Wilson Mathias

Prognostic value of dobutamine-atropine stress echocardiography early after acute myocardial infarction

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.

Prognostic Value of Myocardial Viability in Medically Treated Patients With Global Left Ventricular Dysfunction Early After an Acute Uncomplicated Myocardial Infarction A Dobutamine Stress Echocardiographic Study

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.

Prognostic value of pharmacological stress echocardiography in patients with known or suspected coronary artery disease: A prospective, large-scale, multicenter, head-to-head comparison between dipyridamole and dobutamine test

OBJECTIVES The study compared the prognostic value of dipyridamole and dobutamine stress echocardiography in patients with known or suspected coronary artery disease. BACKGROUND Extensive information is available on the relative diagnostic accuracy of the two tests assessed in a head-to-head fashion, whereas comparative data on their prognostic yield are largely preliminary to date. METHODS Dipyridamole (up to 0.84 mg/kg over 10 min) atropine (up to 1 mg over 4 min) (DIP) and dobutamine (up to 40 microg/kg/min)-atropine (1 mg over 4 min) (DOB) stress tests were performed in 460 patients with known or suspected coronary artery disease. Patients were followed up for 38+/-21 months. RESULTS The DIP was negative in 253 and positive in 207 patients. The DOB was negative in 242 and positive in 218 patients. During the follow-up, there were 80 cardiac events. For all cardiac events, the negative and positive predictive value were 83% and 17% for DOB, 84% and 19% for DIP, respectively (p = NS). Considering only cardiac death, by univariate analysis Wall-Motion Score Index (WMSI) at DIP peak dose (chi-square 13.80, p<0.0002) was the strongest predictor, followed by WMSI DOB (chi2 = 8.02, p<0.004) and WMSI at rest (chi2 = 6.85, p<0.008). By stepwise analysis, WMSI at DIP peak dose was the most important predictor (RR [relative risk] 7.4, p<0.0001). CONCLUSIONS In patients at low-to-moderate risk of cardiac events, pharmacological stress echocardiography with either dobutamine or dipyridamole allows effective and grossly comparable, risk stratification on the basis of the presence, severity and extension of the induced ischemia.

The atropine factor in pharmacologic stress echocardiography

Objectives. This study sought to compare, head to head, the two most popular pharmacologic stress echocardiographic tests-dipyridamole and dobutamin-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 μg/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 (≥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.

Safety of Dobutamine-Atropine Stress Echocardiography: A Prospective Experience of 4033 Consecutive Studies ☆ ☆☆

Dobutamine-atropine stress echocardiography (DASE) is an established method and has been shown to be accurate for the detection of coronary artery disease. Still, there are few large clinical studies that analyze the safety of DASE in general or the safety of performing it on an ambulatory basis. Most studies use a target heart rate as the primary end point regardless of whether asymptomatic ischemia occurs. Such studies have shown a serious cardiac event rate of approximately 0.3%. We prospectively studied 4,033 consecutive patients on an ambulatory basis and in the hospital with the use of DASE from July 1991 to December 1998. All tests were performed by an experienced physician, and all clinical and DASE data were stored in a large database organized at the beginning of the study. Dobutamine was infused in scalar doses of 5, 10, 20, 30, and 40 microg/kg per minute in 3-minute stages. Development of a new wall motion abnormality, achievement of 85% of target heart, and end of the DASE infusion protocol were used as an end point. If 85% of the target heart rate was not achieved, atropine was infused up to 1 mg in the absence of myocardial ischemia, which was used in 1,280 studies. There were 3,645 diagnostic tests, and 388 (10%) were found to be nondiagnostic. This result was due to poor image quality in 115 (3%), end of protocol in negative-submaximal examinations in 124 (3%), and limiting side effects in 149 (4%). Thirty-seven percent of the tests showed positive results for myocardial ischemia. Major test-related cardiac complications occurred in 10 (0.25%) patients and included 1 ventricular fibrillation, 1 case of myocardial infarction, and 8 cases of sustained ventricular tachycardia. Atropine poisoning was observed in 5 (0.12%) patients. No deaths occurred as a direct or indirect consequence of DASE. We conclude that dobutamine-atropine stress echocardiography is a reasonably safe method for detection of coronary artery disease in the hospital or in an ambulatory basis. The use of new wall motion abnormality as 1 of the end points may prevent further ischemia-related complications.

Value of Real Time Three-Dimensional Echocardiography in Patients with Hypertrophic Cardiomyopathy: Comparison with Two-Dimensional Echocardiography and Magnetic Resonance Imaging

Real time three‐dimensional echocardiography (RT3DE) has been demonstrated to be an accurate technique to quantify left ventricular (LV) volumes and function in different patient populations. We sought to determine the value of RT3DE for evaluating patients with hypertrophic cardiomyopathy (HCM), in comparison with cardiac magnetic resonance imaging (MRI). Methods: We studied 20 consecutive patients with HCM who underwent two‐dimensional echocardiography (2DE), RT3DE, and MRI. Parameters analyzed by echocardiography and MRI included: wall thickness, LV volumes, ejection fraction (LVEF), mass, geometric index, and dyssynchrony index. Statistical analysis was performed by Lin agreement coefficient, Pearson linear correlation and Bland‐Altman model. Results: There was excellent agreement between 2DE and RT3DE (Rc = 0.92), 2DE and MRI (Rc = 0.85), and RT3DE and MRI (Rc = 0.90) for linear measurements. Agreement indexes for LV end‐diastolic and end‐systolic volumes were Rc = 0.91 and Rc = 0.91 between 2DE and RT3DE, Rc = 0.94 and Rc = 0.95 between RT3DE and MRI, and Rc = 0.89 and Rc = 0.88 between 2DE and MRI, respectively. Satisfactory agreement was observed between 2DE and RT3DE (Rc = 0.75), RT3DE and MRI (Rc = 0.83), and 2DE and MRI (Rc = 0.73) for determining LVEF, with a mild underestimation of LVEF by 2DE, and smaller variability between RT3DE and MRI. Regarding LV mass, excellent agreement was observed between RT3DE and MRI (Rc = 0.96), with bias of−6.3 g (limits of concordance = 42.22 to−54.73 g). Conclusion: In patients with HCM, RT3DE demonstrated superior performance than 2DE for the evaluation of myocardial hypertrophy, LV volumes, LVEF, and LV mass.

Exercise Training and Caloric Restriction Prevent Reduction in Cardiac Ca2+-Handling Protein Profile in Obese Rats

Previous studies show that exercise training and caloric restriction improve cardiac function in obesity. However, the molecular mechanisms underlying this effect on cardiac function remain unknown. Thus, we studied the effect of exercise training and/or caloric restriction on cardiac function and Ca2+ handling protein expression in obese rats. To accomplish this goal, male rats fed with a high-fat and sucrose diet for 25 weeks were randomly assigned into 4 groups: high-fat and sucrose diet, high-fat and sucrose diet and exercise training, caloric restriction, and exercise training and caloric restriction. An additional lean group was studied. The study was conducted for 10 weeks. Cardiac function was evaluated by echocardiography and Ca2+ handling protein expression by Western blotting. Our results showed that visceral fat mass, circulating leptin, epinephrine, and norepinephrine levels were higher in rats on the high-fat and sucrose diet compared with the lean rats. Cardiac nitrate levels, reduced/oxidized glutathione, left ventricular fractional shortening, and protein expression of phosphorylated Ser2808-ryanodine receptor and Thr17-phospholamban were lower in rats on the high-fat and sucrose diet compared with lean rats. Exercise training and/or caloric restriction prevented increases in visceral fat mass, circulating leptin, epinephrine, and norepinephrine levels and prevented reduction in cardiac nitrate levels and reduced:oxidized glutathione ratio. Exercise training and/or caloric restriction prevented reduction in left ventricular fractional shortening and in phosphorylation of the Ser2808-ryanodine receptor and Thr17-phospholamban. These findings show that exercise training and/or caloric restriction prevent cardiac dysfunction in high-fat and sucrose diet rats, which seems to be attributed to decreased circulating neurohormone levels. In addition, this nonpharmacological paradigm prevents a reduction in the Ser2808-ryanodine receptor and Thr17-phospholamban phosphorylation and redox status.

Value of rapid beta-blocker injectionat peak dobutamine-atropine stressechocardiography for detection of coronary artery disease

OBJECTIVES We studied the value of a rapid beta-blocker injection at peak dobutamine-atropine stress echocardiography (DASE) for the detection of coronary artery disease (CAD). BACKGROUND The presence of tachycardia and hyperdynamic wall motion may make it difficult to recognize a new wall motion abnormality (NWMA) at peak stress. METHODS We studied 101 patients (mean age 58.2 +/- 9.8 years) who underwent effective DASE and coronary angiography. All patients received a rapid intravenous injection of metoprolol immediately after peak DASE image acquisition. Positivity in combined peak plus post-metoprolol images was defined when there was only peak NWMA, maintenance of peak NWMA, or NWMA detected only after metoprolol injection. Significant CAD was defined as >or=50% stenosis by quantitative angiography. RESULTS There were 37 patients without and 64 with CAD. The sensitivity, specificity, accuracy, and positive and negative predictive values for the detection of CAD at peak stress were 84%, 92%, 87%, 95%, and 77%, respectively. Five patients with CAD had negative peak images that became positive only after metoprolol. Extension of peak NWMA during metoprolol was observed in 14 patients, and multivessel CAD was detected in 10 of them. The sensitivity, specificity, accuracy, and positive and negative predictive values for peak plus metoprolol images were 92%, 89%, 91%, 94%, and 87%, respectively. CONCLUSIONS The use of metoprolol injected at peak of dobutamine infusion improved the detection of CAD by DASE.

Effects of Exercise Training on Myocardial Blood Flow Reserve in Patients With Heart Failure and Left Ventricular Systolic Dysfunction

Exercise training has been shown to be effective in improving exercise capacity and quality of life in patients with heart failure and left ventricular (LV) systolic dysfunction. Real-time myocardial contrast echocardiography (RTMCE) is a new technique that allows quantitative analysis of myocardial blood flow (MBF). The aim of this study was to determine the effects of exercise training on MBF in patients with LV dysfunction. We studied 23 patients with LV dysfunction who underwent RTMCE and cardiopulmonary exercise testing at baseline and 4 months after medical treatment (control group, n = 10) or medical treatment plus exercise training (trained group, n = 13). Replenishment velocity (beta) and MBF reserves were derived from quantitative RTMCE. The 4-month exercise training consisted of 3 60-minute exercise sessions/week at an intensity corresponding to anaerobic threshold, 10% below the respiratory compensation point. Aerobic exercise training did not change LV diameters, volumes, or ejection fraction. At baseline, no difference was observed in MBF reserve between the control and trained groups (1.89, 1.67 to 1.98, vs 1.81, 1.28 to 2.38, p = 0.38). Four-month exercise training resulted in a significant increase in beta reserve from 1.72 (1.45 to 1.48) to 2.20 (1.69 to 2.77, p <0.001) and an MBF reserve from 1.81 (1.28 to 2.38) to 3.05 (2.07 to 3.93, p <0.001). In the control group, beta reserve decreased from 1.51 (1.10 to 1.85) to 1.46 (1.14 to 2.33, p = 0.03) and MBF reserve from 1.89 (1.67 to 1.98) to 1.55 (1.11 to 2.27, p <0.001). Peak oxygen consumption increased by 13.8% after 4 months of exercise training and decreased by 1.9% in the control group. In conclusion, exercise training resulted in significant improvement of MBF reserve in patients with heart failure and LV dysfunction.

Left ventricular free wall impeding rupture in post-myocardial infarction period diagnosed by myocardial contrast echocardiography: Case report

Background:Left ventricular free wall rupture occurs in up to 10% of the in-hospital deaths following myocardial infarction. It is mainly associated with posterolateral myocardial infarction and its antemortem diagnosis is rarely made. Contrast echocardiography has been increasingly used for the evaluation of myocardial perfusion in patients with acute myocardial infarction, with important prognostic implications. In this case, we reported its use for the detection of a mechanical complication following myocardial infarction.Case presentation:A 50-year-old man with acute myocardial infarction in the lateral wall underwent myocardial contrast echocardiography for the evaluation of myocardial perfusion in the third day post-infarction. A perfusion defect was detected in lateral and inferior walls as well as the presence of contrast extrusion from the left ventricular cavity into the myocardium, forming a serpiginous duct extending from the endocardium to the epicardial region of the lateral wall, without communication with the pericardial space. Magnetic resonance imaging confirmed the diagnosis of impending rupture of the left ventricular free wall. While waiting for cardiac surgery, patient presented with cardiogenic shock and died. Anatomopathological findings were consistent with acute myocardial infarction in the lateral wall and a left ventricular free wall rupture at the infarct site.Conclusion:This case illustrates the early diagnosis of left ventricular free wall rupture by contrast echocardiography. Due to its ability to be performed at bedside this modality of imaging has the potential to identify this catastrophic condition in patients with acute myocardial infarction and help to treat these patients with emergent surgery.