Articles on Medical Diseases and Conditions

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  • Laboratory Tests and the Medical Literature

    One of the more interesting phenomena in medicine is the scenario under which new tests or new uses for old tests are introduced. In most cases the initial reports are highly enthusiastic. Also in most cases there is eventual follow-up by other investigators who either cannot reproduce the initial good results or who uncover substantial drawbacks to the test. In some cases the problem lies in the fact that there may not be any way to provide an unequivocal standard against which test accuracy can be measured. An example is acute myocardial infarction, because there is no conclusive method to definitively separate severe myocardial ischemia from early infarction (i.e., severe reversible change from irreversible change). Another example is acute pancreatitis. In other cases the initial investigators may use analytical methods (e.g., “homemade” reagents) that are not identical to those of subsequent users. Other possible variances include different populations tested, different conditions under which testing is carried out, and effects of medication. Historical perspective thus suggests that initial highly enthusiastic claims about laboratory tests should be received with caution.

    Many readers of medical articles do not pay much attention to the technical sections where the materials and methods are outlined, how the subjects or patient specimens are selected and acquired, and how the actual data from the experiments are presented. Unfortunately, rather frequently the conclusions (both in the article and in the abstract) may not be proven or, at times, even may not be compatible with the actual data (due to insufficient numbers of subjects, conflicting results, or most often magnifying the significance of relatively small differences or trends). This often makes a test appear to give clear-cut differentiation, whereas in reality there is substantial overlap between two groups and the test cannot reliably differentiate individual patients in either group. Another pitfall in medical reports is obtaining test sensitivity by comparing the test being evaluated with some other procedure or test. While there usually is no other way to obtain this information, the reader must be aware that the gold standard against which the new test is being compared may itself not be 100% sensitive. It is rare for the report to state the actual sensitivity of the gold standard being used; even if it is, one may find that several evaluations of the gold standard test had been done without all evaluations being equally favorable. Therefore, one may find that a new test claimed to be 95% sensitive is really only 76% sensitive because the gold standard test against which the new test is being compared is itself only 80% sensitive. One should be especially wary when the gold standard is identified only as “a standard test” or “another (same method) test.” In addition, even if the gold standard were claimed to be 100% sensitive, this is unlikely because some patients would not be tested by the gold standard test due to subclinical or atypical illness; or patients could be missed because of interferences by medications, various technical reasons, or how the gold standard reference range was established (discussed previously).

  • Effects of Hospital Working Procedures

    Several common hospital conditions may affect laboratory results without such alteration being recognized by the physician. These include intravenous fluids running at the time the test specimen is drawn, the effect of dehydration, the effect of heparin flushes on some tests, the effects of various medications, and in certain cases the administration of medication at a time different from that expected or recorded. The last item refers to the common situation in which several patients are scheduled to receive medication at the same time (e.g., 8 A.M.). Although administration to each may be charted as being the same time, the actual time that any individual receives the medication may vary significantly.

    Another frequent problem is defective communication between the physician and the laboratory. In some cases this takes the form of incorrectly worded, ambiguous, or illegible orders. Nursing or secretarial personnel can easily misinterpret such orders and relay them incorrectly to the laboratory. Nonstandard test abbreviations or acronyms created from the names of new tests not familiar to nursing personnel also cause difficulties. In some cases the physician should supply at least a minimal amount of pertinent clinical information to obtain better service. This information is most vitally needed in the microbiology department. The microbiology technologist must know from what area the specimen was obtained, exactly what type of culture is desired, and especially, whether any particular organism is suspected so that special growth media or special handling may be employed if necessary. Basic clinical information is even more essential to the surgical pathologist and the radiologist. The surgical pathologist must at least know where the tissue specimen originated, and both the pathologist and radiologist can do a much better job providing an answer to the clinician if they could only know what the clinician’s question is (i.e., for what reason is he or she requesting the study).

    A word must be said about stat orders. Stat means emergency to the laboratory. Someone must stop whatever he or she is doing and perform the stat analysis immediately, possibly having to obtain the specimen first. After analysis the report must be delivered immediately. During this time that laboratory person may not do any other work. Stat tests result in great decrease of laboratory efficiency and cost effectiveness. The most efficient and least expensive way to perform tests is to analyze several patient specimens at the same time, so that the initial setup and quality control portions of the test need be performed only once and all specimens can be incubated simultaneously. Extra speed is obtained when a test is ordered stat, but results for everyone else are delayed. Unfortunately, many stat requests, sometimes even the majority, are ordered for reasons other than a true emergency need for the result. In some cases the order originates fromnursing service because someone neglected to send a requisition for a routinetest to the laboratory. In other cases the order is made stat because of convenience to the physician or the patient. Stat orders for these purposes at best are inconsiderate, wasteful, and disruptive. The physician should consider whether some other action-producing order category could be substituted, such as “as soon as possible.” If the actual problem is that of unacceptable turnaround time for routine tests, this is a matter to be discussed with the laboratory director rather than evaded by stat orders.

  • Effects of Medications

    The effect of medications is a major problem since a patient may be taking several drugs or may be taking over-the-counter pharmaceuticals without reporting them to the physician. Medication effects may be manifest in several ways: drug-induced injury to tissues or organs (e.g., isoniazid-induced hepatitis), drug-induced alterations in organ function (e.g., increase in g-glutamyltransferase produced by phenytoin microsomal induction in liver cells), drug competition effect (e.g., displacement of thyroxine from thyroxine-binding proteins by phenytoin), and interference by one drug with theanalysis method of another (e.g., decrease in serum glucose using glucose oxidase when large doses of vitamin C are ingested).

  • Effects of Physiologic Variables

    Physiologic differences between groups of persons may affect test results. These deviations may be attributable to normal metabolic alterations in certain circumstances. Some examples are age (e.g., an increase in alkaline phosphataselevels in children compared with adult values), sex (e.g., higher values for serum uric acid in males than in females), race (e.g., higher values for creatine phosphokinase in African American men than European men); time of day (e.g., higher values for serum cortisol in the morning than in the evening), meals (e.g., effect on blood glucose), and body position (e.g., change in values shown in Table 1-2 due to change in posture, resulting in possible decrease in many serum test values when an ambulatory outpatient becomes a hospital inpatient).

  • Problems with Laboratory Specimens

    Specimen collection and preservation may create laboratory problems. Probably the most frequent offender is contamination of urine from female patients by vaginal or labial secretions. Using more than 10 squamous epithelial cells per low-power field in a centrifuged urine sediment as the index of probable contamination, my surveys have found this present in 20%-30% of female random voided or midstream (“clean catch”) specimens. These secretions may add red blood cells, white blood cells, protein, and bacteria to the urine. Nonfasting blood specimens may occasionally be troublesome, due to increased blood glucose and the effect of lipemia. This is most frequent in patients who are admitted in the afternoon and in outpatients. We have had some success in alleviating this problem by requesting that physicians ask elective presurgical patients either to have admission laboratory tests drawn fasting before admission or to come to the hospital for admission after fasting at least 3 hours. Certain tests, such as blood gas analysis, biochemical acid phosphatase assay, and plasma renin assay, necessitate special preservation techniques to be reliable.

    One of the most well-known specimen collection problems is that of ensuring completeness of 24-hour urine specimens. Some patients are not informed that the 24-hour collection begins only after a urine specimen has been voided and discarded. It is frequently helpful to give the patient written instructions as to how a clean-voided specimen may be obtained and how the 24-hour specimen is collected. The two standard criteria used to evaluate adequacy of collection are the specimen volume and the urine creatinine content. Specimen volume is helpful only when the volume is abnormally low (e.g., <400 ml/24 hours in adults). A small volume that does not have maximal concentration (as evidenced by a high specific gravity or osmolality) suggests incomplete collection. However, renal disease, medications such as diuretics, and other conditions may prevent concentration, so this criterion is difficult to apply unless the patient is known to have good renal function. The second criterion is a normal quantity of urine creatinine. Creatinine is derived from muscle metabolism and has a reasonably constant daily excretion. However, creatinine production and excretion are dependent on body muscle mass. It has also been shown by several investigators that even in the same individual, daily creatinine excretion may vary 5%-25%, with an average variation of about 10%. Meat, especially when cooked for a long time, may increase creatinine excretion up to 40% for short periods of time and possibly 10%-20% over a 24-hour period.

    Since creatinine excretion correlates with muscle mass, it might be helpful to compare measured creatinine excretion with calculated ideal excretion based on body height and ideal body weight. This would be only a rough benchmark, but it might be more helpful than the population reference range, which is rather wide.

  • Normal (Reference) Ranges

    The most important single influence on laboratory test interpretation is the concept of a normal range, within which test values are considered normal and outside of which they are considered abnormal. The criteria and assumptions used in differentiating normal from abnormal in a report, therefore, assume great importance. The first step usually employed to establish normal ranges is to assume that all persons who do not demonstrate clinical symptoms or signs of any disease are normal. For some tests, normal is defined as no clinical evidence of one particular disease or group of diseases. A second assumption commonly made is that test results from those persons considered normal will have a random distribution; in other words, no factors that would bias a significant group of these values toward either the low or the high side are present. If the second assumption is correct, a gaussian (random) distribution would result, and a mean value located in the center (median) of the value distribution would be obtained. Next, the average deviation of the different values from the mean (SD) can be calculated. In a truly random or gaussian value distribution, 68% of the values will fall within ±1 SD above and below the mean, 95% within ±2 SD, and 99.7% within ±3 SD. The standard procedure is to select ±2SD from the mean value as the limits of the normal range.

    Accepting ±2 SD from the mean value as normal will place 95% of clinically normal persons within the normal range limits. Conversely, it also means that 2.5% of clinically normal persons will have values above and 2.5% will have values below this range. Normal ranges created in this way represent a deliberate compromise. A wider normal range (e.g., ±3 SD) would ensure that almost all normal persons would be included within normal range limits and thus would increase the specificity of abnormal results. However, this would place additional diseased persons with relatively small test abnormality into the expanded normal range and thereby decrease test sensitivity for detection of disease.

    Nonparametric calculation of the normal range. The current standard method for determining normal ranges assumes that the data have a gaussian (homogeneous symmetric) value distribution. In fact, many population sample results are not gaussian. In a gaussian value distribution, the mean value (average sample value) and the median value (value in the center of the range) coincide. In nongaussian distributions, the mean value and the median value are not the same, thus indicating skewness (asymmetric distribution). In these cases, statisticians recommend some type of nonparametric statistical method. Nonparametric formulas do not make any assumption regarding data symmetry. Unfortunately, nonparametric methods are much more cumbersome to use and require a larger value sample (e.g., і120 values) One such nonparametric approach is to rank the values obtained in ascending order and then apply the nonparametric percentile estimate formula.

    Problems derived from use of normal ranges

    1.
    A small but definite group of clinically normal persons may have subclinical or undetected disease and may be inadvertently included in the supposedly normal group used to establish normal values. This has two consequences. There will be abnormal persons whose laboratory value will now be falsely considered normal; and the normal limits may be influenced by the values from persons with unsuspected disease, thereby extending the normal limits and accentuating overlap between normal and abnormal persons. For example, we tested serum specimens from 40 clinically normal blood donors to obtain the normal range for a new serum iron kit. The range was found to be 35-171 µg/dl, very close to the values listed in the kit package insert. We then performed a serum ferritin assay on the 10 serum samples with the lowest serum iron values. Five had low ferritin levels suggestive of iron deficiency. After excluding these values, the recalculated serum iron normal range was 60-160, very significantly different from the original range. The kit manufacturer conceded that its results had not been verified by serum ferritin or bone marrow.
    2.
    Normal ranges are sometimes calculated from a number of values too small to be statistically reliable.
    3.
    Various factors may affect results in nondiseased persons. The population from which specimens are secured for normal range determination may not be representative of the population to be tested. There may be differences due to age, sex, locality, race, diet, upright versus recumbent posture (Table 1-2), specimen storage time, and so forth. An example is the erythrocyte sedimentation rate (ESR) in which the normal values by the Westergren method for persons under age 60 years, corrected for anemia, are 0-15 mm/hour for men and 0-20 mm/hour for women, whereas in persons over age 60, normal values are 0-25 mm/hour for men and 0-30 mm/hour for women. There may even be significant within-day or between-day variation in some substances in the same person.

    Decrease in test values after change from upright to supine position

    Table 1-2 Decrease in test values after change from upright to supine position

    4.
    Normal values obtained by one analytical method may be inappropriately used with another method. For example, there are several well-accepted techniques for assay of serum albumin. The assay values differ somewhat because the techniques do not measure the same thing. Dye-binding methods measure dye-binding capacity of the albumin molecule, biuret procedures react with nitrogen atoms, immunologic methods depend on antibodies against antigenic components, and electrophoresis is influenced primarily by the electric charge of certain chemical groups in the molecule. In fact, different versions of the same method may not yield identical results, and even the same version of the same method, when performed on different equipment, may display variance.
    5.
    As pointed out previously, normal values supplied by the manufacturers of test kits rather frequently do not correspond to the results obtained on a local population by a local laboratory, sometimes without any demonstrable reason. The same problem is encountered with normal values obtained from the medical literature. In some assays, such as fasting serum glucose using so-called true glucose methods, there is relatively little difference in normal ranges established by laboratories using the same method. In other assays there may be a significant difference. For example, one reference book suggests a normal range for serum sodium by flame photometry of 136-142 mEq/L, whereas another suggests 135-155 mEq/L. A related problem is the fact that normal ranges given in the literature may be derived from a laboratory or group of laboratories using one equipment and reagent system, whereas results may be considerably different when other equipment and reagents are used. The only way to compensate for this would be for each laboratory to establish its own normal ranges. Since this is time-consuming, expensive, and a considerable amount of trouble, it is most often not done; and even laboratories that do establish their own normal ranges are not able to do so for every test.
    6.
    Population values may not be randomly distributed and may be skewed toward one end or the other of the range. This would affect the calculation of standard deviation and distort the normal range width. In such instances, some other way of establishing normal limits, such as a nonparametric method, would be better, but this is rarely done in most laboratories.

    One can draw certain conclusions about problems derived from the use of the traditional concept and construction of normal ranges:

    1.
    Some normal persons may have abnormal laboratory test values. This may be due to ordinary technical variables. An example is a person with a true value just below the upper limit of normal that is lifted just outside of the range by laboratory method imprecision. Another difficulty is the 2.5% of normal persons arbitrarily placed both above and below normal limits by using ±2 SD as the limit criterion. It can be mathematically demonstrated that the greater the number of tests employed, the greater the chance that at least one will yield a falsely abnormal result. In fact, if a physician uses one of the popular 12-test biochemical profiles, there is a 46% chance that at least one test result will be falsely abnormal. Once the result falls outside normal limits, without other information there is nothing to differentiate a truly abnormal from a falsely abnormal value, no matter how small the distance from the upper normal limit. Of course, the farther the values are from the normal limits, the greater the likelihood of a true abnormality. Also, if two or more tests that are diagnosis related in some way are simultaneously abnormal, it reinforces the probability that true abnormality exists. Examples could be elevation of aspartate aminotransferase (SGOT) and alkaline phosphatase levels in an adult nonpregnant woman, a combination that suggests liver disease; or elevation of both blood urea nitrogen (BUN) and creatinine levels, which occurring together strongly suggest a considerable degree of renal function impairment.
    2.
    Persons with disease may have normal test values. Depending on the width of the normal range, considerable pathologic change in the assay value of any individual person may occur without exceeding normal limits of the population. For example, if the person’s test value is normally in the lower half of the population limits, his or her test value might double or undergo even more change without exceeding population limits.(Fig. 1-2). Comparison with previous baseline values would be the only way to demonstrate that substantial change had occurred.

    Population reference

    Fig. 1-2 How patient abnormality may be hidden within population reference (“normal”) range. Patients A and B had the same degree of test increase, but the new value for patient B remains within the reference range because the baseline value was sufficiently low.

    Because of the various considerations outlined previously, there is a definite trend toward avoiding the term “normal range.” The most frequently used replacement term is reference range (or reference limits). Therefore, the term “reference range” will be used throughout this book instead of “normal range.”

  • Reproducibility and Accuracy

    Reliability of laboratory tests is quite obviously affected by technical performance within the laboratory. The effect of these technical factors is reflected by test reproducibility and accuracy. Reproducibility (precision or inherent error) is a measure of how closely the laboratory can approach the same answer when the test is performed repeatedly on the same specimen. Theoretically, exactly the same answer should be obtained each time, but in actual practice this does not happen due to equipment and human imperfection. These deviations from the same answer are usually random and thereby form a random or gaussian distribution (Fig. 1-1). Variation from the average (mean) value is expressed in terms of standard deviation (SD). The laboratory frequently converts the standard deviation figure to a percentage of the mean value and calls this the coefficient of variation (CV). The majority of tests in a good laboratory can be shown to have reproducibility—expressed as CV—in the neighborhood of 4% (some may be a little better and some a little worse). This means that two thirds of the values obtained are actually somewhere between 4% above and 4% below the true value. Since ±2 SD (which includes 95% of the values) is customarily used to define acceptable limits (just as in determination of normal ranges), plus or minus twice the CV similarly forms the boundaries of permissible technical error. Returning to the 4% CV example, a deviation up to ±8% would therefore be considered technically acceptable. In some assays, especially if they are very complicated and automated equipment cannot be used, variations greater than ±8% must be permitted. The experience and integrity of the technical personnel, the reagents involved, and the equipment used all affect the final result and influence reproducibility expressed as CV. In general, one can say that the worse the reproducibility (as reflected in higher CVs), the less chance for accuracy (the correct result), although good reproducibility by itself does not guarantee accuracy.

    Gaussian (random) value distribution

    Fig. 1-1 Gaussian (random) value distribution with a visual display of the area included within increments of standard deviation (SD) above and below the mean: ±1 SD, 68% of total values; ±2 SD, 95% of total values; ±3 SD, 99.7% of total values.

    These considerations imply that a small change in a test value may be difficult to evaluate since it could be due to laboratory artifact rather than to disease or therapy. Larger alterations or a continued sequence of change are much more helpful.

    Accuracy is defined as the correct answer (the result or value the assay should produce). Besides inherent error, there is the possibility of unexpected error of various kinds, such as human mistake when obtaining the specimen, performing the test, or transcribing the result. Investigators have reported erroneous results in 0.2%–3.5% of reports from one or more areas of the laboratory. The laboratory analyzes so-called control specimens (which have known assay values of the material to be tested) with each group of patient specimens. The assumption is that any technical factor that would produce erroneous patient results would also produce control specimen results different from the expected values. Unfortunately, random inaccuracies may not affect all of the specimens and thus may not alter the control specimens. Examples of such problems are a specimen from the wrong patient, the effect of specimen hemolysis or lipemia, inaccurate pipetting, and insufficient mixing when the assay method uses a whole blood specimen. In addition, clerical errors occasionally occur. In my experience, the majority of clerical difficulties are associated with the patients who have the same last name, patients who have moved from one room to another, decimal point mistakes, transcription of results onto the wrong person’s report sheet, and placement of one person’s report sheet into the chart of someone else. These considerations imply that unexpected laboratory abnormalities greater the time lapse between the original and the new specimen, the more problems will be encountered in differentiating an error in the original specimen from true change that occurred before the next specimen. One of the more frustrating duties of a laboratory director is to receive a question or complaint about a laboratory test result several days or even weeks after the test was performed, when it is usually too late for a proper investigation.

  • Predictive Value

    In recent years, Galen and Gambino have popularized the concept of predictive value, formulas based on Bayes’ theorem that help demonstrate the impact of disease prevalence on interpretation of laboratory test results (Table 1-1). Prevalence is the incidence of the disease (or the number of persons with the disease)in the population being tested. Briefly, predictive value helps dramatizethe fact that the smaller the number of persons with a certain disease in the population being tested, the lower will be the proportion of persons with an abnormal test result who will be abnormal because they have the disease in question (i.e., the higher will be the proportion of false positive results). For example, if test Y has a sensitivity of 95% and a specificity of 95% fordisease Z (both of which would usually be considered quite good), and if theprevalence of disease Z in the general population is 0.1% (1 in 1,000 persons), the predictive value of a positive (abnormal) result will be 1.9%. This meansthat of 100 persons with abnormal test results, only 2 will have disease Z, and 49 of 50 abnormal test results will be false positive. On the other hand, if the prevalence of disease Z were 10% (as might happen in a group of persons referred to a physician’s office with symptoms suggesting disease Z), the predictive value would rise to 68%, meaning that 2 out of 3 persons with abnormal test results would have disease Z.

    Influence of disease

    Table 1-1 Influence of disease prevalence on predictive value of a positive test result

    Predictive value may be applied to any laboratory test to evaluate the reliability either of a positive (abnormal) or a negative (normal) result. Predictive value is most often employed to evaluate a positive result; in that case the major determinants are the incidence of the disease in question for the population being tested and the specificity of the test. However, predictive value is not the only criterion of laboratory test usefulness and may at times be misleading if used too rigidly. For example, a test may have excellent characteristics as a screening procedure in terms of sensitivity, low cost, and ease of technical performance and may also have a low positive predictive value. Whether or not the test is useful would depend on other factors, such as the type and cost of follow-up tests necessary in case of an abnormal result and the implications of missing a certain number of persons with the disease if some less sensitive test were employed.
    There may be circumstances in which predictive value is misleading or difficult to establish. If one is calculating the predictive value of a test, one must first know the sensitivity and specificity of that test. This information requires that some accurate reference method for diagnosis must be available other than the test being evaluated; that is, a standard against which the test in question can be compared (a “gold standard”). This may not be possible. There may not be a more sensitive or specific test or test combination available; or the test being evaluated may itself be the major criterion by which the diagnosis is made. In other words, if it is not possible to detect all or nearly all patients with a certain disease, it will not be possible to provide a truly accurate calculation of sensitivity, specificity, or predictive value for tests used in the diagnosis of that disease. The best one could obtain are estimates, which vary in their reliability.

  • Sensitivity and Specificity

    Interpretation of laboratory test results is much more complicated than simply comparing the test result against a so-called normal range, labeling the test values normal or abnormal according to the normal range limits, and then fitting the result into patterns that indicate certain diseases. Certain basic considerations underlie interpretation of any test result and often are crucial when one decides whether a diagnosis can be made with reasonable certainty or whether a laboratory value should alter therapy.

    All laboratory tests have certain attributes. Sensitivity refers to the ability of the test to detect patients with some specific disease (i.e., how often false negative results are encountered). A test sensitivity of 90% for disease Z indicates that in 10% of patients with disease Z, thetest will not detect the disease. Specificity describes how well test abnormality is restricted to those persons who have the disease in question (i.e., how often false positive results are produced). A specificity of 90% for disease Z indicates that 10% of test results suggestive of disease Z will, in fact, not be due to disease Z.

  • Echocardiography

    Echocardiography uses high-frequency sound waves (also called ultra- sound) to produce a moving image of your heart. The sound waves are introduced into your body through a handheld device called a trans- ducer. They bounce off the structures and ?uids in the heart and return as echoes through the transducer. The echoes are converted into images on a monitor.

    Echocardiogram

    Using different types of echocardiography, your doctor can see the size, shape, and contraction of the heart muscle; watch the heart valves work- ing; and see how blood is ?owing through your heart and arteries. Dur- ing one test, a two-dimensional mode looks at the heart’s structures and function to see a larger picture, including a cross section; and a form called Doppler echocardiography to assess blood ?ow within the heart and to identify abnormal ?ow patterns.
    In conjunction with a stress test, the echocardiogram may show that the wall of the heart does not move as well after exercise, suggesting that part of the heart may not get suf?cient

    blood flow during exercise. That lack of blood can impair the heart muscle’s ability to contract.

    What to Expect

    You can have an echocardiogram in a doctor’s of?ce or a hospital. You do not need to pre- pare in any special way. You will be asked to remove your clothes, and electrodes will be attached to your chest and back, as in the pro- cedure for an ECG (page 122). The techni- cian will spread a gel over your chest to help with transmission. He or she will move the transducer over your heart and chest, pressing ?rmly, and will ask you to lie in several differ- ent positions and breathe slowly, or hold your breath to improve the image. The entire pro- cedure will take 45 minutes to an hour.

    What the Results Mean

    You may have to wait several days for the full results of the echocardiogram. If the test doesn’t reveal anything unexpected, you may get the results by phone. The test will indicate to your doctor how the chambers or walls of your heart have been altered by conditions such as heart attack, high blood pressure, previous heart damage, or heart failure. If you have had echocardio- grams before, the doctor can compare the results of the tests to assess how effective treatment has been.
    The test also allows the doctor to analyze the strength and nature of your heart’s pumping action, which he or she may describe in terms of the “ejection fraction.” A normal ejection fraction is about 55 to 65 per- cent, meaning that more than half of the blood in your left ventricle (the main pumping chamber) is squeezed out in a single heartbeat. If the percentage is signi?cantly lower, the echocardiogram can show where the pumping action is weakened—for example, it may reveal an area of the heart weakened by a heart attack. The test may be especially meaningful for genetic conditions that can pose the risk of sudden death—for example, hypertrophic cardiomyopathy, which is an abnor- mal thickness of a heart muscle segment commonly observed in young athletes who die suddenly.
    The echocardiogram also reveals the condition of each of the four heart valves and how well they are working. The use of the Doppler mode shows in real time how blood passes through the valves, which can indicate the nature of a valve problem; for example, backward ?ow may indicate a leaky valve. The echocardiogram also gives information about the volume of circulating blood, which might be affected by treatments such as diuretics. The echocardiogram answers questions about how several factors are interacting on your heart, how treatment can be tailored to address a speci?c type of malfunction, and how best to maintain the heart’s ability to pump blood.

    Transesophageal Echocardiography

    Your doctor may order a transesophageal echocardiogram (TEE), a form of echocardiography that overcomes some of the limitations of a regular echocardiogram. As the name implies, a transesophageal echocardiogram involves threading a small probe (less than half an inch wide) down your esophagus (the tube from your throat to your stom- ach). Instead of viewing your heart through your chest wall, the trans- esophageal echocardiogram transmits images from within your esophagus, which is much closer to the heart. It may be necessary if your weight, body shape, or other considerations make conventional echocardiographic techniques less useful.
    You should not eat after midnight on the day of the test. However, if the test needs to be done urgently, it is best not to have eaten for 4 hours so that you are less likely to feel nauseous or vomit. Discuss with your doctor any medications you are taking, and whether you should take them before the test.
    The test will probably be done in a hospital. Because you will be given a sedative, you should make arrangements to get a ride home. First you will lie on a table and an intravenous (IV) line will be inserted into your arm to deliver a sedative. The technician will place electrodes on your chest
    that will be hooked up to an electrocardiographic machine to monitor your heart rhythms through- out the test.
    After numbing your throat with an anesthetic spray, the technician will gently insert a probe with the transducer at the end into your throat and down your esophagus. This part of the procedure is the most uncomfortable, and you may feel like gagging. Once the transducer is in place, you will not feel any pain. You will be partially awake for the pro- cedure, because you may be asked to hold your breath or strain as if you were having a bowel movement, which puts your heart under some pressure and may help reveal problems.
    When the test is over, the transducer and IV will be removed and you will be disconnected from the electrocardiographic equipment. You may feel sleepy from the sedative, and the doctor will want to make sure that your heart rate and blood pressure are normal, so you may remain in the hospital for a few hours. Most often you will be advised to wait at least 2 hours before you eat or drink anything, because your throat may still be numb. After the anesthetic wears off, your throat may be sore for a day or two. It’s best not to drive for 24 hours, to be sure that the anes- thetic is entirely out of your system, so arrange for a ride home from the test.