Eugenio Picano

Analysis of interinstitutional observer agreement in interpretation of dobutamine stress echocardiograms

OBJECTIVES This study sought to determine the degree of interinstitutional agreement in the interpretation of dobutamine stress echocardiograms. BACKGROUND Dobutamine stress echocardiography involves subjective interpretation. Consistent methods for acquisition and interpretation are of critical importance for obtaining high interobserver agreement and for facilitating communication of test results. METHODS Five experienced centers were each asked to submit 30 dobutamine stress echocardiograms (dobutamine up to 40 micrograms/kg body weight per min and atropine up to 1 mg) obtained in patients undergoing coronary angiography. Thus, a total of 150 dobutamine stress echocardiograms were interpreted by each center without knowledge of any other patient data. Left ventricular wall motion was assessed using a 16-segment model but was otherwise not standardized. No patient was excluded because of poor image quality or inadequate stress level. Echocardiographic image quality was assessed using a five-point scale. RESULTS Angiographically significant coronary artery disease (> or = 50% diameter stenosis) was present in 95 patients (63%). By a majority decision (three or more centers), the sensitivity, specificity and accuracy of dobutamine echocardiography were 76%, 87% and 80%, respectively. Abnormal or normal results of stress echocardiography were agreed on by four or all five of the centers in 73% of patients (mean kappa value 0.37, fair agreement only). Agreement on the left anterior descending artery territory (78%) was similar to that for the combined right coronary artery/left circumflex artery territory (74%), and for specific segments the agreement ranged from 84% to 97% and was highest for the basal anterior segment and lowest for the basal inferior segment. Agreement was higher in patients with no (82%) or three-vessel coronary artery disease (100%) and lower in patients with one- or two-vessel disease (61% and 68%, respectively). Agreement on positivity or negativity of stress test results was 100% for patients with the highest image quality but only 43% for those with the lowest image quality (p = 0.003). CONCLUSIONS The current heterogeneity in data acquisition and assessment criteria among different centers results in low interinstitutional agreement in interpretation of stress echocardiograms. Agreement is higher in patients with no or advanced coronary artery disease and substantially lower in those with limited echocardiographic image quality. To increase interinstitutional agreement, better standardization of image acquisition and reading criteria of stress echocardiography is recommended.

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.

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.

Standardized Guidelines for the Interpretation of Dobutamine Echocardiography Reduce Interinstitutional Variance in Interpretation

Subjective interpretation of dobutamine echocardiograms provides only moderate interinstitutional observer agreement if nonunified data acquisition and assessment criteria are applied. The present study was undertaken to evaluate parameters associated with low interinstitutional observer agreement in the interpretation of dobutamine echocardiograms and to analyze whether standardized interpretation criteria improve interinstitutional observer agreement. One hundred fifty dobutamine echocardiograms (dobutamine up to 40 microg/kg/min body weight and atropine up to 1 mg) were evaluated at 5 centers. Clinical, procedural, and echocardiographic parameters were included in the analysis of variables with significant impact on interinstitutional agreement. Standardized interpretative criteria were established, and 90 dobutamine echocardiograms were reanalyzed by 3 observers using a standardized image display. Multivariate analysis demonstrated low image quality (odds ratio [OR] 0.19, 95% confidence interval [CI] 0.08 to 0.45, p=0.0002), low severity of induced wall motion abnormality (OR 0.17, 95% CI 0.07 to 0.40, p <0.0001), and a low peak rate-pressure product (OR 0.93, 95% CI 0.43 to 2.27, p=0.0382) to result in a low interinstitutional agreement. Standardization of image display in cine loop format and of dobutamine stress echo interpretation criteria resulted in improvement in test result categorization as normal or abnormal, with a kappa value of 0.50, compared with 0.39 using the original subjective interpretation. In conclusion, image quality, the severity of induced wall motion abnormalities, and the obtained rate-pressure product have a significant impact on the interpretation homogeneity of dobutamine echocardiograms. Standardization of image display in cine loop format and of reading criteria results in improved interinstitutional agreement in interpretation of stress echocardiograms.

In vivo radiofrequency-based ultrasonic tissue characterization of the atherosclerotic plaque.

Background and Purpose The ultrasonic image can offer unique information on the composition of atherosclerotic plaque, ie, the relative content of lipids, fibrous tissue, and calcific deposits. To date, however, the echographic assessment of plaque structure is based on a subjective, qualitative evaluation of the bidimensional images. We evaluated the feasibility and accuracy of assessing, in vivo, the acoustic properties of arterial carotid plaques by means of a suitably modified echographic apparatus allowing direct access to the radiofrequency signal. Methods In 15 patients undergoing carotid thromboendarterectomy, the ultrasonic findings in 70 discrete sites (within the plaque, n=54; normal sites, n=11; or intraluminal thrombi, n=5) were correlated with the histological analysis (hematoxylin-eosin and Mallory trichrome stains) independently performed on the arterial samples. The pathological examination was carried out at a similar level of the insonation; the sites analyzed within the plaque were chosen because of their uniform echoic characteristics. In each ultrasonic region of interest selected from the echographic image, the integrated amplitude of the rectified radiofrequency signal was measured as the integrated backscatter index. Results The intimal-medial layer of normal carotid wall (n=11) exhibited values of −32.5 ± 9.4 dB. The integrated backscatter index in fatty sites (n=11, −40.3 ± 5.4 dB) differed from that of fibrous (n=12, −23.8 ± 5.0 dB) and calcified (n=26, −11.5 ± 5.2 dB, P < .01 for all intergroup differences) sites. Intraluminal thrombotic sites (n=5, −42 ± 5.1 dB, P < .01) differed from fibrous and calcified subsets (P < .01) but overlapped (P=NS) with fatty sites. Histological sampling also showed two sites of intraplaque hemorrhage that exhibited very low backscatter values (−53 and −58 dB) and three fibrofatty sites showing backscatter values (−28, −28, and −32 dB) intermediate between the fibrous and the fatty subsets. Conclusions Quantitative analysis of integrated backscatter of the arterial wall is feasible in humans and provides an operator-independent assessment of plaque echoic structure. In particular, integrated backscatter is effective in distinguishing lipidic, fibrotic, and calcific components in human atherosclerotic plaques.

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.

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.

Normal ultrasonic myocardial reflectivity in athletes with increased left ventricular mass. A tissue characterization study.

BackgroundUltrasonic integrated backscatter of myocardial walls is directly related to the morphometrically evaluated collagen content. The integrated backscatter is also increased in hypertrophic cardiomyopathy, probably because of fiber disarray. The purpose of this study was to investigate myocardial tissue reflectivity in subjects with physiological hypertrophy caused by intense physical training and to assess the relation between the acoustic properties of myocardial tissue and left ventricular wall thickness assessed by conventional two-dimensional echocardiography. Methods and ResultsTwenty-four young male athletes (14 professional cyclists and 10 weight lifters, all in full agonistic activity) were studied together with 10 normal age-matched controls with sedentary life. By means of a commercially available two-dimensional echocardiograph, standard measurements were obtained according to the recommendations of the American Society of Echocardiography. With a prototype implemented in our Institute, an on-line radiofrequency analysis of ultrasound signals was also performed to obtain quantitative operator-independent measurements of the integrated backscatter of the myocardial walls. The integrated values of the radiofrequency signal were normalized for the pericardial interface and expressed in percent integrated backscatter (%IB). Compared with control subjects, athletes showed greater thickness values of septum (controls, 9±1; cyclists, 14±2; weight lifters, 15±1 mm, mean± SD; p < 0.01) and posterior wall (9±1, 12±2, and 12+1 mm, respectively; p < 0.01) but similar values of %IB for both septum (23±4%, 21±7%, and 23±8%, p = NS) and posterior wall (10±2%, 9±2%, and 11±2%, p = NS). In athletes, no correlation was found between septal and posterior wall thickness and the corresponding regional myocardial reflectivity (r = 0.23, p = NS and r = 0.01, p = NS, respectively). Furthermore, we compared the quantitative ultrasonic data between two subsets of 10 athletes and 10 patients with hypertrophic cardiomyopathy and similar degrees of septal thickness (16±1 versus 17±1 mm, respectively, p = NS). Septal and posterior wall %IB results were significantly higher in patients with hypertrophic cardiomyopathy (53±13% and 36±9%o, respectively) than in athletes (21±7% and 10±3%, respectively; p < 0.01 for both). ConclusionsWe conclude that 1) endurance athletes show a normal pattern of quantitatively assessed ultrasonic backscatter despite of a marked left ventricular hypertrophy and 2) athletes and patients with hypertrophic cardiomyopathy and similar degrees of myocardial wall thickness can be differentiated on the basis of quantitative analysis of backscattered signal.

Transient changes in left ventricular mechanics during attacks of Prinzmetal's angina: An M-mode echocardiographic study

M-mode echocardiograms were recorded in 12 patients with Prinzmetals angina during 29 episodes of transient myocardial ischemia at rest (18 spontaneous and 11 ergonovine-induced). At peak ST segment elevation a regional mechanical impairment was observed in the interventricular septum during 23 episodes of angina and in the posterior wall during six episodes. In the 18 spontaneous episodes the left ventricular ischemic wall, when compared to the basal state, was found to have a significant reduction in motion (-76.3 +/- 9.1%) (mean +/- SEM), in diastolic thickness (-11.7 +/- 2.5%), and in percent systolic thickening (-88.0 +/- 5.6%). Increase in left ventricular end-diastolic diameter (+13.1 +/- 2.1%) and decrease in percent fractional shortening (-38.1 +/- 3.7%) were also observed. When ST segment was back to the isoelectric line, a transient overshoot in regional left ventricular function was observed. In induced episodes statistically significant changes could be detected by M-mode echocardiography even before appearance of ST segment elevation and anginal pain. No significant difference was found in type or degree of mechanical impairment between induced and spontaneous episodes. Therefore, in patients with Prinzmetals angina: (1) M-mode echocardiography allows detection of mechanical changes due to transient myocardial ischemia; and (2) mechanical impairment occurs earlier than clinical (pain) and electrocardiographic (ST segment elevation) signs of transmural ischemia.