Prognostic Utility of Stress Testing and Cardiac Biomarkers in Menopausal Women at Low to Intermediate Risk for Coronary ARTery Disease (SMART Study): 5-Year Outcome.

BACKGROUND: In women with low to intermediate risk of coronary artery disease (CAD), prognostic detection strategies have been controversial. We present the follow-up data of the SMART trial in peri/postmenopausal women at low to intermediate risk of CAD. OBJECTIVES: To determine the value of contrast stress echocardiography (CSE), stress electrocardiogram (sECG), and serum biomarkers for prediction of cardiovascular events (CE) in peri/postmenopausal women at low to intermediate risk of CAD. MATERIALS AND METHODS: From January 2004 to August 2007, 400 peri/postmenopausal women were prospectively enrolled. All women had detailed risk factor assessment, and underwent simultaneous CSE (Definity®, Lantheus Medical Imaging) and sECG. Laboratories included brain natriuretic peptide (BNP), atrial natriuretic peptide, endothelin, and high sensitivity C-reactive protein. Wall motion score index was based on a 16-segment model. Abnormal CSE was defined as new or worsening wall motion abnormality at stress, while abnormal sECG was ≥1 mm horizontal/downsloping ST segment depression/elevation (80 mseconds duration). Self-reported outcome data were collected from a mailed Women's Heart Clinic Questionnaire. CE outcomes included all-cause mortality, nonfatal myocardial infarction (MI), heart failure, chest pain hospitalization or development of typical angina (CP), and revascularization (REVASC). Adjusted Cox proportional hazard ratios (HR; 95% confidence intervals) were reported. RESULTS: A total of 366 women (54.4 ± 5.5 years, Framingham risk 6.5% ± 4.4%) completed simultaneous CSE and sECG. Forty-two (11.5%) had abnormal CSE, while sECG was abnormal in 22 (6%) women. Follow-up (4.4 ± 1.2 years) was available in 315/366 (86%) women (78% exercise-CSE, 22% dobutamine-CSE). In those who completed follow-up, CSE was abnormal in 33 women (10.5%) and sECG was abnormal in 21 (6.7%). In 33 women with abnormal CSE, sECG was abnormal in 7 (21.2%) and normal in 26 (79%), p = 0.0004. CE occurred in 27 (8.6%) women: 8 all-cause mortality, 2 nonfatal MI, 13 CP, and 4 REVASC. CE occurred in 21% versus 7% of women with abnormal versus normal CSE, p = 0.014 and 38% versus 6% of women with abnormal versus normal sECG, p < 0.0001. Rest BNP was higher in women with CE versus those without (p = 0.018). Abnormal sECG and abnormal CSE were associated with CE, while only abnormal sECG was an independent predictor of CE (adjusted HR 10.3 [1.9-61.4], p = 0.007). Of the laboratory results, only BNP was associated with CE (adjusted HR 2.9 [1.1-7.3], p = 0.028). CONCLUSIONS: sECG and rest BNP were independent predictors of subsequent CE within 5 years in peri/postmenopausal women at low to intermediate risk of CAD.

Effect of stress echocardiography testing on changes in cardiovascular risk behaviors in postmenopausal women: a prospective survey study.

BACKGROUND: We evaluated the impact of contrast stress echocardiography (CSE) testing results on cardiovascular (CV) risk behaviors in postmenopausal women presenting with chest pain symptoms. This was a substudy of the Stress Echocardiography in Menopausal Women at Risk for Coronary Artery Disease (SMART) trial. METHODS: From 2004 to 2007, 366 women (mean age 54.4 ± 5.5 years, range 40-65; body mass index (BMI) 31.4 ± 6.68; Caucasian in 95%) completed CSE and were invited to participate in the Women's Heart Clinic Risk Assessment Questionnaire (WHCRAQ survey) at the time of CSE and after 2 years. Of the 366, 203 (55%) postmenopausal women completed both the baseline and 2-year follow-up surveys (age 61 ± 5 years; Framingham risk score 6 ± 4%, 81% treadmill CSE, 19% dobutamine CSE). WHCRAQ assessed medical history, hormone therapy (HT), and CV risk behaviors (cigarette smoking history, including current smoking and mean cigarettes smoked per day; physical activity or exercise, including mean exercise minutes per week; and dietary fat intake, alcohol intake, and mean alcohol drinks per week). Abnormal CSE was defined as a new or worsening stress wall motion abnormality. Post-CSE changes in CV risk behaviors were determined by comparing baseline versus 2-year data. RESULTS: Of the 203 women who completed the survey at baseline and 2-year CSE, 29 were excluded to avoid confounding effect (coronary angiography [CA] was performed during follow-up). Of 174 women (55% hypertensive, 10% diabetic, 76% hyperlipidemic, and 25% on HT), CSE was abnormal in 10%. Baseline characteristics were not significantly different in normal versus abnormal CSE, apart from diabetes (8% vs. 24%, p=0.04). Slightly more women with normal CSE were taking HT than not (27% vs. 12%, p=0.19). CV risk behaviors that were different in normal versus abnormal CSE included current smoking, alcohol drinks per week, and higher fat diet (8% vs. 24%, p=0.03; 2.5 ± 3.5 vs. 1.94±5.2, p=0.031; and 92% vs. 76%, p=0.03, respectively). Cigarette smoking decreased (mean difference of -1.5 cigarettes per day, p=0.014) in the abnormal-CSE group, whereas number of alcohol drinks per week increased (mean difference +0.38, p=0.009) in the normal-CSE group. CONCLUSION: We observed an association of lifestyle changes with CSE test results in postmenopausal women.

CUTE-CV: a prospective study of enhanced left atrial appendage visualization with microbubble contrast agent use during transesophageal echocardiography guided cardioversion.

OBJECTIVES: The aim of our study was to demonstrate that the use of contrast microbubbles during transesophageal echocardiography (TEE) guided cardioversion will improve interpretation of the TEE images. BACKGROUND: TEE-guided cardioversion of atrial flutter or fibrillation (AF) is a safe and proven method to restore sinus rhythm. However, artifacts and dense spontaneous echo contrast in the left atrial appendage (LAA) can sometimes decrease the level of confidence in excluding the presence of thrombus. METHODS: One hundred patients referred for TEE-guided cardioversion were prospectively enrolled and microbubble contrast agent (DEFINITY) was administered after the clinical decision had been made regarding suitability for cardioversion. Noncontrast and contrast images were compared during subsequent offline analysis. RESULTS: LAA dimensions and contractility indices were higher, artifacts were significantly differentiated, previously unsuspected LAA filling defects were identified, and the level of confidence in excluding thrombus was enhanced in the contrast images when compared to the noncontrast images. After 4 months follow-up, 1 stroke-associated death occurred in a patient who had LAA thrombus recognized only by contrast. Left atrial appendage visualization is enhanced with microbubble contrast agent use during transesophageal echocardiography guided cardioversion and is useful in identification of intracardiac thrombus.

A multicenter, prospective study to evaluate the use of contrast stress echocardiography in early menopausal women at risk for coronary artery disease: trial design and baseline findings.

AIMS: This multisite prospective trial, Stress Echocardiography in Menopausal Women At Risk for Coronary Artery Disease (SMART), aimed to evaluate the prognostic value of contrast stress echocardiography (CSE), coronary artery calcification (CAC), and cardiac biomarkers for prediction of cardiovascular events after 2 and 5 years in early menopausal women experiencing chest pain symptoms or risk factors. This report describes the study design, population, and initial test results at study entry. METHODS: From January 2004 through September 2007, 366 early menopausal women (age 54±5 years, Framingham risk score 6.51%±4.4 %, range 1%-27%) referred for stress echocardiography were prospectively enrolled. Image quality was enhanced with an ultrasound contrast agent. Tests for cardiac biomarkers [high-sensitivity C-reactive protein (hsCRP), atrial natriuretic protein (ANP), brain natriuretic protein (BNP), endothelin (ET-1)] and cardiac computed tomography (CT) for CAC were performed. RESULTS: CSE (76% exercise, 24% dobutamine) was abnormal in 42 women (11.5%), and stress electrocardiogram (ECG) was positive in 22 women (6%). Rest BNP correlated weakly with stress wall motion score index (WMSI) (r=0.189, p<0.001). Neither hsCRP, ANP, endothelin, nor CAC correlated with stress WMSI. Predictors of abnormal CSE were body mass index (BMI), diabetes mellitus, family history of premature coronary artery disease (CAD), and positive stress ECG. Twenty-four women underwent clinically indicated coronary angiography (CA); 5 had obstructive (≥50%), 15 had nonobstructive (10%-49%), and 4 had no epicardial CAD. CONCLUSIONS: The SMART trial is designed to assess the prognostic value of CSE in early menopausal women. Independent predictors of positive CSE were BMI, diabetes mellitus, family history of premature CAD, and positive stress ECG. CAC scores and biomarkers (with the exception of rest BNP) were not correlated with CSE results. We await the follow-up data.

Rapid detection of coronary artery stenoses with real-time perfusion echocardiography during regadenoson stress.

BACKGROUND: Real-time myocardial contrast echocardiography permits the detection of myocardial perfusion abnormalities during stress echocardiography, which may improve the accuracy of the test in detecting coronary artery stenoses. We hypothesized that this technique could be used after a bolus injection of the selective A2A receptor agonist regadenoson to rapidly and safely detect coronary artery stenoses. METHODS AND RESULTS: In 100 patients referred for quantitative coronary angiography, real-time myocardial contrast echocardiography was performed during a continuous intravenous infusion of 3% Definity at baseline and at 2-minute intervals for up to 6 minutes after a regadenoson bolus injection (400 µg). Myocardial perfusion was assessed by examination of myocardial contrast replenishment after brief high mechanical index impulses. A perfusion defect was defined as a delay (>2 seconds) in myocardial contrast replenishment in 2 contiguous segments. Wall motion was also analyzed. The overall sensitivity/specificity/accuracy for myocardial perfusion analysis in detecting a >50% diameter stenosis was 80%/74%/78%, whereas for wall motion analysis it was 60%/72%/66% (P<0.001 for differences in sensitivity). Sensitivity for myocardial perfusion analysis was highest on images obtained during the first 2 minutes after regadenoson bolus (P<0.001 compared with wall motion), whereas wall motion sensitivity was highest at the 4-to-6-minute period after the bolus. No significant side effects occurred after regadenoson bolus injection. CONCLUSIONS: Regadenoson real-time myocardial contrast echocardiography appears to be a feasible, safe, and rapid noninvasive method for the detection of significant coronary artery stenoses.