Assessment of myocardial blood flow and volume using myocardial contrast echocardiography

The development of new microbubble agents and ultrasound imaging modalities now allows the assessment of myocardial perfusion with echocardiography. Microbubbles also can be administered intravenously as constant infusions, which allows their concentration in blood to reach steady state. If the relation between microbubble concentration and video intensity is within the linear range, then myocardial video intensity will reflect the concentration of microbubbles in that region, which at steady state is the myocardial blood volume. The ability to destroy microbubbles and measure their replenishment into the ultrasound beam provides an opportunity to evaluate microbubble (or red blood cell) velocity. The product of myocardial blood volume and red blood cell velocity represents myocardial blood flow.     

The effect of rapid decreases of blood pressure by different mechanisms on coronary flow and flow reserve in normal coronary arteries

BACKGROUND: Changes in mean blood pressure (MBP) alter coronary blood flow (CBF). We evaluated the acute effects of three hypotensive medications on CBF parameters in angiographically normal coronary arteries. METHODS: We performed CBF measurements using the Doppler wire at rest and during hyperemia produced by intracoronary adenosine (18 microg) as follows: 1) in the normal left circumflex coronary artery in 20 patients with coronary artery disease (measurements were performed without drugs, and after intravenous infusion of nitroprusside [0.5 to 2 microg/kg/min] and nitroglycerin [10 to 90 microg/min]; drugs were titrated to decrease MBP 20% to 25% below the control values, and heart rate was held constant using right atrial pacing); and 2) in the normal left anterior descending coronary artery in 19 patients without coronary artery disease (measurements were performed before and after intravenous clonidine infusion [150 microg in 5 min]; time-averaged peak velocity [APV], CBF, and coronary flow reserve [CFR] were measured). RESULTS: Similar decreases in MBP were obtained in the two patient groups. Lumen diameter at the site of Doppler measurements increased after all medications (P <.005), whereas CBF did not change significantly. The CFR decreased after nitroprusside (1.79 +/- 0.48 v 2.54 +/- 0.45, P=.000), did not change significantly after nitroglycerin (2.74 +/- 0.43 v 2.54 +/- 0.45, P =.097), and increased after clonidine (3.12 +/- 0.70 v 2.76 +/- 0.75, P =.006). CONCLUSIONS: In normal coronary arteries the infusion of three hypotensive medications to produce the same decreases in MBP is associated with different effects on CFR (increase with clonidine, decrease with nitroprusside, and no change with nitroglycerin).     

Coronary blood flow reserve and wall motion recovery in patients undergoing angioplasty for myocardial infarction.

AIMS: The aim of this study was to evaluate the relationship between coronary flow reserve and the recovery of wall motion contractility in patients with recent myocardial infarction. METHODS AND RESULTS: Nineteen patients (55 +/- 8 years) undergoing balloon angioplasty for recent myocardial infarction were studied. After angioplasty, coronary flow reserve was lower in the infarct-related artery than in a reference artery, 2.2 +/- 0.6 and 2.8 +/- 0.7, respectively, P < 0.05. There was no immediate correlation between coronary blood flow reserve measured after angioplasty and wall motion index. There was a negative correlation between coronary flow reserve and the number of necrotic segments (r = -0.43; P0.006). At the 4 month control angiogram, there was a significant increase in both left ventricular ejection fraction (59 +/- 14% vs 51 +/- 13%; P < 0.05) and wall motion index (-0.63 +/- 1.2 vs -1.94 +/- 0.9 units SD, P = 0.005). In patients in whom wall motion improved (> 1 unit SD), the immediate coronary flow reserve was higher (P < 0.05) than in patients without improved wall motion. In this group, the increase in wall motion index was correlated to the coronary blood flow reserve (r = 0.55; P < 0.02). CONCLUSION: These data show that after myocardial infarction, coronary flow reserve is associated with myocardial viability.     

应用实时心肌超声造影定量评价心功能对急性心肌梗死犬心肌血流量的影响

目的:探讨心功能对心肌梗死犬心肌血流灌注的影响。方法:18只健康杂种犬于前降支分出的第1对角支远端约1cm处结扎3h,应用心肌超声造影(MCE)定量分析左室前壁中间段和下壁中间段心肌血流量(MBF)。结果:17只犬成功建立急性心肌梗死模型。根据结扎3h后左室整体射血分数(EF)分为2组:A组(EF≥50%)7只,B组(EF<50%)10只。B组左室前壁中间段和下壁中间段MBF均低于A组,但2组之间差异无统计学意义;与结扎前相比,2组左室前壁中间段MBF均明显降低,差异有统计学意义(P<0.05),A组左室下壁中间段MBF略升高,B组则降低,但均差异无统计学意义。结论:心功能对MBF有一定的影响,可能会低估冠状动脉血流储备和高估狭窄程度,在以MCE诊断冠心病时应注意心功能对MBF的影响。     

Assessment of regional myocardial blood flow with myocardial contrast echocardiography: an experimental study

OBJECTIVES: The aim of this study was to verify the accuracy of using myocardial contrast echocardiography (MCE), to quantify regional myocardial blood flow (MBF), and to evaluate myocardial viability in comparison to that measured by radiolabeled microsphere and pathologic examination. METHODS: Epicardial MCE was obtained in five myocardial ischemic dogs with constant microbubble intravenous infusion. After the video intensity (VI, y) versus pulsing interval plots derived from each myocardial pixel were fitted to an exponential function: y = A(1 - e(-beta t)), the MBF was calculated as the product of A (microvascular cross-sectional area or myocardial blood volume) and beta (mean myocardial microbubble velocity). The MBF was also obtained by radiolabeled microsphere method. RESULTS: The MBF derived by radiolabeled microsphere method in the normal, ischemic, and infarcted region was 1.5 +/- 0.3, 0.7 +/- 0.3, and 0.3 +/- 0.2 ml/min per gram, respectively; P < 0.01. The product of A and beta in those regions was 52.5 +/- 15.1, 24.4 +/- 3.9, and 3.7 +/- 3.8, respectively; P < 0.01. The normalized product of A and beta correlated well with normalized MBF (r = 0.81, P = 0.001). CONCLUSION: Our initial study demonstrated that MCE has an ability to assess MBF in ischemic myocardium in the experimental model. It may provide a potential capability to detect viable myocardium noninvasively after total persistent coronary occlusion in the clinical setting.     

Evaluation of coronary flow reserve using myocardial contrast echocardiography in humans.

To evaluate the applicability of myocardial contrast echocardiography for the assessment of coronary blood flow reserve, 21 consecutive patients undergoing coronary angiography were studied. Only patients with a single left anterior descending lesion or normal coronary angiogram were included. Intracoronary injections of sonicated albumin were performed before and after the administration of intracoronary papaverine. Good quality studies at baseline and after the administration of papaverine were obtained in 14 of 21 patients. Ten patients had a significant (greater than 75%) single left anterior descending lesion and four had normal or insignificant lesions (70% or less stenosis) in the left anterior descending coronary artery. Time-intensity curves for the left anterior descending coronary artery region of interest were generated and then the peak contrast intensity (PCI), washout half-time (T1/2) and the area under the curve (AUC) were calculated. The post-papaverine increases in PCI and in the AUC, compared to baseline, were 55 +/- 22% and 102 +/- 14% in the four patients with 70% or less left anterior descending diameter stenosis serving as a control group and 3 +/- 25% and 40 +/- 10%, respectively, in the 10 patients with significant left anterior descending coronary artery disease (mean +/- 1 SD, P less than 0.01). In patients with normal coronary arteriography T1/2 increased after intracoronary injection of papaverine. In patients with severe lesions, either an increase or a decrease in T1/2 was observed. Significant left anterior descending coronary artery stenosis associated with impaired coronary blood flow reserve can be detected by failure of myocardial contrast echocardiographic parameters to increase after injection of papaverine. Mild and transient side effects were noted in three patients.     

经导管急性微血管栓塞对冠状动脉血流和冠状动脉血流储备的影响

目的　建立经导管的急性微血管栓塞动物模型 ,研究不同微栓塞水平冠状动脉血流(CBF)和冠状动脉血流储备 (CFR)的变化。方法　 10头小型猪 (2 1～ 2 5kg) ,不开胸经导管由前降支重复注入微栓塞球 (4 5 μm) ,使用多普勒导丝、压力导丝和腔内超声导管测量前降支中段平均流速、压力和腔内面积 ,CBF =平均流速×面积。冠状动脉内注射腺苷 18μg达到最大充血状态 ,CFR =充血CBF 基础CBF。在微栓塞前、注入 5万、10万、12万、14万和 15万微栓塞球时分别测量基础状态和充血状态的血流动力学指标。结果　注入 5万微球时基础CBF(rCBF)升高 ,较微栓塞前差异有显著性[(0 30± 0 0 9)ml·s- 1 vs (0 2 6± 0 10 )ml·s- 1 ,P <0 0 5 ],随着微球量的增加rCBF降低。CFR在微栓塞后降低 ,不同微栓塞水平的CFR与微栓塞前比较差异均有显著性。结论　经导管急性微血管栓塞中 ,随着微栓塞球量增加 ,rCBF呈现先增加后下降的双期改变 ;微栓塞后CFR下降 ,CFR在一定微栓塞程度时又有增加。     

Dynamic changes in microcirculatory blood flow during dobutamine stress assessed by quantitative myocardial contrast echocardiography

Background: Although dobutamine‐atropine stress echocardiography (DASE) has been widely used for evaluating patients with coronary artery disease (CAD), dynamic changes that occur at microcirculatory level during each stage of stress have not been demonstrated in humans. Aim: We sought to determine variations in myocardial blood flow (MBF) during DASE using quantitative real time myocardial contrast echocardiography (RTMCE). Methods: We studied 45 patients who underwent coronary angiography and RTMCE. Replenishment velocity of microbubbles in the myocardium (β) and MBF reserves were obtained at baseline, intermediate stage (70% of maximal predicted heart rate), peak stress, and recovery phase. Results: β and MBF reserves were lower in patients with than without CAD at intermediate (1.65 vs. 2.10; P = 0.001 and 2.44 vs. 3.23; P = 0.004) and peak (1.63 vs. 3.00; P < 0.001 and 2.14 vs. 3.98; P < 0.001, respectively). In patients without CAD, β, and MBF reserves increased from intermediate to peak and decreased at recovery, while in those without CAD reserves did not change significantly. Optimal cutoff values of β reserve at intermediate, peak, and recovery were 1.78, 2.09, and 1.70, with areas under the curves of 0.80 (95%CI = 0.67–0.94), 0.89 (95%CI = 0.79–0.99), and 0.69 (95%CI = 0.53–0.85). Sensitivity, specificity and accuracy for detecting CAD at intermediate stage were 68% (95%CI = 48–89), 85% (95%CI = 71–98), and 78% (95%CI = 66–90), at peak stress were 79% (95%CI = 61–97), 96% (95%CI = 89–100), and 89% (95%CI = 80–98), and at recovery were 74% (95%CI = 54–93), 65% (95%CI = 47–84), and 69% (95%CI = 55–82), respectively. Conclusion: RTMCE allows for quantification of dynamic changes in microcirculatory blood flow at each stage of DASE. The best parameter for detecting CAD in all stages was β reserve. (Echocardiography 2011;28:993‐1001)     

血流储备分数指导冠心病介入治疗的研究

目的:讨论血流储备分数(FFR)指导冠心病介入治疗(PCI)的疗效.方法:入选2011年8月至2013年8月共126例需作介入治疗的冠心病患者,根据FFR分组,实验组:FFR≥0.8,63例,行延迟PCI+强化药物治疗(OMT)],共有77处病变;对照组:FFR＜0.8,63例,行PCI+ OMT,共有92处病变.所有患者在术后第12、24、36个月进行电话随访,在PCI术后12个月进行冠脉造影的复查.观察主要心血管不良事件(MACE).结果:实验组平均血管狭窄率明显低于FFR＜0.8组[(49.5±5.3)％比(75.9±10.1)％];术后经过(27.1±8.8)个月的随访,实验组有4例(6.4％)发生MACE事件:1例(1.6％)死亡,与对照组的MACE事件(14.3％,9/63),死亡率4.8％ (3/63)无显著差异,P＞0.05.结论:对于血流储备分数(FFR)≥0.8有手术指征的冠心病患者行延迟PCI+OMT是安全有效的.     

阿托伐他汀对冠状动脉血流缓慢患者冠状动脉血流储备的影响

目的 探讨冠状动脉血流缓慢患者冠状动脉血流储备(CFR)的改变以及阿托伐他汀对这类患者CFR的影响.方法 入选有胸痛症状但冠状动脉造影结构正常的冠状动脉血流缓慢患者91例,分为治疗组(51例)和无治疗组(40例).治疗组给予阿托伐他汀20 mg治疗8周.另选26例冠状动脉造影正常且运动试验阴性的无心脏疾患者为正常对照组.治疗前后测定治疗组和无治疗组的血脂以及利用腺苷负荷超声记录左前降支远端血流频谱,并评价CFR.结果 (1)冠状动脉血流缓慢者接受阿托伐他汀8周治疗后总胆固醇(TC)和低密度脂蛋白胆固醇(LDL-C)较无治疗组及正常对照组明显减低[TC:(3.83±0.80)mmol/L比(5.30±1.18)mmol/L和(5.32±1.17)mmol/L,均P＜0.05:LDL=C:(2.26±0.64)mmol/L比(3.28±0.85)mmol/L和(3.30±0.82)mmol/L,均P＜0.05].(2)给予阿托伐他汀前,治疗组与无治疗组CFR(分别为2.32±0.30和2.25±0.33)均低于正常对照组(3.15±0.34,P＜0.05);8周后,治疗组冠状动脉血流速度(CFV)[(26.06±3.22)cm/s]较无治疗组[(29.02±3.36)cm/s]及治疗前静息状态[(28.43±3.40)cm/s]低(均P＜0.05),最大冠状动脉扩张状态CFV高于无治疗组和对照组[分别为(77.63±8.96)、(65.17±7.22)和(64.58±6.26)cm/s,P＜0.05],CFR低于治疗前和无治疗组(分别为3.07±0.29、2.28±0.35和2.32±0.30,P＜0.05),且与正常对照组差异均无统计学意义.结论 冠状动脉血流缓慢患者CFR明显减低,短期阿托伐他汀在调脂的同时可以有效改善其CFR.     

Regional myocardial perfusion reserve determined using myocardial perfusion magnetic resonance imaging showed a direct correlation with coronary flow velocity reserve by Doppler flow wire

Aims: Quantitative analysis of rest–stress myocardial perfusionmagnetic resonance imaging (MRI) can provide assessments ofregional myocardial perfusion reserve (MPR). The purpose ofthis study was to compare regional MPR determined by myocardialperfusion MRI with coronary flow reserve (CFR) by intracoronaryDoppler flow wire. Methods and results: Twenty patients with suspected coronary artery disease (CAD)were studied. Average peak velocity was measured by Dopplerflow wire in the resting state and during adenosine triphosphate(ATP) stress in 36 coronary arteries. CFR measurements for eachpatient were performed in the culprit and one non-culprit non-stenoticartery. First-pass, contrast-enhanced myocardial perfusion MRimages were obtained in the resting state and during ATP stresswithin the week before the Doppler wire procedure. Regionalmyocardial blood flow (MBF) was quantified in 16 myocardialsegments by analysing arterial input and myocardial output usinga Patlak plot method. MPR was calculated as stress MBF dividedby rest MBF. CFR measured by Doppler flow wire was comparedwith MPR in the myocardial segments corresponding to vesselterritories. The average MPR measured by perfusion MRI was 1.77± 0.62 for the culprit arteries and 3.45 ± 0.78for the non-culprit arteries, respectively (P < 0.001). Theaveraged CFR by Doppler flow wire was 1.72 ± 0.44 inthe culprit arteries and 3.14 ± 0.74 in the non-culpritarteries, respectively (P < 0.001). For both culprit andnon-culprit vessel groups, significant direct correlations wereobserved between MR assessments of MPR and Doppler assessmentsof CFR (culprit artery: R = 0.87, Non-culprit artery: R = 0.86)On Bland–Altman analysis, the mean differences betweenMPR determined by myocardial perfusion MRI and CFR measuredby Doppler wire were 0.05 in culprit arteries (95% limit ofagreement; –0.65 to 0.56) and 0.36 in non-culprit arteries(95% limit of agreement; –1.24 to 0.44). The sensitivityand specificity of MR measurement of MPR for predicting physiologicallysignificant reduction of Doppler CFR (<2) was 88% (95% CI61.7–98.5) and 90% (95% CI 68.3–98.8), respectively. Conclusion: The current results using Doppler flow wire as a reference methoddemonstrated that quantitative analysis of stress–restmyocardial perfusion MRI can provide a non-invasive assessmentof reduced MPR in patients with CAD.     

Effects of smoking on coronary blood flow velocity and coronary flow reserve assessed by transthoracic Doppler echocardiography

BACKGROUND: Smoking is a well-known risk factor for cardiovascular disease. Coronary blood flow velocity (CFV) can be measured directly with transthoracic Doppler echocardiography (TTDE) which is conducted immediately after smoking. PURPOSE: The purpose of this study was to evaluate the chronic and acute effects of smoking on coronary blood flow and coronary flow reserve (CFR) by the use of TTDE. METHODS: Healthy volunteers (11 smokers and 9 nonsmokers) with a mean age of 27 +/- 3 years were included. Smoking was abstained for at least 4 hours before the study. CFV was measured at the distal left anterior descending coronary artery by TTDE at baseline and during intravenous adenosine infusion (140 microg/kg per minute) in all participants. For smokers, CFV was measured immediately after consecutively smoking two cigarettes and during adenosine infusion. RESULTS: CFR and coronary vascular resistance index (CVRI) showed no significant difference between nonsmokers and smokers (CFR: 3.5 +/- 0.8 vs 3.6 +/- 0.6, P = ns, CVRI: 0.28 vs 0.28, P = ns) at baseline. CFR significantly decreased (3.6 +/- 0.6 to 2.8 +/- 0.7, P = 0.008) and CVRI markedly increased (0.28 to 0.35, P = 0.012) after smoking. CONCLUSION: After 4 hours of abstinence from smoking, CFR and CVRI in smokers were similar to those of nonsmokers. However, consecutively smoking two cigarettes acutely reduced CFR and increased CVRI. These findings suggested that smoking could reduce coronary blood flow immediately, even in healthy people.     

Assessment of myocardial viability with myocardial contrast echocardiography

The application of noninvasive imaging techniques to assess myocardial viability has become an important part of routine management of patients with acute myocardial infarction and chronic coronary artery disease. Information regarding the presence and extent of viability may help identify patients likely to benefit from revascularization or therapy directed at attenuating left ventricular remodeling. Myocardial contrast echocardiography (MCE) is capable of defining the presence and extent of viability by providing an accurate assessment of microvascular integrity needed to maintain myocellular viability. It is especially suited for the spatial assessment of perfusion, even when myocardial blood flow is reduced substantially in the presence of severe epicardial stenoses or in a bed dependent on collateral perfusion. The routine use of MCE to evaluate viability in patients with acute and chronic coronary artery disease is now feasible with the advent of new imaging technologies and microbubble agents capable of myocardial opacification from venous injections. The utility of this technique for determining treatment strategies has not been established but is forthcoming.     

临界性高血压患者冠状动脉血流储备功能的研究

目的 :了解无症状临界性高血压患者是否有冠状动脉功能异常。方法 :经食管超声心动描记术研究 2 0例正常人 (正常对照组 )及 17例无症状临界性高血压患者 (临界性高血压组 )的冠状动脉血流储备 (CFR)。以潘生丁静脉注射后和静息时舒张期的最大血流速度比率 (D/R PDV)和收缩期最大血流速度比率 (D/R PSV )作为CFR指标。结果 :1两组受检者静息时的 PDV无显著性差异〔(43± 10 ) m m/s∶ (46± 8) mm /s,P >0 .0 5〕;2静脉注射潘生丁后临界性高血压组的 D/R PDV、D/R PSV较正常对照组明显减少 ,两组之间有显著性差异 (D/RPDV:2 .2 5± 0 .36∶ 2 .86± 0 .42 ,D/R PSV:2 .0 0± 0 .2 6∶ 2 .5 6± 0 .41,P<0 .0 5 )。结论 :无症状临界性高血压患者 CFR能力降低。     

Coronary flow reserve in dipper and non-dipper hypertensive patients

Background. Failure to decrease blood pressure (BP) normally during night-time, which is called non-dipping, in hypertensive individuals is associated with higher cardiovascular morbidity and mortality. In addition, non-dipping BP leads to structural changes in the left ventricle; however, the effect of non-dipping BP on coronary flow reserve (CFR) has not been studied yet. Methods. In this study, we measured CFR of 22 subjects with non-dipper hypertension, and 15 subjects with dipper hypertension using transthoracic second-harmonic Doppler echocardiography (Acuson Sequoia C256®). None of the subjects had any systemic disease or coronary risk factor except hypertension. Results. Age, gender, body mass index, lipids and echocardiographic findings including left ventricular mass index were similar between the groups. Office BP recordings were similar between non-dipper and dipper groups (147.9±6.1/93.9±4.3 vs 144.0±8.0/93.0±3.7). Daytime and 24-h ambulatory BP measurements were similar within the groups, but night-time BPs were significantly greater in non-dipper group than those were in dipper group. Left ventricular diastolic and systolic functions, and both baseline and hyperemic peak diastolic coronary velocity as well as CFR, were similar between the non-dipper and dipper groups (CFR: 2.47±0.59 vs 2.39±0.47). Conclusion. CFR were similar in patients with non-dipper and dipper hypertension in the absence of excessive left ventricular hypertrophy and other cardiovascular risk factors.     

Qualitative and quantitative real time myocardial contrast echocardiography for detecting hibernating myocardium

Background: Real time myocardial contrast echocardiography (RTMCE) is an emerging imaging modality for assessing myocardial perfusion that allows for noninvasive quantification of regional myocardial blood flow (MBF). Aim: We sought to assess the value of qualitative analysis of myocardial perfusion and quantitative assessment of myocardial blood flow (MBF) by RTMCE for predicting regional function recovery in patients with ischemic heart disease who underwent coronary artery bypass grafting (CABG). Methods: Twenty‐four patients with coronary disease and left ventricular systolic dysfunction (ejection fraction <45%) underwent RTMCE before and 3 months after CABG. RTMCE was performed using continuous intravenous infusion of commercially available contrast agent with low mechanical index power modulation imaging. Viability was defined by qualitative assessment of myocardial perfusion as homogenous opacification at rest in ≥2 segments of anterior or ≥1 segment of posterior territory. Viability by quantitative assessment of MBF was determined by receiver‐operating characteristics curve analysis. Results: Regional function recovery was observed in 74% of territories considered viable by qualitative analysis of myocardial perfusion and 40% of nonviable (P = 0.03). Sensitivity, specificity, positive and negative predictive values of qualitative RTMCE for detecting regional function recovery were 74%, 60%, 77%, and 56%, respectively. Cutoff value of MBF for predicting regional function recovery was 1.76 (AUC = 0.77; 95% CI = 0.62–0.92). MBF obtained by RTMCE had sensitivity of 91%, specificity of 50%, positive predictive value of 75%, and negative predictive value of 78%. Conclusion: Qualitative and quantitative RTMCE provide good accuracy for predicting regional function recovery after CABG. Determination of MBF increases the sensitivity for detecting hibernating myocardium. (Echocardiography 2011;28:342‐349)     

Effects of selective injection of contrast media on coronary artery diameter

The purpose of this study was to quantify the effect of Renografin-76 on eplcardial coronary artery diameters, during selective coronary anglography. Using 105 mm-photospot angiograms taken at 0,1, and 5 min, 99 coronary segments from ten patients were measured. Comparing the anglograms at 1 and 5 min to the control anglograms, a7 ± 7% and 6 ± 7% (both p = NS) change in diameter respectively was noted. Comparing the 1 and 5 min anglograms, there was no significant change (-1 ± 7%). Measurements were found to be very reproducible. This study shows that there is a trend toward dilation of the coronary arteries during selective coronary anglography, but this did not reach statistical significance and probably is not clinically important.