Improved specificity of transesophageal dobutamine stress echocardiography compared to standard tests for evaluation of coronary artery disease in women presenting with chest pain

The detection of coronary artery disease (CAD) by noninvasive methods has been hindered in women by the high rate of false-positive results. To determine the feasibility and accuracy of transesophageal dobutamine stress echocardiography for identification of CAD in women, we studied 84 patients (age 51 +/- 11 years) who underwent symptom-limited exercise treadmill testing, exercise thallium-201 scintigraphy, and coronary angiography for evaluation of anginal chest pain. Of the 84 patients, 62 had normal coronary arteries or nonsignificant coronary lesions, and 22 had significant stenosis of > or = 1 major coronary artery. During treadmill exercise, repolarization changes were observed in 16 of 21 patients with CAD and in 19 of 60 patients with normal coronary arteries. With thallium scintigraphy, a reversible defect was observed in 19 of 22 patients with CAD and in 12 of 60 patients with normal coronary arteries. Regional wall motion abnormalities during dobutamine infusion developed in 18 of 22 patients with CAD and in none of the 62 patients with normal coronary arteries. All 3 tests had similar sensitivity for detection of CAD (76% for exercise treadmill test, 86% for thallium scintigraphy, and 82% for transesophageal dobutamine stress echocardiography). However, transesophageal dobutamine stress echocardiography had significantly higher specificity than the other 2 tests (100% vs 68% for exercise treadmill test and 80% for thallium scintigraphy; p = 0.0001). Thus, transesophageal dobutamine stress echocardiography is accurate for evaluation of CAD among women presenting with chest pain; its use should be considered when more conventional tests are equivocal or technically suboptimal.     

Prognostic significance of normal dobutamine-atropine stress sestamibi scintigraphy in women with chest pain

The high risk of vaso-occlusive events in children younger than 4 years with cyanotic congenital heart disease and polycythaemia has been attributed to increased thromboxane (Tx) A2 formation. In older children with cyanotic congenital heart disease, however, the risk of vaso-occlusive events is much lower. We therefore hypothesized that the formation of TxA2 and prostacyclin is not disturbed in this age group. We measured urinary excretion of stable index metabolites of in vivo TxA2 and prostacyclin formation by gas chromatography-mass spectrometry in nine children (age 5.9-14.4, median 8.7 years) with cyanotic congenital heart disease, and in nine healthy, age-matched control subjects. The patients excreted less 2,3-dinor-TxB2 (systemic TxA2 formation, P = 0.03), 2,3-dinor-6-keto-PGF1 alpha (systemic prostacyclin formation. P = 0.03) and TxB2 (renal TxA2 formation, P = 0.01) than the control subjects. We conclude that in children older than 5 years with cyanotic congenital heart disease, endogenous synthesis of TxA2 and prostacyclin is not stimulated. This result may explain the lower risk of vaso-occlusive events in this age group as compared with younger children. In addition, our results suggest that chronic hypoxaemia may affect the in vivo formation of TxA2 and prostacyclin and the metabolic disposition of TxB2.     

Complications of pharmacologic stress echocardiography in coronary artery disease

In the last few years, pharmacologic stress echocardiography is emerging as a promising diagnostic tool with a favorable cost/benefit ratio. Its main clinical applications include the assessment of coronary artery disease, the identification of viable myocardium, and risk stratification before major vascular surgery. However, cardiac (arrhythmic, ischemic, or hemodynamic) as well as noncardiac complications have been reported, so that a risk/benefit analysis is advisable in view of the extensive introduction of this technique in the clinical arena. The most popular pharmacologic agents employed for stress echocardiography are dipyridamole, dobutamine, and adenosine. A comparative analysis with exercise stress testing, the classical standard a reference of all ischemia-provoking tests, confirms that in terms of safety and tolerability pharmacologic stress echocardiography may be considered a good alternative in patients unable to exercise maximally. No appreciable difference among the safety profiles of the most common pharmacologic agents has been found, but a careful evaluation of the risk/benefit ratio is advisable for any stressor in the individual patient by considering the relative importance of the expected diagnostic contribution and the pharmacodynamic impact of the test. Finally, adequate training of the operator and monitoring of the patient during stress and recovery are essential for getting optimal safety conditions.     

Can measures of coronary dynamics explain chest pain without coronary artery disease?

There is reason to believe that clear parathyroid cysts are a separate pathologic entity distinct from degenerative cystic tumors of the parathyroid. They probably derive from enlargement of vestigial tubules or canals associated with parathyroid embryogenesis and they are rarely, if ever, hyperfunctioning. Indeed, if a clear parathyroid cyst is encountered in the clinical setting of primary hyperparathyroidism, then it is important to exclude a concomitant tumor in one of the other parathyroid gland, as in the case presented here. If the ionized serum calcium level is normal then clear parathyroid cysts can be diagnosed and treated definitively by percutaneous needle aspiration of their crystal clear fluid contents.     

Prognostic significance of systolic blood pressure changes during dobutamine-atropine stress technetium-99m sestamibi perfusion scintigraphy in patients with chest pain and known or suspected coronary artery disease

To investigate the prognostic value of dobutamine stress-induced changes in systolic blood pressure (BP) 418 patients (mean age 60 years, 238 men) with chest pain and known or suspected coronary artery disease, who underwent a dobutamine-atropine stress technetium-99m sestamibi myocardial perfusion scintigraphic study, were followed up for 25 +/- 15 months. Blood pressure was measured by automatic sphygmomanometry every 3 minutes. A marked decrease and increase in systolic BP from rest to peak were defined as changes of > or = 20 mm Hg, and > or = 30 mm Hg, respectively. Worst outcome events were cardiac death (n = 30), nonfatal myocardial infarction (n = 17), and hospitalization for congestive heart failure (n = 8). A decrease in systolic BP (prevalence 16%) was associated with older age and higher baseline systolic BP. Fixed and reversible sestamibi perfusion defects and follow-up results were similar to patients without a systolic BP decrease. In contrast, an increase in systolic BP (prevalence 24%) was associated with younger age, lower baseline systolic BP, and with absence of a history of prior congestive heart failure or treatment with angiotensin-converting enzyme inhibitors. Furthermore, these patients had fewer fixed perfusion defects and tended to have fewer annual event rates (3.5% vs 7.5%, p < 0.10). In a multivariate model, an increase in systolic BP was not an independent predictor for subsequent events. In conclusion, a dobutamine-induced decrease in systolic BP is not associated with fixed or reversible sestamibi defects or adverse prognosis. An increase in systolic BP, however, is associated with less fixed sestamibi defects and a tendency toward less annual event rates.     

Prevalence of coronary blood flow reserve abnormalities among patients with nonobstructive coronary artery disease and chest pain

BACKGROUND: Very little is known about the mechanisms underlying adverse reactions to radiocontrast medium. On the basis of the clinical features of the adverse reactions, it has generally been considered that an IgE-dependent mechanism is not involved in these adverse reactions, and only a few studies have demonstrated the presence of IgE antibody to radiocontrast medium in patient sera. METHODS: We assayed for IgE antibody to ioxaglic acid (Hexabrix), a representative radiocontrast medium, in the sera of patients who had developed adverse reactions to ioxaglic acid. A conjugate was prepared by coupling succinyl ioxaglic acid to human serum albumin. Enzyme immunoassay and radioimmunoassay for the detection of IgE antibody to ioxaglic acid in patient sera were constructed by physical adsorption or by covalent coupling of the conjugate on solid supports. RESULTS: When the radioactivity or the absorbance exceeding the mean plus 3 SD for normal healthy subjects was regarded as positive, IgE antibody was detected in the sera of 47.1% of the patients who had a past history of adverse reactions to ioxaglic acid and 16.2% of those who had experienced adverse reactions to ioxaglic acid within 24 h before the blood collection, although the IgE antibody levels were low. On the other hand, IgE antibody to ioxaglic acid was not detected in the sera of patients with no history of adverse reactions to ioxaglic acid. Inhibition experiments revealed the presence of IgE antibody specific to ioxaglic acid in the serum defined as positive for IgE antibody to ioxaglic acid. The presence of IgE antibody to ioxaglic acid did not always correlate with the activation of mast cells due to the occurrence of adverse reactions to ioxaglic acid. CONCLUSIONS: A small amount of IgE antibody to ioxaglic acid was detected in the sera of some patients with a history of adverse reactions to ioxaglic acid, and these adverse reactions may be partly explained by the presence of IgE antibody in the serum of at least some patients.     

Dipyridamole stress echocardiography for risk stratification in hypertensive patients with chest pain

BACKGROUND: The noninvasive prognostic assessment of coronary artery disease (CAD) in hypertensive patients represents an unresolved task to date. In this study, we investigated the value of dipyridamole stress echocardiography in risk stratification of hypertensive patients with chest pain and unknown CAD. METHODS AND RESULTS: Dipyridamole stress echocardiography was performed in 257 hypertensives (110 men; age, 63+/-9 years) complaining of chest pain and without a history of CAD. No major complications occurred. Four tests were interrupted prematurely because of side effects, with 98. 4% feasibility of test. A positive echocardiographic response was found in 72 patients (27 during the low-dose [0.56 mg/kg]). During the follow-up (32+/-18 months), 27 cardiac events occurred: 3 deaths, 8 infarctions, and 16 cases of unstable angina. Moreover, 27 patients underwent coronary revascularization. At multivariate analysis, the positive echocardiographic result (OR, 5.5; 95% CI, 1.4 to 16.6) was the only predictor of hard cardiac events (death, infarction). Considering spontaneous cardiac events (death, infarction, and unstable angina) as end points, the positive echocardiographic result (OR, 4.2; 95% CI, 1.8 to 9.6) and family history of CAD (OR, 4.2; 95% CI, 1.5 to 6. 9) were independently associated with prognosis. The 3-year survival rates for the negative and the positive populations were, respectively, 97% and 87% (P=0.0019) considering hard cardiac events and 96% and 74% (P=0.0000) considering spontaneous cardiac events. CONCLUSIONS: Dipyridamole stress echocardiography is safe, highly feasible, and effective in risk stratification of hypertensives with chest pain and unknown CAD. At present, it represents an attractive option for prognostic assessment of this clinically defined population.     

Dobutamine stress echocardiography for assessing coronary artery disease after transplantation in children

OBJECTIVES: The purpose of this study was to determine the feasibility, safety and diagnostic accuracy of dobutamine stress echocardiography (DSE) for evaluating posttransplant coronary artery disease (TxCAD) in children, and to determine the frequency of selected cardiac events after normal or abnormal DSE. BACKGROUND: Posttransplant coronary artery disease is the most common cause of graft loss (late death or retransplantation) after cardiac transplantation (CTx) in children. Coronary angiography, routinely performed to screen for TxCAD, is an invasive procedure with limited sensitivity. The efficacy of DSE for detecting atherosclerotic coronary artery disease is established, but is unknown in children after CTx. METHODS: Of the 78 children (median age 5.7 years, range 3 to 18) entered into the study, 72 (92%) underwent diagnostic DSE by means of a standard protocol, 4.6 +/- 1.9 years after CTx. The results of coronary angiography performed in 70 patients were compared with DSE findings. After DSE, subjects were monitored for TxCAD-related cardiac events, including death, retransplantation and new angiographic diagnosis of TxCAD. RESULTS: No major complications occurred. Minor complications, most often hypertension, occurred in 11% of the 72 subjects. The sensitivity and specificity of DSE were 72% and 80%, respectively, when compared with coronary angiography. At follow-up (21 +/- 8 months), TxCAD-related cardiac events occurred in 2 of 50 children (4%) with negative DSE, versus 6 of 22 children (27%) with positive DSE (p < 0.01). CONCLUSIONS: DSE is a feasible, safe and accurate screening method for TxCAD in children. Positive DSE identifies patients at increased risk of TxCAD-related cardiac events. Negative DSE predicts short-term freedom from such events.     

Prognostic value of myocardial hypoperfusion indexes in patients with suspected or known coronary artery disease

BACKGROUND: We evaluated the prognostic value of exercise 201Tl indexes of myocardial hypoperfusion in patients with suspected or known coronary artery disease. METHODS AND RESULTS: Patients were divided into two groups: group I consisted of 332 patients with diagnostic electrocardiographic stress test results and group II consisted of 144 patients with nondiagnostic (inadequate or uninterpretable) stress electrocardiograms. At the 2-year follow-up, 20 hard events (16 cardiac deaths and 4 nonfatal myocardial infarctions) and 80 soft events (coronary revascularization procedures) occurred in group I. Considering total events, thallium imaging provided significant prognostic information in addition to clinical and exercise stress test data in the total study population (p < 0.001) and in patients with previous myocardial infarction (p < 0.001); in patients without previous infarction, thallium imaging added incremental prognostic value only in those with positive electrocardiographic stress test results (p < 0.01). When only hard events were considered, thallium variables added further information only in patients with previous myocardial infarction (p < 0.05). In group II at the end of follow-up, 15 hard and 39 soft events had occurred. In these patients occurrence of total (p < 0.001), hard (p < 0.05), and soft (p < 0.001) events was higher in those with abnormal thallium scintigraphic results than in those without. Moreover, no clinical and exercise variable, except history of myocardial infarction, was significantly related to outcome, whereas both indexes of extent and severity of hypoperfusion were significant. CONCLUSIONS: The results of this study demonstrate that scintigraphic indexes of myocardial hypoperfusion obtained by qualitative planar thallium imaging give unique prognostic information in patients with nondiagnostic electrocardiographic stress test results. Thallium imaging provides incremental prognostic information even in patients with diagnostic electrocardiographic stress test results but not in the low-risk subset of patients without previous infarction who have negative electrocardiographic stress test results.     

Evaluation of patients with diabetes mellitus for coronary artery disease using dobutamine stress echocardiography

BACKGROUND: There is a high prevalence of coronary artery disease (CAD) in patients with diabetes mellitus. Detection of inducible ischaemia using treadmill exercise testing may be limited by the relatively poor inherent predictive accuracy of the test. The purpose of this study was to determine the value of dobutamine stress echocardiography (DSE) for the detection of CAD in patients with diabetes mellitus. METHODS: Patients with diabetes mellitus referred for cardiac assessment were considered eligible for study. DSE was performed in a standard fashion. Significant CAD was defined as a > 50% luminal diameter stenosis on coronary angiography. RESULTS: A total of 52 patients (mean age 59 years) with diabetes mellitus were studied prospectively using DSE. Risk factors for CAD included hypertension in 19, family history in 21, hypercholesterolaemia in 14, history of smoking in 38. The sensitivity, specificity, positive and negative predictive values of DSE for detection of CAD were 82, 54, 84 and 50% respectively. CONCLUSION: The specificity of DSE for CAD in patients with diabetes mellitus is low. Whether this reflects an underdetection of small vessel disease by contrast coronary angiography or whether it relates to test performance is unclear.     

Long-term prognostic value of dobutamine-atropine stress echocardiography in 1737 patients with known or suspected coronary artery disease: A single-center experience

BACKGROUND: The purpose of this study was to assess the long-term value of dobutamine-atropine stress echocardiography (DSE) for prediction of late cardiac events in patients with proven or suspected coronary artery disease. METHODS AND RESULTS: Clinical data and DSE results were analyzed in 1734 consecutive patients undergoing DSE between 1989 and 1997. Seventy-four patients who underwent revascularization within 3 months of DSE and 1 patient lost to follow-up were excluded; the remaining 1659 (median age, 62 years; range, 14 to 99 years) were followed up for 36 months (range, 6 to 96 months). Wall motion abnormalities at rest and the presence and extent of stress-induced wall motion abnormalities (ischemia) were scored for each patient. Cardiac events were related to clinical and ECG data and DSE results. Four hundred twenty-eight cardiac events occurred in 366, documented cardiac death in 108 (total death, 247), nonfatal infarction in 128, and late revascularization in 192 patients. In a multivariable Cox proportional-hazards model, the ratio of documented cardiac death or (re)infarction was increased in the presence of stress-induced ischemia (hazard ratio, 3.3; 95% CI, 2.4 to 4.4) and extensive rest wall motion abnormalities (hazard ratio, 1.9; 95% CI, 1.3 to 2.6). The number of ischemic segments was predictive for late cardiac events. A normal DSE carried a relatively good prognosis, with an annual event rate of cardiac death or infarction of 1.3% over a 5-year period. CONCLUSIONS: In a large group of patients, DSE has an added value for predicting late cardiac events during long-term follow-up, improving the separation between high- risk and very-low-risk patients.     

Optimal criteria for the diagnosis of coronary artery disease by dobutamine stress echocardiography

Left ventricular remodeling occurs spontaneously among patients with hypertrophic cardiomyopathy in several ways: (1) wall thickening in children; (2) wall thinning associated with cavity enlargement in midlife; and possibly (3) a very gradual wall thinning process occurring over long periods of time in adulthood.     

Evaluation of coronary artery disease in women

Sepsis syndrome and septic shock remain significant causes of morbidity and mortality. To date, clinical trials of novel agents to treat sepsis have failed to demonstrate clinical efficacy despite considerable animal data to suggest a positive therapeutic benefit. This article reviews the recent major clinical trials on sepsis and discusses the hypotheses on which these therapies are based and the critical issues associated with clinical sepsis. Recommendations for future clinical trials on sepsis are made.     

Comparison of dobutamine stress echocardiography and treadmill exercise electrocardiography for detection of coronary artery disease

BACKGROUND: Critical analysis of treadmill exercise testing (TMET) for the detection of coronary artery disease has revealed many shortcomings. Excellent diagnostic accuracy has been reported for dobutamine stress echocardiography (DSE). METHODS: A prospective comparison of DSE and TMET for the detection of coronary artery disease in routine clinical practice was performed using contrast cineangiography (significant stenosis > or = 50%) as a gold standard. RESULTS: A total of 116 patients (82 men, 34 women) were studied. Significant stenosis was detected by coronary angiography in 92 patients (79%). Single vessel disease occurred in 28, double-vessel disease in 32, and multivessel disease in 32 patients. Although sensitivity of DSE was better than that of TMET (82 versus 40%), specificity was worse (63 versus 79%). Positive predictive values for both DSE and TMET were good at 89 and 87%, respectively, whereas negative predictive values were poor for both (47% for DSE, 26% for TMET). CONCLUSIONS: Overall, DSE performs better than TMET in terms of sensitivity and positive and negative predictive value. Its lower specificity than that of TMET may lead to more patients being referred for diagnostic coronary angiography. The poor negative predictive value of DSE and TMET means that one should not be falsely reassured by normal results.     

Value of dobutamine stress echocardiography in determining the prognosis of patients with known or suspected coronary artery disease

Although the accuracy of dobutamine stress echo (DSE) for detecting coronary artery disease (CAD) has been established, its role in determining prognosis is less well defined. The purpose of this study was to evaluate the prognostic significance of DSE in patients with known or suspected CAD. Follow-up was obtained on 291 patients an average of 15 months after clinically indicated DSE. Studies were stratified with respect to resting and inducible wall motion abnormalities into 1 of 4 responses: normal, ischemic, fixed, and mixed. Hard end points of nonfatal myocardial infarction and cardiac death were tabulated for outcome. Statistically significant differences in the incidence of hard cardiac end points were noted for 2 of 4 DSE responses. A normal DSE was associated with a statistically lower likelihood of a hard cardiac event than was a DSE demonstrating resting or inducible abnormalities (p = 0.001). DSE with a mixed response (resting abnormality with additional inducible ischemia) was associated with a higher likelihood of cardiac events by multivariate analysis (p = 0.003). By multiple logistic regression analysis of dobutamine response, age, and cardiac risk factors, only a mixed response on DSE was independently associated with the occurrence of a hard cardiac event in the follow-up period. In addition, left ventricular dysfunction on the resting echocardiogram was associated with a worse prognosis in patients with major noncardiac disease. We conclude that dobutamine response is an independent predictor of cardiac events compared with traditional risk factor analysis and that DSE can identify high- and low-risk subsets of patients with known or suspected CAD.