DIAGNOSTIC TESTING

0095-4543/00 $15.00 + .OO

CARDIOVASCULAR DISEASE

DIAGNOSTIC TESTING Dan E. Brewer, MD

INTEGRATING CLINICAL DATA

All diagnoses begin with the history and physical examination. When carefully performed, these will yield a diagnosis in most cases and they will direct the physician to judicious diagnostic testing in other case^.^,^^ The results of any diagnostic test must be interpreted within the context of the information already gained from the history and physical examination.13 After a clinical examination, diagnostic testing can provide useful information to help confirm or rule out a diagnosis, however, no diagnostic test is perfect. Even "gold standard tests, such as coronary arteriography for the diagnosis of coronary artery disease, do not correlate perfectly with pathology studies and are not perfect predictors of future pr0gnoses.2~,~~ For this reason, the history and physical examination are used to form a pretest probability that a certain condition is present. The information gained from subsequent diagnostic tests is integrated with that pretest probability to form a posttest probability. The posttest probability is the probability that the diagnosis being considered is correct. Formal quantitative analysis of this process is called Bayesian analysis.@Examples of Bayesian analysis of serial diagnostic tests are shown in Fig. 1. In the case of chest pain, the characteristic qualities of the pain, its relation to exertion, and its location, radiation, and time course combine to characterize the pain as typical angina, atypical angina, or nonanginal pain. Combining these features of the history with the age and sex of the patient plus other risk factors creates a pretest probability for significant coronary artery disease as the cause of the pain (Table 1). This pretest probability is then used to guide the choice and interpretation of further diagnostic testing.@ From the Department of Family Medicine, University of Tennessee, Knoxville, Tennessee PRJMARY CAI& VOLUME 27 NLTMBER 3 SEPTEIMBER 2000

785

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History {Dre-test)

After Exercise ECG After Thallium scanning host-test # l ) SPECT Ipost-test #2) + +-. 47% 2mm 18%

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5%

5%

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0.4%<

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Asymptomatic- 35 yo male <0.5mm

46%

+16%

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1-1.5mm+78%

2mm -90%

80%

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1.5mm

+

-c iI f-

31%

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4%

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89%

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41% 96%

64% Atypical angina 45 yo gale .+98% 94% 74%

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L15% Typical angina - 55 year old woman Figure 1. The effect of independent tests in sequence on probability of disease. (Data from Diamond GA, Forrester JS: Analysis of probability as an aid in the clinical diagnosis of coronary disease. N Engl J Med 300350-1358,1979; and Fleischmann KE, Hunink MG, Kuntz KM, et al: Exercise echocardiography or exercise SPECT imaging? JAMA 280:913-920, 1998.)

For those conditions that have been analyzed quantitatively, the clinical information gained from the history and physical examination is usually a more powerful predictor of diagnosis than subsequent diagnostic tests. A clear story of typical angina is a more consistent and powerful predictor of coronary artery stenosis than a positive nuclear medicine perfusion scan." Creating a pretest probability of disease with a careful history and physical examination helps to clarify the choice of subsequent diagnostic tests. For example, if the physician is trying to rule out coronary disease, a patient with a high pretest probability based on a clear history of typical angina should not be tested with exercise electrocardiography (ECG) for diagnostic purposes because a negative result will still leave an intermediate probability of disease. A positive test result in such a patient will only slightly increase the probability of disease. On the other hand, a person

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Table 1. PROBABILITIESOF CORONARY ARTERY DISEASE Pre-test Likelihood of Coronary Artery Disease Non-anginal Chest Pain Age

Men

Women

30-39 40-49 50-59 60-69

5% 14% 22% 28%

1% 3% 8% 19%

Atypical Angina

Typical Angina

Men

Women

Men

Women

22%

4% 13% 32% 54%

70% 87% 92% 94%

26% 55% 79% 91%

46% 59% 67%

Post-test Likelihood alter 2mm ST Segment Depression on ETT Non-anginal Chest Pain

Atypical Angina

Typical Angina

Age

Men

Women

Men

Women

Men

Women

30-39 40-49 50-59 60-69

38% 65% 75% 81%

8% 24% 50% 72%

76% 91% 94% 96%

33% 63% 84% 93%

96% 99% 99% 99%

79% 93% 98% 99%

Adapted from Diamond G, Forrester J: Analysis of probabitity as an aid in the clinical diagnosis of coronary artery disease. N Engl J Med 3003350-1358,1979; with permission.

with a low pretest probability of sigruficant coronary disease should not be subjected initially to the expense and risk of invasive coronary arteriogra~hy.2~ The ability of a test to discriminatebetween patients with disease and those who do not have the disease is expressed in terms of its sensitivity and specificity. Sensitivity and specificity are characteristics of the particular test, however, and it is often more helpful to consider diagnostic testing from the standpoint of negative and positive predictive value (Fig. 2). Whereas sensitivity and specificity give information about the characteristics of the test, positive and negative predictive value integrate clinical data to give informatioh about the patient. To increase negative predictive value, a highly sensitive test is used. Sensitivity is used to help rule out disease (although in dealing with patients it is rare to be able to truly rule out a disease-physicians must be satisfied with diminishing the probability of disease below a specific threshold). The mnemonic device SNOUT (Sensitive/Negative rules OUT) can be used to remember this concept. A highly specific test produces a high positive predictive value. It helps to rule in disease (SPIN for Specific/Positive rules IN).42 In most cases, as the sensitivity increases in a particular test, the specificity decreases. A I-mm ST-segment depression that occurs at 13 metabolic units (mets) of exercise workload and resolves quickly at rest is likely to be a false-positive finding (i.e., the result has a low specificity and, therefore, a poor positive predictive value). That same 1-mm ST-segment depression occurring at less than 5 mets of exercise is more specific for the diagnosis of coronary artery ~tenosis.'~

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Positive Test Result Negative

j II

Target disorder Present Absent

II

n

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Predictive values (PPVDJPV)

1

14 Test Characteristics (Sensitivity/Specificity) Sensitivity: The proportion of patients with the target disorder who have a positive test result (a/a+c). Specificity:The proportion of patients without the target disorder who have a negative test result (d/b+d). Positive Predictive Value: The proportion of patients who have a positive test who have the target disorder (a/a+b). Negative Predictive Value: The proportion of patients who have a negative test who do not have the target disorder (d/c+d). Pretest probability (prevalence): The proportion of patients who have the target disorder as determined before the test is carried out (a+c/a+b+c+d). Pretest odds:The odds that the patient has the target disorder before the test is carried out (pretest probability/[ 1-pretest probability]). Likelihood ratio (LR):The ratio of the probability of a test result among patients with the target disorder to the probability of that same test result among patients who are free of the target disorder. LR for a positive test = sensitivity/(l-specificity); LR for a negative test = (l-sensitivity)/specificity. Post-test odds:The odds that the patient has the target disorder after the test is carried out (pretest odds x LR). Post-test probability:The proportion of patients with that particular test result who have the target disorder (post-test odds/[ 1+post-test odds]). Figure 2. Terms used for diagnostic testing. (Adapted from Haynes B, Sackett D (eds): Evidence Based Medicine. Philadelphia, British Medical Journal Publishing Group, 1999; with permission.)

Although research papers often present a single dichotomous value for the sensitivity and specificityof a particular test, experienced clinicians recognize that most tests actually have multiple cut-offs and a test result may give far more information than can be expressed with single values of sensitivity and specificity (Table 2). These ideas can be expressed with multiple likelihood ratios for various cut-off points or, more formally, with a receiver operating characteristics curve.'O Whereas the sensitivity of exercise electrocardiography is only about 50% for the presence of any hemodynamically significant coronary artery stenosis in a primary care population, its sensitivity is 85% for triple vessel disease.I9Furthermore, the sensitivity of any particular exercise test increases with the exercise

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Table 2. MULTIPLE DIAGNOSTIC CUTOFFS Target Disorder

Result

Likelihood Ratio

History

75% coronary stenosis

Exercise ECG

75% coronary stenosis

SPECT scan

75% coronary stenosis

Typical angina, male Typical angina, female Atypical angina, male Atypical angina, female >2.5 mm ST depression 2-2.91~1m 1.5-1.9 IIUII 1-1.4 n ~ n 0.5-0.9 n ~ n <0.5 mm Positive Negative

115 120 14 15 39 11 4.2 2.1 0.92 0.23 3.6 0.05

Test

From Sackett DL, Haynes RB, Tugwell F: Clinical Epidemiology. Boston, Little, Brown, 1985; with permission.

workload at which abnormalities are first seen, so that a patient who can achieve greater than 13 mets of exercise (completing the fourth stage of a Bruce protocol) with no ECG changes is less likely to have significant coronary disease than someone who can only perform 5 mets of exercise.I9 Although a test may have an apparently poor sensitivityfor detection of one outcome (e.g., the presence or absence of coronary disease), it may have a desirable sensitivity for detection of a more severe disease state that is actually of greater intere~t.~ Also, the ability of the test to establish a prognosis (chance of death or subsequent myocardial infarction) for a patient may be much more powerful than its diagnostic characteristics. This is the case for exercise treadmill testing, exercise echocardiography, and radionuclide scanning of the heart. They are all more accurate predictors of the patient‘s prognosis than of the patient’s a n a t ~ m y ? ~ This ,~~,~ ability to predict prognosis has been demonstrated in women as well as in men?J1,*OA patient who can accomplish 13 mets of exercise without ECG changes has less than a 1% annual mortality rate from cardiovascular disease.& When considering diagnoses of cardiac disease, the primary care physician is generally in the situation of trylng to rule out serious disease. Cardiac diseases are potentially serious problems with significant morbidity and there are specific medical and surgical interventions that have been proved to improve prognosis. In this setting, it is the job of the primary care physician to sort (or risk s t r a w ) patients into those at higher risk (who should have an expedited evaluation for possible intervention by a cardiologist) from those at lower risk (who can be treated medically to reduce the risk of disease progression). The primary care physician’s first job is to rule out serious or unstable disease; therefore, the sensitivity of a particular cardiac diagnostic test is its most important characteristic in the primary care setting. A sensitive test applied to a patient with a low pretest probability creates a high negative predictive value.

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CORONARY ARTERY DISEASE Stable Angina

The first task of the primary care physician is to distinguish patients with a cardiac cause for their chest pain from those with other causes. The majority of this diagnostic process is accomplished with the clinical history, examination, and readily available tests such as ECG and chest radi~graph?~ Subsequent diagnostic tests may be used to clarify the diagnosis or may be used for risk stratification and therapeutic decisionmaking.& Exercise Electrocardiography

The least expensive and most readily available test for evaluation of the patient with suspected coronary artery disease is exercise ECG, also known as the exercise tolerance test (ETT). It is an appropriate initial test for patients who have the capacity to exercise, are not taking digoxin, and do not have a substantially abnormal resting ECG. Patients with widespread resting ST depression, complete left bundle branch block, left ventricular hypertrophy, preexcitation syndromes, and paced rhythms should have an enhanced imaging study rather than an exercise ECG.% An ETT can be done using a number of protocols with bicycle ergometry, arm-crank ergometry, or treadmill exercise. Treadmill protocols are the most commonly used protocols in America. They have the advantage of creating higher workloads in most patients than other protocols as a larger muscle mass is used in the exercise and there is less problem with fatigue of specific muscle groups. The advantages of bicycle ergometry are that equipment costs are significantlyless, there is often less movement artifact on the ECG tracing, and patients who are not comfortable with the coordination required to walk on a treadmill usually can perform on the bicycle. Arm ergometry is usually reserved for patients with limitations of their lower extremities that preclude either the treadmill or biqcie.15 The most commonly performed treadmill test protocol is the Bruce protocol, which uses 3-minute intervals of increasing slope.and speed. The Bruce protocol is best used in patients who can be expected to perform at least 8 mets of exercise, which is the equivalent of walking briskly up stairs. There are many other protocols available with shorter stages, more gradual increases in workload, or lower initial workloads. Several of these are specifically designed for patients with poor exercise capacity or who should not be stressed to their maximum capacity (such as a patient who has had a recent myocardial infarction). Each protocol has its own advantages and most treadmill operators have a few favorite ones. Anyone who performs ETT should be familiar with several protocols to select an appropriate protocol for any particular patient. With the use of any protocol, the patient’s ECG is monitored during and after exercise to detect evidence of ST-segment changes or dysrhyth-

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mia. ST-segment abnormalities should be characterized by their shape (upsloping, flat, or downsloping depressions or ST elevations) and the magnitude of the ST deviation from the baseline, by the workload at which they appeared, and by how quickly they resolve when exercise is stopped. Many upsloping ST-segment depressions are normal effects of exercise, and some expertise is required for interpretation. Flat or downsloping ST-segmentdepressions are abnormal. ST-segment elevation in an area of the heart that does not show corresponding Q waves of a previous infarction are also abnormal and may represent an area of severe coronary stenosis, but this is a relatively rare finding. ST-segment depression is typically the main variable cited in interpreting the ETT as 'positive' or 'negative,' but many other pieces of information are also available from the test that should be included in the interpretation. Blood pressure response, symptoms, dysrythmias, and the patient's perceived exertion should all be recorded during the test. Work capacity (described in mets achieved) and double product (peak systolic blood pressure X peak heart rate) are both important prognostic indicators independent of any ischemic response seen during the test. Abnormal hemodynamic responses that suggest ventricular systolic dysfunction with exercise (failure to raise the heart rate appropriately or a drop in systolic blood pressure) are suggestive of severe coronary d i s e a ~ e . ' ~ , ~ ~ Work capacity, character of chest pain, and the ST-segment response to an exercise test can be combined to form the Duke treadmill score (DTS) for This scoring system for the ETT, which has been validated in both inpatient and outpatient populations, can give an estimate of the patient's chance of coronary morbidity over the subsequent year. Alternatives to Exercise Electrocardiography

Other diagnostic tests have been devised that allow stress testing in patients who cannot exercise and improve interpretation when the exercise ECG is likely to be inconclusive.These tests may increase the accuracy of stress testing in situations in which the exercise ECG leaves significant uncertainty. The disadvantage of each of these tests is that they are significantly more expensive and inconvenient than the exercise ECG (Table 3). Because they are often performed by a specialty consultant, the primary care physician loses the intangible information gained from watching the patient exercise. Patients who cannot exercise require some type of pharmacologic stress. Pharmacologic stress can be generated with dobutamine, dipyridamole, or adenosine. Dipyramidole and adenosine cause coronary vasodilatation and thereby enhance coronary blood flow. This flow increase is limited in arteries with significant stenosis, leading to relative hypoperfusion in areas supplied by those arteries. This relative hypoperfusion can be detected by advanced imaging techniques. The beta adrenergic effects of dobutamine in high doses raise heart rate, systolic blood pressure, and myocardial contractility. There is an increase in myocardial blood flow secondary to this increased metabolic demand. Dobutamine is

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Table 3. COMPARATIVE COSTS FOR CARDIAC DIAGNOSTICTESTS Procedure

ECG Chest radiograph Exercise ECG SPECT Imaging Echocardiography Doppler Color Doppler Exercise ECHO PET scan, heart MRI, heart Angiography Holter monitor Pharm Stress SAECG TE ECHO Right heart cath EP study Tilt table test

CPT Code

RBRVS “Units”

“ W o r k Component

93000 71020 93015 78465 93307 93320 93325 93350 78459 75554 93510+93545 93230 93024 93278 93312 93501 93619 93660

0.80 0.96 3.25 14.15 5.96 2.61 3.12 3.56 N/A* 14.01 46.55 4.95 3.76 1.81 7.60 23.99 24.11 3.50

0.17 0.22 0.75 1.46 0.92 0.38 0.07 0.78 1.83 4.73 0.52 1.17 0.25 2.20 3.02 7.32 1.89

*Medicare has not established a fee for this procedure. It is considered experimental. Charges for PET scans of heart are generally 1.5 to 2 times the charge for S E C T scan of the heart but may vary.

typically used as the agent for stress induction in echocardiography, and adenosine or dipyramidole are used more frequently in radionuclide scanning for patients who cannot exercise. Although these agents act in different ways, their diagnostic performance characteristics in clinical settings is remarkably similar.Iz Stress-induced ischemia can be detected by echocardiography or by radionuclide scintigraphy (single-photon emission computed tomography or SPECT) with technetium-99 or thallium-201 based agents. Thallium acts as an analogue of potassium and is taken up by cardiac muscle in proportion to the blood flow to any area of muscle. An image is obtained after the agent is infused during stress, which indicates if there are areas of relative ischemia or hypoperfusion. During rest, the tracer then redistributes over several hours in the areas that were initially underperfused during stress. A second image is obtained 3 to 4 hours after exercise and the two images are compared. An area that does not show evidence of significant perfusion on either image is considered to be nonviable muscle (most commonly the site of a completed infarction). Areas with tracer uptake at rest but not during exercise are interpreted as viable muscle that is underperfused. These areas may benefit from revascularization by surgery or angioplasty. Occasionally delayed reperfusion may be seen in a scan taken at 24 hours. These prolonged scans improve the sensitivity of SPECT scanning for detecting viable muscle.41 Technitium 99m-based agents are similar to thallium 201 but have a shorter half-life and higher emission energy levels and do not redistribute during rest. The shorter half-life and higher energy allow higher doses of

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tracer to be given and produce clearer images with less artifact. Examples of such artifacts include attenuation of the signal from breast tissue, the diaphragm, or obesity. Because there is no redistribution of technetium, this agent can be injected in the emergency department during acute pain and images obtained after the patient has been stabilized.23A second injection for rest images is required in a typical exercise protocol using technitium. Studies indicate that the diagnostic performance of technitium is similar to that of thallium.4l Echocardiography detects ischemia by imaging regional ventricular wall motion abnormalities when the patient is stressed. The stress can be exercise or an agent such as dobutamine. Echocardiography has the advantage of providing additional information on ventricular function, ventricular hypertrophy, and valvular anatomy. It is also less expensive in most institutions than radionuclide scanning (Table 3). Exercise echocardiography requires more operator expertise than radionuclide scanning and is theoretically less sensitive for mild ischemia. Published studies, however, indicate that radionuclide scanning and exercise echocardiographyhave similar test characteristicsin practice.I4Most experts advise that the choice of tests be made primarily on the basis of the expertise available within a particular institution rather than on any substantial difference in test characteristic^'^ (Table 4). Several other imaging modalities are under development for diagnosing ischemic heart disease. Positron emission tomography (PET) has been extensively studied for the diagnosis of ischemia and for determining the viability of myocardial muscle? It appears to be the most accurate modality available for determining viability, but the high cost of PET for its relatively small incremental diagnostic gain over other modalities is prohibitive in most Gated magnetic resonance (MR)imagingI6 and electron beam computed tomography (CT)’ are being developed for the noninvasive imaging of coronary anatomy. Their place in clinical practice is not yet determined. Table 4. TEST CHARACTERISTICS-DIAGNOSISOF CORONARY STENOSIS Exercise ECG

A11 patients Sensitivity Specificity Severe disease-any abnormality Sensitivity Specificity Severe disease-multiple abnormalities Sensitivity Specificity

Exercise SPECT

Exercise ECHO

65% 77%

87% 64%

85% 77%

83% 85%

92% 21 %

92% 54%

44%

60% 88%

60%

Data from Gibbons R, Galady G, Bearsley JW, et ak ACC/AHA guidelines for exercise testing: A report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee on Exercise Testing). J Am Coll Cardiol30260-315,1997; and FleischmannKE, Hunink MG, Kuntz KM, et al: Exercise echocardiography or exercise SPECT imaging: A meta-analysis of diagnostic test performance. JAh4A 280913-20,1998,

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Coronary arteriography is the ”gold standard” for diagnosing coronary artery stenoses. It offers detailed imaging of the coronary arteries that other tests cannot reproduce and is a necessary prelude to any definitive therapeutic procedure such as angioplasty or atherectomy.It can offer direct measurement of systolic ejection fraction, which is important for risk stratification and consideration of surgery. The obvious disadvantages of arteriography are its cost and invasive nature. In recent literature it has been pointed out that arteriography tends to underestimate diffuse atherosclerosis and cannot accurately predict which stenoses are likely to rupture and create myocardial infarctions.l8 Acute Manifestations of Coronary Artery Disease

Coronary artery disease manifests itself clinically in a spectrum of diseases, from stable angina to acute coronary syndromes (unstable angina and non-Q wave infarction) to completed myocardial infarction. Categorizing patients with coronary disease into these three categories helps to organize their subsequent diagnostic evaluation and treatment.7 The diagnosis of acute myocardial infarction (AMI) is usually made on the basis of the clinical scenario, ECG changes, and biochemical serum markers of myocardial damage. Other tests such as echocardiography, PET scanning, and nuclear medicine scanning also can be used when the diagnosis is uncertain. They are also used to contribute prognostic information or to guide specific treatments such as long-term angiotensin-converting enzyme (ACE) inhibitors after the AM1 in patients with reduced left ventricular systolic function. The most definitive ECG finding of completed myocardial infarction is a significant Q wave in at least two contiguous leads. In the acute setting, myocardial infarction can have less specific ECG changes such as ST-segment elevation, ST-segment depression, T-wave inversion, peaked T waves, or a new onset of left bundle branch block. In the era of acute myocardial salvage techniques such as thrombolysis and acute angioplasty, many infarctions do not go on to develop large Q waves (which presumably represent a relatively large area of dead myocardium). Patients with such non-Q wave infarctions are most commonly treated in the same manner as those with unstable angina. Further diagnostic testing is often needed for these patients to assess the amount of myocardium at risk for recurrent infarction and the possible need for revascularization. Those at high risk for complications are best triaged directly to coronary arteriography, but recent trials have suggested that those who are at low risk can be managed with a more conservative diagnostic strategy of noninvasive testing similar to that described in the previous section on stable angina? Serum Markers of Myocardial Damage

Creatinine kinase (CK) and its subforms (CK-MB) are the most established biochemical markers for acute myocardial infar~tion.2~ Lactate de-

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hydrogenase (LD) and its subfractions have been used in the past as supplemental tests because they are present in the serum for a longer time than CK, but LD is now supplanted by cardiac troponins, which are much more specific for cardiac damage than LD. In many centers, cardiac troponins have replaced CK-MB as well. Some emergency department protocols also use myoglobin, which is very sensitive for myocardial injury and appears in the serum earlier than the other markers. Its early appearance in the serum makes it potentially valuable for decision making in the first few hours after the onset of chest pain, but its lack of specificity means that it cannot be used to make a definitive diagnosis of AMI.37 Creatinine kinase is found in many tissues of the body, but the MB subfraction is found in highest concentrationsin cardiac muscle. It can be identified in the serum as early as 30 minutes after cardiac injury but typically appears a few hours after injury, peaks at 24 hours after injury, and is cleared from the serum in 72 hours. Ongoing or recurrent injury as well as decreased renal clearance can make the CK-MB remain elevated for longer periods of time. Summary characteristics of the serum markers are shown in Table 5. The cardiac troponins (troponin T and troponin I) are believed to be both more sensitive and specific than CK-MB for the diagnosis of myocardial injury." Their performance in clinical practice is still undergoing evaluation. Troponin I is theoretically more specific to cardiac muscle than troponin T because it is not expressed by other tissues, but trials that look at both markers do not show a significant difference in a clinical setting.35 Troponin T can sometimes give false-positive results in patients with renal failure and extensive skeletal muscle damage.49 All the biochemical markers should be tested serially over 12 to 24 hours to maximize their diagnostic accuracy.The more elevated the serum level of the marker, the more specific it is for myocardial injury and the more useful for establishingthe diagnosis of myocardial infarction. Levels that are just above a minimal cut-off are more likely to be false positives (owing to diminished specificity), although calling such levels positive maximizes the sensitivity of the markers. The magnitude of the rise of the serum marker is also correlated with the amount of myocardium that is damaged in the infarction." In acute chest pain syndromes, troponin levels seem to be able to help stratlfy patients into high and low risk for subsequent A patient with a typical clinical syndrome of unstable angina (pain at rest, Table 5. SERUM MARKERS OF MYOCARDIALDAMAGE

Initial levels Peak Duration Sensitivity*<6 h Sensitivity 24 h

Myoglobin

CK-MB

Troponin T

Troponln I

1-3 h 6-10 h 24-36 h 70% 95%

3-8 h 9-30 h 48-72 h 45% 96%

2-6 h 10-24 h 10-15 days 44% 85%

2-6 h 12-24 h 7-10 days 56% 84%

Snsitivity for myocardial infarction.

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new onset of typical exertional pain, or typical anginal pain at lower levels of exertion than previously) but negative serial troponin levels appears to be at very low risk of immediate complications.The combination of a lowrisk assessment by ETT done prior to discharge and negative troponin levels consistently identifies a group of patients who have a risk of serious coronary morbidity of less than 1%over the next year.3o HEART FAILURE

Heart failure is defined as the inability to pump an adequate amount of blood to meet the metabolic demands of vital organs. It may present clinically as fatigue, anorexia, dyspnea, peripheral edema, or orthopnea. The physical examination may show a gallop rhythm, jugular venous distention, dependent edema, or pulmonary rales. Often, however, the physical examination shows only minimal abnormalities. All patients who present with a syndrome of cardiac failure should have a thorough investigation to search for reversible underlying systemic causes (such as hypothyroidism, iron storage diseases, or anemia). The initial anatomic investigations should distinguish systolic dysfunction from diastolic dysfunction of the ventricle and uncover less common causes such as valvular disease and restrictive pericarditis. A key task is to establish any diagnosis that can be arrested or slowed if not reversed (such as hypertensive left ventricular Ischemic cardiomyopathy is the most common cause of heart failure in the developed and the majority of patients with heart failure require an investigation for reversible ischemic disease. Transthoracic echocardiography is generally the first test used to investigate cardiac function in a patient with heart failure.28It allows visualization of anatomic detail such as valve structure and regional wall motion abnormalities. It can estimate ventricular systolic function, and, with Doppler technology, can quantitate abnormal flow across valves. In addition, it is relatively moderately priced, widely available, noninvasive, and can be done at the bedside for unstable patients. Transesophageal echocardiographycan be used to give finer resolution of specific anatomy when necessary. The main disadvantage of echocardiography is that it often cannot visualize structures well in patients with poor sonographic "windows" such as obese patients or patients with emphysema. In spite of these limitations, echocardiographyalmost always provides important information for the management of the patient with cardiac failure. Radionuclide scanning using a first pass technique can also be used to provide an accurate measure of left ventricular systolic ejection fraction.4I This can be done at the same time as imaging for ischemia. It costs somewhat more in most institutions than echocardiography but is generally more reproducible and is not affected as much by obesity and emphysema. Radionuclide techniques do not, however, give detailed anatomic information on heart valves, pericardium, or Ventricular muscle.

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Although its cost is a limiting factor, MR imaging gives excellent twoor three-dimensional anatomic detail of the heart and great vessels that is not available with any other imaging technique. Gated MR techniques can give an accurate measure of the ejection fraction.I6 In many cases, cardiac catheterization is a necessary part of the evaluation of the patient with heart failure. It allows direct measurement of intravascular pressures and ventricular ejection fraction, visualization of valvular structures, and coronary anatomy. This information is necessary for the patient who is considering cardiac surgery. Endocardia1biopsy is rarely necessary for establishing an underlying cause of heart failure.4s VALVULAR HEART DISEASE

Many patients have cardiac murmurs on physical examination, but most do not have significant valvular heart disease.Although the presence of symptoms associated with an auscultation abnormality may increase the likelihood of a particular murmur being pathologic, many important murmurs are asymptomatic. It is beyond the scope of this article to fully define the characteristics of physical examination that should prompt investigation for valvular heart disease. In general, all diastolic murmurs, most systolic murmurs of grade 3/6 or greater intensity, and murmurs associated with chest radiograph or ECG abnormalities should be investigated. Asymptomatic patients with grade 1 or 2 midsystolic murmurs and otherwise normal physical findings should generally not have any further investigation? Patients who are suspected of having valvular heart disease or abnormalities of the great vessels are usually studied first with echocardiography because of its ability to visualize anatomy, its relatively low cost, and because it is non-invasive.6 Doppler scanning helps to establish the functional severity of flow abnormalities associated with diseased heart valves. Other high resolution techniques such as gated MR imaging are beginning to be used in the investigation of valvular disease but are not yet widely available. Most patients need to undergo catheterization prior to surgery. RHYTHM DISTURBANCES AND SYNCOPE

Many patients present to primary care physicians with complaints of light-headedness, palpitations, or syncope but only a small percentage of these have serious cardiac rhythm disturbances. Historical features that should make the physician suspicious of a cardiac cause include loss of consciousness,particularly with injury owing to loss of protectivereflexes, known ischemic coronary disease, and a history of palpitations associated with other cardiac symptoms. Conversely, a patient without any of these high-risk features who has a clear story of a vasovagal prodrome prior to

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a syncopal episode generally does not need any further evaluation. The physical examination should focus on finding an irregular heart rate, orthostatic changes in the vital signs, or murmurs consistent with ventricular outflow obstruction. The history and examination should also seek out signs and symptoms of heart failure because this greatly increases the chance that any dysrhythmia might cause an adverse outcome. A resting ECG is the initial step in evaluating a patient with a history of syncope, especially if the history suggests a serious etiology. The resting ECG is adequate for the diagnosis in some patients, particularly in bradydysrhythmias and high grade atrioventricular blocks in the elderly. In other cases the ECG is not diagnostic but provides a clue to the diagnosis. If any further investigation of a potential rhythm disturbance is necessary, the Holter monitor, which provides a continuous recording of the ECG over 24 hours, is the most common first step. Minor rhythm disturbances are common findings on Holter monitor tracings, thus the results must be correlated with the patient’s symptoms. If significant abnormalities are found on the Holter monitor tracing that correlate with the patients symptoms, they are diagnostic; however, the sensitivity for finding rhythm disturbances is sometimes low. This is particularly true when the patient is not symptomatic on the day the Holter monitor is worn. Event monitors can be worn by patients for days or weeks at a time. The patient triggers the device to record the ECG during symptomatic episodes. This improves sensitivity for finding rhythm disturbances that are not frequent and reduces the chance of finding dysrhythmias that are not responsible for the symptoms. The signal-averaged ECG (SAECG) can be used to identify patients who are at increased risk for ventricular dysrhythmias. Data are obtained in the same manner as a routine ECG, but multiple cardiac cycles are averaged and filtered to allow the tracing to recognize low-amplitude signals. Patients with decreased ejection fractionswho have late potentials on the SAECG are at greater risk than others for sustained ventricular tachycardia and ventricular fibrillation. These patients may be candidates for more invasive testing? Because of the toxicity of medications used to treat ventricular dysrhythmias, the role of the primary care physician is to choose those patients who need cardiology consultation and more invasive testing. It is only rarely appropriate to treat such patients empirically. Many patients receive electrophysiologic studies (EPS) to diagnose their rhythm disturbances and help guide their therapy. EPS is a specialized catheterization procedure in which multiple electrodes are used to map abnormal electrical forces associated with cardiac dysrythmias. Dysrhythmias often can be induced during the procedure, and antiarrhythmic drugs may be tested for their ability to suppress the dysrhythmias. Others may have ablation of abnormal conduction pathways by radiofrequency or cryotherapy at the time of the EPS to control the rhythm. Patients with unexplained recurrent episodes of syncope that do not seem to be owing to tachydysrhythmias may require tilt-table testing. In this test, the patient is passively tilted to an upright position with or with-

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out isoproterenol stimulation. In a positive tilt test the patient experiences hypotension, bradycardia, or syncope. The specific response that occurs is used to help guide subsequent therapy? SUMMARY The results of cardiac tests must always be interpreted through the lens of pretest probabilities created by the history and physical examination. Tests should be chosen with a clear diagnostic and prognostic purpose in mind. Although a rigid algorithmic approach is not appropriate to cardiac diagnosis, most chest pain patients who can exercise and have a normal resting ECG should be tested first with exercise ECG (Fig. 3). Patients at high risk of adverse events should have cardiac catheterization as their initial diagnostic test. Patients with potential valvular disease and cardiac failure syndromes should have echocardiography as the initial diagnostic test. The evaluation of possible rhythm disturbance and syncope is usually begun with resting ECG and a careful history. Many of these patients do not need any further testing.

High risk features present? l

C

8

ECG normal?

9

$

B V

Exercise ECG with prognostic score

High risk

Intermediate risk

Enhanced imaging study

High risk

* b

Low risk

1

Low risk

1

Risk Factor Management/ Symptomatic treatment

Figure 3.Treatment algorithm.

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The choice of second-line diagnostic tests, such as exercise echocardiography or SPECT scanning for patients with resting ECG abnormalities, should be guided by local expertise at a particular institution. Occasionally, one testing modality should be chosen over another because it can give secondary information such as evidence of valvular function as well as an ischemic evaluation. A clear understanding of the relationship between the history and physical examination and more technologic diagnostic testing improves primary care physicians’ ability to evaluate potential cardiac disease in an efficient and cost-effective manner.

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