and, 128 characteristics of, 120b Viral myocarditis, 245 Visceral pericardium, 1, VLDL (see Very low density lipoproteins (VLDL)) Voltage-sensitive gating, 13 VPB (see Ventricular premature beats (VPB)) W Wall stress, 220–221, 230 Warfarin, 250, 358 460 77237_ind.indd 460 8/11/10 8:26:39 AM Index Wavy myofibers, 168 Wenckebach block, 282, 282 Wide complex tachycardias, 297t Widened splitting, 33, 33–34 Williams syndrome, 381b Wolff-Parkinson-White (WPW) syndrome, 272–273, 291–292, 291–293 WPW syndrome (see Wolff-Parkinson-White (WPW) syndrome) X X-rays (see Radiography) Y Yellow softening, 170 Z Zona glomerulosa, 404 461 77237_ind.indd 461 8/11/10 8:26:39 AM ... treatment of acute and chronic heart failure 20 08: the Task Force for the Diagnosis and Treatment of Acute and Chronic Heart Failure 20 08 of the European Society of Cardiology Eur Heart J 20 08 ;29 :23 88 24 42. .. Peripheral edema 23 2 7 723 7_ch09.indd 23 2 8/11/10 8:13:45 AM Heart Failure Table 9.5 New York Heart Association Classification of Chronic Heart Failure Class Definition I No limitation of physical... systolic function) and (2) heart failure with preserved EF (e.g., diastolic dysfunction) 24 2 7 723 7_ch09.indd 24 2 8/11/10 8:13:45 AM Heart Failure Compensatory mechanisms in heart failure that initially