| Part One Assessment of myocardial perfusion and viable myocardium by real-time myocardial contrast echocardiography in chronic myocardial ischemia pigsObjectives The purpose of this study was to evaluate the myocardial perfusion, and perfusion reserve in chronic myocardial ischemia pigs using dipyridamole stress real-time myocardial contrast echocardiography (RT-MCE). We sought to investigate the role of dipyridamole stress RT-MCE in identification of myocardial ischemia with semiquantitative and quantitative analysis methods and to explore the diagnostic value of stress RT-MCE in detecting viable myocardium(hibernating myocardium) compared with 99mTc- MIBI SPECT and 18F-fluorodeoxyglucose (FDG) SPECT.Methods Ameroid constrictors were placed around the circumflex artery in 22 pigs to induce chronic myocardial ischemia by chronic vessel occlusion. Philips SONOS 7500 prototype system with a broadband S3 transducer (1 to 3MHz) was used. The second-generation contrast agent Sonovue was used. MCE was performed during rest and dipyridamole stress in the parasternal short-axis view using low power continuous MCE (color-coded power-modulation technique) at a mechanical index of 0.1 before and 4-6 weeks after the Ameroid constrictors were placed. We applied 3-point scale semiquantitative visual analysis and quantitative analysis of regions of interest for assessing myocardial perfusion and its reserve. 99mTc- MIBI SPECT combining with 18F-FDG SPECT and multimodality MR imaging (cine MRI, dipyridamole stress myocardial perfusion imaging and delayed contrast-enhanced MRI) were also performed in 7 pigs to evaluate the viable myocardium. TTC staining, Hematine- Eosine staining, Poley staining and electron microscope studies were performed at the end of the experiment.ResultsChronic myocardial ischemia models were successfully established in 15 pigs.①semiquantitative visual analysis showed that, the detection rate of abnormal segments by using rest MCE, dipyridamole stress MCE, dipyridamole stress echocardiography and combining the analysis of myocardial opacification and wall motion both at rest and under stress was 63.3％, 78.3％, 76.7％and 90％, respectively.②Quantitative analysis of regions of interest showed that at rest, A,βand A×βwere significantly higher in the groups of normal and ischemic segments than those of the infarcted segments (all P＜0.05) , and A×βwere significantly lower in the groups of ischemic segments than that of the normal segments; when under dipyridamole stress, A,β, A×β,βreserve and A×βreserve were significantly higher in the groups of normal and ischemic segments than those of the infarcted segments (all P＜0.05), and A,β, A×β,βreserve and A×βreserve were significantly higher in the group of normal segments than that of the ischemic segments (all P＜0.01).③we used the ROC (receiver operating characteristic) curve to determine the value of different quantitative parameters to detect the ischemic segments. Area under the curve(AUC) of A,. and A×. at baseline were between 0.7 to 0.8.; however, under dipyridamole stress, AUC ofβ(0.924) and A×β(0.916) increased significantly compared with those at rest (both P＜0.01).④we separated segments with contractile reserve from those without contractile reserve by dipyridamole stress echocardiography. At baseline, there was no significantly difference in all the quantitative parameters between the segments with contractile reserve and those without contractile reserve, however, under dipyridamole stress,β, A×βand their reserve were all significantly higher in segments with contractile reserve than those without contractile reserve (all P＜0.05).⑤we used the SPECT imaging results and the pathologic results as the standard reference to evaluate infracted segments, viable segments and normal segments. Kappa index of dipyridamole stress MCE in concordance with golden standard was 0.770. When combining analysis of myocardial opacification and wall motion both at rest and under stress, kappa index increased to 0.855, higher than separate analysis of myocardial opacification or wall motion only. Multimodality MR imaging also showed good agreement with standard reference (Kappa=0.906).ConclusionsRT-MCE in conjunction with dipyridamole stress echocardiography can semiquantitative or quantitatively evaluate the myocardial perfusion and perfusion reserve. Quantitative analysis myocardial perfusion under stress could increase the diagnostic accuracy for detecting ischemic myocardium. Combining analysis of myocardial opacification and wall motion both at rest and under stress can improve the diagnostic accuracy for detecting ischemic myocardium and viable myocardium.Lib classification R5Part TwoUsefulness of real-time myocardial contrast echocardiography in predicting functional recovery and left ventricular remodeling after revascularization in patients with ischemic heart diseaseObjectives The purpose of this study was to evaluate the myocardial perfusion, perfusion reserve and contractile reserve in patients with ischemic heart disease using real-time myocardial contrast echocardiography(RT-MCE) combined with low dose dobutamine stress test. We sought to investigate the role of RT-MCE in predicting left ventricular(LV) functional recovery and remodeling after revascularization and to explore the diagnosis value of different analysis methods using for RT-MCE.Methods 31 patients with ischemic heart disease and resting regional LV dysfunction were included. Philips SONOS 7500 prototype system with a broadband S3 transducer(1 to 3MHz) was used. LV volume, global and regional function were evaluated by 2-D echocardiography before and 6～9 months after revascularization. Regional wall motion was scored according to a standard 16-segment model and graded on a 4-point scale. MCE was performed before revascularization at baseline and under low dose dobutamine stress in the standard apical 4-, 2-, and long-axis view using low power continuous MCE(color-coded power-modulation technique) at a mechanical index of 0.1. The second-generation contrast agent Sonovue was used. We applied the following three methods for analyzing the images of RT-MCE:①3-point scale semiquantitative visual analysis: 1=homogenous contrast opacification, 0.5=reduced or patchy contrast opacification, or 0=minimal or absent contrast opacification.②3-point scale semiquantitative parametric imaging: green=homogenous contrast opacification, yellow=mildly reduced contrast opacification, or red=severely reduced or absent contrast opacification.③quantitative analysis of regions of interest: the images of RTMCE were analyzed quantitatively from microbubble replenishment curves to assess myocardial perfusion and its reserve.Results①Visual analysis showed that wall motion improvement was found 94.6%, 45.5% and 16.1% respectively (. 2=70.9, P＜0.01) in homogenous, patchy and absent contrast opacification segments. Using regional myocardial contrast opacification score≥0.5 to predict recovery of function after revascularization, the sensitivity, specificity, and accuracy was 90.7%, 51.10%, 71.4%, respectively.②Semiquantitative parametric imaging showed that wall motion improvement was found to be 98.0%, 50.0% and 20.3%(.2=73.1, P＜0.01) in homogenous, mildly reduced and severely reduced contrast opacification segments respectively. Segments predominantly coded yellow or green were identified as viable, and the sensitivity, specificity, and accuracy to predict recovery of function after revascularization was 84.5%, 64.9%, and 74.6%, respectively.③Low dose dobutamine stress test showed that wall motion improvement was found to be 77.5% and 29.2%(.2=39.360, P＜0.01) in segments with or without contractile reserve respectively. The sensitivity, specificity, and accuracy of low dose dobutamine stress to predict recovery of function after revascularization was 70.5%, 77.7% and 73.9%, respectively.④Quantitative real-time myocardial contrast echocardiography in conjunction with low dose dobutamine stress showed that at baseline, significant differences in. and Ax. (both P＜0.01) were observed between segments with or without recovery of function, when under stress, A,., Ax. and their reserve values were all significantly higher in segments with recovery of function than those without recovery of function (all P＜0.01). At baseline,, and Ax. were significantly higher in segments with contractile reserve than those without contractile reserve (both P＜0.01), and under dobutamine stress, A,., Ax. and their reserve values were all significantly higher in segments with contractile reserve than those without contractile reserve (all P＜0.01).⑤We used the ROC(receiver operating characteristic) curve to determine the value of different quantitative parameters to predict recovery of function after revascularization. Area under the curve(AUC) of A,. and Ax. at baseline were low, however, under dobutamine stress, AUC of all the parameters and their reserve increased significantly compared to those at rest(all P＜0.01). The best quantitative MCE parameter to predict recovery of function was Ax. reserve. The sensitivity, specificity, positive predictive value and negative predictive value of Ax. reserve＞1. 31 for recovery of function were 85.2%,74.1%,78.1% and 82.2%. The sensitivity, specificity, positive predictive value and negative predictive value of. reserve＞0.39 for recovery of function were 73.9%,79.01%,79.3% and 73.6%.⑥There was no significant difference in AUC among the visual analysis, parametric imaging and low dose dobutamine stress test, but AUC of., Ax. and their reserve derived from MCE combined with low dose dobutamine stress were all significantly higher than those of visual analysis, parametric imaging and low dose dobutamine stress test.⑦Patients were divided into 2 groups according to contrast score index(CSI): Group A, patients with CSI. 0.5; Group B, patients with CSI＜0.5. At baseline, there was no statistically significant difference in LV volume and global function between the two groups. After revascularization, LV volume was improved and LV function was recovered (all P＜0.05) in group A; however, in group B, LVEDV was deteriorated (P＜0.05) and LVESV, LVEF as well as WMSI did not change significantly. There were moderate negative relations between CSI and LVEDV change value (r=-0.672, P＜0.001).Conclusions:①RT-MCE combined with low dose dobutamine stress can quantitatively evaluate the myocardial perfusion, perfusion reserve and contractile reserve in patients with ischemic heart disease. It provides a promising approach for detecting viable myocardium.②Semiquantitative analysis methods such as visual analysis and parametric imaging have high sensitivity but low specificity. Parametric imaging is a novel and quick approach to evaluate the myocardial perfusion, which has relatively higher specificity than visual analysis. Quantitative analysis of regions of interest indicate that quantitative parameters under dobutamine stress can increase the diagnosis accuracy for detecting viable myocardium compared with the semiquantitative analysis and the quantitative analysis at rest only.③Contrast score index can predict LV remodeling after revascularization in patients with ischemic heart disease.In summary, the maintenance of tissue-level perfusion detected by RT-MCE can predict functional recovery and LV remodeling after revascularization in patients with ischemic heart disease, which might be helpful in clinical decision-making and risk stratification.Part ThreeReal-time three-dimensional echocardiographic quantification of left ventricular systolic synchronicity in patients with dilated cardiomyopathyObjectives Real-time three-dimensional echocardiography(RT3DE) is a novel approach for assessment of left ventricular(LV) dyssynchrony. The purpose of this study was to quantitatively evaluate the left ventricular systolic synchronicity in patients with dilated cardiomyopathy (DCM) by RT3DE and investigate the correlation of systolic dyssynchrony derived by RT3DE and the most widely accepted method Tissue Doppler Imaging(TDI).Methods Thirty-two patients with DCM and thirty-one healthy volunteers were enrolled in this study. Full volume RT3DE and TDI were performed and analyzed using Philips iE33 echocardiographic imaging system with the X3-1 matrix array 3D transducer and the S5-1 2-D transducer. Data were analyzed using Qlab software(version 4.2). The global and 17-segmental time-volume curves were obtained. The RT3DE asynchrony timing and indexes were derived from the basal, mid, and apical 16-segmental volumes, excluding the apex. The time to minimal systolic volume in each segment (Tmsv) was taken to derive the following RT3DE indexes of systolic asynchrony: Tmsv 16-SD, Tmsv 16-Dif, Tmsv 12-SD, Tmsv 12-Dif, Tmsv 6-SD and Tmsv 6-Dif, which represented the standard deviation or the maximal difference of Tmsv among the 16, 12 and 6 segments of the left ventricle respectively. The software also provided with each of the above parameters as a percentage of the cardiac cycle. TDI data included the SD of time to peak isometric contraction(Ti-SD), peak systolic velocity (Ts-SD) and minimum strain(T.-SD) among the 6 basal and 6 mid segments.Results①The global time-volume curves showed DCM patients with LV dysfunction had significantly larger EDV and ESV, with significantly reduced LVEF compared with the healthy subjects.②All the indexes of systolic asynchrony derived from the 17-segmental timevolume curves (Tmsv 16-SD, Tmsv 12-SD, Tmsv 6-SD, Tmsv 16-dif, Tmsv 12-dif and Tmsv 6dif) were significantly larger in the two DCM groups than those of the control group (all P＜0.01).③Tmsv 16-SD, Tmsv 12-SD, Tmsv 16-Dif and Tmsv 12-Dif were significantly larger in the subgroup DCM patients with moderate to severe LV dysfunction than those with mild LV dysfunction (Tmsv 16-SD: 72.3±30.2ms vs. 38.9±22.8ms; Tmsv 12-SD: 51.9±41.2ms vs. 22.1±16.7ms; Tmsv 16-Dif: 301.3±130.0ms vs. 154.8±99.3ms; Tmsv 12Dif: 178.6±146.1ms vs. 154.8±99.3ms, all P＜0.05).④There were moderate negative relations between the LVEF determined by RT3DE and each of the indexes of systolic asynchrony derived from the 17-segmental time-volume curves. Among all the indexes, Tmsv 16-SD and Tmsv 16-Dif% had best correlation (r=-0.773 and-0.771 respectively).⑤The LVEF determined by Simpson's modified biplane method correlated significantly with LVEF determined by RT3DE (r=0.912, Y=0.908X+7.121, P＜0.001).⑥T. in the inferior wall and the mid of the posterior wall were significantly longer in DCM group than those of the control group (all P＜0.05); Ts in each segment of the LV was significantly longer in DCM group than that of the control group (all P＜0.05); T. in the anterior wall and the basal of the anterior septal and lateral wall were significantly longer in DCM group than those of the control group (all P＜0.05).⑦All the systolic dyssynchrony indexes derived from tissue Doppler imaging were significantly larger in the DCM group than those of the control group (Ti-SD: 16.3±9.1 ms vs. 6.2±2.3ms; Ts-SD: 36.9±27.5 ms vs. 17.6±10.2ms; T.-SD: 66.8±37.7 ms vs. 30.5±14.8ms, all P＜0.01).⑧There were moderate correlation between Tmsv 16-SD and each of the indexes derived from TDI (For Ti-SD, Ts-SD and T.-SD, r=0.709, r=0.567 and r=0.598 respectively, all P＜0.01); Similar correlations were found for Tmsv 12-SD (For Ti-SD, Ts-SD and T.-SD, r=0.681, r=0.414 and r=0.559, respectively, all P＜0.01).Conclusions①Patients with DCM had higher prevalence of intraventricular dyssynchrony compared with the normal individuals by analyzing 17-segmental time-volume curves using real-time three-dimensional echocardiography.②The severity of mechanical dyssynchrony is increasing with worsening LV systolic function.③There were moderate correlation between real-time 3D echocardiography and tissue Doppler imaging to evaluate the LV dyssynchrony.④Real-time three-dimensional echocardiography with the QLab software can quantitatively evaluate the systolic synchronicity of all the left ventricular segments simultaneously, besides, it provided highly accurate data for assessing global function based on LV volume and ejection fraction. It provides a novel, simple and promising approach for detecting dyssynchrony in future clinical use. But whether it can be used to select suitable candidates for CRT, predict and evaluate the effects of CRT remains to be further studied.
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