Fabio Lattanzi

Stress echocardiography and the human factor: The importance of being expert

The aim of this study was to evaluate how the diagnostic accuracy of a stress echocardiographic procedure, such as a dipyridamole echocardiography test, depends on the specific experience of the physician interpreting the test. Recordings of 50 consecutive dipyridamole echocardiographic tests were selected for the first part of the study. They were analyzed by 20 experienced echocardiographers with different backgrounds in stress echocardiography: 10 beginners (less than 20 stress studies interpreted with trained staff) and 10 experienced observers (greater than or equal to 100 stress studies performed). Diagnostic accuracy (true positive + true negative/total number of tests) versus the angiographic reference standard (greater than 70% coronary stenosis of at least one major coronary artery) was 62 +/- 6% for beginners and 85 +/- 3% for experienced observers (p less than 0.0001). In the second part of the study, 10 observers (5 beginners and 5 experienced observers) evaluated 2 different sets of 50 dipyridamole echocardiographic test studies before and after the training of the beginners. Before training, the accuracy of beginners was lower than that of experienced observers (61 +/- 7% versus 85 +/- 3%; p less than 0.001). After training, the accuracy gap was closed (83 +/- 3% versus 86 +/- 2%; p = NS). Therefore, interpretation of stress echocardiographic tests by an echocardiographer without specific training severely underestimates the diagnostic potential of this technique. One hundred stress echocardiographic studies are more than adequate to build the individual learning curve and reach the plateau of diagnostic accuracy that the test can yield.

High dose dipyridamole echocardiography test in effort angina pectoris

The dipyridamole echocardiography test (intravenous dipyridamole with two-dimensional echocardiographic monitoring) was performed in 93 patients with effort chest pain and in 10 control subjects. The test was considered positive when regional asynergy appeared after dipyridamole administration. When negative at the low dose (0.56 mg/kg body weight in 4 minutes), the test was repeated on a different day with a higher dose (0.84 mg/kg in 10 minutes). All 93 patients underwent coronary arteriography; 72 of them had significant (greater than 70% luminal reduction) coronary artery disease. Thirty-eight of the 93 patients had a positive low dose dipyridamole echocardiography test; 15 other patients with a negative low dose test had a positive high dose test. All 53 patients with a positive test had significant coronary artery disease; 12 of them had a negative exercise stress test. In relation to the presence of coronary artery disease, the dipyridamole echocardiography test had an overall specificity higher than that of the exercise stress test (100 versus 71%) and a similar overall sensitivity (74 versus 69%). The dipyridamole echocardiography test is feasible in all patients with a good baseline echocardiogram. It detects the site of apparent ischemia more precisely than does an exercise stress test, and can unmask electrocardiographically silent ischemia. If performed in patients with a negative low dose dipyridamole echocardiography test, the high dose test adds sensitivity (probably by achieving maximal dilation in patients in whom the low dose is only partially effective), without any loss in specificity and with no apparent increase in risk.

In vivo quantitative ultrasonic evaluation of myocardial fibrosis in humans.

The aim of this study was to assess in vivo whether the regional ultrasonic reflectivity, evaluated by a real-time integrated backscatter analysis, was related to the local content of connective tissue in human myocardium as estimated by quantitative histology of endomyocardial biopsies. Sixteen patients with presumptive diagnosis of cardiomyopathy were ultrasonically studied by means of an M-mode-based echocardiographic system with quantitative integrated backscatter analysis capabilities. A 2.25-MHz transducer was used. The integrated value of the rectified radiofrequency signal of the interventricular septum was taken as integrated backscatter index and expressed in percent normalized for the pericardial interface (assumed to be 100%). All patients also underwent multiple left ventricular endomyocardial biopsies, which were stained with Massons trichrome and studied with the use of a computer-assisted image analysis system. The percent integrated backscatter index was significantly higher in the presence of connective tissue area greater than 20% (eight patients) versus less than 20% (eight patients): 51 +/- 25% versus 26 +/- 11%, p less than 0.05. A significant correlation (p less than 0.05, R = 0.55) was found between percent integrated backscatter index and percent connective tissue area. In vivo on-line quantitative ultrasound analysis is feasible in man and reliably identifies variations in the regional extent of fibrosis in human myocardium.

Dipyridamole-echocardiography test in effort angina pectoris.

This study assesses the clinical feasibility and usefulness of dipyridamole infusion for the detection of coronary artery disease (CAD) by using 2-dimensional echocardiography (2-D echo) and 12-lead electrocardiographic monitoring. Dipyridamole infusion (0.14 mg/kg/min for 4 minutes) was performed in 66 consecutive patients with effort chest pain and in 9 control subjects. Among the 28 patients with positive dipyridamole-echocardiography test responses, 18 had diagnostic electrocardiographic changes (ST-segment depression on anterolateral leads), but these changes were unrelated to the site of asynergy. The dipyridamole-echocardiography test had an overall sensitivity of 56% and specificity of 100% for the presence of CAD. Exercise stress testing (EST) had an overall sensitivity of 62% and a specificity of 80%. Thus, the dipyridamole-echocardiography test, which is feasible in essentially all patients with good basal echocardiograms, has a lower overall sensitivity in detecting CAD than EST but a higher specificity, detects the site of apparent ischemia as identified by regional asynergy more precisely than EST, and can unmask electrocardiographically silent effort ischemia.

Prognostic importance of dipyridamole-echocardiography test in coronary artery disease.

We studied the value of dipyridamole-echocardiography test in comparison with clinical, resting electrocardiogram and echocardiogram variables in predicting cardiac events occurring in 539 consecutive patients referred for dipyridamole-echocardiography test from 1984 to 1987. There were 118 cardiac events: 11 cardiac deaths, 12 nonfatal myocardial infarctions, and 95 coronary revascularization (bypass or angioplasty) procedures. A Cox survival analysis identified echocardiographic positivity after dipyridamole administration as the best predictor of cardiac events (relative risk ratio, 2.7). The next most powerful predictor was angina after dipyridamole administration (relative risk ratio, 1.9). Cardiac events occurred in 14 (6%) of 253 patients with normal high-dose dipyridamole echocardiographic test results, in 21 (26%) of 82 patients with high-dose dipyridamole echocardiographic positivity (0.84 mg/kg during 10 minutes), and in 83 (41%) of 204 patients with low-dose dipyridamole echocardiographic positivity (0.56 mg/kg during 4 minutes) (p less than 0.0001). In a subset of 341 patients, exercise electrocardiography stress test and coronary angiography were also available. A Cox survival analysis again identified echocardiographic positivity after dipyridamole as the best predictor of cardiac events (relative risk ratio, 1.9) followed by a pathologic coronary arteriography (relative risk ratio, 1.2). We conclude that the presence and timing of a transient dyssynergy during dipyridamole stress are useful predictors of subsequent cardiac events.

Diagnostic and prognostic value of dipyridamole echocardiography in patients with suspected coronary artery disease. Comparison with exercise electrocardiography.

BACKGROUND Before any new diagnostic test is accepted in clinical practice, such a test should be compared with established diagnostic tools in an appropriately large series of patients encompassing the complete spectrum of challenges to which the test is exposed. The aim of the present study was to assess the relative diagnostic and prognostic accuracies of high-dose dipyridamole echocardiography (two-dimensional echocardiographic monitoring during dipyridamole infusion up to 0.84 mg/kg over 10 hours) versus maximal symptom-limited bicycle exercise ECG test in patients with angina. METHODS AND RESULTS We studied 429 consecutive in-hospital patients who met the following inclusion criteria: history of chest pain, off antianginal therapy for at least 2 days (1 week for beta-blockers), no previous myocardial infarction and/or obvious regional left ventricular dyssynergy of contraction (akinesis or dyskinesis) at baseline, and acceptable acoustic window under resting conditions. All patients underwent dipyridamole echocardiography and exercise ECG--on different days and in random order--within 1 week of coronary angiography (which was performed independent of test results) and were followed up for 37.8 +/- 14 months (range, 1 to 73 months). Criteria of positivity were for dipyridamole echocardiography, a transient regional dyssynergy absent in the baseline examination; for exercise ECG, an ST-segment shift of > or = 0.1 mV from baseline; and for coronary angiography, a luminal reduction of > or = 75% in at least one major coronary vessel (50% for left main). There were 183 patients without and 246 with coronary artery disease; 132 had one-, 70 had two-, and 44 had three- and/or left main vessel disease. The specificity was higher for dipyridamole echocardiography than for exercise ECG (90% versus 51%, P < .001). The overall sensitivity of dipyridamole echocardiography was similar to that of exercise ECG (75% versus 74%, P = NS), with no significant differences in the subset with one- (67% versus 69%, P = NS), two- (79% versus 77%, P = NS), or three- (93% versus 86%, P = NS) vessel disease. During the follow-up, there were 20 deaths, 13 nonfatal myocardial infarctions, and 126 revascularization procedures. In the univariate analysis, dipyridamole resulted in higher chi 2 values than did exercise stress testing. A Cox forward stepwise survival analysis identified the dipyridamole time as the most powerful prognostic predictor of death (chi 2 = 19.4, P < .0001) of all invasive and noninvasive parameters. The dipyridamole time also provided independent and additional prognostic information when it was adjusted for age, diabetes, resting ECG, and exercise stress test according to a modified, interactive stepwise procedure. This is true when death only, death and myocardial infarction, and death, myocardial infarction, and revascularization procedures were considered end points. CONCLUSIONS In patients with no previous myocardial infarction and good resting left ventricular function, compared with exercise ECG, dipyridamole echocardiography has a similar sensitivity and a higher specificity for the noninvasive detection of angiographically assessed coronary artery disease. Dipyridamole echocardiography also provides information in addition to that provided by exercise ECG for predicting death, infarction, and all events when the presence as well as the timing, severity, and extension of dipyridamole-induced wall motion abnormalities are considered.

High Dose Dipyridamole-Echocardiography Test in Women: Correlation With Exercise-Electrocardiography Test and Coronary Arteriography

The value of the exercise-electrocardiography test in detecting coronary artery disease in women is limited. Recently, the high dose dipyridamole-echocardiography test (two-dimensional echocardiographic monitoring during intravenous dipyridamole infusion, up to 0.84 mg/kg body weight over 10 min) was proposed as an alternative to exercise testing for the diagnosis of coronary artery disease. To establish the diagnostic usefulness of the exercise-electrocardiography and dipyridamole-echocardiography tests in this disease, the two tests were performed--on different days and in random order--in 83 consecutive women evaluated for a chest pain syndrome. All 83 women had taken no medications for greater than 48 h, and 15 had had a previous myocardial infarction. Positivity of the dipyridamole-echocardiography test was based on detection of a transient asynergy of contraction that was absent or of lesser degree at rest; the exercise-electrocardiography test (by upright cycloergometer) was considered positive when the ST segment was shifted greater than 0.1 mV 0.08 s after the J point. Coronary angiography showed significant coronary artery disease (greater than 70% luminal reduction of at least one major coronary vessel) in 39 women. No significant complications occurred in any patient during either test. Sensitivity and predictive value of a negative test were similar for the dipyridamole-echocardiography and the exercise-electrocardiography test (79 versus 72% and 84 versus 68%, respectively, whereas the dipyridamole-echocardiography test had greater specificity (93 versus 52%, p less than 0.001), accuracy (87 versus 62%, p less than 0.001) and a higher predictive value of a positive test (91 versus 57%, p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Usefulness of a High-Dose Dipyridamole- Echocardiography Test for Diagnosis of Syndrome X

This study assesses whether the high-dose dipyridamole-echocardiography test (DET, 2-D echocardiographic and 12-lead electrocardiographic monitoring during dipyridamole infusion, up to 0.84 mg/kg over 10 minutes) can help to identify patients with syndrome X. DET was performed in 10 control subjects (group A) and in 19 patients with syndrome X (group B). Patients in group B had chest pain on effort, a positive exercise stress response (more than 0.1 mV of ST-segment depression), negative ergonovine test response and normal left ventricular function and coronary angiographic findings. During DET no subject in group A showed transient asynergy or ST-segment depression and none had chest pain; in group B, no patient had transient asynergy, 13 (68%) had chest pain and 16 (84%) had more than 0.1 mV of ST-segment depression. Percent fractional shortening was not significantly different in the 2 study groups, either basally (group A, 35 +/- 7; group B, 37 +/- 8) or at peak hyperkinesia during DET (group A, 48 +/- 8; group B, 54 +/- 10). Thus, dipyridamole-induced chest pain and ST-segment depression in patients with syndrome X are not associated with impaired regional or global left ventricular function. This entity of echocardiographically silent myocardial ischemia during DET may be a clue to noninvasive detection of syndrome X.

Assessment of anatomic and physiological severity of single-vessel coronary artery lesions by dipyridamole echocardiography. Comparison with positron emission tomography and quantitative arteriography.

BackgroundThe aim of this study was to compare the results of dipyridamole-echocardiography test (DET: twodimensional echo monitoring during dipyridamole infusion up to 0.84 mg/kg over a period of 10 minutes) with both anatomic and physiological parameters of coronary artery disease severity, assessed by computer-assisted quantitative coronary arteriography, and regional coronary flow reserve, measured by [13N]ammonia (13NH3) and dynamic positron emission tomography (PET), respectively. Methods and ResultsWe studied 31 patients with a history of chest pain and neither previous myocardial infarction nor resting wall motion abnormalities. Eighteen patients had single- vessel disease (>50% stenosis of one major coronary vessel), and 13 had normal coronary arteries. The criterion for DET positivity was the appearance of a new transient regional wall motion abnormality. In patients with a positive DET, two parameters were evaluated: the dipyridamole time (ie, the time from the beginning of drug infusion to the development of obvious dyssynergy) and the wall motion score index WMSI, a semiquantitative integrated estimation of extent and severity of the stress-induced dyssynergy). WMSI was derived by summation of individual segment scores divided by the number of segments interpreted. Quantification of regional myocardial blood flow was obtained by PET measurements of 13NTH3 arterial input function and left ventricular myocardial tissue concentration both at control and after dipyridamole 0.56 mg/kg over 4 minutes). Maximal regional blood flow after dipyridamole in the region supplied by the stenotic vessel was significantly lower in the 11 patients with coronary artery disease and positive DET than in the 7 patients with coronary artery disease and negative DET (1.08±0.33 versus 1.98±0.37 mL ·min−1 · g−1, P < .01). In patients with a positive DET, regional coronary flow reserve correlated well with dipyridamole time (r = .87, P < .01) but not with peak WMSI (r = .25, P = NS). Patients with dipyridamole-induced akinesia or dyskinesia (n=6) had a greater reduction in regional coronary flow reserve than did those showing hypokinesia (n=5): 1.38±0.51 versus 2.17±0.42, P < .05. Percent area reduction was more severe in patients with DET positivity than in those with DET negativity (93.7±8.7% versus 77±10.3%, P < .01), and it correlated with regional coronary flow reserve (r = .64, P < .01) and dipyridamole time (r = − .59, P < .01). ConclusionsIn patients with single-vessel disease, DET shows an excellent specificity but a limited sensitivity; in these patients, DET positivity is associated with a physiologically important coronary stenosis. Severity of the anatomic stenosis and impairment in regional flow reserve are greater when the dipyridamole-induced dyssynergy appears earlier during the test. Therefore, a stratification of the anatomophysiological severity of coronary artery disease can be obtained with DET, based mainly on the temporal allocation of the transient dyssynergy.

Quantitative assessment of ultrasonic myocardial reflectivity in hypertrophic cardiomyopathy

The purpose of this study was to investigate the relation between acoustic properties of the myocardium and magnitude of left ventricular hypertrophy in patients with hypertrophic cardiomyopathy. An on-line radio frequency analysis system was used to obtain quantitative operator-independent measurements of the integrated backscatter signal of the ventricular septum and posterior free wall in 25 patients with hypertrophic cardiomyopathy and 25 normal age-matched control subjects. The integrated values of the radio frequency signal were normalized for the pericardial interface and expressed in percent. Tissue reflectivity was significantly increased in the hypertrophied ventricular septum, as well as in the nonhypertrophied posterior free wall, in patients with hypertrophic cardiomyopathy (58 +/- 15% and 37 +/- 12%, respectively) compared with values in normal subjects (33 +/- 10% and 18 +/- 5%, respectively; p less than 0.001). Furthermore, measurements of reflectivity of the septum or posterior free wall, or both, were beyond 2 SD of normal values in greater than 90% of the patients and were also abnormal in each of the five study patients who had only mild and localized left ventricular hypertrophy. No correlation was identified between myocardial tissue reflectivity and left ventricular wall thickness in the patients with hypertrophic cardiomyopathy (correlation coefficient r = 0.4; p = NS). These findings demonstrate that myocardial reflectivity is abnormal in most patients with hypertrophic cardiomyopathy and is largely independent of the magnitude of left ventricular hypertrophy. Moreover, quantitative analysis of ultrasonic reflectivity can differentiate patients with hypertrophic cardiomyopathy from normal subjects independently of clinical features and conventional echocardiographic measurements.