CHAPTER 11 Multisystem disorders 436 Takayasu arteritis Epidemiology \200 \200 Global incidence of 2.6 cases per million population annually Typically affects women (80% \200\22390% of cases) in their second and third decade Pathology \200 Idiopathic, segmental, granulomatous vasculitis of large and medium- sized arteries occurs, particularly involving the aorta and its branches, the pulmonary arteries, and, consequent ly, all major organs. Subsequent arterial stenosis (90% of cases), occlusion, thrombosis, a nd aneurysm formation (27% of cases) produce end-organ ischemia. Heart failure due to hyper tension, myocarditis, and aortic regurgitation is common. It is associated with HLA-A10, B5 , Bw52, DR2, and DR4 in Japan and Korea, but with HLA-B22 in the United States. Clinical features \200 Systemic: fever, night sweats, fatigue, weight loss, myalgia, arthralgia or arthritis, rash (erythema nodosum, pyoderma gangrenosum or lupoid), headaches, dizziness, and syncope Loca l: transient ischemic attack, visual disturbances, carotidynia, abdominal pain, limb claudi cation, asymmetric pulses (common), absent pulses (rare), post-stenotic dilations producing bounding pulses (common), and bruits (over subclavian arteries and aorta). Pregnancy with hemodynamic monitoring, malignant hypertension, pre-eclampsia and fetal complications. heart failure, angina, hypertension (may be paroxysmal), stroke, does not affect the vasculitis. Patients may have problems Imaging Angiography shows stenosis, occlusions, or aneurysms of the aorta and its primary b ranches or large arteries in the proximal upper or lower extremities. Changes are focal or segmental and not due to atherosclero- sis, \201 bromuscular dysplasia, or similar causes . Magnetic resonance imaging, magnetic resonance angiography, and com- puted tomography are u seful for serial examinations and diagnosis in the early stages. They show mural thickening and thrombi of aorta and steno- sis. Distal vessels are not imaged as well. Contrast may r eveal pre-stenotic in \202 ammatory lesions that may be missed on angiography. Echocardiography is used to assess ventricles, aortic root, and valve. Blood work \200 \200 No speci \201 c markers Normochromic normocytic anemia (50% of cases), mild leucocytosis, thrombocytosis, and elevated ESR (more than 50 mm initially) Transaminitis, hypoalbuminemia , negative ANA, and positive rheumatoid factor (15% of cases) TAKAYASU ARTERITIS 437 Treatment \200 \200 Give high-dose steroids for 4 \200\2236 weeks until ESR is normalized. If patient is steroi d-resistant or relapses, consider weekly intravenous methylprednisolone or methotrexate, da ily or monthly intravenous cyclophosphamide, cyclosporine (renal toxicity and hypertension) , azathioprine, or mycophenolate mofetil. Antihypertensives, antiplatelet drugs, and antico agulants. Balloon angioplasty and stenting, bypass surgery, and replacement with synthetic grafts. \200 Prognosis \200 \200 This is determined by the severity of vascular and end-organ damage. 60% of patients respon d to steroids but 40% relapse. Survival can be up to 95% at 15 years. CHAPTER 11 Multisystem disorders 438 Polyarteritis nodosa and other systemic vasculitides Epidemiology \200 \200 4 \200\2239 cases per million-population per year Typically affects men between the ages of 40 \200\22370 years Pathology \200 \200 Usually involves small and medium-sized muscular arteries Fibrinoid necrotizing vasculitis beginning in the tunica media and spreading to the intima and adventitia. Immune complex me diated Sequelae: aneurysm formation, hemorrhage, and thrombosis Macroscopic ( \200\234class ic \200\235) form affects kidneys (80% \200\22390%), heart (<70% and excluding pulmonary ar teries), gastrointestinal tract (50% \200\22370%), liver (50% \200\22360%), spleen (45%), a nd pancreas (25% \200\22335%). Microvasculature is typically spared. Microscopic ( \200\234 microscopic polyangiitis \200\235) form also involves the microvasculature, typically glome ruli and pulmonary capillaries. \200 Clinical features \200 \200 Fever, malaise, weight loss (>50% cases) Arthralgia, arthritis, tender subcutaneous nodules (15% cases), abdominal pain, nausea and vomiting (>60% cases), retinopathy, gastrointestin al hemorrhage (6% cases), bowel perforation (5% cases), and infarction (1.4% cases) Renal f ailure, hypertension, myocardial infarction, heart failure, and pericarditis Unique feature s of Churg \200\223Strauss syndrome include allergic rhinitis, polyposis, recurrent bronchi tis, and asthma. The heart is involved in 85% cases, causing pericardial effusion, myocardi tis, and restrictive cardiomyopathy with systolic and diastolic dysfunction. Wegener \200 \231s granulomatosis rarely causes pericarditis and coronary arteritis (10% \200\22320% cas es antemortem). It can cause myocardial infarction and sudden death. Imaging \200 \200 Selective angiography remains the gold standard. Saccular microaneurysms (2 \200\2235 mm di ameter) are seen in 60% \200\22380% of cases, with usually at least 10 per single visceral circulation. They are typically at branching points and bifurcations. Vessel ectasia and ir regularity, segmental stenosis, occlusions, and hypervascularity are also found. Similar ap pearances are found in vasculitis associated with rheumatoid disease, SLE, and Churg \200 \223Strauss syndrome. POLYARTERITIS NODOSA AND OTHER SYSTEMIC VASCULITIDES 439 Blood work \200 Elevated ESR, positive anti-neutrophilic cytoplasmic antibodies (ANCA), hypergammaglobuline mia, and hepatitis B surface antigenemia (30% cases) Churg \200\223Strauss syndrome is char acterized by peripheral blood eosinophilia (90% untreated cases), high serum IgE levels, an d positive rheumatoid factor (70% cases). Hepatitis B surface antigen testing is usually ne gative. Treatment and prognosis \200 High-dose steroids and cyclophosphamide produce remission in 90% of cases. The relapse rate is up to 40%. Five-year survival if untreated is 15%, with death from progressive renal fa ilure or gastrointestinal complications. Morbidity and mortality in Churg \200\223Strauss s yndrome are mainly due to severe asthma, heart failure, and gastrointestinal complications. Prognosis is similar to that of polyarteritis nodosa. \200 CHAPTER 11 Multisystem disorders 440 Ankylosing spondylitis Epidemiology \200 Incidence is 0.1% \200\2231% in the general population and 1% \200\2232% among HLA-B27-posi tive individuals. It is usually seen in northern Europeans, with onset during late adolesce nce and early adulthood. Juvenile onset (before 16 years) occurs especially among Native Am ericans, Mexicans, and in developing countries. It is three times more frequent in males. Pathology \200 Chronic multisystem in \202 ammatory disease. Other seronegative spondyloarthropathies inc lude reactive arthritis (Reiter \200\231s syndrome), juvenile chronic arthritis, and those in association with psoriasis and in \202 ammatory bowel disease. There is a strong associ ation with HLA-B27 and genetic predisposition. 10% \200\22320% of \201 rst-degree relativ es positive for HLA-B27 develop the disease. Typically it affects ligament and capsule atta chments to bone in sacroiliac joints and axial skeleton-enthesitis. It culminates in joint erosion, \201 brosis, and ossi \201 cation producing vertebral fusion. Cardiac involveme nt usually manifests late but occasionally precedes overt joint disease. Aortic regurgitati on (1% \200\22310% cases) causes 1) ascending aortitis (1% \200\22310% cases), resulting in thickening, stiffness, and dilation of aorta; 2) aortic valve \201 brosis, causing cusp thickening, nodularity, and shortening. Pericarditis (<1% of cases) Myocardial \201 brosi s causing systolic and diastolic dysfunction appears on echocardiography. It may progress t o dilated cardiomyopathy. Myocardial function may be further compromised by secondary amylo idosis. Atrioventricular node conduction problems with complete heart block. \200 \200 Clinical features \200 \200 Fever and weight loss Insidious low back pain progressing proximally in a relapsing \200 \223remitting pattern Chronic pain and morning stiffness (>70% cases); fatigue (65% cases); reduced mobility (47% cases) Depression (20% cases, especially females) and neurological d e \201 cits Acute unilateral iritis (25% \200\22330% cases) Chest tightness and breathless ness from restricted chest movements \200 \200 Imaging \200 \200 Erosions and sclerosis of sacroiliac joints Squared-off vertebral bodies and syndesmophytes culminating in the bamboo spine ANKYLOSING SPONDYLITIS 441 Bloods \200 \200 No diagnostic tests are needed. Elevated ESR and CRP (75% cases) are found. Treatment \200 \200 Nonsteroidal anti-in \202 ammatory drugs and sulfasalazine Specialist treatment for compli cations. Patients may require spinal or cardiac surgery. Genetic counseling Prognosis \200 Disease of the aorta and valves is more frequent with increasing disease duration. It may b e progressive or resolve. Death can be due to cardiac complications such as complete heart block. CHAPTER 11 Multisystem disorders 442 Polymyositis and dermatomyositis Cardiac involvement is frequent but usually subclinical. F ifteen percent of cases are symptomatic and 55% are noted on echocardiography. T cell \200\223mediated cytotoxicity against muscle \201 bers is found in polymyosi- tis. Complement-mediated lysis of cell membranes with vascular smooth muscle hyperplasia, coagu lation, and infarction occurs in dermatomyosi- tis. This produces a small vessel and capill ary vasculopathy that does not cause signi \201 cant deterioration in ventricular function . One-fourth of cases have myocarditis at postmortem with microscopic interstitial \201 bro sis, nonspeci \201 c in \202 ammatory in \201 ltrates, and necrosis. Ventricular functio n is usually preserved. Conducting tissues are particularly affected, producing nonspeci \201 c ST- and T-wave cha nges, atrial arrhythmias, and atrioventricular and bundle branch block. These problems are more commonly seen in children. Pericarditis is rare and seen in 25% of cases on echocardio graphy. Coronary vasospasm may occur, and provocation testing has demon- strated endothelia l dysfunction with vasoconstriction in response to intra- coronary acetylcholine. Cor pulmonale may occur secondary to primary lung disease and pul- monary hypertension. Overt cardiac complications should be treated using steroids, immuno- suppressive drugs, an d calcium channel blockers. Cardiac complications are an important cause of death, together with malignancy and lung problems. RHEUMATOID DISEASE 443 Rheumatoid disease This multisystem disease is characterized by a symmetrical, deforming, p eripheral arthropathy. Prevalence is 1%. Typically it affects females, with peak onset in the \201 fth decade. Cardiac involvement is seen in 60% of cases echocardiographically with 10% \200\22315% bein g symptomatic. It is directly related to the severity of joint disease and the presence of nodules. Half of cases have a subclinical \201 brinous pericarditis with effusions seen in 40% of cases on echocardiography. From 1% to 2% of cases are symp- tomatic. This is usually indepe ndent of disease duration and may precede it. Cardiac tamponade and constrictive pericardit is are rare and usually respond to treatment with steroids and disease-modifying drugs. More than 50% of patients with subcutaneous nodules have myocar- dial and endocardial nodul ar granulomas. They rarely compromise cardiac function through mitral valve deformity and r egurgitation or conduction problems such as \201 rst-degree (most common), left bundle br anch, and complete heart block. Of patients with severe disease, 20% have a diffuse myocarditis with nonspeci \201 c in \202 ammatory in \201 ltrates, myocyte necrosis, and \201 brosis that may cause biventri cular failure, arrhythmias, and conduction problems. Ventricular function may also be compr omised by secondary amyloidosis. Coronary arteritis is noted in 20% of cases postmortem. It is now appre- ciated that many autoimmune and systemic in \202 ammatory diseases con- tri bute to the progression, sometimes in accelerated fashion, of clinically signi \201 cant c oronary artery disease. Rheumatoid patients have an increased incidence of clinical coronar y artery disease, compared with age-matched controls. Nonspeci \201 c valvulitis produces \201 brotic, hyalinized valves with occa- sional inc ompetence. The aortic valve is affected more commonly than the mitral valve. This page intentionally left blank 445 Chapter 12 Stress testing and cardiac imaging Exercise ECG 446 Transthoracic echocardiography (TTE) 449 Transthoracic Doppler imaging 453 The standard TTE 456 Assessment of wall motion 460 Assessment of LV systolic function 462 Assessment of LV diastolic function 464 Echocardiography in aortic stenosis 468 Transesopha geal echocardiography (TEE) 470 TEE for a cardiac source of embolism 474 TEE in aortic diss ection 475 TEE in endocarditis 476 TTE/TEE in mitral regurgitation (MR) 478 Mitral valve pr olapse 480 TEE in chronic ischemic MR 482 TTE/TEE for mitral stenosis 482 TEE for prostheti c valve dysfunction 483 TEE assessment of mitral valve prosthesis 484 Echocardiography in a ortic regurgitation 486 TEE for aortic valve prosthesis 487 Intraoperative TEE 489 Echocard iographic assessment of cardiac masses 491 SPECT perfusion imaging 492 PET scanning 497 Equ ilibrium radionuclide angiography (ERNA) 501 Cardiac CT 503 Cardiac magnetic resonance imag ing (CMR) 505 Metallic prostheses and CMR 508 CHAPTER 12 Stress testing and cardiac imaging 446 Exercise ECG This is a commonly used test involving a treadmill, BP measurement, and contin uous electrocardiogram (ECG) monitoring. Overall sensitivity for coronary heart disease is around 68% and speci \201 city is 77%. This increases when considering prognostically sign i \201 cant disease, for which the test has a sensitivity of 86%. In intermediate- to high-risk patients (e.g., men with ischemic symp- toms), the test has a predictive accuracy of >90%. The test is of least value in populations who are least likel y to be suffering from ischemic heart disease, e.g., asymptomatic middle-aged women, for wh om the test has a positive predictive value of <50%. Indications \200 Diagnosis of coronary artery disease in select patients (those with higher pretest probabil ity of disease [see above]. Post-MI in patients treated with thrombolytics: pre-discharge ( submaximal test in days 4 \200\2237 to assess prognosis, decide on exercise rehabilitation program, and evaluate adequacy of treatment and need for invasive evaluation/revascularizat ion) or late post-discharge (symptom limited 3 \200\2236 weeks) testing may be used. Pre- a nd post-revascularization, especially if symptomatic, to determine the degree of exercise l imitation. Evaluation of arrhythmias: optimizing rate-responsive pacemaker function, evalua tion of known or suspected exercise-induced arrhythmias, and evaluation of treatment of the se disorders. Preoperative evaluation in select patients. Cardiopulmonary stress testing to evaluate congestive heart failure (CHF) patients for heart transplant. Evaluating the phys iological signi \201 cance of valvular lesions in asymptomatic patients, usually done with echocardiography (i.e., assessing for exercised-induced pulmonary hypertension in patients with mitral stenosis). \200 Contraindications \200 \200 \200 \200 \200 \200 \200 \200 Fever or acute viral illness Myo- or pericarditis Symptomatic severe aortic stenosis Aortic dissection Severe uncontrolled hypertension Decompensated heart failure Unstable angina or acute-phase of myocardial infarction (MI) Signi \201 cant resting arrhythmia (e.g., uncon trolled atrial \201 brillation or complete heart block) Known severe left main disease Ph ysical disability impairing ability to exercise ECG abnormality rendering interpretation of ST segment dif \201 cult (e.g., LBBB, LVH with strain or digoxin effect, WPW/pre-excitati on). In such patients, addition of exercise imaging is generally necessary to assess induci ble ischemia. \200 \200 EXERCISE ECG 447 When to stop \200 Target heart rate achieved (>85% age-predicted maximal heart rate [= 220 minus age in years ]) Exercise-limiting angina or dyspnea Dizziness Fatigue or patient requests to stop Atrial arrhythmia other than ectopic beats Frequent ventricular ectopic beats or VT ST-segment el evation in leads without Q waves or ST depression more than 5 mm Hypotension (implies globa l LV ischemia and decreased cardiac output with exercise) Exaggerated hypertensive response to exercise (SBP >220 mmHg or DBP > 120 mmHg) New high-grade AV block or bundle branch blo ck \200 \200 \200 \200 \200 Criteria for a positive test (see Fig. 12.1) \200 Flat or down-sloping ST depression J point (junction between the QRS and ST segment). Up-sl oping ST depression at least 1.5 mm (less speci \201 c). ST elevation* Increase in QRS vol tage (ischemic LV dilatation) Failure of BP to rise or hypotension during exercise (ischemi c LV dysfunction)* Ventricular arrhythmias* Typical ischemic symptoms during exercise Inabi lity to increase heart rate Also ST depression at low workload (<<6 min Bruce) in multiple lead groups, persisting into recovery, >2 mm, down-sloping pattern of at least 1 mm 80 ms after the \200 \200 \200 \200 \200 These features are indications for urgent angiography. Causes of false-positive ECG exercise tests are listed in Box 12.1. Normal Upsloping ST depression Planar ST depression Downsloping ST depression Figure 12.1 Criteria for a positive test. CHAPTER 12 Stress testing and cardiac imaging 448 Box 12.1 Causes of false-positive tests \200 \200 \200 \200 \200 \200 Cardiomyopathies Hypertension LVOT obstruction Mitral valve prolapse Hyperventilation Resti ng ECG abnormality (LBBB, LVH with strain, pre-excitation, digoxin) Electrolyte abnormaliti es (hypokalemia) Tricyclic antidepressants Syndrome X Coronary artery spasm Sympathetic ove ractivity \200 \200 \200 \200 TRANSTHORACIC ECHOCARDIOGRAPHY (TTE) 449 Transthoracic echocardiography (TTE) Introduction Despite dramatic advances in new cardiac imaging technologies, echocar- diography remains the most widely used diagnostic imaging to ol in clinical practice. Since its development by Edler and Herz almost \201 ve decades a go and routine clinical implementation a decade later, echocardiography has developed into a comprehensive and practical method to rapidly and repeatedly evaluate cardiac morphology and function. There are now published guidelines regarding the appropriate use of echocardiography in cli nical practice. Correct interpretation of an echocardiogram \201 rst requires an understa nding of the physical principles underlying the available modalities. Ultrasound physics All forms of ultrasonic imaging are based on generation of high-frequenc y (>1 mHz) acoustic pressure waves from a transducer comprised of one or more piezoelectric crystals. Current is passed across the crystal leading to material deformation and wave tr ansmission. The piezoelectric element also serves as a receiver, and waves returning from i nsoni \201 ed objects (e.g., walls, valves) deform the crystal(s), which in turn generate a current that can be sampled over time. Because the velocity of sound is constant, object location (spatial res- olution) can be de termined through timing of the returning signal. The amplitude of the returning signal is b ased on the angle of incidence (sur- faces perpendicular to the ultrasound beam are stronge r re \202 ectors) and the interface of acoustic impedances (greater differences, as occurs in the left ventricle at the tissue \200\223blood interface, lead to greater re \202 ecti vity). Returning ultrasound information is processed for maximum image integrity and then mapped t o pixels for display and storage. Although images may be stored on videotape, current metho ds of digital storage and retrieval enable optimal image integrity, easy access to archived stud- ies for comparison and research purposes, and of \202 ine processing. M-mode This was the \201 rst clinically available form of echocardiography and, while sti ll available on modern machines, has been virtually replaced in cur- rent practice by newer two-dimensional (2-D) imaging techniques. M-, or \200\234motion- \200\234, mode images de pict a single line of ultrasound data over time (Fig. 12.2). Its advantage lies in its high sampling rate (>1 kHz) and superb temporal resolution, resul ting in the ability to depict rapidly moving structures. It is especially useful for measur ing chamber dimensions and the timing of vari- ous events during the cardiac cycle. CHAPTER 12 Stress testing and cardiac imaging 450 Chest wall RV AO AV LV LV MV Chest wall RV outflow RV IVS AO AV LV MV LA PW e ANT f POST 1. Normal mitral valve 2. Mitral stenosis reduced e \200\223f slope OPEN CLOSED CLOSED a b 4. (a) Systolic anterior leaflet movement (SAM) in HOCM (b) Mitral valve prolapse (late sys tole) 3. Aortic regurgitation \200 fluttering of ant. leaflet Figure 12.2 Normal M-mode echocardiogram. AO, aortic valve; IVS, interventricular septum; L A, left atrium; LV, left ventricle; MV, mitral valve; PW, posterior wall of LV; RV, right v entricle. Adapted from R Hall, Med International 17: 774. Reprinted with permission from Lo ngmore M, Wilkinson I, Rajagopalan S (2004). Oxford Handbook of Clinical Medicine, 6th ed. Oxford University Press. TRANSTHORACIC ECHOCARDIOGRAPHY (TTE) 451 Two-dimensional or sector scanning When an ultrasound beam is swept across a chosen cardiac window, rapid sequential sampling can be performed, leading to a display of multiple \200 \234scan lines \200\235 of information and a sector image created nearly instantane- ously. Since a \201 nite number of scan lines is possible, interpolation of data between lines is performed and an image slice or sector (hence, the term sector scanning) is stored in di gital form. Through reiterative acquisition over a cardiac cycle, a movie com- posed of sequentially ac quired sectors is created demonstrating structural motion, which can then be displayed on a monitor. Beam sweeping can be performed by mechanical rotation of one or more crystals or through the use of programmed \201 ring of a bank of crystals (phased array). Sampling rates were previously dictated and limited by videotape stand- ards but, with digi tal capabilities appearing in some form on virtually all machines and replacing outdated ta pe technology, higher frame rates are possible. The availability of harmonic tissue imaging has substantially improved image resolution by eliminating artifact and improving the signal-to-noise ratio. Low-level signals emanating f rom tissue and comprising the \201 rst har- monic of the transmitted ultrasound are selec tively sampled. In this way, extraneous re \202 ections such as reverberations are \201 ltered out, leaving a cleaner image. Three-dimensional imaging While 2-D echocardiography presents user-selected sector or tomo- graphic information, 3-D echocardiography has the potential to provide a comprehensive eva luation of cardiac anatomy similar to that of more quantitatively mature technologies such as magnetic resonance imaging (MRI) or computerized tomography (CT) (see Figs. 12.3 and 12. 4). Three-dimensional echocardiography can be performed using the \200\234free- hand \200\235 approach in which multiple 2-D sectors are acquired from a probe positionally mapped using a \200\234spark gap \200\235 or magnetic tracking system. Both image and position data are stored for post-hoc 3-D reconstruc- tion. The development of the matrix array transducer and improved com- putational capabilities has made post-hoc, 3-D chamber reconstruction a reality, with accurate volumetric assessment comparable to th at of MRI. More recently, real-time acquisition of spatially limited cardiac segments has b een made available. Although there are still some limitations with the currently available technology, it is li kely that this modality will gain wider application in future clinical practice. CHAPTER 12 Stress testing and cardiac imaging 452 Long axis Coronal Sagittal Transverse Short axis Right Left Figure 12.3 The so-called anatomical position. The subject is upright and facing the observ er. Any structure within the body can be described within the references of the three ortho gonal planes \200\224two in the long axis and the third in the short axis. Reprinted with p ermission from Anderson RH, Ho SY, Brecker SJ (2001). Anatomic basis of cross-sectional ech ocardiography. Heart 85(6):716 \200\223720. Long axis of body Long axis of heart 1/3 2/3 Figure 12.4 The heart lies in the mediastinum with its own long axis tilted relative to the long axis of the body. Appreciation of this discrepancy is important in the setting of cro ss-sectional echocardiography. Reprinted with permission from Anderson RH, Ho SY, Brecker S J (2001). Anatomic basis of cross-sectional echocardiography. Heart 85(6):716 \200\223720. TRANSTHORACIC DOPPLER IMAGING 453 Transthoracic Doppler imaging \200 Analysis and quanti \201 cation of object motion within the heart is performed using Doppl er-based technologies. In brief, the same equipment described earlier propagates ultrasound aimed at moving red blood cells or tissue. Frequencies of returning ultrasound are shifted upward and downward by cells traveling toward and away from the transducer, respectively. The frequency shift is proportional to an object \200\231s velocity as described by the Dop pler equation. The signal intensity is dependent on the number of cells moving at a particu lar velocity. Velocity information is depicted graphically as a spectral pattern over time (similar to the M-mode display) or mapped to pixels as color overlaying the 2-D or 3-D imag e (color Doppler). The ultrasound beam must be as parallel as possible to the target, as of f-axis angulation by >20 causes signi \201 cant underestimation of velocities. Doppler is restricted in its ability to sample high velocities by the Nyquist limit, which is dependent on the sampling rate (the lower the frequency, the higher the evaluable veloci ty) and object depth (the deeper the object, the lower the sampling rate). When the frequen cy shift of moving objects (i.e., velocity) exceeds the Nyquist limit, aliasing occurs, pre cluding veloc- ity assessment. Pulsed Doppler Pulsed Doppler imaging allows accurate sampling of blood velocities aver- aged within a lim ited region of interest or \200\234sample volume. \200\235 Transducer elements serve both as transmitters and receivers, which allows for the selective sampling of re \202 ected ul trasound with accurate range and spatial information. Pulsed Doppler spectral displays portray velocity vectors over time (see Box 12.2). Laminar \202 ow is found within normal vessels and chambers and character- ized by a grad ual increase in \202 ow velocities from the vessel wall to the center of the lumen. It is characterized by a narrow spectral trace repre- senting a relatively discrete population o f blood velocities. Box 12.2 Flow quanti \201 cation from pulsed Doppler Quanti \201 cation Pulsed Doppler spectral traces can provide important information regard ing \202 ow quanti \201 cation and timing. By assuming that sampling occurs at an ori \201 ce with a relatively \201 xed area over the cardiac cycle (e.g., the left ventricula r out \202 ow tract) and integrating the time velocity spectral curve (time \200\223veloci ty integral [TVI]), the area under this curve can be multiplied by the area of the ori \201 ce (determined from 2-D or M-mode Echo), resulting in the stroke volume. CHAPTER 12 Stress testing and cardiac imaging 454 Turbulent \202 ow occurs across stenotic or regurgitant ori \201 ces (valves, shunts, et c.) where high pressure gradients lead to high red cell kinetic energy and disordered, high -velocity motion. It is graphically portrayed as spectral broadening. Aliasing often occurs with high-velocity jets, leading to \200\234wraparound. \200\235 Continuous wave (CW) Dop pler permits beam steering. Transducer ele- ments are shared for purposes of CW and intermi ttent 2-D imaging. A virtual cursor positioned over the 2-D image can be moved to guide and minimize off-axis sampling angulation. CW Doppler velocities are depicted as a \201 lled-in spectral tracing as all of the veloc ities along the sampling cursor (or ultrasound beam) are measured. Blood cells traveling at the fastest velocities are represented at the outer edge of the spectral trace (peak) or d arkest line of the trace (modal) velocities. Color Doppler \202 ow imaging employs multigate pulsed Doppler to portray blood \202 ow overlying the 2-D image. Information is used to detect regur- gitant or stenotic lesions a nd shunts. Qualitative assessment of velocity amplitude and direction is possible using col or maps. \200 Pixels are assigned a color based on user-con \201 gurable mapping parameters. Pixel color is based on average velocity in the pixel region of interest. By convention, a color map s ystem is used in all machines, with blue representing \202 ow away from the transducer an d red depicting \202 ow toward the transducer (see Fig. 12.5). The lighter the color, the higher the velocity. Turbulent velocities can be displayed as a green hue with variance ma pping. Aliasing is depicted as a mix of colors, or a \200\234mosaic \200\235 pattern. \200 (a) (b) Red Red Blue Red Figure 12.5 Color Doppler (red: \202 ow toward transducer; blue: \202 ow away from tran sducer). (a) Top: systolic blue \202 ow of left ventricular ejection; bottom: red \202 ow of diastolic mitral in \202 ow, shown from parasternal long-axis window. (b) Left: red \202 ow of diastolic tricuspid in \202 ow; right: red \202 ow of diastolic mitral in \202 ow shown from apical four-chamber window. TRANSTHORACIC DOPPLER IMAGING 455 Tissue Doppler imaging (TDI) is used to assess low-velocity displacement of myocardium. A h igh pass \201 lter excludes higher frequency blood \202 ow signals, leaving only low-ve locity shifts attributable to tissue motion. \200 Mitral or tricuspid annular motion can be tracked and correlates with systolic and diastoli c performance of the associated ventricles. Regional wall motion can be assessed for displa cement that may be affected by overall cardiac motion or local tethering. Strain rate imaging can measure regional thickening and thinning inde- pendent of the exter nal in \202 uences on wall motion that can affect tissue Doppler measurements. With strain rate imaging, two sampling sites are simultaneously acquired and intersample displacement (strain) over time (strain rate) can be determined. Strain and strain rate can be determine d in the radial, longitudinal, and circumferential directions. For calculations from Doppler measurements, see Box 12.3. Box 12.3 Calculations from Doppler measurements Valve gradients The velocity of blood cells traveling through a narrow ori \201 ce is dire ctly proportional to the pressure gradient at that point in time. This relation- ship is ap proximated by the simpli \201 ed Bernoulli formula: Gradient (mmHg) = 4 V (where V = peak Doppler velocity in m/sec) In situations where there are high \202 ow velocities (e.g., aortic steno- sis with high LVOT velocities), the \202 ow before the stenosis must be accounted for. 2 \200\223 V1 2 ) Gradient (mmHg) = 4(V2 lesion and V1 = velocity proximal to the lesion) (where V2 = velocity across the Both peak and mean gradients can be determined by measuring the maximal velocity and veloci ty \200\223time integral (VTI). Valve area (continuity equation) This is based on the principle that \202 ow proximal to the valve = \202 ow across the valve. The most common application is the calculation of a ortic valve area in patients with aortic stenosis, as shown below. LVOT \202 ow = LVOT ar ea \227 LVOT (VTI) by pulsed Doppler LVOT area = (cid:89) (LVOT diameter in PLAX/2)2 Aorti c valve \202 ow = Aortic valve area \227 Aortic valve VTI by CW Doppler Aortic valve \202 ow = LVOT \202 ow, Aortic valve area = (LVOT VTI/Aortic valve VTI) \227 LVOT area CHAPTER 12 Stress testing and cardiac imaging 456 The standard TTE Most laboratories employ imaging protocols incorporating acquisition of im ages from standard views in a speci \201 c sequence. Image quality is maxi- mized by avoid ing overlying lung artifacts and rib re \202 ections. Pulsed and color \202 ow Doppler i s performed following 2-D imaging in each view. Standard echo windows (and views) and the main cardiovascular struc- tures visualized are as follows: Left parasternal window \200 Long axis (PLAX): left atrium and ventricle, aortic root, mitral and aortic valves, and rig ht ventricle (see Figs. 12.6 and 12.7) Short axis (PSAX): 4 levels \200 Aortic valve/left atrial level: includes tricuspid valve (TV), right ventricular out \202 ow tract (RVOT), pulmonic valve (PV), and pulmonary artery (Pa) (see Fig. 12.6) \200 Left ventricular base/mitral valve \200 Mid-left ventricle/papillary muscle \200 Left ventr icular apex Right ventricular in \202 ow Apical window \200 4 chamber (A4C): both atria, ventricles and AV valves, inferior septal and anterolateral LV walls (Fig. 12.7). Pulmonary veins may also be seen. 5 chamber (A5C): A4C angled anteriorl y to LV out \202 ow tract (the \200\234 \201 fth chamber \200\235 in this view is the ao rtic root) 2 chamber (A2C): left atrium, anterior and inferior LV walls 3 chamber/apical lo ng axis (A3C): apical version of PLAX view with anteroseptal, posterior or inferolateral wa lls and LV out \202 ow tract \200 Suprasternal window (SS) \200 Aortic arch and head vessels \200 Proximal descending tho racic aorta Subcostal window (SC) \200 \200 4 chamber and short axis views are often imaged The inferior vena cava (IVC) and descending aorta can also be seen Right parasternal window (optional) \200 Ascending aorta and CW Doppler of aortic valve Chamber evaluation Chambers are routinely measured from M-mode tracings or, more com- monly , using digital calipers to perform assessment from 2-D images. The PLAX view is the standa rd for most chamber measurements. Area tracings provide enhanced accuracy but require adequate endo- cardial visualization for optimal accuracy. Chamber volumes are derived from 2-D measurements using geometric modeling. The most common volumetric approaches include the modi \201 ed Simpson \200\231s biplane method of disks and the area \200\223length formula. THE STANDARD TTE 457 (a) (b) Pa RVOT Rcc Ao Ncc Lcc RV Ao LV LA RA LA Figure 12.6 (a) Parasternal long axis view; (b) parasternal short axis view (aortic level). Ao, aorta; LA, left atrium; Lcc: left coronary cusp; LV, left ventricle; Ncc: noncoronary cusp; Pa, pulmonary artery; RA, right atrium; Rcc Ao: right coronary cusp of aortic valve, RVOT, right ventricular out \202 ow tract. (a) (b) RV RV LV RA IVC (c) (d) RV LV Ao Pa RA LA Figure 12.7 (a) Parasternal long axis view (RV in \202 ow); (b) parasternal short axis (mi tral valve level); (c) apical 4 chamber view; (d) suprasternal long axis view. For abbrevia tions see Figure 12.6; IVC, inferior vena cava. CHAPTER 12 Stress testing and cardiac imaging 458 3-D echo has also been validated as an accurate and reproducible method of chamber volume q uanti \201 cation and is superior to standard 2-D imaging if done properly. Most clinical labs perform measurements in real time during image acquisition, though moder n workstations allow for comprehensive off- line analysis. End-diastole is usually de \201 ned as the beginning of the QRS complex and end-systolic measurements are performed at max imum LV contraction. The American Society of Echocardiography has published guidelines for standard chamber quanti \201 cation and it is recommended that these can be applied in rou tine clinical practice. Left atrium \200 \200 Measure at ventricular end-systole. Linear (anteroposterior [AP]) measurement is made from PLAX view at aortic cusp level. Area (A4C) and volume (modi \201 ed Simpson \200\231s form ula or area \200\223length method using the A4C and A2C views) are also often quanti \201 ed. Left ventricle \200 Measure chamber diameter from PLAX at mitral lea \202 et tips at end- diastole and end-sys tole. Septal and posterior wall thickness should be measured from PLAX at mitral lea \202 et tips in end-diastole. Volumes (modi \201 ed Simpson \200\231s biplane method of disks) Derived variables \200 \200 Fractional shortening : FS = ([LVIDd \210\222 LVIDs]/LVIDs) x 100 where LVID = LV internal diameter in diastole (d) and systole (s). Ejection fraction (from 2-D- or 3-D-generated vo lumes or derived from M-mode [e.g., Teicholz formula]) Mass can be derived from M-mode meas ures (ASE-modi \201 ed Penn formula), 2-D volumetric models, or 3-D reconstruction. M-mode mass calculations tend to overquantify LV mass. Aortic root and ascending aorta \200 Linear measurements from 2-D PLAX view or M-mode at end- diastole. The root is measured at cusp level, and aorta is measured at sinotubular junction and 2 cm above this. Right atrium \200 Area, inferior/superior and lateral/medial diameter measurements from A4C view THE STANDARD TTE 459 Right ventricle \200 Irregular shape makes standardized quanti \201 cation and geometric modeling dif \201 cul t. Diameter typically is measured in A4C view at base or mid-ventricle. Qualitative compari son of size relative to left ventricle (if normal in size). \200 Pulmonary artery \200 Diameter measurement in PSAX at aortic valve level. CHAPTER 12 Stress testing and cardiac imaging 460 Assessment of wall motion Overall assessment is based on review of wall segments from multi ple standard views. In general, abnormalities of LV regional function should be apparent in more than one view. Regional wall motion is best described using the standard 16-segment model recommended by the American Society of Echocardiography: \200 Basal (6): posterior), inferior, inferoseptal Mid LV (6): Apical (4): tip of the apex is in cluded as a 17th segment.) anteroseptal, anterior, anterolateral, inferolateral (or \200 same as above anterior, lateral, inferior, and septal. (In some systems the Regional functional assessment Systolic function should be classi \201 ed as normal, globa ly hypokinetic, or demonstrating the presence of regional wall motion abnormalities. Global hypokinesis is consistent with cardiomyopathy, either ischemic or nonischemic. Some degree of regional wall motion abnormality may be present in nonischemic cardiomyopathy. The presence of distinct regional wall motion abnormalities with large areas of normal regi onal function is suggestive of underlying coronary artery disease, either areas of infarct or stunned/hibernating myocardium. Evaluation of regional wall thickening is preferable to endocardial motion, which may be in \202 uenced by tethering of adjacent segments. Unfortu nately, this is not always possible when endocardial or epicardial border de \201 nition i s suboptimal.