Abstract: OBJECTIVE: To compare the prognostic value of stress echocardiography results in men and women with known and suspected coronary artery disease. METHODS: We analyzed the data of 8737 patients (5529 men and 3208 women) who underwent stress echocardiography (exercise in 523 patients, dipyridamole in 6227 patients, dobutamine in 1987) for evaluating known (n=3857) or suspected (n=4880) coronary artery disease. Patients were followed up for the occurrence of overall mortality or nonfatal myocardial infarction. RESULTS: During a median follow-up of 25 months, 1218 cardiac events (693 deaths and 525 infarctions) occurred. Moreover, 2263 patients (1731 men [31%] and 532 women [17%]; P<.0001) underwent coronary revascularization and were censored. Stress echocardiography results added prognostic information to that of clinical findings and resting wall motion score index in men and women with both known and suspected coronary artery disease. In patients with known coronary artery disease, women had a higher (P=.01) event rate than men in the presence of ischemia. The annual event rate was worse for nondiabetic women (P=.007) but not diabetic women; age had a neutral prognostic effect in the 2 sexes. In patients with suspected coronary artery disease, men without ischemia had a higher (P<.0001) event rate than women. The annual event rate was worse in men aged less than 65 years (P<.0001) or more than 65 years (P=.04), and those with (P=.03) or without (P<.0001) diabetes. CONCLUSION: Prognosis is at least comparable in men and women with ischemia and in those with coronary artery disease and no ischemia at stress echocardiography. In these clinical settings, availability for major procedures should be similar for both genders.

Abstract:

Abstract: OBJECTIVES: The aim of the study was to assess the prognostic value of stress echocardiography after CABG. METHODS: We evaluated 500 (100 women) patients who had undergone exercise or pharmacological SE after a median of 69 months after CABG. Of these, 351 (70%) complained of symptoms suggestive of ischemic origin while 149 (30%) were tested for asymptomatic progression of the disease. RESULTS: SE was positive for ischemia in 196 (39%) patients. During a median follow-up of 25 months, 61 patients died, 33 had a nonfatal myocardial infarction, and 112 underwent late (>3 months) revascularization. Multivariable Cox' regression analysis indicated age (HR=1.04; 95% CI 1.01-1.06; p<0.003), and peak WMSI (HR=3.07; 95% CI 1.96-4.81; p=0.0001) as independent predictors of hard (total mortality and myocardial infarction) events. SE information provided a significant improvement in predictive power of the statistical model (chi-square increase 34%, p<0.0001 for hard and 91%, p<0.0001 for major events, respectively). Survival analysis showed ischemia at SE to be associated with significantly higher hard and major event rate in both symptomatic and asymptomatic patients. DISCUSSION: SE represents an effective tool for the risk stratification of patients with previous CABG independently of the presence of symptoms suggestive of ischemic origin.

Abstract: AIM: To prospectively assess the prognostic value of the Stress-Recovery Index (SRI) in women with typical chest pain. METHODS: 165 women without known coronary artery disease, who complained of typical chest pain, were exercise tested and prospectively followed-up for the occurrence of cardiac death and nonfatal myocardial infarction. SRI, defined as the difference in absolute values between the area of heart rate-adjusted ST-segment depression during exercise and recovery, was derived in all. Clinical data, resting ejection fraction, and exercise testing data were entered into a sequential Cox's model; SRI was entered last. Model validation was performed by bootstrap adjusted by the degree of optimism in estimates. Survival curves were set up using Kaplan-Meier method and compared by the log-rank test. RESULTS: During a median follow-up time of 42 months, 19 events (14 cardiac deaths and 5 nonfatal myocardial infarction) were observed. Age (hazard ratio 3.58, 95% CI 0.87-15) and SRI (hazard ratio 0.62, 95% CI 0.42-0.92) were multivariate predictors of outcome. However, the addition of SRI increased the prognostic power of the model on top of clinical and exercise testing variables, as demonstrated by the significant (p=0.003) increase of the area under the ROC curve of the risk function. Survival analysis showed ascending SRI quartiles to identify a significant (p=0.005) increase in event-free survival. CONCLUSIONS: SRI is of value in predicting outcome of women with typical chest pain and provides additional prognostic information on the top of clinical and standard exercise testing data.

Abstract: Objectives: Several methodological problems arise when health outcomes and resource utilization are collected at different sites. To avoid misleading conclusions in multi-center economic evaluations the center effect needs to be taken into adequate consideration. The aim of this article is to compare several models, which make use of a different amount of information about the enrolling center. Methods: To model the association of total medical costs with the levels of two sets of covariates, one at patient and one at center level, we considered four statistical models, based on the Gamma model in the class of the Generalized Linear Models with a log link, which use different amount of information on the enrolling centers. Models were applied to Cost of Strategies after Myocardial Infarction data, an international randomized trial on costs of uncomplicated acute myocardial infarction (AMI). Results: The simple center effect adjustment based on a single random effect results in a more conservative estimation of the parameters as compared with approaches which make use of deeper information on the centers characteristics. Conclusions: This study shows, with reference to a real multicenter trial, that center information cannot be neglected and should be collected and inserted in the analysis, better in combination with one or more random effect, taking into account in this way also the heterogeneity among centers because of unobserved centers characteristics.

Abstract: The usage of the Aalen additive approach is proposed to model cost data. Using a Monte Carlo simulation, in a wide set of scenarios, we showed that the Aalen model is performing well and can be a reasonable alternative to the standard Gamma regression models. In addition, with reference to the COSTAMI trial data, we highlighted the ability of the Aalen model to offer additional information about the relationships between costs and specific covariates, as compared with standard regression techniques. Copyright (c) 2008 John Wiley & Sons, Ltd.

Abstract: This review article summarizes the results of histopathological studies to assess heart failure in humans. Different histopathological features underlying the clinical manifestations of heart failure are reviewed. In addition, the present role of echocardiographic techniques in assessing the failing heart is briefly summarized.

Abstract: This study investigated the value of pharmacologic stress echocardiography for risk stratification of patients > or =65 years of age. The study cohort consisted of 2,160 patients > or =65 years of age (1,257 men, mean +/- SD 71 +/- 5 years of age) undergoing dipyridamole (n = 1,521) or dobutamine (n = 639) stress echocardiography for evaluation of known (n = 913) or suspected (n = 1,247) coronary artery disease. Of 2,160 patients, 753 (35%) had a normal test result, whereas 772 (36%) showed a myocardial ischemic pattern and 635 (29%) a scar pattern. During a median follow-up of 26 months, 241 deaths and 87 nonfatal myocardial infarctions occurred. Patients (n = 568) undergoing revascularization were censored. Of 16 analyzed variables, age (hazard ratio [HR] 1.07 per unit increment), wall motion score index at rest (HR 2.63 per unit increment), ischemia at stress echocardiography (HR 1.81), and diabetes (HR 1.57) were multivariable predictors of death, whereas age (HR 1.06 per unit increment), ischemia at stress echocardiography (HR 2.60), wall motion score index at rest (HR 1.98 per unit increment), scar pattern (HR 1.99), and diabetes (HR 1.48) were multivariable predictors of death or myocardial infarction. Using an interactive stepwise procedure, stress echocardiography showed incremental prognostic value over clinical and echocardiographic data at rest, which decreased with increasing age. In addition, the annual hard event rate associated with a normal test result progressively increased with age. In conclusion, pharmacologic stress echocardiography provides useful prognostic information in patients > or =65 years of age. However, its prognostic value decreases with increasing age.

Abstract: To verify whether the stress recovery index (SRI) improves risk stratification in patients with a negative exercise electrocardiogram (ECG) using standard criteria, the SRI was derived in 708 consecutive patients with a negative exercise ECG. All-cause mortality and the combination of death or nonfatal myocardial infarction were target end points. The individual effect of clinical and exercise testing data on outcome was evaluated using Cox regression analysis with separate models for each group of variables. Model validation was performed using bootstrap adjusted by degree of optimism in estimates. Survival analysis was performed using a product-limit Kaplan-Meier method. During a 37-month follow-up, 22 deaths and 40 nonfatal acute coronary syndromes occurred. After adjusting for confounding variables, age (hazard ratio 1.62, 95% confidence interval [CI] 1.14 to 2.31 for interquartile difference), hypertension (hazard ratio 1.74, 95% CI 1.04 to 2.89), and SRI (hazard ratio 0.75, 95% CI 0.65 to 0.86 for interquartile difference) were predictive of death or nonfatal myocardial infarction. Moreover, SRI increased the prognostic power of the model on top of clinical and exercise testing variables and provided significant discrimination of survival. In conclusion, the SRI may help refine the prognostic stratification of patients with a negative exercise test result using standard electrocardiographic criteria.

Abstract: The aim of this study was to compare the prognostic value of pharmacologic stress echocardiography in diabetic and nondiabetic patients with chest pain and intermediate- to high-threshold positive exercise electrocardiographic results. A total of 935 patients with chest pain (131 diabetic patients) with ST-segment depression > or =1 mm on exercise electrocardiography at > or =75-W workload underwent dipyridamole (n = 786) or dobutamine (n = 149) stress echocardiography and were followed up for the occurence of hard (death and infarction) and major events (death, infarction, and late revascularization). During a median follow-up of 26 months, 158 events (51 deaths, 28 myocardial infarctions, and 79 late revascularizations) occurred: 34 in diabetic and 124 in nondiabetic patients (26% vs 15%, p = 0.003). Independent predictors of hard events were age, diabetes, and ischemia at stress echocardiography. Five-year hard event rates were 24% in patients with and 4% in those without ischemia (p <0.0001). Independent predictors of major events were age, diabetes, hypercholesterolemia, smoking habit, antianginal therapy at the time of testing, and ischemia at stress echocardiography. Five-year major event rates were 46% in patients with and 7% in those without ischemia (p <0.0001). Stress echocardiography results yielded effective prognostic information in diabetic and nondiabetic patients. However, the latter had worse outcomes in both the presence and absence of ischemia. Nevertheless, a nonischemic test result predicted an uneventful 6-month period and 2% major event rate at 1-year follow-up in both populations. In conclusion, stress echocardiography was effective in risk stratifying diabetic and nondiabetic patients with intermediate- to high-threshold ischemic exercise electrocardiographic results. However, major event rates associated with a nonischemic test result were similar in diabetic and nondiabetic patients during the first year of follow-up and markedly increased in the former thereafter.

Abstract: BACKGROUND: The evaluation of the economic impact of ischemic disease has gained increasing interest. Such field of investigation is suffering however of the heterogeneity of methods used in evaluating costs, limiting the comparison of study results. OBJECTIVE: The aim of the study is to show how estimates of 1-year costs of treatment of patients with uncomplicated acute myocardial infarction can vary significantly in relation to the statistical method adopted in the analysis. RESEARCH DESIGN AND METHODS: The study analyses post-IMA costs as a function of demographic and clinical covariates, by applying the following statistical survival models: the parametric survival model assuming Weibull distribution, the Cox proportional hazard (PH) model and the Aalen additive regression for modelling costs. The Aalen approach is robust both for the non-proportionality in hazard and for departures from normality. In addition it is able to easily model the effect of covariates on the extreme costs. This cost analysis is based on data collected in the two COSTAMI trials (N=487). RESULTS: There is agreement in all models with the effects of the considered covariates (age, sex, duration of disease and presence of other pathologies). There is a clear tendency of both the Aalen and the Cox model to provide a lower mean cost estimate than the other model, but with the additional feature for the Aalen model to be able to cope with all the other models in furnishing unbiased estimates with the advantage of a greater flexibility in representing the covariates' effect on the cost process. CONCLUSIONS: An appropriate choice of the model is crucial in avoiding mis-interpretation of cost determinants of IMA patients. For our data set the Aalen model proved itself to be a realistic and informative way to characterize the effect of covariates on costs.

Abstract: AIM: To evaluate the interaction between prognostic effect of revascularization and viability in diabetic and non-diabetic patients with ischaemic left ventricular dysfunction. METHODS: 612 patients with angiographically proven coronary artery disease and left ventricular ejection fraction <35% underwent dobutamine stress echocardiography to assess viability (peak-rest wall motion score index >0.4). 262 patients (75 diabetics, 187 non-diabetics) underwent revascularization and 350 (88 diabetics, 262 non-diabetics) were on medical therapy. RESULTS: During follow-up 215 patients died. Independent predictors of mortality in revascularized patients were resting left ventricular ejection fraction (HR=0.93, 95% CI 0.89-0.97, p<0.0001), Delta WMSI>40 (HR=0.44, 95% CI 0.23-0.85, p=0.01), and age (HR=1.03, 95% CI 1.00-1.06, p=0.04). In medically treated patients, independent predictors of mortality were diabetes mellitus (HR=1.64, 95% CI 1.13-2.38, p=0.009), number of diseased vessels (HR=1.27, 95% CI 1.03-1.56, p=0.02), and age (HR=1.02, 95% CI 1.00-1.04, p=0.03). In revascularized patients, 4-year mortality was 15% in those with viability and 26% in those without viability (p=0.04), there was no difference between diabetics and non-diabetics (24% vs 22%; p=0.24). CONCLUSIONS: Viability at dobutamine stress echocardiography independently predicts improved outcome following revascularization in non-diabetics as well as diabetic patients with ischaemic left ventricular dysfunction.

Abstract: OBJECTIVES: We sought to compare the prognostic value of pharmacological stress echocardiography (SE) in diabetic and nondiabetic patients with known or suspected coronary artery disease. BACKGROUND: Although SE is a useful tool for risk stratification of patients with diabetes, it has not been established whether it retains the same prognostic information in diabetic patients compared with nondiabetic patients. METHODS: A total of 5,456 patients (749 diabetics) undergoing dipyridamole (n = 3,306) or dobutamine (n = 2,150) SE were prospectively followed up for the occurrence of hard events (death and/or nonfatal myocardial infarction). RESULTS: During a median time of 31 months, 411 deaths and 236 infarctions occurred. There were 132 events in diabetic patients and 515 in nondiabetic patients (18% vs. 11%, respectively; p < 0.0001). Moreover, 1,607 (29%) patients underwent coronary revascularization and were censored. Ischemia at SE, resting wall motion score index, and age were independent predictors of death and hard events in both diabetic and nondiabetic patients. Compared with a normal test, ischemia and scar test patterns were associated to significantly lower age-corrected five-year hard event-free survival in diabetic as well as nondiabetic patients. However, a normal test was associated with a greater than two-fold annual event rate in diabetic patients as compared with nondiabetics who were either younger (2.6% vs. 1.0%) or older (5.5% vs. 2.2%) than 65 years of age. CONCLUSIONS: Stress echocardiography is equally effective in risk stratifying diabetic and nondiabetic patients independently of age. However, the normal test result predicts a less favorable outcome in diabetic than in nondiabetic patients.

Abstract: OBJECTIVES: This study sought to test the hypothesis that thrombus removal, with a new manual thrombus-aspirating device, before primary percutaneous coronary intervention (PPCI) may improve myocardial reperfusion compared with standard PPCI in patients with ST-segment elevation acute myocardial infarction (STEMI). BACKGROUND: In STEMI patients, PPCI may cause thrombus dislodgment and impaired microcirculatory reperfusion. Controversial results have been reported with different systems of distal protection or thrombus removal. METHODS: One-hundred forty-eight consecutive STEMI patients, admitted within 12 h of symptom onset and scheduled for PPCI, were randomly assigned to PPCI (group 1) or manual thrombus aspiration before standard PPCI (group 2). Patients with cardiogenic shock, previous infarction, or thrombolytic therapy were excluded. Primary end points were complete (>70%) ST-segment resolution (STR) and myocardial blush grade (MBG) 3. RESULTS: Baseline clinical and angiographic characteristics were similar in the 2 groups. Comparing groups 1 and 2: complete STR 50% versus 68% (p < 0.05); MBG-3 44% versus 88% (p < 0.0001); coronary Thrombolysis In Myocardial Infarction (TIMI) flow grade 3 78% versus 89% (p = NS); corrected TIMI frame count 21.5 +/- 12 versus 17.3 +/- 6 (p < 0.01); no reflow 15% versus 3% (p < 0.05); angiographic embolization 19% versus 5% (p < 0.05); direct stenting 24% versus 70% (p < 0.0001); and peak creatine kinase-mass band fraction 910 +/- 128 mug/l versus 790 +/- 132 mug/l (p < 0001). In-hospital clinical events were similar in the 2 groups. After adjusting for confounding factors, multivariate analysis showed thrombus aspiration to be an independent predictor of complete STR and MBG-3. CONCLUSIONS: Manual thrombus aspiration before PPCI leads to better myocardial reperfusion and is associated with lower creatine kinase mass band fraction release, lower risk of distal embolization, and no reflow compared with standard PPCI. (Thrombus Aspiration Before Standard Primary Angioplasty Improves Myocardial Reperfusion in Acute Myocardial Infarction; http://clinicaltrials.gov/ct/show/NCT00257153).

Abstract: OBJECTIVE: This study was aimed at verifying whether combined information on left ventricular perfusion and function by electrocardiogram-gated single-photon emission computed tomography (SPECT) retains its known prognostic value in patients with systemic hypertension. METHODS: A total of 415 hypertensive patients underwent rest and stress (exercise in 278 and dipyridamole in 137) gated 99mTc-sestamibi SPECT and prospective follow-up for the composite endpoint of death and acute coronary syndrome. Patients undergoing revascularization were censored. The individual effect of clinical and stress imaging data on outcome was evaluated by Cox regression analysis. Model validation was performed using bootstrap methods adjusted by the degree of optimism in estimates. Survival analysis was performed using the product-limit Kaplan-Meier method. RESULTS: During a median follow-up of 24 months, 12 cardiac deaths and 32 acute coronary syndromes occurred. After adjusting for the most significant covariates, age [hazard ratio (HR) 1.62, 95% confidence interval (CI) 1.02-2.57], diabetes (HR 7.51, 95% CI 1.61-35.2), summed stress score (HR 2.06, 95% CI 1.07-4), and peak end-systolic volume (HR 3.62, 95% CI 1.35-9.69) were multivariable predictors of outcome. The normal perfusion pattern was associated with a low event rate independently of peak end-systolic volume. Conversely, in the case of moderate to severe perfusion abnormalities, a peak end-systolic volume greater than 74 ml was able to identify an increased risk of adverse outcome. Moreover, peak end-systolic volume was significantly higher among patients who died of a cardiac cause compared with those with different outcomes. CONCLUSION: A combined assessment of left ventricular perfusion and function by gated SPECT significantly improves risk stratification in hypertensive patients.

Abstract: This article focuses on recent advances on exercise electrocardiography (ECG) for the diagnostic and prognostic assessment of coronary artery disease. In particular, the pathophysiological background of comparative heart rate-adjusted ST-segment analysis during exercise and recovery phase is discussed. In addition, the results of recent studies dealing with the application of this ECG analysis modality to different clinical settings are presented.

Abstract: This review article is aimed at comparing the results of histopathological and clinical imaging studies to assess coronary collateral circulation in humans. The role of collaterals, as emerging from morphological studies in both normal and atherosclerotic coronary vessels, is described; in addition, present role and future perpectives of echocardiographic techniques in assessing collateral circulation are briefly summarized.

Abstract: Risk stratification of patients with recurrent chest pain and normal coronary angiogram is a relevant but still definitely unsolved clinical problem. In this article the relative value of mostly used noninvasive stress testing modalities is reviewed. In addition, future perspectives derived from alternative pathophysiological insights and new diagnostic approaches are briefly discussed.

Abstract: The prediction of functional recovery or ventricular remodeling plays a central role in the prognostic assessment of acute myocardial infarction (MI) in the reperfusion era. This article reviews the advances of echocardiographic techniques, focusing on the role of low-dose dobutamine stress echocardiography, contrast echocardiography, transthoracic Doppler of the left anterior descending coronary artery, and transmitral Doppler in detecting myocardial viability and predicting outcome after an acute MI. Moreover, the definition of risk for further ischemic events is another major objective in conservatively managed patients post infarction. As such, the prognostic and economic implication of stress echocardiography compared with that of traditional exercise electrocardiography was considered.

Abstract: OBJECTIVE: To compare in a prospective, randomised, multicentre trial the relative merits of pre-discharge exercise ECG and early pharmacological stress echocardiography concerning risk stratification and costs of treating patients with uncomplicated acute myocardial infarction. DESIGN: 262 patients from six participating centres with a recent uncomplicated myocardial infarction were randomly assigned to early (day 3-5) pharmacological stress echocardiography (n = 132) or conventional pre-discharge (day 7-9) maximum symptom limited exercise ECG (n = 130). RESULTS: No complication occurred during either stress echocardiography or exercise ECG. At one year follow up there were 26 events (1 death, 5 non-fatal reinfarctions, 20 patients with unstable angina requiring hospitalisation) in patients randomly assigned to early stress echocardiography and 18 events (2 reinfarctions, 16 unstable angina requiring hospitalisation) in the group randomly assigned to exercise ECG (not significant). The negative predictive value was 92% for stress echocardiography and 88% for exercise ECG (not significant). Total costs of the two strategies were similar (not significant). CONCLUSION: Early pharmacological stress echocardiography and conventional pre-discharge symptom limited exercise ECG have similar clinical outcome and costs after uncomplicated infarction. Early pharmacological stress echocardiography should be considered a valid alternative even for patients with interpretable baseline ECG who can exercise.

Abstract: BACKGROUND: Cardiac allograft vasculopathy (CAV) limits survival after heart transplantation (HTx). Between immunologic and non-immunologic factors, reactive oxygen species generation has been proposed as pathogenetic mechanism. This study was aimed at evaluating redox status in HTx recipients and verifying whether it could be independently associated with CAV. METHODS: Fifty-five consecutive male HTx recipients, median [interquartile range] age 60 yr [50, 64], underwent angiography 67 months [21, 97] after HTx to assess CAV, defined as significant stenosis in >or=1 epicardial vessel or any distal vessel attenuation. All patients underwent blood sampling 89 months [67, 119] after HTx for biochemical (glucose, creatinine, total and LDL cholesterol, and cyclosporin levels) and redox evaluation [plasma reduced and total homocysteine, cysteine, cysteinylglycine, glutathione, blood reduced glutathione (GSH(bl)) and vitamin E]. Univariate Odds Ratios (OR) with 95% confidence interval (95% CI, highest vs. lowest quartile) were estimated on the basis of a logistic regression analysis between clinical, conventional biochemical and redox data. Only the significant variables at univariate entered into multivariate analysis. RESULTS: CAV was documented in 15 (27%) patients. Univariate analysis showed that time from HTx to angiography (OR 3.97, 95% CI 1.15-14, p = 0.03) and GSH(bl) (OR 0.31, 95% CI: 0.14-0.70, p = 0.005) were significantly associated with CAV. However, multivariate analysis revealed GSH(bl) as the only independent predictor of CAV (OR 0.31, 95% CI: 0.13-0.74, p = 0.008). CONCLUSIONS: In HTx recipients reduced levels of GSH(bl) are independently associated with CAV. Given its potent intracellular scavenger properties, GSH(bl) may serve as a marker of antioxidant defence consumption, favouring CAV development.

Abstract:

Abstract: BACKGROUND: Echocardiography and myocardial scintigraphy associated with dobutamine stress are used for assessing risk in coronary artery disease. We compared the accuracy of the two modalities applied simultaneously for predicting long-term cardiac mortality in normotensive and hypertensive patients. METHODS: Three hundred and fifty-one consecutive patients underwent dobutamine stress with simultaneous echocardiography and Tc-sestamibi single photon emission computed tomography (SPECT). Fifty patients underwent early (<60 days) revascularization and were excluded; the analysis is based on 301 patients (131 hypertensives and 170 normotensives). RESULTS: The prevalence of additional risk factors, heart failure, prior myocardial infarction and prior revascularization was similar in the two groups of patients. An abnormal stress echocardiogram was detected in 101 (59%) normotensives and 80 (61%) hypertensives (NS), while 113 (66%) normotensives and 83 (63%) hypertensives (NS) showed abnormal myocardial perfusion. The agreement was 81% (kappa = 0.59) in hypertensives and 82% (kappa = 0.62) in normotensives. During 7.3 +/- 2.8 years of follow-up, 17 (13%) hypertensives and 26 (15%) normotensives died from cardiac causes (P = 0.62). In normotensives, the annual mortality rate was 0.8 for normal echo and 1.3 for normal scan, 2.8 for abnormal echo and 2.6 for abnormal scan. In hypertensives, it was 0.5 for normal echo, 0% for normal scan, 2.6 for abnormal echo and 2.8 for abnormal scan. Each test was associated with higher survival in the case of negative compared to positive results in both normotensive and hypertensive patients (log-rank chi-square 16.4, P < 0.001). CONCLUSIONS: Dobutamine stress echocardiography and SPECT are equally effective in predicting long-term cardiac death in both normotensive and hypertensive patients.

Abstract: To set up a prognostic score including clinical data and stress echocardiographic findings, the data of 3,969 patients who underwent dipyridamole stress were analyzed. Age (hazard ratio [HR] 3.21), peak wall motion score index (HR 2.62), diabetes mellitus (HR 2.36), and male gender (HR 1.69) were independent predictors of mortality and were incorporated into a prognostic score allowing us to estimate 1-, 3-, and 5-year survival in the patient cohort. The multiparametric risk score, immediately available at the bedside, can be used to predict the survival of patients undergoing dipyridamole stress echocardiography.

Abstract: BACKGROUND: Stress echocardiography is a cost-effective tool for the modern noninvasive diagnosis of coronary artery disease. Several physical and pharmacological stresses are used in combination with echocardiographic imaging, usually exercise, dobutamine and dipyridamole. The safety of a stress is (or should be) a major determinant in the choice of testing. Although large scale single center experiences and multicenter trial information are available for both dobutamine and dipyridamole stress echo testing, complications or side effects still can occur even in the most experienced laboratories with the most skilled operators. CASE PRESENTATION: We decided to present a case collection of severe complications during pharmacological stress echo testing, including a ventricular tachycardia, cardiogenic shock, transient ischemic attack, torsade de pointe, fatal ventricular fibrillation, and free wall rupture. CONCLUSION: We believe that, in this field, every past complication described is a future complication avoided; what happens in your lab is more true of what you read in journals; and Good Clinical Practice is not "not having complications", but to describe the complications you had.

Abstract: OBJECTIVE: To compare artificial neural networks (ANN) and robust Bayesian classifiers (RBC) in predicting outcome following acute myocardial infarction (AMI). METHODS: Clinical, exercise ECG and stress echo variables by 496 patients with AMI were used to predict the cumulative end-point of cardiac death, nonfatal reinfarction and unstable angina. Revascularized patients were censored. Short (200 days)-, medium (400 days)- and long (1000 days)-term observation intervals, including 50%, 75% and 90% of the events, respectively, were considered. At each interval, any patient was binary assigned to the "event" or "no event" class. A multilayer feedforward ANN, trained by a back propagation algorithm, was used. RBC, using the leave-one-out technique, were derived. The accuracy of both techniques was compared to the default accuracy (DA) obtained by assigning all subjects to the largest class. RESULTS: 14 death, 27 reinfarction and 29 unstable angina were observed during a mean follow-up of 24 [95% confidence interval (CI) 19 to 22] months. The accuracy of ANN and RBC and DA were 70%, 81% and 74% at short, 67%, 73% and 56% at medium and 64%, 68% and 62% at long-term follow-up. CONCLUSIONS: (1) ANN do not improve the prognostic classification of patients with uncomplicated AMI as compared to RBC. (2) In particular, short-term prognostic accuracy seems insufficient.

Abstract: BACKGROUND: Preoperative screening for coronary artery disease is recommended in high-risk renal transplant candidates. Aim of this study was to prospectively assess the value of a comprehensive risk stratification strategy including clinical, resting echo, and dipyridamole stress echo findings before renal transplantation. METHODS: The study group consisted of 71 renal transplant candidates (47 men; age 54+/-11 years) fulfilling one or more of the following high-risk clinical criteria: history of coronary artery disease, wall motion abnormalities at resting echo, dialysis dependency lasting >5 years, presence of 2 or more risk factors. Clinical history, resting echo, and dipyridamole stress echo (up to 0.84 mg over 10 min + atropine up to 1 mg) were obtained in all subjects. RESULTS: Mean number of risk factors was 2.5+/-1.0. Known coronary artery disease and diabetes were present, respectively, in 2 (3%) and 11 (15%) persons. No patient had left ventricular ejection fraction <45%. Left ventricular hypertrophy was found in 53 (74%) cases. Stress echo showed 100% safety and 97% overall feasibility. Inducible ischemia (new wall motion abnormalities) was detected in 3 (4%) subjects. During follow-up (36+/-12 months), 8 (11%) cardiac events occurred: 2 deaths, 2 myocardial infarctions, 3 coronary interventions, and 1 pulmonary edema. The perioperative period and subsequent follow-up (22+/-12 months) was uneventful among 32 patients who received renal transplantation. Four-year event-free survival was 92% in those without ischemia; it was 96% in the non-diabetic population. Diabetes (HR=4.78), age (HR=1.14), and left ventricular mass index (HR=1.02) were independent prognostic indicators among clinical and resting echo variables. The global chi-square of the statistical model was 18.8; it increased to 27.3 (+45%) after the addition of stress echo result. CONCLUSIONS: Renal transplant candidates can undergo effective stratification of risk by combining clinical, resting echo and dipyridamole stress echo findings.

Abstract: OBJECTIVE: To prospectively assess the prognostic value of the stress recovery index (SRI) following coronary bypass surgery. DESIGN AND PATIENTS: Two hundred seventy-eight patients who had undergone coronary bypass surgery and participated in a secondary prevention program were exercise tested and prospectively followed up for a median of 36 months. Cardiac death, nonfatal infarction, and need for further revascularization were target end points. SRI, defined as the difference in absolute values between the area of heart rate-adjusted ST-segment depression during exercise and recovery, was derived in all. Clinical data, resting ejection fraction, and exercise testing data of patients were entered into a sequential Cox model; SRI was entered last. Model validation was performed by bootstrap adjusted by the degree of optimism in estimates. Survival curves were set up using Kaplan-Meier method and compared by the log-rank test. RESULTS: SRI was the only significant and independent prognostic indicator (hazard ratio, 0.68; 95% confidence interval, 0.53 to 0.89) and increased the prognostic power of the model on top of clinical and exercise testing variables, as demonstrated by the significant (p = 0.01) increase of the area under the receiver operating characteristic curve of the risk function. Survival analysis showed ascending SRI quartiles to identify a significant (p = 0.001) increase in event-free survival. CONCLUSIONS: SRI is of value in predicting outcome after coronary bypass surgery and provides additional prognostic information over clinical and exercise testing data.

Abstract: The association between admission electrocardiogram and 6-month change in left ventricular function and volume was assessed in 200 patients who had acute myocardial infarction that was treated with primary percutaneous coronary intervention. Logistic regression analysis indicated peak creatine phosphokinase-MB, number of Q-wave leads, QRS interval distortion, wall motion score index, and angiographic Thrombolysis In Myocardial Infarction flow grade as predictors of no functional recovery and QRS interval distortion and Thrombolysis In Myocardial Infarction flow grade as predictors of left ventricular remodeling.

Abstract: BACKGROUND: Heart rate-adjusted ST-segment depression (ST/HR) analysis improves the diagnostic accuracy of exercise testing, but its prognostic value has not been evaluated in unselected populations. We prospectively used comparative exercise-recovery ST/HR analysis to predict outcome in a consecutive cohort of outpatients referred for exercise testing. METHODS: The stress-recovery index, defined as the difference between ST/HR areas during exercise and recovery,was derived in 1163 patients (median age, 60 years; interquartile range, 54-65 years). All-cause mortality and the combination of death or nonfatal myocardial infarction were target end points. The individual effect of clinical and exercise-testing data on outcome was evaluated by Cox regression analysis using separate models for each group of variables. Model validation was performed using bootstrap methods adjusted by the degree of optimism in estimates. Survival analysis was performed with the product-limit Kaplan-Meier method. RESULTS: During a 33-month follow-up, 48 deaths and 72 nonfatal myocardial infarctions occurred. After adjusting for confounding variables, hypertension (hazard ratio, 1.80; 95% confidence interval, 1.26-2.59), ST/HR index (hazard ratio, 1.32; 95% confidence interval, 1.04-1.66; for interquartile difference), and stress-recovery index (hazard ratio, 0.75; 95% confidence interval, 0.65-0.86; for interquartile difference) were predictive of death or nonfatal myocardial infarction, whereas hypertension (hazard ratio, 3.67; 95% confidence interval, 2.00-6.73) and stress-recovery index (hazard ratio, 0.55; 95% confidence interval, 0.48-0.63; for interquartile difference) were predictive of all-cause mortality. In addition, stress-recovery index increased the prognostic power of the model on top of clinical and exercise-testing variables and provided significant discrimination for survival. CONCLUSION: Combined evaluation of ST/HR analysis during exercise and recovery improves the prognostic capacity of standard exercise electrocardiography.

Abstract: This review article summarizes the results of histopathological and clinical imaging studies to assess myocardial necrosis in humans. Different histopathological features of myocardial cell necrosis are reviewed. In addition, the present role of echocardiographic techniques in assessing irreversible myocardial damage is briefly summarized.

Abstract: BACKGROUND: Exercise testing after acute myocardial infarction has limited prognostic accuracy. We prospectively used stress-recovery, heart rate-adjusted, ST-segment analysis to predict cardiac death in this clinical setting. METHODS: The stress-recovery index, defined as the difference in absolute values of the areas designated by ST depression in the heart-rate domain during exercise and recovery, was derived in 708 survivors of a first myocardial infarction. To assess whether it contributed additional prognostic information to routinely obtained information, clinical data, resting ejection fraction, and exercise testing data were entered into a sequential Cox model; the stress-recovery index was entered last. Model validation was performed by bootstrapping adjusted for the degree of optimism in estimates. Survival curves were set up using Kaplan-Meier analysis and compared by the log-rank test. RESULTS: Hypertension (OR 1.3, 95%CI 0.9-4.6), exercise capacity (OR 0.6, 95%CI 0.3-1.1 for the interquartile difference in kilopounds per minute), and the stress-recovery index (OR 0.7, 95%CI 0.5-0.9 for the interquartile difference) were independent predictors of cardiac death at a median follow-up of 32 months. However, the stress-recovery index enhanced the prognostic power of the model on top of clinical and exercise testing variables in all diagnostic subgroups according to ST-segment analysis and significantly discriminated survival. A simple nomogram was generated from the fitted Cox model to estimate risk in individual patients. CONCLUSIONS: Stress-recovery, heart rate-adjusted, ST-segment analysis predicts cardiac death after acute myocardial infarction and provides additional prognostic information over clinical and exercise testing data.

Abstract: BACKGROUND: The aim of this study was to determine whether antianginal medications affect the prognostic value of pharmacological stress echocardiography. METHODS AND RESULTS: From the EPIC-EDIC Data Bank, 7333 patients (5452 men; age; 59+/-10 years) underwent pharmacological stress echocardiography with either high-dose dipyridamole (0.84 mg/kg over 10 minutes; n=4984) or high-dose dobutamine (up to 40 microg x kg(-1) x min(-1); n=2349) (DET) for diagnostic purposes. At the time of testing, 1791 patients were on antiischemic therapy (nitrates and/or calcium antagonists and/or beta-blockers). Patients were followed up for a mean of 2.6 years (range, 1 to 206 months). DET was positive for myocardial ischemia in 2854 patients (39%) and negative in 4479 (61%). Total mortality was 336 (4.5%). Death was attributed to cardiac causes in 161 patients (2.1%). Survival was highest in patients with negative DET off therapy and lowest in patients with positive DET studied on therapy (95% versus 81%; P=0.0000). Survival was comparable in patients with a negative test on therapy and in patients with a positive test off therapy (88% versus 84%, P=NS). CONCLUSIONS: Ongoing antiischemic therapy at the time of testing heavily modulates the prognostic value of pharmacological stress echo. In the presence of concomitant antiischemic therapy, a positive test is more prognostically malignant, and a negative test less prognostically benign.

Abstract: BACKGROUND: Exercise electrocardiography has limited prognostic accuracy in hypertensives because of unsatisfactory specificity. We prospectively used comparative stress-recovery heart rate-adjusted ST (ST/HR) analysis to predict mortality in a consecutive population of hypertensives with chest pain. METHODS: The stress-recovery index (SRI), defined as the difference between ST/HR areas during exercise and recovery, was derived in 460 hypertensive with known (n=360, 78%) or suspected (n=100, 22%) coronary artery disease. To assess whether it added prognostic information to routinely obtained information, clinical data, the resting ejection fraction, and exercise testing data were entered into a sequential Cox's model; the SRI was entered last. Model validation was performed by bootstrap adjusted by the degree of optimism in estimates. Survival analysis was performed using the product-limit Kaplan-Meier method. RESULTS: During a median follow-up of 28 months (interquartile range, 13-44 months), 32 (7%) patients died, 23 (5%) suffered from acute myocardial infarction and 60 (13%) underwent late (> 3 months) revascularization. Male gender (hazard ratio, 1.53; 95% confidence interval, 1.01-2.34), peak double product (hazard ratio, 0.70; 95% confidence interval, 0.54-0.90) and the SRI (hazard ratio, 0.69; 95% confidence interval, 0.59-0.81 for interquartile difference) were independent predictors of outcome. The SRI increased the prognostic power of the model on top of clinical and exercise testing variables (concordance index, + 10%; discrimination index, + 32%) and showed the widest area under the ROC curve to predict outcome as compared with exercise-only ST analysis and the ST/HR index. Moreover, it provided a significant discrimination of survival. CONCLUSIONS: The SRI predicts all-cause mortality in hypertensive patients with chest pain and provides additional prognostic information over clinical and standard exercise testing data.

Abstract: STUDY OBJECTIVES: Pharmacological therapy can reduce diagnostic and prognostic accuracy of exercise stress testing. However, the risk of withdrawing drugs early after myocardial infarction (MI) has not been established. We assessed safety and clinical implications of drug withdrawal in patients undergoing stress testing after uncomplicated MI. METHODS: A total of 362 MI patients underwent ECG Holter recording before and after withdrawing beta-blockers, calcium-antagonists and nitrates. QRS (QRS/h) and ventricular premature beats (VPB/h) count per hour, repetitive ventricular arrhythmias, ST segment changes and patient complaints were evaluated for reproducibility using kappa statistics and Bland-Altman method. RESULTS: No major complications occurred. Forty-three patients complained of >1 symptom on and 37 off therapy. QRS/h and VPB/h count were significantly (p<0.0001) higher off therapy but correlated with the corresponding values on therapy. A mean heart rate increase of 8 beats/min (agreement range -8 to +14 beats/min) and a five-fold increase in VPB/h (agreement range -141 to +151) were observed after withdrawing therapy. Repetitive ventricular arrhythmias and ST changes were also more frequent off therapy but intra-patient reproducibility was poor: kappa 0.12 (95% confidence interval (CI) -0.01 to 0.25) for arrhythmias, -0.02 (95% CI -0.46 to 0.39) for ST depression and -0.01 (95% CI -0.66 to 0.64) for ST elevation. CONCLUSIONS: The withdrawal of therapy is well tolerated soon after uncomplicated MI; however, a generic but not individual risk of ventricular arrhythmias and/or transient myocardial ischemia has to be taken into account.

Abstract: BACKGROUND: The incidence of late severe heart failure after primary angioplasty is not clear and few data are available about the clinical prognostic predictors of this event. The aims of our study were a) to evaluate the incidence of cardiac death and heart failure after an extensive acute myocardial infarction treated with primary angioplasty, and b) to identify, among clinical, ECG, functional, and angiographic variables, the outcome predictors and their incremental prognostic value. METHODS: Two hundred and thirty-three patients with ST-segment elevation in > or = 4 leads, without cardiogenic shock, underwent primary angioplasty within 12 hours of symptom onset and were prospectively followed up for a median of 21 months for the combined endpoint of cardiac death and heart failure. The effects of clinical, ECG, functional, and angiographic data on the combined endpoint were evaluated using Cox's analysis. Separate models were developed including all variables of a given model plus significant variables of previous models to reproduce the usual clinical information flow. RESULTS: Twelve (5%) deaths and 23 (10%) heart failures occurred. Diabetes (hazard ratio [HR] 6.46, 95% confidence interval [CI] 1.99-20.98) and peak creatine kinase-MB (HR 1.002, 95% CI 1.001-1.004 per unit increment), wall motion score index (HR 1.46, 95% CI 0.35-6.15 per 0.1 unit increment), and TIMI flow grade < 3 after angioplasty (HR 5.35, 95% CI 2.04-14.02) were the only significant and independent prognostic indicators. ECG information did not improve the model, whilst functional and angiographic data provided incremental prognostic value over clinical information. CONCLUSIONS: At mid-term follow-up, extensive acute myocardial infarction patients undergoing primary angioplasty have a moderate heart failure event rate. The integrated evaluation of data routinely available from diagnostic work-up allows accurate prediction of the outcome; functional and angiographic data provide incremental prognostic information over clinical and ECG variables.

Abstract: This review article is aimed at comparing the results of histopathological and clinical imaging studies to assess coronary atherosclerotic plaques in humans. In particular, the gap between the two techniques and its effect on the understanding of the pathophysiological basis of coronary artery disease is critically discussed.

Abstract: OBJECTIVES: To assess the link between perfusion, metabolism, and function in viable myocardium before and early after surgical revascularisation. DESIGN: Myocardial blood flow (MBF, thermodilution technique), metabolism (lactate, glucose, and free fatty acid extraction and fluxes), and function (transoesophageal echocardiography) were assessed in patients with critical stenosis of the left anterior descending coronary artery (LAD) before and 30 minutes after surgical revascularisation. SETTING: Tertiary cardiac centre. PATIENTS: 23 patients (mean (SEM) age 57 (1.7) years with LAD stenosis: 17 had dysfunctional viable myocardium in the LAD territory, as shown by thallium-201 rest redistribution and dobutamine stress echocardiography (group 1), and six had normally contracting myocardium (group 2). RESULTS: LAD MBF was lower in group 1 than in group 2 (58 (7) v 113 (21) ml/min, p < 0.001) before revascularisation and improved postoperatively in group 1 (129 (133) ml/min, p < 0.001) but not in group 2 (105 (20) ml/min, p = 0.26). Group 1 also had functional improvement in the LAD territory at intraoperative echocardiography (mean regional wall motion score from 2.6 (0.85) to 1.5 (0.98), p < 0.01). Oxidative metabolism, with lactate and free fatty acid extraction, was found preoperatively and postoperatively in both groups; however, lactate and free fatty acid uptake increased after revascularisation only in group 1. CONCLUSIONS: MBF is reduced and oxidative metabolism is preserved at rest in dysfunctional but viable myocardium. Surgical revascularisation yields immediate perfusion and functional improvement, and increases the uptake of lactate and free fatty acids.

Abstract: PURPOSE: To investigate the prognostic implications of conduction defects in subjects without proven coronary artery disease who had been referred for stress echocardiography. METHODS: The study sample consisted of 1230 patients (574 men and 656 women; mean [+/- SD] age, 63 +/- 10 years) who underwent stress echocardiography with dipyridamole (n = 780) or dobutamine (n = 450) to evaluate suspected coronary artery disease. A summary wall motion score (on a 1 to 4 scale) was calculated. Patients were followed for a mean of 41 +/- 27 months; mortality was the only endpoint. RESULTS: Four hundred and twenty patients (34%) had intraventricular conduction defects on a resting electrocardiogram (173 with complete left bundle branch block, 98 with isolated right bundle branch block, 43 with right bundle branch block with left anterior hemiblock, and 106 with left anterior hemiblock). Ischemia at stress echo (new or worsening of preexisting wall motion abnormality) was found in 250 patients (20%). There were 56 deaths during follow-up; 138 patients underwent revascularization and were censored. Multivariate predictors of mortality were resting wall motion score index (hazard ratio [HR] = 6.0 per unit increase; 95% confidence interval [CI]: 2.3 to 16; P <0.0001), ischemia at stress echo (HR = 3.9; 95% CI: 2.2 to 6.7; P <0.0001), age >65 years (HR = 3.2; 95% CI: 1.7 to 5.9; P <0.0001), hypertension (HR = 1.8; 95% CI: 1.1 to 3.2; P = 0.03), and right bundle branch block with left anterior hemiblock (HR = 3.7; 95% CI: 1.8 to 7.5; P <0.0001). The other three forms of intraventricular conduction defects (left bundle branch block, isolated complete right bundle branch block, and left anterior hemiblock) were not associated with mortality in multivariate analyses, or among the 980 patients who did not have ischemia. CONCLUSION: Right bundle branch block with left anterior hemiblock is an independent predictor of mortality in patients with suspected coronary artery disease undergoing stress echocardiography, whereas isolated right bundle branch block is associated with outcomes similar to those observed in patients with no conduction defects.

Abstract: BACKGROUND: Echocardiography may permit the detection of a nonviable myocardium. The aim of this study was to test if resting pulsed wave-tissue Doppler imaging (PW-TDI) might yield additional markers. METHODS: Fifty patients (38 males, 12 females, mean age 63 +/- 6 years) with left ventricular dysfunction (ejection fraction 35 +/- 10%) underwent echocardiography. The posterior septum, anterior septum, lateral, inferior, anterior and posterior walls were sampled on the basal segments in the apical views at PW-TDI. The following variables and cardiac phases were tested: 1) the isovolumic contraction phase velocity, polarity or detectability, 2) the ejection phase velocity, a detectable interval between the ejection phase and aortic valve closure, or ejection phase shape, and 3) the isovolumic relaxation phase velocity or ejection velocity/post-systolic shortening ratio. From the tested PW-TDI variables, viable and nonviable patterns were assembled, taking rest-redistribution 201thallium single-photon emission computed tomography as the independent reference for myocardial viability. Patients with significant loading alterations, mitral or aortic valve disease, and arrhythmias were excluded. RESULTS: Out of 219 dyssynergic segments, viability as identified according to conventional rest echocardiographic criteria appeared in 94 (47%), as identified at PW-TDI in 116 (53%), and as identified at nuclear imaging in 105 (48%). The resting PW-TDI variables consistent with absent myocardial viability were as follows: 1) an isovolumic contraction phase velocity equal to the ejection phase velocity +/- 1 cm/s, or absent, 2) an ejection phase velocity < or = 4 cm/s, usually with a gap between the ejection phase and aortic valve closure, or any shape of ejection but the typical single phase, and 3) an isovolumic relaxation phase velocity < 5 cm/s with an ejection phase velocity/isovolumic relaxation phase velocity ratio < 0.8. The accuracy for the identification of myocardial viability was: agreement 73%, kappa 0.44 for echocardiography, and agreement 75%, kappa 0.47 for PW-TDI. CONCLUSIONS: PW-TDI nonviable patterns may be a helpful additional tool for the identification of patients without residual myocardial viability.

Abstract: Recent diagnostic and therapeutic advances have been questioning the role of exercise electrocardiography (ECG) for risk stratification of patients recovering from an acute coronary syndrome. The aim of this review was to verify whether evidence still exists supporting the use of exercise ECG as first choice stress testing modality in this clinical setting in the light of the most recent prognostic data and of cost effectiveness considerations. It was concluded that a large body of evidence supports the use of exercise ECG as a cost-effective tool for prognostic purposes and for quality of life assessment following acute coronary syndromes.

Abstract: BACKGROUND: Predischarge stress testing provides suboptimal prediction of spontaneous hard events following uncomplicated acute myocardial infarction (AMI). HYPOTHESIS: This study was aimed at assessing whether soft cardiac ischemic events requiring late revascularization could be predicted more accurately. METHODS: In all, 428 patients undergoing exercise electrocardiography (ECG) and stress echocardiography (SE, 345 dobutamine and 83 dypiridamole) within 15 days of uncomplicated AMI were followed up for 425 (range 20-2220) days. Soft ischemic events (effort angina>class II [Canadian Cardiovascular Society Classification] and unstable angina) driving late (>6 months) revascularization were regarded as endpoints. RESULTS: A total of 58 events (29 effort and 29 unstable angina with subsequent 47 coronary artery bypass grafts and 11 percutaneous transluminal coronary angioplasties) occurred: 26 in patients with positive exercise ECG and 34 in patients with positive SE. Univariate predictors of revascularizations were positive exercise ECG (p = 0.0001), peak wall motion score index (WMSI) (p = 0.0009), low workload (p = 0.0018), rest WMSI (p = 0.02) and positive SE (p = 0.02). Cox multivariate analysis selected peak WMSI, positive exercise ECG, and low workload positive exercise ECG as independent predictors of late revascularizations. CONCLUSIONS: Predischarge stress testing identifies the long-term occurrence of soft ischemic events driving late revascularization after uncomplicated AMI.

Abstract: Exercise electrocardiography (ECG) is of limited usefulness in hypertensive patients, whereas pharmacologic stress echocardiography can provide diagnostic and prognostic information. The aim of this study was to compare the prognostic value of clinical data, exercise ECG, and pharmacologic stress echocardiography in hypertensive patients with chest pain and to identify the best strategy for their risk stratification. Three hundred sixty-seven hypertensive patients (189 men, age 61 +/- 9 years) with chest pain of unknown origin underwent exercise ECG and pharmacologic stress echocardiography (237 with dipyridamole and 130 with dobutamine) and were followed up for 31 +/- 24 months. Positive exercise ECG (ST-segment shift of > or =1 mm at 80 ms after the J point) and stress echocardiography (new wall motion abnormalities) were found in 130 (35%) and 86 (23%) patients, respectively. During follow-up, there were 13 deaths and 16 myocardial infarctions. Additionally, 43 patients underwent coronary revascularization and were censored accordingly. Of 12 clinical, electrocardiographic, and echocardiographic variables analyzed, a positive result of stress echocardiography was the only multivariate predictor of either death (hazard ratio [HR] 4.7, 95% confidence interval [CI] 1.5 to 14.5, p = 0.007) or hard events (death, myocardial infarction) (HR 4.1, 95% CI 1.8 to 9.3, p = 0.0009). Using an interactive stepwise procedure, stress echocardiography provided additional prognostic information to clinical evaluation and exercise ECG. However, the negative predictive value of the 2 tests was similarly (p = NS) high in assessing 4-year event-free survival. In conclusion, a negative exercise electrocardiographic test identifies low-risk hypertensive patients with chest pain and should be the first-line approach for risk stratification. In contrast, positive exercise ECG is unable to distinguish between patients with different levels of risk. In this case, stress echocardiography provides strong and incremental prognostic power over clinical and exercise electrocardiographic data.

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Abstract: OBJECTIVE: To make a prospective assessment of the clinical and prognostic correlates of angiographically diffuse non-obstructive coronary lesions. DESIGN: Angiographic vessel and extent scores were calculated in 228 clinically stable patients (mean (SD) age, 60 (11) years; 43 women, 185 men) undergoing prospective follow up for the composite end point of death and myocardial infarction. The effect on outcome of clinical variables (age, sex, previous myocardial infarction, diabetes mellitus, smoking habit, systemic hypertension, hypercholesterolaemia, ejection fraction) and angiographic variables (vessel and extent score) was evaluated by Cox's proportion hazard model. RESULTS: The vessel score was 3 in 34 patients (15%), 2 in 78 (34%), 1 in 87 (38%), and 0 in 29 (13%). Median extent score was 60 (range 6-110; first quartile 40, third quartile 70). Forty one events (nine deaths and 32 myocardial infarcts) occurred over a median follow up period of 30 months. Age and extent score were the only multivariate predictors of outcome, but the latter provided 28% additional prognostic information after adjustment for the most predictive variables (gain in chi2 = 7, p < 0.01). A vessel score of 3 was associated with worse survival, while no significant discrimination was possible among the other groups. However, assignment of patients to two groups according to an ROC curve derived cut off value for the extent score made it possible to obtain significant discrimination of survival even in cases with vessel scores of 0 to 2. Age and diabetes were clinical markers of a higher extent score. CONCLUSIONS: The angiographic extent score is a powerful marker of adverse outcome independent of severity and the number of flow limiting coronary lesions, and may reflect the link between clinical risk profile and diffusion of coronary atherosclerosis. Thus it should be of clinical value for targeting aggressive preventive measures.

Abstract: Right bundle branch block (RBBB) is independently associated with all-cause mortality in patients referred for noninvasive evaluation of coronary artery disease. However, further stratification of risk in these patients has not been specifically addressed. The aim of this study was to risk stratify patients with RBBB who were referred for stress echocardiography. The study population was comprised of 343 patients (267 men; age 66 +/- 9 years) with RBBB who underwent pharmacologic stress echocardiography (231 dipyridamole, 112 dobutamine) for evaluation of suspected or known coronary artery disease. Overall mortality was the only end point. Stress echocardiography was positive for ischemia in 109 patients (32%). During follow-up (38 +/- 32 months), 36 deaths occurred. Seventy-three patients underwent revascularization and were censored. Ischemia at stress echocardiography (hazard ratio [HR] 2.9, 95% confidence interval [CI] 1.5 to 5.5, p=0.002), left anterior fascicular block (LAFB) (HR 2.8, 95% CI 1.4 to 5.6, p = 0.002), age >65 years (HR 2.1, 95% CI 1.0 to 4.3, p=0.047), and wall motion score index at rest (HR 2.5, 95% CI 1.0 to 6.5, p=0.057) were multivariate predictors of mortality. On the basis of stress echocardiographic result and presence and/or absence of LAFB, 3 levels of risk were identified: (1) low-risk, in cases of no ischemia and no LAFB (49% of the entire study population); (2) intermediate-risk, in cases of ischemia or LAFB only; and (3) high-risk, in cases of ischemia and LAFB. Clinical data, electrocardiography at rest, and stress echocardiographic results can provide effective stratification of risk in patients with RBBB.

Abstract: We evaluated clinical and economic outcomes of diagnostic strategies on the basis of pharmacologic stress echocardiography (PhSE) versus exercise electrocardiography test (EET) in 527 patients with chest pain (274 women; age 59 +/- 10 years) who underwent both EET and PhSE. We investigated 3 strategies, ie, coronary angiography: after positive EET (strategy 1); after positive PhSE (strategy 2); or after a positive PhSE performed after a positive EET (strategy 3). A patient was correctly identified if he or she had negative test results and no events, or had positive test results and abnormal coronaries. The cost per patient correctly identified was calculated as the ratio between the cost of each strategy and the number of patients correctly identified. The accuracy in correctly identifying the patients was 78%, 92%, and 91% with strategies 1, 2, and 3, respectively. The cost of each patient correctly identified was 1572 US dollars, 1097 US dollars, and 1081 US dollars with strategies 1, 2, and 3, respectively. In conclusion, PhSE-based strategies are cost-effective versus EET.

Abstract: This study assesses the prognostic value of myocardial viability recognized as a contractile response to inotropic stimulation in patients with left ventricular (LV) dysfunction in a large-scale prospective, multicenter, observational study. Four hundred twenty-five patients (mean age 61 +/- 10 years) with angiographically proven coronary artery disease, previous (>3 months) myocardial infarction, and severe LV dysfunction (ejection fraction <35%; mean 28 +/- 6%) were enrolled in the study. Each patient underwent low-dose dobutamine echocardiography (up to 10 microg/kg/min). Myocardial viability was identified as a rest-stress variation (Delta) in the wall motion score index (WMSI), in which each segment was scored from 1 = normal to 4 = dyskinetic in a 16-segment model of the left ventricle. Myocardial viability was identified as an improvement of >/=0.40 in WMSI. All patients were followed for a median of 3.1 years. One hundred eighty-eight were revascularized either by coronary artery bypass grafting (n = 118) or coronary angioplasty (n = 70). The only end point analyzed was cardiac death. In the revascularized group, cardiac death occurred in 4 of the 52 patients with and in 37 of the 136 patients without myocardial viability (7.7% vs 27.2%, p <0.003). Kaplan-Meier survival estimates showed a better outcome for those patients with compared to patients without myocardial viability who underwent coronary revascularization (90.1% vs 62%, p <0.0078). Thus, in severe LV ischemic dysfunction, myocardial viability by low-dose dobutamine echocardiography is associated with improved survival in revascularized patients.

Abstract: OBJECTIVES: Studies on the diagnostic value of exercise electrocardiography in right bundle branch block produced controversial results, and data on the accuracy of stress echo are still lacking. The aim of the study was to compare the diagnostic value of exercise electrocardiography and dipyridamole stress echo in chest pain patients with right bundle branch block, and to verify whether stress testing accuracy is affected by history of hypertension. METHODS: The study group was made up of 71 patients (56 men, aged 63 +/- 8 years) with chest pain of unknown origin and complete right bundle branch block. Of them, 35 were hypertensives and 36 normotensives. Patients performed, on different days and in random order, exercise electrocardiography and dipyridamole stress echo and underwent coronary angiography. RESULTS: Significant (> or = 70% diameter stenosis) coronary artery disease was found in 34 patients (17 hypertensives and 17 normotensives). Positive exercise electrocardiography (ST-segment shift > 1 mm at 80 ms after the J point in leads V5 and V6 or leads II and Vf) and dipyridamole stress echo (new wall motion abnormalities) were observed in 38 and 30 patients, respectively. The result of tests was concordant in 69% of hypertensives and 92% of normotensives. The two tests shared the same sensitivity in hypertensives (82%) and normotensives (71%). Of 37 patients without coronary artery disease, 12 had a false-positive result during exercise electrocardiography and four during stress echo. The specificity was lower for exercise electrocardiography than for stress echo in hypertensives (50 versus 89%, P = 0.0006), while no difference was evidenced in normotensives (84 versus 89%, P = 0.4). In hypertensives, the accuracy, positive, and negative predictive values were 66, 61, and 75% for exercise electrocardiography, and 86, 87, and 84% for stress echo. Corresponding figures in normotensives were 78, 80, and 76% for exercise electrocardiography, and 81, 86, and 77% for stress echo. CONCLUSIONS: In chest-pain patients with right bundle branch block, dipyridamole stress echo was effective to diagnose coronary artery disease in both normotensives and hypertensives. Moreover, it exhibited superior diagnostic information than exercise electrocardiography in hypertensives, due to significantly higher specificity. However, the two tests had similar diagnostic value in normotensives.

Abstract: OBJECTIVE: To assess the relative influence of contractile reserve and inducible ischaemia on subsequent left ventricular volume changes after myocardial infarction. DESIGN: Left ventricular end diastolic and end systolic index volumes were calculated prospectively at discharge and at six months in 143 patients referred for early postinfarction dobutamine stress echocardiography. On the basis of their responses to this test, patients were divided into three groups: scar (n = 48; group 1); contractile reserve (n = 36; group 2); inducible ischaemia (n = 59; group 3). RESULTS: At six months, the left ventricular end diastolic index volume decreased in group 2 (mean (SD), -3.9 (9.4) ml/m2) and increased in both group 1 (+2.8 (10.6) ml/m2, p = 0.009 v group 2) and group 3 (+7.5 (11.4) ml/m2, p < 0.0001 v group 2). The end systolic index volume decreased in group 2 (-4.9 (7.3) ml/m2) and increased in both group 1 (+1.3 (8.3) ml/m2, p = 0.0015 v group 2) and group 3 (+2.8 (8.9) ml/m2, p = 0.0002 v group 2). In multivariate analysis, the contractile reserve (hazard ratio 0.19, 95% confidence interval (CI) 0.14 to 0.47), inducible ischaemia (5.86, 95% CI 1.54 to 29.7), and end systolic index volume at discharge (1.04, 95% CI 0.99 to 1.11) were independent predictors of an increase in end diastolic index volume of > or = 15 ml/m2 at six months. CONCLUSIONS: Contractile reserve and inducible ischaemia, as detected by early dobutamine stress echocardiography, identify patients with differences in long term left ventricular remodelling after acute myocardial infarction.

Abstract: AIMS: Risk stratification after uncomplicated acute myocardial infarction is mostly applied by either symptom-limited post discharge exercise electrocardiography or pre-discharge submaximal exercise test. Aim of the present study was to determine if early pharmacological stress echocardiography and discharge within 24 hours of the test in cases without induced myocardial ischemia leads to lower costs and similar clinical outcome during 1 year follow up when compared to clinical evaluation and exercise electrocardiography after discharge. METHODS AND RESULTS: Four-hundred fifty-eight patients from 10 participating centers with a recent uncomplicated myocardial infarction were randomized to pharmacological stress echocardiography on day 3-5 followed by early discharge in the case of negative test result (early discharge strategy) (n=233) or clinical evaluation with hospital discharge on day 7-9 and symptom-limited post-discharge exercise electrocardiography at 2-4 weeks after myocardial infarction (usual care strategy) (n=225). At 1 year follow up there were 63 events (4 deaths, 9 non fatal reinfarctions, 50 chest pains requiring hospitalization) in patients randomized to early discharge, and 69 events (6 deaths, 13 reinfarctions, 50 chest pains requiring hospitalization) in usual care (p=ns). Total median individual costs calculated on the basis of hospitalizations, investigations and interventions during 1 year follow up were 3561 for early discharge strategy vs 3850 for usual care strategy (p<0.05). CONCLUSIONS: Early pharmacological stress echocardiography followed by early discharge in case of negative test result gives similar clinical outcome and lower costs after uncomplicated myocardial infarction than clinical evaluation and delayed post-discharge symptom-limited exercise electrocardiography.

Abstract: The aim of this report was to assess the relation between heart rate response to dipyridamole infusion and perfusion defects at quantitative sestamibi single-photon emission computed tomographic imaging. We demonstrated in 166 heart transplant recipients that chronotropic incompetence to dipyridamole is the only significant and independent predictor of perfusion defects.

Abstract:

Abstract: OBJECTIVES : To establish whether safety and feasibility of dobutamine and dipyridamole stress echocardiography are affected by history of hypertension. METHODS : Data on 2200 consecutive pharmacologic stress echocardiography (959 dobutamine and 1241 dipyridamole) performed between October 1990 and February 2001 at a single cardiology centre, were analysed. RESULTS : There were two complications (1/480 tests) during dobutamine (one sustained ventricular tachycardia and one severe asthmatic attack following antidote administration) and two (1/620 tests) during dipyridamole (one non-Q wave myocardial infarction and one sustained ventricular tachycardia) stress. Complications or limiting side effects were observed in 83/959 patients (48/430 hypertensives and 35/529 normotensives) with dobutamine and in 34/1241 patients (17/571 hypertensives and 17/670 normotensives) with dipyridamole stress. Therefore, the overall feasibility was 88.8% in hypertensives and 93.4% in normotensives (P = 0.013) for dobutamine, and 97% in hypertensives and 97.5% in normotensives (P = 0.64) for dipyridamole. Dipyridamole was significantly more feasible than dobutamine in both hypertensive (P < 0.0001) and normotensive (P = 0.0006) subjects. Logistic regression analysis failed to identify clinical or echocardiographic predictors of adverse reactions with dipyridamole, while history of hypertension [odds ratio (OR) = 1.8, 95% confidence interval (CI) 1.1-2.8, P = 0.0138] was the only independent predictor of cumulative adverse reactions with dobutamine stress. In addition, history of hypertension (OR = 3.2, 95% CI, 1.2-8.5, P = 0.0166), resting wall motion abnormalities (OR = 1.8, 95% CI, 1.1-3.1, P = 0.0282), and age over 70 years (OR = 4.8, 95% CI, 1.5-15.3, P = 0.0087) predicted hypertensive response, ventricular tachycardia, and atrial fibrillation, respectively. No covariate was associated with hypotensive response during dobutamine test. CONCLUSIONS : Dipyridamole has a slightly better safety profile and significantly higher feasibility than dobutamine stress both in hypertensives and in normotensives. In addition, the history of systemic hypertension is an independent predictor of cumulative adverse effects during dobutamine but not during dipyridamole stress.

Abstract: AIMS: Aim of the study was to assess the role of early inducible ischaemia for determining left ventricular remodelling in patients with acute myocardial infarction. METHODS AND RESULTS: In 179 consecutive patients with first myocardial infarction the occurrence of new wall motion abnormalities during dobutamine stress echocardiography at discharge was related to the left ventricular volume changes at 6 months. Left ventricular end-diastolic and end-systolic index volumes (mL/m(2)) were echocardiographically detected at discharge and at 6 months and the relative changes were calculated. The study population consisted of 105 patients without and 74 patients with inducible ischaemia; of these, 46 patients had > or =4 ischaemic segments. At 6 months, the end-diastolic index volume increased in patients with inducible ischaemia compared to patients without (+7.5+/-11.2 vs -0.1+/-10.2 mL/m(2); P=0.0049) and final mean end-diastolic volume was greater in patients with inducible ischaemia than without (70.8+/-16.0 vs 61.1+/-17.0 mL/m(2); P=0.0012). The end-systolic volume increased at 6 months in patients with inducible ischaemia and it decreased in patients without (+2.8+/-8.6 vs -1.4+/-7.8 mL/m(2); P=0.021). At the multivariate analysis, inducible ischaemia in > or =4 segments (odds ratio=6.43), the wall motion score index at the peak of dobutamine infusion (odds ratio=1.14) and the end-systolic index volume at discharge (odds ratio=1.06) were independent predictors of subsequent left ventricular end-diastolic index volume increase > or =15 mL/m(2). CONCLUSION: In patients with first myocardial infarction the presence and the severity of inducible ischaemia, as detected by dobutamine stress echocardiography at discharge, indicates an unfavourable left ventricular remodelling.

Abstract:

Abstract: One hundred twenty-five patients (60 +/- 10 years old, 60 women) with known (35, previous myocardial infarction) or suspected (90) coronary artery disease (CAD) and no more than 50% coronary stenoses underwent pharmacologic (48 dipyridamole and 77 dobutamine) stress echocardiography (SE) and prospective follow-up (36 +/- 22 months) for cardiac death, nonfatal infarction, and unstable angina. The ability of clinical and SE variables to predict the outcome was assessed by the Cox model. A significant increase in the global chi-square of the model indicated an incremental prognostic value. Nine events occurred: 2 fatal and 5 nonfatal infarctions and 2 hospitalizations for unstable angina. Hypertension, positive SE, and peak wall motion score index were multivariate predictors of outcome, but SE provided an 87.5% increase in the global chi-square (P <.001). Patients with positive SE had a significantly lower event-free survival compared with those with negative SE. Therefore, we conclude that SE provides incremental prognostic information in patients with chest pain without critical coronary artery disease.

Abstract: The classical risk factors for acute myocardial infarction (AMI) fail to explain all the epidemiological variations of the disease. Among the risk factors recently reported, several infectious agents appear to increase the risk of AMI. Helicobacter pylori (H. pylori) infection, a bacterium involved in duodenal and gastric ulcer, gastric cancer and MALT-lymphoma, seems to be strongly associated with AMI. More virulent (anti-CagA positive) strains of the bacterium are almost exclusively the causative agents of such diseases. To determine the prevalence of H. pylori infection and of virulent strains, a case-control study was conducted in a group of male patients with AMI. A group of patients consecutively admitted to the Emergency Care Unit served as controls. We studied 223 consecutive male patients, mean age 60.2 (range 40-79) years, admitted for AMI to the Coronary Care Units at Hospitals in two towns of Northern Italy, 223 age matched male patients (mean age 61.8, range 40-79 years) admitted to the Emergency Care Unit, served as control. H. pylori seroprevalence was assessed by presence of antibodies (IgG) against H. pylori and anti-CagA in circulation. Among the patients we investigated the presence of hypertension, levels of cholesterol and glucose in serum, fibrinogen in plasma and smoking habits. H. pylori infection was present in 189/223 (84.7%) of the patients and in 138/223 (61.8%) of the control population (p < 0.0001 OR 3.42 [IC 95% 2.12-5.54]). The anti-CagA antibodies were detected in 33.8% of infected patients with AMI (64/189) versus 26.8% in the control subjects (37/138) (p:0.17, OR 1.40 [IC 95% 0.84-2.33]). Classical risk factors for AMI did not differ among patients with and without H. pylori infection. Patients admitted to the Coronary Care Unit for acute myocardial infarction had a notably higher prevalence of anti-H. pylori not restricted to virulent strains, when compared to a population of patients referred to the Emergency Care Unit. The classical risk factors for coronary disease were present in the patients with AMI irrespective of H. pylori status.

Abstract: OBJECTIVE: To assess the prognostic value of stress echocardiography as an adjunct to exercise electrocardiography in patients with uncomplicated acute myocardial infarction. DESIGN: 496 patients underwent a maximum exercise ECG and pharmacological stress echocardiography (406 dobutamine and 90 dipyridamole) within 15 days of uncomplicated acute myocardial infarction and were followed for a mean of 25 months (range 1-74 months) for reinfarction, unstable angina, and cardiac death. Patients undergoing revascularisation were omitted. RESULTS: Exercise ECG was positive in 162 patients (32.6%) and low threshold positive (< 100 W) in 91 (18%). Stress echocardiography was positive in 239 patients (48%) (194 with dobutamine and 45 with dipyridamole stress). The agreement between the two tests was 63% (kappa = 0.24, 95% confidence interval 0.15 to 0.33). Sixty nine spontaneous events occurred (14 cardiac deaths, 26 reinfarctions, and 29 with unstable angina requiring hospital admission), and 126 patients underwent revascularisation (39 coronary angioplasty and 87 bypass surgery). By receiver operating characteristic curve analysis, stress echocardiography provided incremental prognostic information compared with clinical data. A low threshold positive exercise ECG was associated with a worse outcome, but there was a fivefold increase in risk in patients with positive stress echocardiography who also had a high threshold (> 100 W) positive exercise ECG. Event-free survival of patients with both tests positive was significantly less than in patients with only one positive test or with both tests negative. CONCLUSIONS: Stress echocardiography provides additional prognostic information after uncomplicated acute myocardial infarction, but the greatest gain is found in patients with a high threshold positive exercise ECG.

Abstract:

Abstract: Dobutamine stress echocardiography (DSE) accurately detects viable myocardium and residual ischemia in patients with acute myocardial infarction (AMI). The prognostic interaction of viability and ischemia has not been completely clarified in these patients. This study assesses the long-term effect of viability, ischemia, or their combination on survival in patients with AMI and mildly impaired left ventricular (LV) function. Four hundred eleven patients (age 57 +/- 9 years) underwent predischarge DSE (up to 40 microg/kg/min plus atropine if needed) after uncomplicated AMI and were prospectively followed for 23 months (range 1 to 78). According to DSE findings, patients were divided into 4 groups: viability only, ischemia only, combination of viability and ischemia, and scar. Adverse outcome occurred in 64 patients: 34 patients had hard events (9 cardiac deaths, 25 nonfatal AMI) and 30 patients had unstable angina requiring hospitalization. The combination of viability and ischemia, diabetes mellitus, and non-Q-wave AMI were significant predictors of all events at univariate and multivariate analysis. The same variables were also univariate predictors of hard events, but multivariate analysis indicated only the combination of viability and ischemia and diabetes as independent predictors. The event-free survival of patients with combined viability and ischemia was significantly lower (hazard ratio 3 [95% confidence interval 1.8 to 11]) compared with patients with ischemia only. Thus, viability and ischemia show a significant adverse prognostic interaction in patients with AMI and preserved LV function.

Abstract: Whole body oxygen consumption and some hemolymph parameters such as pH, partial pressure of gases, level of ions and lactate were measured in the estuarine crab Chasmagnathus granulata after both acute (96 h) and chronic (2 weeks) exposure to cadmium at concentrations ranging from 0.4 to 6.3 mg/l. In all instances, the crabs developed hemolymph acidosis, but no respiratory (increased PCO2) or lactate increases were evident. Hemolymph levels of sodium and calcium were always increased by cadmium exposure. The chronic toxicity of cadmium was enhanced at 12 per mil salinity, even causing a significantly higher mortality in comparison with the higher salinity (30 per mil ) used. A general metabolic arrest took place at 12 per mil salinity in the crabs chronically exposed to cadmium, as indicated by decreases of oxygen consumption and PCO2, an increase of PO2, along with no changes in lactate levels. These imbalances were associated with severe necrosis and telangiectasia in the respiratory gills, probably leading to respiratory impairment and finally histotoxic hypoxia and death of the animals.

Abstract: A rational utilization of resources represents a key issue in modern treatment of cardiac patients. The aim of our study was to highlight a few essential aspects for an efficient and appropriate management of patients with an acute coronary syndrome. Clinical evaluation of the patient's risk (i.e. clinical assessment of the probability of developing a cardiac event), incremental value of the chosen test for risk stratification, value of a strategy in modifying outcome and direct determinants of medical cost of the strategy are selected as the main aspects to be considered in order to optimize management of these patients.

Abstract: The ability of different dobutamine-induced wall motion patterns to define the anatomic status of the infarct-related artery (IRA) was evaluated in 159 patients who underwent dobutamine stress echocardiography (DSE) and coronary angiography 10 +/- 2 and 18 +/- 3 days, respectively, after hospital admission. The DSE result was classified as: (1) biphasic: improvement with a low dose followed by deterioration with a high dose; (2) worsening: direct deterioration at low or high doses; (3) sustained improvement: improvement with a low dose that was maintained at high dose; and (4) no change: no change during the entire protocol. A diameter narrowing >70% (50% for the left main stem) of major coronary arteries indicated a severe lesion. Angiograms were classified according to the jeopardy score and collateral circulation graded according to Rentrop's classification. DSE was positive in 92 patients (22 had biphasic results and 70 had worsening results) and negative in 67 patients (14 had sustained improvement and 53 had no changes). Biphasic response was associated with more frequent anterior infarction (p <0.05) and higher resting (p <0.001) and peak (p <0.01) wall motion score indexes. The IRA was totally occluded in 4 of the 92 patients (4%) with positive (worsening pattern) and 12 of the 67 patients (18%) with negative (no change pattern) tests. The biphasic pattern was associated with the highest jeopardy score and was significantly (p <0.05) more specific (100%) compared with worsening (78%) in identifying a severe stenosis of the IRA. The combination of ischemic patterns provided a significantly superior sensitivity (p <0.0001). Logistic regression analysis identified the biphasic pattern as the only significant predictor. Conversely, the prediction of total occlusion of the IRA was poor. Sustained improvement was the most specific (100%) predictor of absence of severe stenosis of the IRA, whereas the combination with no change pattern provided a significantly superior sensitivity (p <0.0001). Thus, DSE effectively predicts the residual stenosis of the IRA. In particular, the biphasic response has an excellent specificity and positive predictive value and is the only significant predictor among clinical and echocardiographic variables.

Abstract: AIMS: Revascularization procedures are increasingly applied in patients with single-vessel coronary artery disease in spite of the fact that a prognostic benefit has been proved only for soft end-points. This review summarizes the results of stress echocardiography in the diagnostic and prognostic assessment of these patients. METHODS AND RESULTS: The diagnostic and prognostic assessment of patients with single-vessel disease using stress (exercise, dobutamine, adenosine and dipyridamole) echocardiography are focused upon in the light of pathophysiological considerations and the results of clinical studies. Factors affecting test accuracy are individually addressed and comparisons made with different stress testing modalities, including exercise electrocardiography and nuclear techniques. Finally, therapeutic options are discussed and the superior accuracy of the physiological assessment of coronary stenosis as compared to the simple anatomic evaluation emphasized. CONCLUSIONS: Patients with single-vessel disease represent an anatomically heterogeneous group. Although the suboptimal performance of any technique in their evaluation has to be acknowledged, stress echocardiography can effectively contribute to selection of the management strategy.

Abstract: AIMS: To investigate whether myocardial ischaemia elicitable during pharmacological stress echocardiography portends different prognosis in men and women.METHODS AND RESULTS: The study group was made by 1733 patients (941 men, 792 women) who underwent dipyridamole (n=1008) or dobutamine (n=725) stress echo for evaluation of known or suspected coronary artery disease. An ischaemic response was found in 460 patients (308 men, 152 women). Considering the whole ischaemic population, women were older (P<0.0001) and more likely to have hypertension (P=0.02) and hypercholesterolaemia (P=0.04) than men. No difference in age and risk factors was evidenced between the two sexes in the subset of 203 patients with ischaemia and suspected coronary artery disease. During follow-up (25 +/- 24 months for the ischaemic and 37 +/- 25 months for the non-ischaemic sample), there were 113 cardiac events (45 deaths and 68 infarctions) and 232 revascularizations. Revascularization rate in ischaemic population was similar in both sexes (P=0.36). Multivariate predictors of cardiac events in the whole ischaemic group were resting WMSI (HR=2.7, 95% CI 1.3--3.3;P=0.0050), female gender (HR=2.2, 95% CI 1.2--3.7;P=0.0062), age > or = l65 years (HR=1.9, 95% CI=1.0--3.6;P=0.0427), and Delta WMSI (HR=2.1, 95% CI=1.0--3.7;P=0.0447). Female gender (HR=2.7, 95% CI 1.1--6.3;P=0.0233) was the only independent prognostic predictor in patients with ischaemia and suspected coronary artery disease. Five-year infarction-free survival was 82% in men and 71% in women in the whole ischaemic population (P=0.0041) as well as in the ischaemic group with suspected coronary artery disease (CAD) (P=0.0175). In the non-ischaemic sample resting WMSI (HR=4.8), history of myocardial infarction (HR=2.5), and hypercholesterolaemia (HR=1.8) were independent predictors of outcome at multivariate analysis, whilst the gender had no prognostic importance.Conclusions: Our results show that female gender is an independent predictor of cardiac events in patients with myocardial ischaemia induced by pharmacological stress echocardiography.

Abstract: PURPOSE: Although coronary artery disease is a frequent cause of left bundle branch block, the prognostic value of myocardial ischemia in patients with this conduction abnormality has not been defined. We investigated the value of pharmacologic stress echocardiography in risk stratification of patients with left bundle branch block. PATIENTS AND METHODS: Three hundred eighty-seven patients [230 men and 157 women, mean (+/- SD) age, 64 +/- 9 years] with complete left bundle branch block on the resting electrocardiogram underwent dobutamine (n = 217) or dipyridamole (n = 170) stress echocardiography to evaluate suspected or known coronary artery disease. A summary wall motion score (on a one to four scale) was calculated. The primary end points were cardiac death and nonfatal myocardial infarction. RESULTS: A positive echocardiographic result (evidence of ischemia) was detected in 109 (28%) patients. During a mean follow-up of 29 +/- 26 months, there were 21 cardiac deaths and 20 myocardial infarctions, 63 patients underwent coronary revascularization, and 1 patient received a heart transplant. In a multivariate analysis, four clinical and echocardiographic variables were associated with increased risk of cardiac death: resting wall motion score index [hazard ratio (HR) = 7.5 per unit; 95% confidence interval (CI), 2.8 to 20; P = 0.001], previous myocardial infarction (HR = 2.9; 95% CI, 1.1 to 7.3; P = 0.02), diabetes (HR = 2.7; 95% CI, 1.1 to 6.6; P = 0.03), and the change in wall motion score index from rest to peak stress (HR = 3.0 per unit; 95% CI, 1.0 to 8.6; P = 0.04). The 5-year survival was 77% in the ischemic group and 92% in the nonischemic group (P = 0.02). Four variables were associated with increased risk of cardiac death or infarction: previous myocardial infarction (HR = 3.4; 95% CI, 1.7 to 6.8; P = 0.0005), diabetes (HR = 2.4; 95% CI, 1.2 to 4.6; P = 0.01), resting wall motion score index (HR = 2.2 per unit; 95% CI, 1.1 to 4.1; P = 0.02), and positive echocardiographic result (HR = 2.2; 95% CI, 1.1 to 4.5; P = 0.03). The 5-year infarction-free survival was 60% in the ischemic group and 87% in the nonischemic group (P < 0.0001). Stress echocardiography significantly improved risk stratification in patients without previous myocardial infarction (P = 0.0001), but not in those with previous myocardial infarction (P = 0.08). In particular, it provided additional value over clinical and resting echocardiographic findings in predicting cardiac events among patients without previous infarction. CONCLUSIONS: Myocardial ischemia during pharmacologic stress echocardiography is a strong prognostic predictor in patients with left bundle branch block, particularly in those without previous myocardial infarction.

Abstract: STUDY OBJECTIVE: To assess the diagnostic and prognostic value of cardiac output assessed by cardiopulmonary exercise testing in patients with anterior acute myocardial infarction (AMI) and left ventricular dysfunction. PATIENTS AND SETTING: Forty-six patients with AMI (7 female patients; mean +/- SD age, 55 +/- 8 years; ejection fraction, 39 +/- 7%) underwent cardiopulmonary exercise testing and coronary angiography following hospital discharge. MEASUREMENT AND RESULTS: Cardiac output was estimated from oxygen uptake (VO(2)) during exercise according to a method based on the linear regression between arteriovenous oxygen content difference and percent maximum VO(2). Angiograms were scored using Gensini and Duke "jeopardy" scores. Cardiac output at anaerobic threshold (COAT) < or = 7.3 L/min was the best cutoff value for identifying multivessel coronary artery disease (relative risk, 3.1). Angiographic scores were significantly higher in patients with COAT < 7.3 L/min as compared to those with COAT > 7.3 L/min (82 +/- 8 vs 53 +/- 7 and 6 +/- 2 vs 4 +/- 3, respectively; p < 0.05) and were inversely and significantly correlated to COAT. Conversely, no correlation was found with ECG changes. COAT, VO(2) at anaerobic threshold, and peak VO(2) were univariate prognostic indicators. However, using Cox's model, COAT was the only multivariate predictor of outcome (odds ratio, 0.28; 95% confidence interval [CI], 0.09 to 0.9). Moreover, COAT < 7.3 L/min was associated to an increased risk of further cardiac events (odds ratio, 5; 95% CI, 1.4 to 17) and provided a significant discrimination of survival for the combined end point of cardiac death, reinfarction, and clinically driven revascularization. CONCLUSIONS: COAT is a safe and feasible tool providing additional diagnostic and prognostic information in patients with AMI.

Abstract: OBJECTIVE: Coronary artery disease (CAD) is a leading cause of mortality and morbidity in diabetic patients; therefore, their risk stratification is a relevant issue. Because exercise tolerance is frequently impaired in these patients, pharmacological stress echocardiography (SE) has been suggested as a valuable alternative. Our aim was to evaluate the prognostic value of this technique in diabetic patients with known or suspected CAD. RESEARCH DESIGN AND METHODS: A total of 259 consecutive diabetic patients underwent pharmacological SE (dobutamine in 108 patients and dipyridamole in 151 patients) and follow-up for 24 +/- 22 months. A comparison between the prognostic value of SE and exercise electrocardiography (ECG) was made in a subgroup of 120 subjects. RESULTS: A total of 13 cardiac deaths and 13 nonfatal infarctions occurred during follow-up, and 58 patients were revascularized. Univariate predictors of outcome were known CAD, positive SE, rest and peak wall motion score index (WMSI), and peak/rest WMSI variation. Peak WMSI was the only significant and independent prognostic indicator (odds ratio 11; 95% CI 4-29, P < 0.0001) on multivariate Cox's analysis. After adjustment for the most predictive clinical and exercise ECG variables, SE provided 43% additional prognostic information (gain in X(2) = 7, P < 0.01). Moreover, positive SE was associated with a significantly lower event-free survival. CONCLUSIONS: SE effectively predicts cardiac events in diabetic patients with known or suspected CAD and adds additional prognostic information as compared with exercise ECG.

Abstract: Echocardiography combined with either exercise or pharmacological stress is a widely used method for the noninvasive assessment of coronary artery disease. This is due to the high diagnostic accuracy that does not differ substantially among the various stress modalities. In addition, stress echocardiography has a useful role in risk stratification of patients with known or suspected coronary artery disease. In particular, evidence of inducible ischemia is predictive of an unfavorable outcome, whilst its absence is associated with a very low risk of future cardiac events. These findings have strong implications in clinical decision-making. One of the main characteristics of the echographic marker of ischemia is that it is significantly more specific than the electrocardiographic one. The higher specificity of stress echocardiography translates into increased prognostic value as compared to exercise electrocardiography. Nevertheless, exercise electrocardiography has a very high negative predictive value. Moreover, compared to stress echocardiography it is safer, simpler, less costly and requires no specific competence. Based on these data, exercise electrocardiography remains the cornerstone of the noninvasive evaluation of coronary artery disease. Stress echocardiography, on the other hand, is particularly useful in those cases when exercise electrocardiography is not feasible, non-interpretable (owing to the presence of left bundle branch block or of a pacemaker or of other electrocardiographic baseline abnormalities), or when it gives inconclusive data, or a positive result at an intermediate or high workload (in such cases, precise knowledge of the site and extension of ischemia can be of crucial importance in deciding between conservative and aggressive treatment), as well as in cases in which ischemia during the test is frequently a false positive response, as in hypertensive patients, in women and in all cases of left ventricular hypertrophy.

Abstract: AIMS: The aim of this study was to assess the prognostic value of myocardial viability recognized as a contractile response to vasodilator stimulation in patients with left ventricular dysfunction in a large scale, prospective, multicentre, observational study. METHODS AND RESULTS: Three hundred and seven patients (mean age 60 +/- 10 years) with angiographically proven coronary artery disease, previous (>3 months) myocardial infarction and severe left ventricular dysfunction (ejection fraction <35%; mean ejection fraction: 28 +/- 7%) were enrolled in the study. Each patient underwent low dose dipyridamole echo (0.28 mg x kg(-1) in 4 min). Myocardial viability was identified as an improvement of >0.20 in the wall motion score index. By selection, all patients were followed up for a median of 36 months. One-hundred and twenty-four were revascularized either by coronary artery bypass grafting (n=83) or coronary angioplasty (n=41). The only end-point analysed was cardiac death. In the revascularized group, cardiac death occurred in one of the 41 patients with and in 16 of the 83 patients without a viable myocardium (2.4% vs 19.3%, P<0.01). Outcome, as estimated by Kaplan-Meier survival, was better for patients with, compared to patients without, a viable myocardium, who underwent coronary revascularization (97.6 vs 77.4%, P=0.01). Using a Cox proportional hazards model, the presence of myocardial viability was shown to exert a protective effect on survival (chi-square 4.6, hazard ratio 0.1, 95% CI 0.01-0.8, P<0.03). The survival rate in medically treated patients was lower than in revascularized patients irrespective of the presence of a viable myocardium (79.7% vs 86.2, P=ns). CONCLUSION: In severe left ventricular ischaemic dysfunction, myocardial viability, as assessed by low dose dipyridamole echo, is associated with improved survival in revascularized patients.

Abstract: The aim of our study was to compare the prognostic value of stress echocardiography and exercise electrocardiography after uncomplicated non-Q-wave acute myocardial infarction in a series of 89 female patients. Our data show that stress echocardiography has independent predictive value in a female patient population recovering from uncomplicated acute myocardial infarction.

Abstract: We followed 229 consecutive patients exhibiting negative T waves on infarct-related electrocardiographic leads; these patients underwent dobutamine stress echocardiography within 10 days after a first uncomplicated acute myocardial infarction. T-wave normalization, but not ST-segment elevation, recognized patients at higher risk of cardiac events and optimized the prognostic accuracy of both myocardial viability and ischemia, to which it was correlated and became an independent predictor in cases of subdiagnostic stress echocardiography.

Abstract: BACKGROUND: There is evidence that after uncomplicated acute myocardial infarction, T wave positivization during stress testing may unveil myocardial viability. We evaluated in a prospective study the clinical value of T wave positivization during dobutamine stress echocardiography in patients with recent, first uncomplicated acute myocardial infarction. METHODS: Two hundred twenty-nine patients, who underwent dobutamine stress echocardiography within 10 days of uncomplicated acute myocardial infarction, were selected for exhibiting negative T waves in the infarct area. A mean follow-up of 2.1 +/- 1 years (up to 6 years) was obtained. RESULTS: T wave positivization appeared during dobutamine test in 76 (33%) patients. The agreement of T wave positivization for myocardial viability was 65% (95% confidence interval 59-71). Compared to myocardial viability during dobutamine stress echocardiography, the combination with T wave positivization was more sensitive (55 vs 24%, 95% confidence interval 46-64 vs 17-33) for predicting cardiac events, albeit less specific. Kaplan-Meier survival curves showed 47 (62%) cardiac events in patients with T wave positivization and 70 (46%) cardiac events in the remaining patients (p < 0.05). Soft (n = 91) prevailed over hard (n = 26) cardiac events. CONCLUSIONS: T wave positivization during dobutamine stress echocardiography after uncomplicated acute myocardial infarction identifies patients at higher cardiac risk, and is more sensitive, albeit less specific, for cardiac events than viability alone. T wave positivization is helpful in the case of inconclusive stress echocardiography. The pathophysiology of T wave positivization and its relative value among other variables warrant further analysis.

Abstract: BACKGROUND: The classical risk factors for acute myocardial infarction (AMI) fail to explain all the epidemiological variations of the disease. Among the new risk factors recently reported, several infectious agents appear to increase the risk of AMI. In particular, acute and chronic respiratory diseases due to Chlamydia pneumoniae, and Helicobacter pylori (H. pylori) infection seem to be strongly involved. The aim of this work is to determine the prevalence of H. pylori infection in a group of male patients with AMI, in a case-control study, where a group of blood donors matched for sex and age served as control. We searched for the classical risk factors in all patients. METHODS: We studied 212 consecutive male patients, aged 40-65 years, admitted for AMI at the Coronary Care Units at Hospitals in three towns of Northern Italy. H. pylori infection was assessed by the highly specific and sensitive 13C-urea breath test and by presence of antibodies (IgG) against H. pylori in circulation. Volunteer blood donors attending our Hospital Blood Bank served as controls. Among the patients we investigated the presence of hypertension, cholesterol and glucose levels in serum, fibrinogen in plasma and the smoking habit. RESULTS: H. pylori infection was present in 187/212 (88%) of the patients and in 183/310 (59%) of the control population (p < 0.0001). Classical risk factors for AMI did not differ among patients with and without H. pylori infection. CONCLUSION: Patients admitted to the Coronary Care Unit for acute myocardial infarction had a notably higher prevalence of H. pylori infection than the general population. The classical risk factors for coronary disease were equally present in all patients with AMI irrespective of H. pylori status.

Abstract: The aim of our study was to compare the prognostic value of stress echocardiography and exercise electrocardiography after uncomplicated non-Q-wave acute myocardial infarction in a series of 68 consecutive patients. Our data show that stress echocardiography and exercise electrocardiography offer similar prognostic information after uncomplicated non-Q-wave AMI.

Abstract: BACKGROUND: The presence of tissue viability is of great importance in the prognostic work-up of patients recovering from acute myocardial infarction. However, uncertainty still exists concerning the optimal tool for its assessment. The present study was undertaken in order to compare low-dose dobutamine echocardiography and rest-redistribution thallium SPECT for predicting late improvement of regional left ventricular function after acute myocardial infarction. METHODS: Fifteen patients undergoing coronary angiography, low-dose dobutamine echocardiography and rest-redistribution thallium SPECT after thrombolyzed anterior acute myocardial infarction were studied. A 3 month follow-up echocardiogram was performed in all patients and 9 underwent coronary revascularization. RESULTS: A significant (> or = 70%) residual stenosis of the infarct-related artery was present in 14 patients, whilst a total occlusion was observed in 1. At 3 month follow-up, 41% of the dyssynergic segments improved. The sensitivity, specificity and accuracy for late wall motion improvement was 61, 89 and 77% for low-dose dobutamine echocardiography and, respectively, 76, 45 and 58% for rest-redistribution thallium SPECT. Tissue viability was detected in 65 and 31% of dyssynergic segments by rest-redistribution thallium SPECT and low-dose dobutamine echocardiography, respectively (p < 0.001). The agreement between the two techniques was 48%. CONCLUSIONS: Low-dose dobutamine echocardiography is more accurate than rest-redistribution thallium SPECT for predicting 3 month wall motion improvement in patients with acute anterior myocardial infarction, mainly due to its significantly better specificity.

Abstract: Prevalence and prognostic significance of painful and silent ischemia detected by exercise electrocardiography (ECG) and dobutamine stress echocardiography (DSE) were evaluated in 407 consecutive patients recovering from acute myocardial infarction. Painful ischemia assessed by both tests was not associated with different clinical characteristics of patients; on the other hand, it identified a higher risk subgroup compared with silent ischemia during exercise ECG but not during DSE.

Abstract: Stress-induced asynergies in the infarct area following thrombolytic therapy are considered to reflect incomplete recanalization of the culprit vessel. However, reperfusion is a dynamic process with successive pathophysiological phases, so that the timing of assessment of residual ischemia may have relevant clinical implications. We studied the time-course of dobutamine-induced homozonal asynergies in 61 (group B) survivors of uncomplicated infarction as compared to 54 (group A) control subjects showing normal response to dobutamine stress echocardiography within 10 days of acute myocardial infarction. The 79 (43 of group A and 36 of group B) patients not presenting new cardiac events underwent further dobutamine stress echo within 90 +/- 17 days, which was positive in 20 and negative in 59. Persistence of test positivity was observed in just 17/36 (47%) patients, who showed significantly more extensive dobutamine-induced asynergies as compared to pre-discharge evaluation and less frequent (p < 0.01) evidence of viable myocardium. These results arise question about the decisional impact of stress-induced wall motion abnormalities in the culprit vessel area early after thrombolysis in low-risk patients and emphasize the need to further clarify the time factor role in this setting.

Abstract: OBJECTIVES: This study sought to verify the effectiveness of pharmacologic stress echocardiography in risk stratification of patients with single-vessel disease. BACKGROUND: Noninvasive prognostic assessment of single-vessel disease is an unresolved issue to date. METHODS: The study evaluated prospectively collected data from 754 patients with angiographic single-vessel disease who underwent either dipyridamole (n = 576) or dobutamine (n = 178) stress echocardiography. Invasive treatment (coronary revascularization within 3 months of stress testing) was performed in 260 patients and medical treatment in 494. RESULTS: Echocardiographic positivity was observed in 421 patients (56%). Patients treated invasively had a higher incidence of stress test positivity (69% vs. 49%, p < 0.001) and left anterior descending coronary artery involvement (60% vs. 46%, p < 0.001) than patients maintained with medical therapy. During a mean follow-up of 37 months, 54 hard cardiac events occurred (14 deaths, 40 nonfatal infarctions): 37 in medically and 17 in invasively treated patients (7.5% vs. 6.5%, p = NS). On Cox analysis, a positive result on stress testing was the only independent prognostic predictor in medically treated patients (relative risk 2.92, 95% confidence interval 1.29 to 6.59). The 4-year infarction-free survival rate was higher for a negative than a positive stress test result in medically (93.9% vs. 87.3%, p = 0.009) but not invasively treated patients (92.7% vs. 97.1%, p = 0.545). Moreover, a significantly higher 4-year infarction-free survival rate was found in invasively versus medically treated patients with a positive (p = 0.012), but not in those with a negative, stress test result (p = 0.853). CONCLUSIONS: Pharmacologic stress echocardiography is effective in risk stratification of single-vessel disease and can accurately discriminate patients in whom coronary revascularization can have the maximal beneficial effect. These findings have a potential favorable impact on the cost-effectiveness of invasive procedures.

Abstract: BACKGROUND: The aim of the study was to evaluate the usefulness of low-dose dobutamine echocardiographic testing performed within 48 hours from anterior AMI in order to identify the extent of viable myocardium and predict its functional outcome. The early echo-dobutamine test was also compared with a predischarge test in order to evaluate the effects of different timing on the accuracy of the test. METHODS: Nineteen consecutive patients, aged 54 +/- 11 years, with a first anterior AMI entered the study. All patients underwent a low-dose dobutamine echocardiographic test within 48 hours from hospital admission and at predischarge. In all the patients, a rest follow-up echocardiogram was performed three months after hospital discharge. Eleven patients underwent a revascularization procedure (7 underwent PTCA and 4 CABG). RESULTS: Of the 159 dyssynergic segments, 26% improved spontaneously at predischarge and 51% improved at the three-month follow-up. Of the 145 predischarge dyssynergic segments, 38% improved at three months. Considering the results on a segmental basis, early low-dose dobutamine echocardiography showed a sensitivity of 52%, a specificity of 87%, a positive predictive value of 81%, a negative predictive value of 64% and a diagnostic accuracy of 69% for wall-motion improvement at three months. The predischarge test showed very similar values. A slight enhancement of the sensitivity of both tests was observed considering the akinetic segments only. Finally, considering the amount of segmental reversible dysfunction inside the infarct area in the single patients, early low-dose dobutamine echocardiography showed a sensitivity of 86% and a specificity of 80%. CONCLUSIONS: Our results indicate that: 1) recovery of regional wall motion after AMI is slow and progressive, with substantial improvement ensuing within the first days after infarction; 2) considering results on a segmental basis, low-dose dobutamine echocardiography performed within 48 hours of AMI shows a high specificity but a low sensitivity for late recovery of regional function, although it gave information similar to what was obtained performing the test at predischarge; 3) the efficiency of test can be improved by considering the amount of reversible segmental dysfunction inside the infarct area in the single patients.

Abstract: BACKGROUND: Thrombolysis has reduced early and longterm mortality by about 20%; sometimes, however, there is a re-occlusion of the infarct related artery or an unsuccessful thrombolysis. In these situations, there is a possible increase in detrimental events in the follow-up. OBJECTIVES: The aim of the study was to compare the prognostic value of dobutamine echocardiography (DET) and ECG exercise test (EET) in pts submitted to thrombolysis. METHODS: One hundred and fifty-one pts, with acute uncomplicated myocardial infarction, were enrolled. The pts were able to perform EET and had a sufficient echocardiographic window; 58 had anterior myocardial infarction (38%), 79 had inferior (52%), 2 had lateral (1%), 12 had non-Q (8%). EET was performed with an initial load of 25 Watt, and thereafter, 25 W every two minutes. DET was performed with step-wise infusion every three minutes (5, 10, 20, 30 and 40 mcg/kg/min.). If the target heart rate was not reached, a further dose of 40 mcg/kg/min. together with atropine 0.25-1 mg was administered, in the absence of signs and symptoms of ischemia. RESULTS: During a mean (+/- SD) follow-up period of 8 +/- 4.5 months (range 1-23), 16 spontaneous events happened (4 deaths, 5 non-fatal re-infarctions, 7 unstable angina). One-hundred and three EET (68%) were negative for ongoing ischaemia, while 48 were positive, 79 DET (52%) were negative for ongoing ischaemia and 72 were positive (48%). Statistical results: DET and EET had a sensitivity of 41% and 54%, a specificity of 57% and 74%, a positive predictive value of 7% and 14%, a negative predictive value of 91% and 95%, an accuracy of 56% and 73%. Kaplan-Maier survival curves demonstrated that patients with Peak Wall motion > 1.8 and EET score > 3, had the higher risk of spontaneous events. CONCLUSION: A few spontaneous events happened in the follow-up. These data demonstrate that patients treated with thrombolysis are not at high risk of spontaneous events. DET and EET, therefore, have had a high negative predictive value. For this reason, we can conclude that pts with negative tests can be considered at low risk and do not need any further investigations.

Abstract: BACKGROUND: Residual viable myocardium identified by dobutamine stress after myocardial infarction may act as an unstable substrate for further events such as subsequent angina and reinfarction. However, in patients with severe global left ventricular dysfunction, viability might be protective rather than detrimental. The aim of this study was to assess the impact on survival of echocardiographically detected viability in medically treated patients with global left ventricular dysfunction evaluated after acute uncomplicated myocardial infarction. METHODS AND RESULTS: The data bank of the large-scale, prospective, multicenter, observational Echo Dobutamine International Cooperative (EDIC) study was interrogated to select 314 medically treated patients (271 men; age, 58+/-9 years) who underwent low-dose (</=10 microg x kg-1 x min-1) dobutamine for the detection of myocardial viability and high-dose dobutamine for the detection of myocardial ischemia (</=40 microg x kg-1 x min-1 with atropine </=1 mg) performed 12+/-6 days after an acute uncomplicated myocardial infarction and showing a moderate to severe resting left ventricular dysfunction (wall motion score index [WMSI] >1.6). Patients were followed up for 9+/-7 months. Low-dose dobutamine stress echocardiography identified myocardial viability in 130 patients (52%). Dobutamine-atropine stress echocardiography was positive for ischemia in 148 patients (47%) and negative in 166 patients (53%). During the follow-up, there were 12 cardiac deaths (3.8% of the total population). With the use of Cox proportional hazards model, delta low-dose WMSI (the variation between rest WMSI and low-dose WMSI) was shown to exert a protective effect by reducing cardiac death by 0.8 for each decrease in WMSI at low-dose dobutamine (coefficient, -0.2; hazard ratio, 0.8; P<0.03); WMSI at peak stress was the best predictor of cardiac death in this set of patients (hazard ratio, 14.9; P<0.0018). CONCLUSIONS: In medically treated patients with severe global left ventricular dysfunction early after acute uncomplicated myocardial infarction, the presence of myocardial viability identified as inotropic reserve after low-dose dobutamine is associated with a higher probability of survival. The higher the number of segments showing improvement of function, the better the impact is of myocardial viability on survival. The presence of inducible ischemia in this set of patients is the best predictor of cardiac death.

Abstract: OBJECTIVES: The aim of this multicenter, multinational, prospective, observational study was to assess the relative value of myocardial viability and induced ischemia early after uncomplicated myocardial infarction. BACKGROUND: Dobutamine-atropine stress echocardiography allows evaluation of rest function (at baseline), myocardial viability (at low dose) and residual ischemia (peak dose, up to 40 micrograms with atropine up to 1 mg) in one test. METHODS: Dobutamine-atropine stress echocardiography was performed 12 +/- 5 days (mean +/- SD) after a first uncomplicated acute myocardial infarction in 778 patients (677 men; mean age 58 +/- 10 years) with technically satisfactory rest echocardiographic study results. Patients were followed-up for 9 +/- 7 months. RESULTS: Dobutamine-atropine stress echocardiographic findings were positive for myocardial ischemia in 436 of patients (56%) and negative in 342 (44%). During follow-up, there were 14 cardiac-related deaths (1.8% of the total cohort), 24 (2.9%) nonfatal myocardial infarctions and 63 (8%) hospital readmissions for unstable angina. One hundred seventy-four patients (22%) underwent coronary revascularization (bypass surgery or coronary angioplasty). Spontaneous events occurred in 61 of 436 patients with positive and 40 of 342 patients with negative findings on dobutamine-atropine stress echocardiography (14% vs. 12%, p = 0.3). When only spontaneously occurring events were considered, the most important predictor was myocardial viability (chi-square 9.7). Using the Cox proportional hazards model, only the presence of myocardial viability (hazard ratio [HR] 2.0, p < 0.002) and age (HR 1.03, p < 0.001) were predictive of spontaneously occurring events. When only hard cardiac events were considered, age was the strongest predictor (chi-square 3.6, p = 0.056), followed by wall motion score index (WMSI) at peak dose (chi-square 3.3, p = 0.06) and remote ischemia (chi-square 2.25, p = 0.1). When cardiac death was considered, WMSI at peak dose was the best predictor (HR 9.2, p < 0.0001). CONCLUSIONS: During dobutamine stress, echocardiographic recognition of myocardial viability is more prognostically important than echocardiographic recognition of myocardial ischemia for predicting unstable angina, whereas WMSI at peak stress was the best predictor of cardiac-related death. Different events can be recognized with different efficiency by various stress echocardiographic variables.

Abstract: High Altitude Pulmonary Edema (HAPE) is an uncommon type of non-cardiogenic pulmonary edema. Few data are available regarding ECG abnormalities in patients with HAPE. They are usually slight and related to acute pulmonary hypertension. This paper describes a case of prolonged ECG abnormalities in a subject with HAPE, with no proven cardiac diseases. The Authors discuss the pathopysiological aspects of this kind of hypoxic-induced right ventricular overload with extensive T-wave negativity in precordial leads.

Abstract: BACKGROUND: Risk stratification after uncomplicated myocardial infarction is major clinical problem. In particular, the prognostic value of residual inducible ischaemia is still controversial. We compared the relative prognostic value of exercise ECG and dobutamine stress echocardiography performed in the early post-infarction period. METHODS: Four hundred and six patients (53 female) aged 57 +/- 9 years, undergoing maximal exercise ECG and dobutamine stress echocardiography within 10 days of an uncomplicated myocardial infarction off therapy, were prospectively followed-up for 8.8 months. Age, sex, diabetes, smoking habit, hypertension, dyslipidaemia, infarct location, thrombolysis and resting wall motion score index were taken into account among clinical variables. Prognostic correlations were made vs spontaneous events (cardiac death, non-fatal reinfarction and unstable angina requiring hospitalization) whilst patients undergoing revascularization (by means of percutaneous transluminal coronary angioplasty or coronary artery bypass surgery) at the time of the procedure were censored. RESULTS: One hundred and twenty-seven events occurred during the follow-up: 41 (10%) were spontaneous (five deaths, 12 reinfarctions and 24 unstable angina) and 86 procedural (27 angioplasty and 59 bypass surgery). Spontaneous events were not predicted by any clinical, exercise ECG or dobutamine stress echocardiography variable, but the negative predictive value of both tests was excellent (91% and 90% respectively). With a multivariate Cox analysis, male gender, positive low-workload (< 100 W) exercise ECG (P < 0.0001), positive low-dose dobutamine stress echocardiography (P < 0.0001) and rest-stress wall motion score index variation (P < 0.001) were found to predict cumulative cardiac events with an independent and additive value. Dobutamine stress echocardiography was significantly more sensitive (P < 0.05) and less specific (P < 0.01) in predicting the outcome of patients with anterior infarction, whilst exercise ECG was significantly more sensitive (P < 0.05) in patients with non-Q wave infarction. CONCLUSIONS: (1) Spontaneous events are poorly predicted by provocative tests in low-risk patients after uncomplicated myocardial infarction. (2) However, both exercise ECG and dobutamine stress echocardiography can predict a favourable outcome with a very high negative predictive value. (3) Dobutamine stress echocardiography should be considered a secondary option in cases where the exercise ECG is equivocal or when the location of ischaemia is a relevant issue. (4) The possibility that the two tests have a differential utility depending on the infarct location and type (Q wave vs non-Q wave) may be clinically relevant and deserves further evaluation.

Abstract: We analyzed the relation between dobutamine-induced Q-wave ST-segment elevation and regional contraction during low (5 to 10 microg/kg/min) and high doses (20 to 40 microg/kg/min) of dobutamine in a series of 391 dobutamine echocardiographic tests performed 10 +/- 2 days after a first uncomplicated acute myocardial infarction (AMI). ST-segment elevation was defined as > or = 1 mm new or additional J-point elevation with a horizontal or upsloping ST segment lasting 80 ms. Wall motion score index at rest was derived using a 16 segment-4 grade score model. Patients with dobutamine-induced ST-segment elevation had a higher wall motion score index at rest (anterior wall AMI: 1.67 +/- 0.27 vs 1.43 +/- 0.30, p = 0.0001; inferior wall AMI: 1.44 +/- 0.27 vs 1.30 +/- 0.18, p = 0.0001) and similar incidence and extent of myocardial viability and homozonal ischemia in comparison with those without ST-segment elevation. The sensitivity, specificity, and accuracy of dobutamine-induced ST-segment elevation for detecting residual homozonal ischemia were 51%, 55%, and 54%, respectively, in patients with anterior wall AMI, and 42%, 68%, and 58%, respectively, in patients with inferior wall AMI. In conclusion, dobutamine-induced ST-segment elevation is not associated with higher incidence and extent of viable or jeopardized myocardium but rather to a greater extent of wall motion abnormalities at rest. Thus, this finding does not represent a clinically reliable discriminator for selecting patients for coronary angiography and possible revascularization procedures.

Abstract: OBJECTIVES: We sought to assess whether the site of future myocardial infarction can be predicted on the basis of induced dyssynergy ("area at risk") recognized by stress echocardiography. BACKGROUND: The severity and extent of stress-induced dyssynergy are strong predictors of subsequent major cardiac events. However, high grade stenotic lesions are not strictly associated with the site of future coronary occlusions. METHODS: From the stress echocardiography multicenter trials data bank, we selected 70 patients (56 men; mean age +/- SD 58 +/- 11 years) meeting the following inclusion criteria: 1) dipyridamole (n = 53) or dobutamine (n = 17) stress echocardiography; 2) a spontaneously occurring infarction, with no intercurrent revascularization procedure between the initial study and the infarction; and 3) a follow-up rest echocardiogram obtained 41 +/- 90 days after the infarction. RESULTS: A complete ischemia-infarction mismatch (infarct-related dysfunction in a patient with negative stress test results) occurred in 29 patients (41%). A partial mismatch (ischemic dysfunction in a territory different from the infarct area) occurred in nine patients (13%). A match (ischemia-related and infarction-related dyssynergy involving the same region) occurred in 32 patients (46%). The average time interval between the stress examination and the occurrence of infarction or reinfarction was 144 +/- 160 days in patients with a match and 439 +/- 622 days in patients with a mismatch (p < 0.05). CONCLUSIONS: Induced ischemia (imaged as transient dyssynergy by pharmacologic stress echocardiography) inconsistently identifies the site of future infarction. The majority of spontaneous coronary occlusions leading to infarction are unheralded by induced ischemia. However, most infarctions occurring within 1 year of stress testing are in the area identified as ischemic during testing.

Abstract: OBJECTIVES. This study sought to compare, head to head, the two most popular pharmacologic stress echocardiographic tests--dipyridamole and dobutamine--with state of the art protocols in a large multicenter prospective study. BACKGROUND. In the continuing quest for ideal diagnostic accuracy, pharmacologic stress echocardiography has quickly moved over the years from low to high dose regimens and is currently performed with atropine coadministration. METHODS. Dobutamine (up to 40 microgram/kg body weight per min) plus atropine (up to 1 mg over 4 h) and dipyridamole (up to 0.84 mg/kg per min over 10 h) plus atropine (up to 1 mg over 4 h) stress echocardiography was performed on different days, in random order and within 1 week in 360 patients with chest pain syndrome. Thirteen different echocardiographic laboratories, all fulfilling quality control criteria for stress echocardiographic reading, contributed to the study. RESULTS. No major complications occurred during either test. The test was interrupted before achievement of predetermined end points for limiting side effects in 37 dobutamine-atropine and 7 dipyridamole-atropine stress echocardiographic studies (feasibility 90% vs. 98%, p < 0.01). Diagnostic accuracy was assessed in a subset of 110 patients with no obvious rest dyssynergy (akinesia or dyskinesia) who underwent coronary angiography independently of test results and within 1 week of testing. Significant coronary artery disease (> or = 50% diameter reduction in at least one major coronary vessel by quantitative coronary angiography) was found in 92 patients. Sensitivity for detection of coronary artery disease was 84% (77 of 92) for dobutamine-atropine and 82% (75 of 92) for dipyridamole-atropine stress echocardiography (p = NS), with a specificity of 89% (16 of 18) for dobutamine-atropine and 94% (17 of 18) for dipyridamole-atropine stress echocardiography (p = NS). A significant correlation was present between peak wall motion score index during dipyridamole-atropine and dobutamine-atropine stress echocardiography (r = 0.83, p < 0.0001). CONCLUSIONS. Dobutamine-atropine and dipyridamole-atropine stress echocardiography are safe and feasible, although submaximal studies are more frequent with dobutamine. The two stresses have comparable accuracy in the detection of angiographically assessed coronary artery disease, although dobutamine is marginally more sensitive and dipyridamole marginally more specific. Stratification of the ischemic response in the space domain is also comparable with the two stresses.

Abstract: 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.

Abstract: Our aim was to verify whether the sensitivity of pharmachological stress echocardiography for multivessel disease after acute myocardial infarction may be improved by a more aggressive protocol, i.e. not considering the appearance of the first wall motion abnormality as the absolute end-point if it occurs in the infarcted area without clinical or instrumental markers of extensive ischemia or left ventricular dysfunction. One-hundred twenty-one consecutive patients (age 32-71 years) prospectively underwent dobutamine-atropine stress echo (dobutamine infusion up to 40 micrograms/kg/min with additional atropine 1 mg) 11.8 +/- 4.8 days after uncomplicated myocardial infarction and coronary angiography within 6 weeks. Criteria for stopping the test were: significant ST depression or elevation, typical chest pain, major arrhythmias and left ventricular dysfunction. The test was considered as positive if a deterioration of basal wall motion pattern was observed: it was defined homozonally positive (the deterioration occurred in the myocardial area fed by the culprit vessel) or heterozonally positive (the deterioration occurred in a different vascular area). A coronary stenosis > 70% of vessel lumen was defined as critical. Thirty-four patients showed a negative test result. Among the 87 patients with positive test, 65 had no further wall motion deterioration from the first-induced wall motion abnormality (WMA) to peak test (Group A), whereas nine patients showed further homozonal (Group B) and 13 further heterozonal (Group C) asynergies. Sensitivity, specificity and accuracy of dobutamine stress echocardiography for multivessel disease were, respectively, 63%, 96% and 82% using the first-induced wall motion abnormality as test end-point, whilst they were 84% (P < 0.01), 93% and 89% according to the aggressive approach previously described. Dobutamine stress time of patients with multivessel disease was higher in Groups B and C (13.1 +/- 3.6 min) than in Group A (9.8 +/- 3.7 min, P < 0.01) and, finally, the mean obstruction of non-culprit vessel was higher in Group A (62.2%) than in Group C (47.4%, P < 0.05). No major complications were found. We conclude that the sensitivity of dobutamine stress echocardiography for multivessel disease following recent myocardial infarction is critically dependent on the test end-point. It may be improved by a more aggressive approach capable to identify less severe heterozonal coronary lesions.

Abstract: Although previous studies have confirmed the safety of dobutamine stress echocardiography, complex ventricular arrhythmias have been reported. Our aim was (1) to identify the markers of increased arrhythmic risk during dobutamine stress echocardiography and (2) to assess whether the occurrence of major ventricular arrhythmias during the test may represent a clinically useful marker of electrical instability. Three hundred and seventy-seven consecutive survivors from acute myocardial infarction, off cardioactive therapy, underwent dobutamine stress echocardiography 11.4 days after the acute event. Holter monitoring with assessment of heart rate variability and echocardiographic determination of left ventricular ejection fraction. In addition, exercise stress testing, signal averaged ECG and coronary angiography were carried out, respectively, in 357, 150 and 273 patients. Ten subjects showed complex ventricular arrhythmias (eight non-sustained and one sustained ventricular tachycardia and one ventricular fibrillation) during dobutamine stress echocardiography (group A), whilst 366 did not (group B). Complex ventricular arrhythmias were detected by Holter monitoring in 8/10 patients in group A and 45/367 patients in group B (odds ratio 28.6, 95% CI 5.4-92.2) and by exercise testing in 4/10 patients in group A and 33/347 patients in group B (odds ratio 6.3, 95% CI 1.4-27.2). Ejection fraction < 40% was present in 3/10 patients in group A and 50/367 in group B (odds ratio 2.7, 95% CI 0.3-12.2), whilst multivessel disease was present, respectively, in 8/10 and 176/263 patients (odds ratio 1.9, 95% CI 0.3-25.5). Reduced heart rate variability and the presence of late potentials on signal averaged ECG were found in, respectively, 40/367 and 13/140 patients in group B, but none were found in group A. A total of 61 events (35 CABG, 15 PTCA, four cardiac deaths and seven non-fatal reinfarctions) occurred during the follow-up (11.4 months, range 6 to 20): four in group A and 57 in group B. No documented major arrhythmic event was reported. We conclude that (1) complex arrhythmias during dobutamine stress may occur in patients early after acute myocardial infarction; (2) the preexisting evidence of frequent, as well as repetitive, arrhythmias represents a potential marker of increased risk in this connection and, finally, (3) dobutamine-induced arrhythmias seem to represent an uncommon, even though potentially dangerous, event but not a useful new "window' on electrical instability of post-MI patients.

Abstract: The demonstration of extensive coronary artery disease (CAD) after acute myocardial infarction (AMI) has important prognostic implications. Exercise-induced ST segment depression is commonly used for detecting the presence of CAD and evaluating its extension. However, even though there have been many attempts to increase its diagnostic yield, the accuracy of the electrocardiographic signal for identifying multivessel disease (MVD) is relatively low, particularly in post-MI patients. The aim of this study was to evaluate the ability of a simple index, combining information on the amount and kinetics of ST depression in the heart rate domain during exercise and recovery, to identify MVD after AMI. Seventy patients (mean age 53.4 years) underwent a bicycle, symptom-limited exercise stress test and coronary angiography 2-3 weeks and 6 weeks respectively, after uncomplicated AMI while cardioactive therapy was discontinued. After obtaining a computer-derived measurement of ST levels based on incremental averaging of normal complexes, the area subtended to baseline and limited by the ST trend against heart rate during both exercise (A1) and recovery (A2) was calculated. The difference (A1-A2) was defined as the 'Stress-Recovery Index' (SRI) and dichotomized, by means of receiver-operating characteristics curve analysis, at 5 mm x beats.min-1 to define an increased risk of MVD. The SRI of patients with MVD was significantly lower than that of patients with single vessel disease. The sensitivity of SRI < -5 mm x beats.min-1 (65%) for predicting MVD was significantly higher than that obtained by other conventional parameters, without appreciable loss of specificity (81%).(ABSTRACT TRUNCATED AT 250 WORDS)

Abstract: Diagnostic tests that are hazardous or infeasible, or both, may become accepted before inadequacies are recognised; only multicentre trials can provide the necessary information for an unrestricted acceptance of any new diagnostic procedure. We prospectively studied the results obtained in 24 experienced echocardiography laboratories. 2949 tests were done in 2799 patients. In 341 tests (12% of the overall population, 21% of the negative tests) the test could not be completed because of complex ventricular tachyarrhythmias (134, 38% of all submaximal studies); nausea and/or headache (71, 20%); hypotension and/or bradycardia (62, 17%); supraventricular tachyarrhythmias (44, 12%); hypertension (24, 7%); and others (20, 6%). Dangerous events (life-threatening complications or side-effects requiring specific treatment and lasting more than 3 hours, or new hospital admission) occurred in 14 cases (1 every 210 tests)--9 cardiac (3 ventricular tachycardias; 2 ventricular fibrillations; 2 myocardial infarctions; 1 prolonged antidote-resistant myocardial ischaemia; 1 severe, persistent hypotension) and 5 extracardiac (atropine poisoning with hallucinations lasting several hours in the absence of either myocardial ischaemia or hypotension). Life-threatening and/or longlasting complications may occur during dobutamine/atropine stress echocardiography. The test is generally well tolerated, although may be interrupted by minor, self-limiting, usually symptomless side-effects.

Abstract: The agreement between the results of standard ECG (CX) and cardiopulmonary (CPX) exercise stress tests performed in randomized sequence was evaluated in 40 patients with known coronary artery disease but who were not taking cardioactive therapy. Systolic blood pressure and heart rate were significantly higher during CPX only at low workload (less than 100 W). Exercise time and rate-pressure product at both peak exercise and ischaemic threshold were not significantly different between the two tests, even though their variability exceeded the value of 20%, which is generally accepted as the cut-off point for defining CX parameters as reproducible. However, the metabolic response to exercise, assessed by means of blood lactate kinetics analysis, was highly reproducible between the two tests. We conclude that the provocative role of exercise testing is not altered by the gas exchange analysis technique used in CAD patients. However, the common indexes of myocardial as well as of global physical performance may be influenced, thus requiring caution in comparing data with those derived from CX or from reference values.

Abstract: The effect on cardiac rhythm of intravenous administration of salbutamol during prolonged aminophylline infusion was evaluated by means of ECG Holter monitoring in 20 patients with chronic obstructive lung disease (COLD) without respiratory failure. Data were compared with a baseline 24-hour Holter monitoring during which an individual arrhythmia pattern was established for each patient. Intravenous administration of aminophylline with fast achievement of therapeutic plasma levels, has a variable and nonsignificant influence on supraventricular arrhythmias, whilst a statistically significant increase of premature ventricular contractions (PVCs) has been observed. However, such an increase concerns only isolated PVCs, is conditioned by the pattern of preexisting arrhythmias and is independent of plasma aminophylline level. Acute intravenous administration of salbutamol during infusion of aminophylline is not associated with a higher incidence of major arrhythmias. So we conclude that such a pharmacological combination does not represent an additional risk of serious cardiac rhythm disturbances in a selected population of COLD patients without further known arrhythmogenic risk factors. Moreover, plasma aminophylline levels are not predictive of a possible higher incidence of ventricular arrhythmias.

Abstract:

Abstract: The effect of acute i.v. administration of diltiazem on pulmonary haemodynamics was compared to that produced by oxygen in 10 hypoxemic patients with chronic obstructive lung disease and pulmonary hypertension (PAPm greater than 20 mmHg), without left ventricular dysfunction. Determinations were carried out at baseline, during 100% oxygen inhalation, at least 20 minutes after oxygen withdrawal and 15 minutes after i.v. diltiazem loading dose of 0.25 mg/kg followed by the infusion of 1 mcg/kg/min. Oxygen inhalation produced no significant modifications of haemodynamic variables, whilst a significant (p less than 0.05) decrease of PAPm, pulmonary arteriolar resistance (PAR) and peripheral resistance (TPR) was observed after diltiazem administration (respectively 14%, 23% and 11.6%). Heart rate, cardiac index and blood pressure did not change significantly even with diltiazem. These results could support the inclusion of diltiazem in the therapeutic regimen of pulmonary hypertension due to chronic obstructive lung disease, but further investigations are needed to clarify the predictive value of its acute administration in assessing long term efficacy.

Abstract: