The effects of 3-month atorvastatin therapy on arterial inflammation, calcification, abdominal adipose tissue and circulating biomarkers.

PURPOSE: (18)F-Fluorodeoxyglucose (FDG) positron emission tomography (PET)/CT has the potential to track vascular inflammation and monitor therapeutic response. The purpose of this study was to determine the association between arterial inflammation, calcification and serological biomarkers in subjects with atherosclerosis, and to assess their therapeutic response to 12-week atorvastatin treatment. METHODS: Forty-three statin-naïve subjects with atherosclerosis received atorvastatin (40 mg/day) for 12 weeks and underwent (18)F-FDG PET/CT, coronary calcification and abdominal adipose tissue volume measurements. A panel of serological biomarkers was analysed. Arterial inflammation was measured at seven arterial segments and normalized to venous FDG activity to produce target to background ratios (TBR). Thirty-four subjects without cardiovascular disease who repeated PET 1-4 years apart for routine health check-ups were retrospectively evaluated for comparison. RESULTS: The baseline mean TBR values in atherosclerotic patients were positively correlated with age (R = 0.36), body mass index (R = 0.54), abdominal visceral adipose tissue volume (R = 0.65), coronary calcification score (R = 0.40), levels of low-density lipoprotein cholesterol (R = 0.54), matrix metalloproteinase (MMP)-9 (R = 0.46) and fatty acid binding protein 4 (FABP4) (R = 0.67, all p < 0.05). The TBR as well as high-sensitivity C-reactive protein (hsCRP), E-selectin, MMP-9, monocyte chemotactic protein 1, FABP4 and follistatin values were reduced significantly after the 12-week atorvastatin treatment. The TBR reduction marginally correlated with changes in MMP-9 levels (R = 0.56, p = 0.05). The control group, whose median age was younger, by comparison had lower hsCRP and arterial TBR than the subjects with atherosclerosis (all p < 0.05), and moreover had a slight but insignificant increase in mean TBR at their 2.5±0.8 year follow-up. CONCLUSION: The medium dose of atorvastatin over a 12-week period resulted in a significant reduction of arterial inflammation as well as various circulating biomarkers.

Association of circulating matrix metalloproteinase-1, but not adiponectin, with advanced coronary artery disease.

OBJECTIVE: Recent evidence suggests that high tissue matrix metalloproteinase-1 (MMP-1) and low adiponectin may serve as biomarkers of atherosclerosis. Results on the associations of circulating MMP-1 and adiponectin concentrations are scarce. We hypothesized that patients with multivessel coronary artery disease (CAD) have elevated high-sensitivity C-reactive protein (hs-CRP), MMP-1 but low adiponectin levels, and concomitant measurements of these biomarkers could improve predictive strength for advanced CAD. RESEARCH DESIGN AND METHODS: We analyzed concentrations of MMP-1, hs-CRP and adiponectin in 217 subjects with angiographically documented multivessel CAD (two-, or three-vessel disease by luminal stenosis >or=50%) and 81 controls. MMP-1 and hs-CRP were notably higher in patients with CAD; while adiponectin was not significantly different between two groups. Levels of hs-CRP positively correlated with body mass index and left ventricular dysfunction (R(2)=0.16, P<0.0001); while adiponectin was significantly associated with age, gender, and levels of cholesterol and triglyceride (R(2)=0.09, P<0.0001). On the contrary, MMP-1 was not associated with any clinical cardiovascular risk factors, and still an independent predictor (OR=1.49, P<0.0001) of multivessel CAD after the adjustment of clinical risk factors and hs-CRP. CONCLUSION: Elevated MMP-1 and hs-CRP, but not low adiponectin concentrations, could predict the presence of advanced coronary atherosclerosis. In addition, MMP-1 may serve as a more specific marker for significant CAD independent of hs-CRP.

High serum level of matrix metalloproteinase-1 and its rapid surge after intervention in patients with significant carotid atherosclerosis.

High tissue matrix metalloproteinase (MMP) activity has been reported to be associated with atherosclerosis and plaque rupture. The aim of this study was to elucidate the diagnostic value of serum MMP-1 in carotid stenosis and its dynamic change after stenting. We measured high-sensitivity C-reactive protein (hs-CRP) and MMP-1 in 37 patients with carotid stenosis (>or= 50%) and 84 controls. In 30 patients who underwent stenting, MMP-1 and hs-CRP were assessed immediately after stenting. We found that patients with carotid stenosis exhibited significantly higher MMP-1 compared with controls, but there was no difference in hs-CRP. Moreover, MMP-1 was elevated immediately after stenting. In multivariate analyses, MMP-1 was negatively correlated with statin and angiotensin converting enzyme inhibitor/angiotensin-II receptor blocker use in controls. In conclusion, higher levels and rapid surge after stenting in patients with carotid stenosis indicate that MMP-1 is an important composition of plaques, and suggest its potential role in the assessment of plaque burden and stability of carotid stenosis.

Enhanced diagnosis of coronary artery disease in women by dobutamine thallium-201 ST-segment/heart rate slope and thallium-201 myocardial SPECT.

BACKGROUND/PURPOSE: The diagnosis of coronary artery disease (CAD) in women presents a great challenge because of poor exercise capacity and inadequate heart rate response during stress test. The clinical significance of stress-related ST-segment/heart rate slope (ST/HR slope) value for evaluating CAD in women remains controversial. Therefore, we conducted the present study to assess the diagnostic performance of dobutamine ST/HR slope in women, compared with myocardial perfusion study using thallium-201 single-photon emission computed tomography (Tl-201 SPECT). METHODS: A total of 51 female patients with suspected CAD underwent simultaneous 12-lead electrocardiographic recording during 3-minute stages of dobutamine infusion as well as Tl-201 SPECT, and coronary angiography was performed within 2 weeks post Tl-201 SPECT. The sensitivity, specificity, positive predictive value and negative predictive value of dobutamine ST/HR slope and Tl-201 SPECT were assessed, and the results of coronary angiography were used as a gold standard. RESULTS: The sensitivity, specificity and accuracy of dobutamine ST/HR slope in detecting CAD were 43%, 83% and 61%, and those of Tl-201 SPECT were 71%, 87% and 78%, respectively. However, using both positive results of Tl-201 SPECT and ST/HR slope for detecting CAD, the diagnostic specificity increased from 87% to 96%. Using both negative results of Tl-201 SPECT and ST/HR slope to exclude CAD, the negative predictive value increased from 71% to 85%. The accuracy of dobutamine ST/HR slope in detecting CAD was not affected by the use of beta-blockers. CONCLUSION: Dobutamine ST/HR slope is less sensitive and less accurate than Tl-201 SPECT for detecting CAD in women. However, it adds diagnostic benefit to Tl-201 SPECT with only a little extra calculation.

Characterization of plaques using 18F-FDG PET/CT in patients with carotid atherosclerosis and correlation with matrix metalloproteinase-1.

UNLABELLED: High tissue matrix metalloproteinase (MMP) activity has been associated with advanced atherosclerosis and plaque rupture. 18F-FDG uptake has been reported to detect inflammation. This investigation examined the vascular 18F-FDG uptake by PET/CT and its correlation with circulating MMP-1 levels. METHODS: We examined 25 consecutive patients with significant carotid stenosis and 22 healthy control subjects using 18F-FDG PET/CT. The leukocyte counts, C-reactive protein (CRP), and MMP-1 were measured. RESULTS: 18F-FDG arterial uptake, as well as calcifications, was significantly higher in extensive distributions in patients with established carotid stenosis. However, their distribution was not consistently overlapping. The values of circulating MMP-1 and leukocyte counts were significantly higher in patients with carotid stenosis (all P < 0.05). In addition, subjects with higher 18F-FDG uptake (maximum SUV > 2.0) in target lesions had higher baseline and poststenting MMP-1 levels (all P < 0.05). CONCLUSION: We provide a link between 18F-FDG uptake and circulating MMP-1. 18F-FDG PET/CT could be used as an adjunct to the clinical management of high-risk atherosclerosis and an in vivo tool to study plaque biology.

Extensive scar myocardium in hypertrophic cardiomyopathy with severe myocardial bridge.

We present a patient with hypertrophic cardiomyopathy and a large scar in the apex demonstrated on 201Tl SPECT and 18F-FDG PET images. Subsequent coronary angiography revealed no significant coronary artery stenosis but a myocardial bridge with severe systolic milking in the middle segment of the left anterior descending artery.

99mTc-HL91 is inferior to 201Tl in scintigraphic detection of chronic myocardial ischaemia.

AIM: 99mTc-HL91 is a new hypoxia agent and can identify acutely ischaemic viable myocardium in a canine model using a standard gamma camera. The purpose of the study was to determine whether this tracer could be used to detect regional ischaemia in chronic ischaemic myocardium in a swine model. METHOD: Using a porcine model of chronic myocardial ischaemia, five mini-pigs with proximal left anterior descending artery (LAD) stenoses were studied. Injection of 462.5 MBq (12.5 mCi) 99mTc-HL91 was followed by imaging over 2 h. Coronary angiography and dipyridamole stress-re-injection 201Tl single photon emission computed tomography (SPECT) were performed within 1 day of each other. RESULTS: None of the five pigs demonstrated positive hot 99mTc-HL91 uptake throughout the 2 h imaging, whereas four of the five animals showed significant myocardial ischaemia on 201Tl SPECT. The region of interest analysis of LAD/left circumflex artery count ratios at 1 and 2 h demonstrated similar 99mTc-HL91 uptake and retention in chronic ischaemic as well as non-ischaemic myocardium. CONCLUSION: 99mTc-HL91 is inferior to 201Tl in scintigraphic detection of chronic myocardial ischaemia.

Assessment of myocardial viability using F-18 fluorodeoxyglucose/Tc-99m sestamibi dual-isotope simultaneous acquisition SPECT: comparison with Tl-201 stress-reinjection SPECT.

BACKGROUND: This study compared technetium 99m sestamibi/fluorine 18 fluorodeoxyglucose dual-isotope simultaneous acquisition (DISA) with stress-reinjection thallium 201 single photon emission computed tomography (SPECT) with regard to their ability to detect myocardial viability. METHODS AND RESULTS: The study cohort consisted of 42 angiographically significant coronary artery disease patients with symptomatic congestive heart failure or regional wall motion abnormalities. In total, 398 dysfunctional segments in 40 patients were analyzed (2 patients were excluded because of poor-quality F-18 fluorodeoxyglucose images). Of the segments, 217 were diagnosed as viable and 144 as nonviable by both DISA and Tl-201, 33 were viable by DISA but nonviable by Tl-201, and 4 were viable by Tl-201 but nonviable by DISA. Most discrepancies were in the inferior wall. Of the 40 patients, 16 underwent revascularization. From the follow-up results for the 105 dysfunctional segments in these 16 patients, DISA viability appears to be a significant predicting factor (P = .014) for functional recovery after revascularization statistically whereas Tl-201 viability does not (P = .09). CONCLUSION: Our study suggests that DISA viability provides more accurate prediction of postrevascularization functional recovery than Tl-201 viability. Given the small number of patients who underwent revascularization, the superiority of DISA over Tl-201 in detecting myocardial viability may be firmly established by further study on a large scale for patients with profound left ventricular dysfunction.

Usefulness of progressive inhomogeneity of myocardial perfusion and chronotropic incompetence in detecting cardiac allograft vasculopathy: evaluation with dobutamine thallium-201 myocardial SPECT.

BACKGROUND: The aim of the study was to investigate the value of longitudinal follow-up of dobutamine thallium-201 single photon emission tomography ((201)Tl SPECT) in the development of significant cardiac allograft vasculopathy (CAV) after orthotopic heart transplantation. METHODS: We studied 38 cardiac recipients (mean age 57 +/- 12 years) who underwent at least two follow-up dobutamine (201)Tl SPECT since January 1998. All patients had normal coronary angiography and normal left ventricular function initially. RESULTS: After 2.3 +/- 1.8 years, 12 patients developed significant CAV and there were 4 cardiac deaths (1 died suddenly). Of the 99 scans retrospectively analyzed, patients with significant CAV had elevated values of inhomogeneity score, lung/heart ratio (LHR) at stress and lower left ventricular ejection fraction (all p < 0.05). The higher values of inhomogeneity were significantly correlated with higher stress LHR (r = 0.301, p = 0.021), and lower ejection fraction (r = -0.379, p < 0.001). Progressive inhomogeneity was noted in all heart recipients, and more rapid, although statistically insignificant, in patients who developed significant CAV. Ten patients had inadequate chronotropic response to dobutamine infusion up to 40 mug/kg/min in the follow-up studies. The late onset of chronotropic incompetence was an independent predictor of CAV development (p = 0.03). CONCLUSIONS: Progressive inhomogeneity of myocardial perfusion, higher lung uptake at stress and chronotropic incompetence assessed by dobutamine (201)Tl myocardial SPECT provide incremental diagnostic value in detecting significant CAV.

Diagnostic and prognostic value of dobutamine thallium-201 single-photon emission computed tomography after heart transplantation.

BACKGROUND: Cardiac allograft vasculopathy (CAV) is a major cause of mortality in heart transplant recipients. We investigated the diagnostic and prognostic value of dobutamine thallium-201 ((201)Tl) single-photon emission computed tomography (SPECT) in heart transplant recipients. METHODS: We studied 47 patients (age 51.6 +/- 11.7 years, 37 men), at a mean of 34.0 +/- 21.4 months after heart transplant, who received dobutamine (201)Tl SPECT, echocardiography and coronary angiography within 1 month of each other. SPECT was considered abnormal in the presence of reversible or fixed defects in >/=2 segments. Significant CAV was defined as >/=50% luminal stenosis. RESULTS: Coronary angiograms were normal in 37 patients. Non-significant CAV was detected in 1 patient and significant CAV in 9 patients. The sensitivity, specificity, positive predictive value and negative predictive value of SPECT for the detection of significant angiographic CAV were 89%, 71%, 42% and 96%, respectively. Large reversible perfusion defects (>/=6 segments) always indicated significant CAV. In patients with normal left ventricular function, a lung/heart ratio (LHR) of >/=0.37 during stress was also an independent predictor of significant CAV (odds ratio 15.5, p = 0.04). A higher stress LHR was associated with greater vessel involvement (r = 0.516, p = 0.0002). Patients with impaired left ventricular function also had higher stress and resting LHR. Over 40.3 +/- 21.9 months after the first SPECT, 1 patient developed significant angiographic CAV and another 4 had cardiac death. Large reversible perfusion defect was a significant predictor of cardiac death (p = 0.002). CONCLUSIONS: Dobutamine (201)Tl SPECT is a useful method for detecting patients with significant CAV and assessing prognosis. It is reasonable and safe to design individualized surveillance intensity of coronary angiography for post-transplant patients on the basis of non-invasive monitoring of dobutamine (201)Tl testing.

The relation between myocardial cyclic variation of integrated backscatter and serum concentrations of procollagen propeptides in hypertensive patients.

Cyclic variation of integrated backscatter (IBS), or CVIBS, provides a noninvasive method to measure myocardial collagen deposition and ischemia in hypertensive patients. We hypothesized that serum procollagen propeptides can offer additional values to CVIBS for evaluating cardiac changes related to fibrosis or ischemia. A total of 21 patients were enrolled in this study and were divided into three groups according to the presence of hypertension and serum carboxyterminal propeptide of type I procollagen (PICP) concentration; these were: 7 hypertensive patients with PICP > or = 127 microg/L (group 1), 7 hypertensive patients with PICP < 127 microg/L (group 2), 7 normotensive subjects with PICP < 127 microg/L (group 3). In addition to PICP, serum aminoterminal propeptide of type III procollagen (PIIINP), stress 201thalium scintigraphy and CVIBS were examined. Phase-compensated amplitudes of CVIBS at mid posterior and mid anteroseptal segments were significantly lower in group 1 (p < 0.05). Patients with fixed 201thallium perfusion defects had lower phase-compensated amplitudes of CVIBS at mid anteroseptal segment and higher PIIINP concentrations (p < 0.05). In conclusions, decrease of myocardial phase-compensated amplitude accompanied with increase of serum PICP concentration may be indicative of the underlying fibrotic process of hypertensive myocardium. Decrease of this CVIBS parameter with increase of serum PIIINP implies concomitant myocardial ischemia.

Value of circulating adhesion molecules in assessing cardiac allograft vasculopathy.

Circulating adhesion molecules have been implicated in the development of spontaneous and transplant coronary artery disease. We analyzed soluble (s) intercellular adhesion molecule 1 (sICAM-1), vascular cell adhesion molecule 1 (sVCAM-1), and sE-selectin levels from the coronary sinuses of 25 cardiac allograft recipients, and we correlated these molecules with the degree of acute rejection detected in endomyocardial biopsy specimens and the presence of transplant vasculopathy assessed with coronary angiography. We found that sVCAM-1 significantly increased in patients with transplant vasculopathy compared with those without transplant vasculopathy, whereas sE-selectin and sICAM-1 did not. Therefore, increased coronary sinus levels of sVCAM-1 is a reliable marker in assessing cardiac transplant vasculopathy.

The correlation between expression of apoptosis-related proteins and myocardial functional reserve evaluated by dobutamine stress echocardiography in patients with dilated cardiomyopathy.

The relation between myocardial functional changes and the apoptosis-related proteins in patients with dilated cardiomyopathy (DCM) has not yet been reported. The purpose of this study was to assess this issue through the use of dobutamine stress echocardiography. A total of 81 segments of left ventricles (from 6 patients with DCM) were collected in this study. Segments from another 5 patients who had died of noncardiac causes were used as the control. Apoptosis-related proteins (bax, bcl-2, and p53) and apoptosis were evaluated in these segments by immunocytochemical stain and terminal deoxynucleotidyl transferase-mediated DNA nick end-labeling assay. There were 26 segments with dobutamine-induced contractile reserve. There were significant differences in numbers of segments with overexpression of bcl-2 and bax in the study and control groups. However, p53 was not found in either group. The total terminal deoxynucleotidyl transferase-mediated DNA nick end-labeling-positive nuclei in explanted hearts of DCM was 0.73%. The myocardial contractile reserve was inversely associated with an overexpression of bcl-2 (P <.01) rather than bax. In conclusion, the expression of bax and bcl-2 proteins in patients with DCM is enhanced and independent of p53. Loss of contractile reserve is associated with overexpression of bcl-2 protein in failing myocardium.

Tl-201 myocardial SPECT in differentiation of ischemic from nonischemic dilated cardiomyopathy in patients with left ventricular dysfunction.

BACKGROUND: The differentiation between ischemic and nonischemic cardiomyopathy by noninvasive modalities is of clinical importance. Whether thallium 201 single photon emission computed tomography (SPECT) could accurately distinguish the two groups remains unclear. METHODS AND RESULTS: Twenty-nine patients with chronic heart failure (left ventricular ejection fraction < or =40%), including fourteen patients with ischemic cardiomyopathy and fifteen patients with nonischemic dilated cardiomyopathy, underwent Tl-201 SPECT. The stress protocols included treadmill exercise in 8 patients, dipyridamole in 6 patients, and dobutamine infusion in 15 patients. Myocardial SPECT was interpreted with the use of a 17-segment model and 0- to 4-point scale system. Patients with ischemic cardiomyopathy had higher summed stress defect scores (27.9 +/- 9.4 vs 20.6 +/- 8.9, P =.04), more fixed defect segments (5.9 +/- 2.9 vs 3.8 +/- 2.9, P =.05), and more moderate or severe perfusion defect segments on stress scan (7.2 +/- 2.0 vs 4.5 +/- 2.6, P =.004) than did those with nonischemic dilated cardiomyopathy. However, considerable overlap of the scan patterns between the two groups existed. Moderate or severe perfusion defects on stress scan in at least 7 segments were noted in 71% of patients (10/14) with ischemic cardiomyopathy, as compared with 20% of patients (3/15) with nonischemic cardiomyopathy (P =.016). CONCLUSIONS: Assessment of Tl-201 myocardial SPECT yields only modest value to distinguish nonischemic dilated cardiomyopathy from ischemic cardiomyopathy in patients with chronic heart failure. This technique cannot clearly differentiate individual patients.

Assessment of zebrafish cardiac performance using Doppler echocardiography and power angiography.

The zebrafish (Danio rerio) has become a new animal model for cardiac researches. Although it is equipped with a prototypical vertebrate heart, the zebrafish studies for cardiac mutations and genetic control of development can reveal some hints for solving human problems. Despite the simplicity of the zebrafish heart, the objective parameters of cardiac performance are not easily available, except for the morphological description, due to its small size. Because the four components (sinus venosus, atrium, ventricle and bulbus arteriosus) of the zebrafish heart are connected in series, we studied it by applying ultrasonic imaging methods for the vascular system. A total of 20 fishes that were ages of 3 to 4 months were studied. Their mean body weight and height were 562 +/- 173 mg and 4.6 +/- 0.7 cm, respectively. Power angiography and routine Doppler echocardiography were used to evaluate the cardiac performance of zebrafish at 25 degrees C and 15 degrees C. The zebrafish hearts could be easily identified with color Doppler (8.5 MHz) or power angiography (7 MHz). The ventricular filling flow contained two components (E and A-flow). The E-flow velocities were lower than the A-flow velocities at both 25 and 15 degrees C. The cycle length was prolonged (p < 0.05) and the velocities of ventricular filling and bulbus arteriosus decreased significantly at 15 degrees C (p < 0.05). A significant decrease in early diastolic deceleration slope and significant prolongation in early diastolic and late-diastolic deceleration times were found at a lower temperature (15 degrees C). The acceleration:deceleration ratio for early and late diastole also showed a significant difference at 15 degrees C. In conclusion, the cardiac performance of the zebrafish could be approached using commercially available clinical instruments equipped with Doppler echocardiography and power angiography.

Assessment of quality of life in a double-blind, randomized clinical trial of imidapril and captopril for hypertensive Chinese in Taiwan.

PURPOSE: Although the role of angiotensin-converting enzyme (ACE) inhibitors for the treatment of hypertension has been well established, no data has been generated regarding the influence of ACE inhibitors for health-related quality-of-life (QOL) dimensions for Chinese patients. MATERIALS: A double-blind, active-control, randomized clinical trial was used to compare the effects of two ACE inhibitors, imidapril and captopril, on quality-of-life dimensions in one outpatient clinic in one tertiary clinical-care facility. After a 2-3 week washout period with placebo, 59 patients with mild-to-moderate hypertension were randomly assigned to receive imidapril (5 to 10 mg per day) or captopril (25 to 50 mg twice per day) for 12 weeks. Patients completed the Short-form 36 (SF 36) health survey questionnaire, which evaluates 8 QOL dimensions, just before treatment, during the 8th week, and at the end of treatment (12th week). ANOVA for repeated measures was used to analyze the QOL-score changes over time and compare treatments, and to assess the interaction of treatment duration and group on these scores. RESULTS: No significant differences were demonstrated for changes in blood-pressure, frequency of adverse effects and withdrawal of patients from the study comparing the two drugs. Significant improvement, however, was demonstrated for mental-component summary scores after 12 weeks of treatment for both drugs (P = 0.029). No significant differences were established for individual QOL dimensions comparing the two drugs. A significantly higher baseline systolic blood pressure was found in the participants who did not complete the questionnaire than in those who did. CONCLUSIONS: Similar and significant improvements were determined for the mental-component QOL summary scores for the two ACE inhibitors, imidapril and captopril, and no significant differences were demonstrated comparing treatments.

Assessment of menopause-induced myocardial changes by integrated backscatter during inotropic stimulation and atropine injection.

Estradiol has been considered as an L-type calcium channel blocker in animal studies. The concentration of estradiol decreases after menopause. Therefore, we hypothesized that human myocardial functional changes developed after menopause, and those changes could be evaluated through the use of cyclic variation of integrated backscatter (CVIBS). A total of 16 patients with menopause (native and surgical menopause), follicular stimulating hormone > 40 IU/L and estradiol < 20 pg/mL underwent dobutamine stress IBS examination (study group). Another 12 women with normal menstruation, follicular stimulating hormone < 40 IU/L and estradiol > 20 pg/mL were enrolled as a control group. All patients had a low likelihood of coronary artery disease and negative results of dobutamine stress echocardiography and (201)thallium scintigraphy. To avoid the phenomenon of anisotropy, the amplitude and phase of IBS were acquired only in the midanteroseptal segment from the parasternal short axis view. The baseline amplitudes of CVIBS differed between the control and study groups (5.9 +/- 1.2 dB vs. 8.1 +/- 2.1 dB; p = 0.007). The amplitudes during low-dose (20 microg/kg-min) and peak-dose (40 microg/kg-min) dobutamine infusion were also different between these 2 groups (5.7 +/- 0.9 dB vs. 8.4 +/- 1.7 dB; p < 0.001; 6.0 +/- 1.0 dB vs. 7.7 +/- 2.4 dB; p = 0.026). However, there were no significant differences in amplitudes between these two groups after atropine injection (control group 4.5 +/- 1.2 dB, study group 5.3 +/- 1.0 dB; p = NS). No significant differences of phase were found either at baseline or under dobutamine infusion between the two groups. Multivariate linear regression analysis showed that only menopause status associated significantly with the amplitudes at different doses of dobutamine infusion (p < 0.05). In conclusion, human myocardial functional changes are observed by CVIBS after menopause. Postmenopausal women have higher values of amplitude than premenopausal women. These phenomena persist during low and peak doses of dobutamine infusion, but are abolished by atropine injection.