Lauro Cortigiani

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.

Stress echo results predict mortality: a large-scale multicenter prospective international study

OBJECTIVES The purpose of this study was to assess the long-term value of pharmacologic stress echocardiography with either dipyridamole or dobutamine (DET) for prediction of cardiac death in patients with proven or suspected coronary artery disease (CAD). BACKGROUND Stress echocardiography is an established, cost-effective technique for the detection of CAD. METHODS From the Echo Persantine International Cooperative-Echo Dobutamine International Cooperative data bank, 7,333 patients (5,452 males; 59 +/- 10 years) underwent pharmacologic stress echocardiography with either high-dose dipyridamole (0.84 mg/kg over 10 min) (n = 4,984) or high-dose dobutamine (up to 40 microg/kg/3 min) (n = 2,349) for diagnostic purposes. Patients were followed up for a mean of 2.6 years (range 1 to 206 months). RESULTS The DET was positive for myocardial ischemia in 2,854 (35%) patients and negative in 4,479 (61%) patients. During the follow-up there were 161 cardiac deaths (sudden death and fatal myocardial infarction) (2.1% of the total population). Kaplan-Meier survival estimates showed a significantly better outcome for those patients with a negative pharmacologic stress echocardiography test compared with those with a positive test (92 vs. 71.2%, p = 0.0000). CONCLUSIONS Pharmacologic stress echocardiography with either dipyridamole or dobutamine is effective in predicting cardiac death during a long-term follow-up. A negative stress echocardiography test result is related to a favorable outcome.

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.

Additive Prognostic Value of Coronary Flow Reserve in Patients With Chest Pain Syndrome and Normal or Near-Normal Coronary Arteries

In patients with angiographically normal coronary arteries and chest pain, pharmacologic stress echocardiography can identify a subgroup of patients with a less benign prognosis. Coronary flow reserve (CFR) in the left anterior descending artery (LAD) can currently be combined with wall motion analysis during vasodilator stress echocardiography. The aim of this study was to assess the prognostic value of CFR response in patients with normal coronary arteries and normal wall motion during stress. We selected 394 patients (171 men, 61 +/- 11 years of age) who underwent dipyridamole stress echocardiography (0.84 mg/kg over 6 minutes) with 2-dimensional echocardiography and CFR evaluation of the LAD by Doppler. All had angiographically nonsignificant (<50% quantitatively assessed) stenosis in any major vessel, normal left ventricular function (wall motion score index 1), and test negativity for conventional wall motion criteria. Images were independently read by a core laboratory for wall motion and a core laboratory for CFR. Mean CFR was 2.5 +/- 0.6 and 87 patients (22%) had an abnormal CFR <2. During a median follow-up of 51 months, 31 events occurred, namely 4 deaths and 27 nonfatal myocardial infarctions (3 ST-elevated myocardial infarctions and 24 non-ST-elevated myocardial infarctions). Kaplan-Meier survival estimates for hard events showed a better outcome for those patients with a normal CFR compared with those with an abnormal CFR (96% vs 55%, p = 0.001, at 48 months of follow-up). In conclusion, in patients with angiographically normal or near-normal coronary arteries and preserved at-rest regional and global left ventricular function at baseline and during stress, CFR adds incremental value to the prognostic stratification achieved with clinical and angiographic data.

Prognostic value of pharmacological stress echocardiography in women with chest pain and unknown coronary artery disease.

OBJECTIVES In this study we sought to investigate the prognostic value of pharmacological stress echocardiography in women referred for chest pain, having unknown coronary artery disease. BACKGROUND The noninvasive identification of a high-risk subgroup among women with chest pain and unknown coronary artery disease is an unresolved task to date. METHODS A total of 456 women (mean [+/-SD] age 63+/-10 years) underwent pharmacological stress echocardiography with either dipyridamole (n = 305) or dobutamine (n = 151) for evaluation of chest pain and were followed-up for 32+/-19 months. None of them had a previous diagnosis of coronary artery disease. RESULTS No major complication occurred during stress testing. Five tests (1.1%) were prematurely interrupted because of the appearance of side effects. Echocardiographic positivity was identified in 51 patients. During the follow-up, 23 cardiac events occurred: 3 deaths, 10 infarctions and 10 cases of unstable angina; an additional 21 patients underwent coronary revascularization. At Cox analysis, the echocardiographic evidence of ischemia was found as the only independent predictor of hard cardiac events (death, infarction) (odds ratio [OR] = 27.5; 95% confidence interval [CI] = (6.5 to 115.5; p = 0.0000). When spontaneous cardiac events (death, infarction and unstable angina) were considered as endpoints, the positive echocardiographic result (OR = 23.9; 95% CI = 8.6 to 66.8; p = 0.0000) and family history of coronary artery disease (OR = 3.7; 95% CI = 1.5 to 9.1; p = 0.0037) were independently correlated with prognosis. By using an interactive stepwise procedure, the prognostic value of stress echocardiography was found to be incremental to that provided by clinical variables, both considering hard and spontaneous cardiac events as endpoints. The 3-year survival rate for the negative and the positive population was respectively, 99.5% and 69.5% (p = 0.0000) considering hard cardiac events, 99.2% and 50.6% (p = 0.0000) considering spontaneous cardiac events. CONCLUSIONS Pharmacological stress echocardiography is safe, highly feasible and effective in risk stratification of women with chest pain and unknown coronary artery disease, also when hard endpoints are considered. Its use can have relevant implications in daily clinical practice for selection of patients needing further investigations.

Prognostic value of left atrial enlargement in patients with idiopathic dilated cardiomyopathy and ischemic cardiomyopathy

Previous studies have shown that abnormal mitral flow patterns and left atrial (LA) enlargement are independently associated with survival in patients with left ventricular (LV) dysfunction. However, it is not known whether these outcome indicators can provide different information in patients of various age groups. This study was designed to assess the prognostic value of the restrictive mitral flow pattern (RMFP) and increased LA size in patients with LV dysfunction (ejection fraction <45%) grouped into those < or = 70 years old (n = 102; mean age 61) and those >70 years old (n = 105; mean age 78). Echocardiographic and Doppler indexes were recorded in patients with LV systolic dysfunction due to dilated cardiomyopathy who were followed up for 22 plus minus 14 months. In patients >70 years, indexed LA size (>26 mm/m(2)) was the single best predictor of death (hazard ratio [HR] 3.0, p = 0.018) and emerged as the most important outcome variable of the combined end point (HR 2.2, p = 0.016) on multivariate analysis. In patients < or =70 years, RMFP, characterized by an early wave deceleration time <140 ms, was independently associated with cardiac death or heart failure hospitalization (HR 5.7, p = 0.0013). When demographics, clinical, echocardiographic, and Doppler measurements were analyzed in hierarchical order, indexed LA size yielded the most valuable contribution in predicting the combined end point in older patients (global chi-square from 11.5 to 18.7). RMFP was associated with the higher additional prognostic value in younger patients (global chi-square from 14.4 to 24.1). These data suggest that LA enlargement has an independent and additional prognostic value in elderly patients with LV dysfunction.

Prognostic Significance of the Dobutamine Echocardiography Test in Idiopathic Dilated Cardiomyopathy

Dobutamine stress echo provides potentially useful information on idiopathic dilated cardiomyopathy (IDC). From February 1, 1997, to October 1, 1999, 186 patients (131 men and 55 women, mean age 56 +/- 12 years) with IDC, ejection fraction <35%, and angiographically normal coronary arteries were studied by high-dose (up to 40 micro/kg/min) dobutamine echo in 6 centers, all quality controlled for stress echo reading. In all patients, wall motion score index (WMSI) (from 1 = normal to 4 = dyskinetic in a 16- segment model of the left ventricle) was evaluated by echo at baseline and peak dobutamine. One hundred eighty-four patients were followed up (mean 15 +/- 13 months) and only cardiac death was considered as an end point. There were 29 cardiac deaths. Significant parameters for survival prediction at univariate analysis are: DeltaWMSI (chi-square 20.1; p <0.0000), New York Heart Association (NYHA) class (chi-square 17.57; p <0.0000), rest ejection fraction (chi-square 10.41; p = 0.0013), angiotensin-converting enzyme inhibitors (chi-square 8.23; p = 0.0041), and hypertension (chi-square 8.08, p = 0.0045). In the multivariate stepwise analysis only DeltaWMSI and NYHA were independent predictors of outcome (DeltaWMSI = hazard ratio 0.02, p < 0.0000; NYHA class = hazard ratio 3.83, p < 0.0000). Kaplan-Meier survival estimates showed a better outcome for patients with a large inotropic response (DeltaWMSI > or =0.44, a cutoff identified by receiver-operating characteristic curves analysis) than for those with a small or no myocardial inotropic response to dobutamine (93.6% vs 69.4%, p = 0.00033). Thus, in patients with IDC, an extensive contractile reserve identified by high-dose dobutamine stress echocardiography is associated with a better survival.

Coronary flow reserve during dipyridamole stress echocardiography predicts mortality.

OBJECTIVES The goal of this study was to evaluate the ability of coronary flow reserve (CFR) over regional wall motion to predict mortality in patients with known or suspected coronary artery disease (CAD). BACKGROUND CFR evaluated using pulsed Doppler echocardiography testing on left anterior descending artery is the state-of-the-art method during vasodilatory stress echocardiography. METHODS In a prospective, multicenter, observational study, we evaluated 4,313 patients (2,532 men; mean age 65 ± 11 years) with known (n = 1,547) or suspected (n = 2,766) CAD who underwent high-dose dipyridamole (0.84 mg/kg over 6 min) stress echocardiography with CFR evaluation of left coronary descending artery (LAD) by Doppler. Overall mortality was the only endpoint analyzed. RESULTS Stress echocardiography was positive for ischemia in 765 (18%) patients. Mean CFR was 2.35 ± 0.68. At individual patient analysis, 1,419 (33%) individuals had CFR ≤2. During a median follow-up of 19 months (1st quartile 8; 3rd quartile 36), 146 patients died. The 4-year mortality was markedly higher in subjects with CFR ≤2 than in those with CFR >2, both considering the group with ischemia (39% vs. 7%; p < 0.0001) and the group without ischemia at stress echocardiography (12% vs. 3%; p < 0.0001). At multivariable analysis, CFR on LAD ≤2 (hazard ratio [HR]: 3.31; 95% confidence interval [CI]: 2.29 to 4.78; p < 0.0001), ischemia at stress echocardiography (HR: 2.40, 95% CI: 1.65 to 3.48, p < 0.0001), left bundle branch block (HR: 2.26, 95% CI: 1.50 to 3.41; p < 0.0001), age (HR: 1.08, 95% CI: 1.06-1.10; p < 0.0001), resting wall motion score index (HR: 3.52, 95% CI: 2.38 to 5.21; p < 0.0001), male sex (HR: 1.74, 95% CI: 1.12 to 2.52; p = 0.003), and diabetes mellitus (HR: 1.47, 95% CI: 1.03 to 2.08; p = 0.03) were independent predictors of mortality. CONCLUSIONS CFR on LAD is a strong and independent indicator of mortality, conferring additional prognostic value over wall motion analysis in patients with known or suspected CAD. A negative result on stress echocardiography with a normal CFR confers an annual risk of death <1% in both patient groups.

Value of pharmacologic stress echocardiography in risk stratification of patients with single-vessel disease: a report from the echo-persantine and echo-dobutamine international cooperative studies

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.