Value of Low-Dose Dobutamine Stress Real-Time Myocardial Contrast Echocardiography in the Diagnosis of Coronary Heart Disease.

To investigate the value of low-dose dobutamine stress real-time myocardial contrast echocardiography (RT-MCE) in the diagnosis of coronary heart disease (CHD). A total of 65 hospitalized patients with suspected or confirmed CHD were detected by RT-MCE combined with low-dose dobutamine stress (0.84 mg/kg). Perfusion curves were quantitatively analyzed using QLAB software. Peak intensity (A), slope of curves (ß), and perfusion (A × ß) were also calculated. Based on the results of coronary angiography, patients were divided into no obvious stenosis group (<50%), mild stenosis group (50%-74%), moderate stenosis group (75%-89%), and severe stenosis group (≥90%). The A, ß, and A × ß values before and after low-dose dobutamine stress of each group were compared. In the basal state and after low-dose dobutamine stress, the A, ß, and A × ß values significantly decreased as the stenosis degree of the myocardial segments increased. The same variation tendency was also found in the A, ß, and A × ß reserve values, and there was significant difference in these reserve values between moderate and severe stenosis groups and no obvious stenosis and mild stenosis groups. Collateral circulation had marked effects on the values of myocardial perfusion parameters and their reserve values, especially in the segments with severe stenosis. Low-dose dobutamine stress RT-MCE can be a sensitive method for clinical diagnosis and risk assessment of CHD and may provide a basis for further treatment of CHD.

A computer-aided diagnostic algorithm improves the accuracy of transesophageal echocardiography for left atrial thrombi: a single-center prospective study.

OBJECTIVES: We investigated whether transesophageal echocardiography (TEE) assisted with a computer-aided diagnostic (CAD) algorithm was superior to TEE in diagnosing left atrial (LA)/left atrial appendage (LAA) thrombi in patients with atrial fibrillation (AF) in a single prospective study. METHODS: Transesophageal echocardiography was performed in patients with AF, and images were reconstructed. Gray level co-occurrence matrix-based features were calculated and then classified using an artificial neural network. The original data and processed images by the CAD system were studied by 5 radiologists independently in a blind manner. The diagnostic performance of each radiologist was evaluated. RESULTS: One hundred thirty patients with AF were investigated. Thirty-one patients (23.9%) had a diagnosis of LA/LAA thrombi. The mean sensitivity ± SD of TEE for LA/LAA thrombi was 0.933 ± 0.027, which was noticeably improved by CAD (0.955 ± 0.021; P < .05). The specificity of TEE was 0.811 ± 0.055, which was markedly lower than that by TEE plus CAD (0.970 ± 0.009; P < .05). The positive predictive value of TEE was low (0.613 ± 0.073) compared to that of TEE plus CAD (0.908 ± 0.027; P < .001), whereas the negative predictive values were comparable for TEE, CAD, and TEE plus CAD. Diagnosis of an LA/LAA thrombus by TEE plus CAD had a higher accuracy rate (0.966 ± 0.011) than that by TEE (0.840 ± 0.047; P < .01). The mean area under the receiver operating characteristic curve (Az) for TEE was 0.834 ± 0.009 (95% confidence interval [CI], 0.815-0.852), which was markedly lower than the Az for TEE plus CAD (0.932 ± 0.005; 95% CI, 0.921-0.943). The use of CAD significantly improved the Az values for all 5 radiologists (P < .001). CONCLUSIONS: The CAD algorithm significantly improves the diagnostic accuracy of TEE for LA/LAA thrombi in patients with AF.

Effect of graft patency on the prediction of myocardial viability by dobutamine stress and myocardial contrast echocardiography before coronary artery bypass surgery.

BACKGROUND: Myocardial functional recovery after revascularization is considered the "gold standard" for myocardial viability (MV) assessment. However, the patency of the revascularized coronary artery affects myocardial functional recovery in patients subjected to coronary artery bypass grafting (CABG). The influence of graft patency on viability results has not been widely studied. PURPOSE: We evaluated the effect of graft patency on the prediction of MV after CABG by myocardial contrast echocardiography (MCE) and low-dose dobutamine stress echocardiography (LD-DSE). METHODS: Fifty-three subjects with chronic ischemic heart disease scheduled for CABG were divided randomly into groups A (n = 26) and B (n = 27). They underwent MCE and LD-DSE preoperatively. Patients were followed up 12 months after CABG. Group B patients underwent multislice computed tomography angiography to assess CABG patency, and patients with obstructed grafts were excluded. Group A patients were not subjected to multislice CT angiography. The accuracy of MCE and LD-DSE for assessing MV between the two groups was compared. RESULTS: The accuracy and positive predictive values of MCE and LD-DSE for predicting MV were higher in group B than in group A (p < 0.05). CONCLUSIONS: Preoperative LD-DSE and MCE ability to predict MV depends on the patency of CABG.

[Effects of Trimetazidine upon ventricular remodeling and GLUT4 in diabetic rats after myocardial infarction].

OBJECTIVE: The aim of study is to investigate the changes of structure and function of heart in diabetic rat after myocardial infarction, and to study the expression of the GLUT4 and the effects of trimetazidine on the ventricular remodeling. METHODS: Type 2 diabetes rat was made by feeding with a diet enriched with sucrose, fat and cholesterol for six weeks and then injecting streptozocin intraperitoneally, then the myocardial infarction by ligating coronary artery. The living rats were randomly divided into three groups twenty-four hours after operation: placebo; trimetazidine and sham operated with diabetes. And other rats which was fed with normal diet were divided into myocardial infarction group without diabetes and sham operated group without diabete. The treat group was intragastric administrated with trimetazidine which was solved in distilled water (30 mgxkg(-1) 1xd(-1)), and others were poured with parts aequalis distilled water. After six weeks, echocardiographic and hemodynamic studies were performed, ventricular were weighed, myocardial infarct size and myocardial collagen volume fraction (CVF) of non-infarction area were detected also. GLUT4 mRNA in the myocardium away from infarction region were measured with fluorescent quantitation RT-PCR and GLUT4 protein were measured with Western blot. RESULTS: Six weeks after diabetes complicating with myocardial infarction, comparing with sham operated group without diabete, diabetes sham operated group and myocardial infarction group without diabete, LVDd of diabetes complicating with myocardial infarction group was increased significantly; the systolic and diastolic function with left ventricular were decreased significantly, VWI and CVF were increased significantly; comparing with placebo group, diastolic function of left ventricular in trimetazidine group was improved significantly (4.7 +/- 1.7 vs 6.8 +/- 1.6, P < 0.05); CVF (3.9 +/- 0.2)% vs (6.3 +/- 0.4)%, (P < 0.05) was decreased significantly, but LVDd, VWI and the systolic function was not chang significantly. The expression of GLUT4 mRNA and protein in sham operated with diabetes and diabetic with myocardial infarction descended significantly compared with sham operated group without diabete (P < 0.01). And in trimetazidine group, GLUT4 protein moderately increased (P < 0.05) compared with placebo group. CONCLUSION: Trimetazidine could improve the diastolic function of left ventricular. The expression of GLUT4 mRNA and protein in type 2 diabetes complicating with myocardial infarction decreased. Trimetazidine could improve the expression of GLUT4 mRNA and protein in diabetes complicating with myocardial infarction and inhibited myocardial fibrosis.

[On angiotensin II receptor distribution after myocardial infarction in dogs].

OBJECTIVE: To investigate the effects of valsartan on expression of angiotensin II receptors in different regions of heart after myocardial infarction (MI). METHODS: Canines were divided into sham-operated control group (n=7), infarction group (n=7) and Valsartan group (10 mg x kg(-1) x day(-1) for 4 weeks after MI operation, n=7). Four weeks after operation, Doppler tissue imaging (DTI) was used to evaluate regional ventricular function in the noninfarcted myocardium (apical and basal near to the infarction region). The mRNA and protein expressions of angiotensin II type 1 receptor (AT1-R) and angiotensin II type 2 receptor (AT2-R) on the corresponding regions were detected by competitive reverse-transcriptase polymerase chain reaction technique and immunohistochemical technique respectively. Results The protein and mRNA expressions of AT1-R were significantly increased in both apical and basal regions near to the infarction in dogs with MI compared with those in control group (P < 0.05) which could be downregulated by valsartan (P < 0.05). AT2-R expressions were significantly upregulated in infarction group in both apical and basal regions compared with those in control group and valsartan further increased AT2-R expressions in both areas (P < 0.05). Myocardial peak systolic velocity (Sm), myocardial peak early diastolic velocity (Em) and myocardial peak late diastolic velocity (Am) at both apical and basal regions near to the infarction regions were significantly lower in MI group than those in the control group which could be significantly improved by valsartan. CONCLUSION: Both mRNA and protein expressions of AT1-R and AT2-R are upregulated in noninfarcted regions near MI, valsartan improved myocardial function via inhibiting AT1-R upregulation and enhancing AT2-R upregulation.

Relationship between testosterone and indexes indicating endothelial function in male coronary heart disease patients.

AIM: To investigate the relationship between androgen level and the indexes indicating endothelial function in male patients with coronary heart disease (CHD). METHODS: We registered the following data for 106 50-70-year-old men: age, weight, blood lipid, including total cholesterol, low density lipoprotein cholesterol, high density lipoprotein cholesterol and triglyceride, whether a smoker, sugar levels, blood pressure, free testosterone (FT), vascular cell adhesion molecule-1 (VCAM-1) and the intima-media thickness (IMT) of common carotid artery, common carotid diameter, maximum velocity in systolic phase, minimum velocity in diastolic phase and resistant index. Among the 106 men, 51 were patients with CHD. The relationships between FT level, VCAM-1 concentration and IMT were examined, respectively, using a stepwise linear regression technique among all the 106 men. RESULTS: There was no statistical difference in terms of age, blood pressure, whether a smoker, sugar levels, HDL-C, minimum velocity in diastolic phase, resistant index between male CHD patients and controls; whereas results for weight, total cholesterol, low density lipoprotein cholesterol, triglyceride, VCAM-1 and IMT of male CHD patients were higher than those of controls; FT level and maximum velocity in systolic phase were lower. It was found that among all the objects, FT level was inversely correlated with IMT and VCAM-1 concentration. CONCLUSION: FT level was inversely correlated with VCAM-1 concentration and IMT which are indicators of endothelial function.

Chronic blocking of beta 3-adrenoceptor ameliorates cardiac function in rat model of heart failure.

BACKGROUND: Stimulation of the heart beta 3-adrenoceptor (AR) may result in a negative inotropic effect. Being up-regulated, beta 3-AR plays a more important role in the regulation of cardiac function during heart failure. However, the effect of chronic blocking of beta 3-AR on heart failure has not been fully elucidated. In this study, we used a selective beta 3-AR antagonist SR59230A to treat a well defined heart failure rat model chronically, then evaluated its effect on cardiac function and investigated the mechanism. METHODS: Male Wistar rats were chosen randomly as controls (n = 8). Isoproterenol induced heart failure rats were randomly divided into ISO group (n = 10) and SR group (n = 10). The ISO group received intraperitoneal injection of 1 ml saline twice a day; the SR group received intraperitoneal injection of SR59230A 85 nmol in 1 ml saline twice a day; and the control group received no treatment. The treatment was started 24 hours after the last isoproterenol injection and continued for 7 weeks. Then we measured the following indexes: the ratio of heart weight to body weight (HW/BW) and the ratio of left ventricular weight to body weight (LVW/BW), collagen volume fraction (CVF), left ventricular end diastolic dimension (LVEDd), left ventricular end systolic dimension (LVESd), ejection fraction (EF), fractional shortening (FS) and the ratio of E wave to A wave (E/A), the mRNA and protein expression of beta 3-AR and eNOS, and cGMP level in the heart. RESULTS: The ratios HW/BW and LVW/BW were significantly increased in the ISO group compared with the control group (P < 0.01), but they were limited in the SR group (P < 0.05 compared with the ISO group). CVF increased in the ISO group and the SR group (P < 0.01), but it was significantly attenuated in the SR group (P < 0.01). LVEDd, LVESd and E/A ratio were significantly increased in the ISO group compared with the control group (P < 0.01), while EF and FS were significantly decreased (P < 0.01). Compared with the ISO group, the SR group showed that LVEDd, LVESd and E/A ratio were significantly decreased (P < 0.01), whereas EF and FS were significantly increased (P < 0.01). beta(3)-AR and eNOS mRNA and protein in the ISO group were significantly increased when compared with the control group (P < 0.01). These increases were all attenuated in the SR group compared with the ISO group (P < 0.01). The level of cGMP in myocardial tissue was significantly increased in the ISO group compared with the control group (P < 0.01), whereas SR59230A treatment normalized this increment (P < 0.01). CONCLUSIONS: Chronic blocking of beta 3-AR could ameliorate cardiac function in heart failure rats and its mechanism involves inhibition of the negative inotropic effect and attenuation of cardiac remodeling.

[The effects of combined beta(1) adrenergic receptor antagonist and beta(2) adrenergic receptor agonist therapy on cardiac function and myocardial apoptosis in heart failure rats].

OBJECTIVE: To observe the effects of combined beta(1) adrenergic receptor (AR) antagonist with beta(2)AR agonist therapy on cardiac function and cardiomyocyte apoptosis in heart failure rats. METHODS: Heart failure was induced by isoproterenol and rats were randomly divided into metoprolol group (50 mg/kg twice daily/gavage, n = 11), combined treatment group (fenoterol 125 microg/kg and metoprolol 50 mg/kg twice daily/gavage, n = 11) and placebo group (saline, n = 10), another normal 9 male Wistar rats served as control group. After 8 weeks' treatment, cardiac function, apoptosis index (AI), Caspase-3 activity, expression levels of bcl-2 and bax protein, organ weight/body weight and collagen volume fraction (CVF) were evaluated. RESULTS: (1) Left ventricular end diastolic dimension, left ventricular end systolic dimension and E/A ratio were significantly increased and fractional shortening, ejection fraction significantly reduced post isoproterenol (all P < 0.05 vs. control) and these changes were significantly attenuated by metoprolol alone (all P < 0.05 vs. placebo) and further attenuated by the metoprolol and fenoterol combination therapy (all P < 0.05 vs. placebo and metoprolol). (2) Left ventricular weight to body weight ratio, lung weight to body weight ratio and CVF were also significantly reduced in metoprolol and combined treatment group than those in placebo group (all P < 0.01). (3) Compared with placebo group, AI and Caspase-3 activity were significantly lower in metoprolol group (all P < 0.01 vs. placebo) and further reduced in combined treatment group (all P < 0.01 vs. metoprolol). (4) The expression level of bax protein was significantly lower in metoprolol group while bcl-2/bax significantly higher than those in placebo group. These changes were more significant in combined treatment group (all P < 0.01 vs. metoprolol). CONCLUSIONS: beta(1)AR antagonist in combination with beta(2)AR agonist further improved the cardiac function and prevented cardiac remodeling compared with using beta(1)AR antagonist alone in heart failure rats. Downregulated bax and upregulated bcl-2/bax expressions might contribute to the observed beneficial therapy effects by reducing cardiomyocyte apoptosis in these animals.

[Effects of adenovirus-mediated gene transfer of ICOSIg fusion protein on experimental autoimmune myocarditis in Lewis rats].

OBJECTIVE: To explore the effects of adenovirus vector-mediated gene transfer of ICOSIg fusion protein on experimental autoimmune myocarditis (EAM) in Lewis rats. METHODS: Expression vector containing ICOSIg (p-Adeno-ICOSIg) was constructed by fusion of human ICOS and IgGFc segment. Adenovirus vector was digested by PacI enzyme and transfected into HEK 293 cells. Adenovirus expressing ICOSIg was produced. EGFP was constructed into adenovirus vector and used as control. EAM was induced in Lewis rats by injection of porcine cardiac myosin. All immunized Lewis rats were divided into 4 groups. Group A (n = 15) and B (n = 15) received adenovirus containing ICOSIg on day 0 and day 14 respectively to study the effects of costimulatory molecules gene therapy on T cell activation and inflammation; group C (n = 10) and group D (n = 10) received adenovirus containing EGFP on day 0 and day 14 respectively as controls. Group E (n = 10) was normal controls that did not receive immunization. On day 28, all rats were killed after echocardiography examination. Histopathological examination was performed to observe myocardial inflammation. Protein levels of ICOS, ICOSL, B7-1 and B7-2 were detected by Western blot. INF-gamma, IL-2 and IL-4 mRNA were determined by realtime RT-PCR. RESULTS: On day 28, cardiac function was significantly improved and myocardial inflammation significantly attenuated in group B compared to group A, C and D (all P < 0.05). B7-1 expression at protein level was significantly lower in group B than that of group C (P < 0.05). ICOS and ICOSL expressions at protein level were significantly decreased in both group A and B compared with group C and D (P < 0.05). IFN-gamma mRNA level significantly decreased and IL-4 mRNA significantly increased in group A and B compared to group C and D (P < 0.05). CONCLUSIONS: Blockade of costimulatory pathway with gene therapy of ICOSIg alleviated autoimmune inflammatory damage and improved cardiac function in Lewis rats with EAM. Down-regulated costimulatory molecules in the myocardium and reduced inflammatory cytokine secretion might be responsible for the beneficial effects of ICOSIg in this model.

[Evaluation of right ventricular function by tissue Doppler echocardiography and Tei index in right ventricular myocardial infarction].

OBJECTIVE: With tissue Doppler imaging and right ventricular Tei index, right ventricular function in patients with right ventricular myocardial infarction (RVMI) was assessed. METHOD: 51 patients admitted to coronary care units and diagnosed as acute inferior myocardial infarction were further studied with the ECG criterion of ST segment elevation >or= 1mm in V(4R) to establish the diagnosis of RVMI. 23 patients were thus diagnosed as RVMI and 28 patients not. 20 healthy subjects served as controls. Clinical and echocardiography index were recorded. Peak systolic and peak early and late diastolic velocities (Sm, Em, Am) and Em/Am were acquired from the apical four-chamber view at the lateralside of tricuspid annulus, the septal side of the tricuspid annulus and the RV free mid-wall using DTI. Interval between tricuspid closing and reopening and ejection time (ET) from parasternal short-axis view were recorded by pulse-wave Doppler. RV Tei index was calculated. RESULTS: Sm and Em at the lateral side of tricuspid annulus and the RV free mid-wall reduced significantly in patients with RVMI as compared with those without RVMI and healthy individuals (Sm at the lateral (7.0 +/- 2.0) cm/s vs (8.7 +/- 1.9) cm/s and (10.6 +/- 2.1) cm/s, P < 0.01; Em at the lateral (6.3 +/- 1.9) cm/s vs (7.9 +/- 1.8) cm/s and (9.6 +/- 1.9) cm/s, P < 0.01; Sm at the RV free mid-wall (6.4 +/- 1.9) cm/s vs (8.0 +/- 1.9) cm/s and (9.4 +/- 2.0) cm/s, P < 0.05; Em at the RV free mid-wall (6.1 +/- 2.0) cm/s vs (7.6 +/- 2.0) cm/s and (9.2 +/- 2.3) cm/s, P < 0.05). RV Tei index in patients with RVMI also increased as compared with that in the other two groups (0.65 +/- 0.19 vs 0.40 +/- 0.15 and 0.26 +/- 0.10; P < 0.01). CONCLUSIONS: The evaluation of velocities at the lateral side of tricuspid annulus and the RV free mid-wall using DTI and RV Tei index provides a noninvasive and rapid method for assessing right ventricular function in patients with RVMI.

[Relationship between plasma brain natriuretic peptide concentration and clinical prognosis in patients of acute myocardial infarction].

OBJECTIVE: To evaluate the value of brain natriuretic peptide (BNP) in estimating risk stratification in patients with acute myocardial infarction (AMI) and to determine the relationship between BNP and adverse cardiac events after AMI. METHODS: The 135 subjects were selected into the study, including 25 healthy subjects and 110 patients with a first AMI. The plasma concentrations of BNP were measured at two to four days after infarction in patients and healthy controls. Left ventricular function was evaluated by echocardiography with the parameters of left ventricular ejection function (LVEF) after 3 months. Patients were followed up at 12 months. The main outcome measures were heart failure, left remodeling, mortality and other adverse cardiac events at one year. RESULTS: Plasma BNP concentrations in patients with AMI were much higher than those in the health control people (416.7 +/- 208.0 ng/L versus 61.8 +/- 34.1 ng/L, P < 0.01). The BNP count ranged from 5 to 2500 ng/L in AMI patients. There was no association between the BNP count and mortality rate. The development of new congestive heart failure (CHF) was associated with a higher BNP count (P = 0.02). The development of any of the clinical end points (death/CHF/shock) occurred more frequently in patients with a higher BNP count (13.8% for BNP count of < 100 ng/L, 39.1% for BNP count of 100 - 200 ng/L, 43.3% for BNP count of 200 - 400 ng/L, 46.4% for BNP count of > 400 ng/L; P = 0.019). Plasma BNP concentrations remained independently associated with the development of clinical end points in multivariable model that adjusted for potential confounding variables. CONCLUSION: The results of the present study confirm that the elevated BNP count related to the risk stratification and prognosis in patients with AMI. Elevations in BNP count are associated with a higher incidence of new CHF and adverse clinical outcomes after AMI. It could serve as a strong predictor for the subsequent development of poor outcomes in AMI patients.