Evaluation of myocardial perfusion and deformation in patients with acute myocardial infarction treated with primary angioplasty and stent placement.

PURPOSE: To prospectively compare the usefulness of myocardial perfusion and deformation imaging for the prediction of functional recovery and left ventricular (LV) remodeling in patients with ST-elevation myocardial infarction (STEMI). METHODS: We prospectively examined 36 patients with reperfused STEMI, 12+ or -9 h after primary angioplasty and stent placement. LV function was reevaluated at 4-6 months of follow-up, to assess relative improvement of LV-ejection fraction (DeltaEF%) and increase in end-diastolic volume (DeltaEDV). RESULTS: During the follow-up period, 19 of 36 patients showed LV function improvement (DeltaEF%> or =10%), whereas 10 patients had LV remodeling (DeltaEDV> or =20%). Peak negative strain (epislon (peak)), peak negative strain rate (SRpeak), and myocardial blood flow (Axbeta) correlated with DeltaEF% (r=-0.55, -0.57, and 0.46, respectively, P<0.01 for all), and allowed for prediction of LV remodeling on an individual level (area under the curve of 0.85 for strain rate, 0.95 for strain, and 0.90 for regional blood flow, P<0.001 for all). The combined assessment of myocardial perfusion and deformation correctly predicted LV remodeling in four additional patients, compared with each technique separately. CONCLUSION: Contrast echocardiography, strain Doppler imaging, and possibly the combination of both are useful for the prediction of adverse LV remodeling and for the early risk stratification of patients with STEMI.

Caught in the act: entrapped embolus through a patent foramen ovale.

A patent foramen ovale (PFO) is detected frequently by transesophageal echocardiography. The diagnosis of paradoxical embolism is usually presumptive when arterial emboli occur in the appropriate clinical setting. Presumably, paradoxical embolism of small thrombi arise in the venous system and pass through the PFO during a transient right-to-left shunt; however, cases demonstrating a thrombus traversing the PFO are relatively few.

Evaluation cardioprotective effects of atorvastatin in rats by real time myocardial contrast echocardiography.

BACKGROUND: The ability to assess myocardial perfusion in small animals is important, especially to investigate models of myocardial ischemia. Myocardial perfusion is usually assessed by postmortem techniques, eliminating the possibility of follow-up in intervention studies. The purpose of the study was to examine the feasibility of real time myocardial contrast echocardiography (MCE) to evaluate cardioprotective effects of atorvastatin in a rat model of acute ischemia-reperfusion injury. METHODS: The rats (n=15) underwent 20 minutes of mechanical left descending coronary artery (LAD) occlusion followed by 180 minutes of reperfusion. The animals received either atorvastatin (10 mg/kg), atorvastatin and the nitric oxide synthase (NOS)-inhibitor N-Nitro-L-Argininemethylester (L-NAME) (15 mg/kg), or vehicle. MCE was performed to assess the size of the perfusion defect and the myocardial signal intensities (A(max)) at the baseline, during occlusion, and during reperfusion. For comparison, the infarct size, risk area, and regional myocardial blood flow (MBF) were determined by the standard techniques as well. RESULTS: The dynamics of ischemia-reperfusion injury could be visualized serially by MCE. The infarct size-to-risk area ratio progressively increased during reperfusion and was markedly reduced in the atorvastatin group. Triphenyltetrazolium chloride (TTC) staining confirmed a 23% reduction in the infarct size by atorvastatin. The infarct size by MCE correlated well with the histological methods (r=0.86, P < 0.001). A(max) was reduced in the anterior segments during LAD occlusion (0.08 +/- 0.01 dB) compared to the baseline (2.9 +/- 0.4 dB), approached higher levels post revascularization of LAD (3.22 +/- 0.50 dB), but decreased during 180 minutes of reperfusion (2.32 +/- 0.40 dB). After 180 minutes of reperfusion, A(max) in the risk area was significantly higher in the atorvastain-treated group compared to the vehicle-treated group (2.32 +/- 0.40 dB vs 1.3 +/- 0.4 dB, P

Quantitative evaluation of myocardial blush to assess tissue level reperfusion in patients with acute ST-elevation myocardial infarction: incremental prognostic value compared with visual assessment.

BACKGROUND: Tissue level reperfusion gauges functional recovery in acute ischemic syndromes. However, its current clinical assessment is based upon visual interpretation of myocardial blush grade (MBG), which is operator dependent. The purpose of the study was to test whether quantification of MBG can enhance the predictive value of visual assessment for functional recovery in patients with acute ST-elevation myocardial infarction (STEMI). METHODS: Myocardial blush grade was assessed in 124 consecutive patients with STEMI visually and quantitatively, analyzing the time course of blush intensity rise. We defined Gmax as the peak gray level intensity and Tmax as the time to peak intensity. Ejection fraction >50% at 4 to 6 months of follow-up was deemed as the primary end point for assessment of successful tissue reperfusion. RESULTS: Ejection fraction >50% at follow-up was predicted by visual MBG with moderate sensitivity (65%) and specificity (64%). However, a cutoff value of Gmax/Tmax = 3.1/s yielded significantly higher sensitivity and specificity (91% and 96%, respectively, for both P < .01). Gmax/Tmax was the most powerful predictor of follow-up ejection fraction >50% (relative risk of 4.6 vs 3.2 for visual MBG). CONCLUSIONS: Quantitative MBG is highly predictive for functional recovery in patients with STEMI and provides incremental prognostic value to visual assessment. Thus, this simple approach may be used to gauge reperfusion strategies in acute ischemic syndromes.

Intravenous delivery of autologous mesenchymal stem cells limits infarct size and improves left ventricular function in the infarcted porcine heart.

Systemic delivery of bone marrow-derived mesenchymal stem cells (MSCs) is a noninvasive approach for myocardial repair. We aimed to test this strategy in a pig model of myocardial infarction. Pigs (n = 8) received autologous MSCs (1 x 10(6)/kg body weight) labeled with fluorescent dye 48 h post proximal left anterior descending artery (LAD) occlusion. Hemodyamics, infarct size, and myocardial function were assessed at baseline and after 1 month. Morphologic analysis revealed that labeled MSCs migrated in the peri-infarct region, resulting in smaller infarct size (32 +/- 7 vs. 19 +/- 7%, p = 0.01), higher fractional area shortening (23 +/- 3 vs. 34.0 +/- 7%, p = 0.001), lower left ventricular end diastolic pressure (18.7 +/- 5 vs. 10.2 +/- 4 mmHg, p = 0.02) and higher +dp/dt (4,570 +/- 540 vs. 6,742 +/- 700 mmHg/s, p = 0.03) during inotropic stimulation. Systemic intravenous delivery of MSCs to pigs limits myocardial infarct size and is an attractive approach for tissue repair.

Impact of microbubbles on shock wave-mediated DNA uptake in cells in vitro.

Gas-filled microbubbles have been successfully used as gene delivery reagents in combination with diagnostic ultrasound. Although shock wave exposure has been shown to transfect cells with naked DNA in vitro, it has not been tested whether the addition of microbubbles would augment DNA uptake under those conditions. Therefore, the aim of this study was to test the impact of microbubbles on transgene expression in vitro under shock wave exposure conditions. HEK 293 cells were treated with 60 or 120 pulses of shock waves at varying energy levels. Cells were mixed with either 100 microg/mL luciferase expressing plasmid DNA or with microbubbles that were produced with the same amount of this DNA. Cell death was evaluated after 1 h and transgene expression, after 24 h. In the presence of microbubbles, transgene expression was significantly higher (as much as 29-fold) relative to that obtained without microbubbles. Cells exposed to 120 pulses demonstrated higher transgene expression (as high as 2.7-fold) compared with cells exposed to 60 pulses. The use of microbubbles resulted in greater cell death, varying from 26% (low energy) to 78% (high energy). In conclusion, DNA-loaded microbubbles can significantly increase shock wave mediated gene transfer. However, this effect is associated with increased levels of cell destruction.

Real-time myocardial perfusion imaging for pharmacologic stress testing: added value to single photon emission computed tomography.

BACKGROUND: Little is known about the incremental value of real-time myocardial contrast echocardiography (MCE) as an adjunct to pharmacologic stress testing. This study was performed to evaluate the diagnostic value of MCE to detect abnormal myocardial perfusion by technetium Tc 99m sestamibi-single photon emission computed tomography (SPECT) and anatomically significant coronary artery disease (CAD) by angiography. METHODS: Myocardial contrast echocardiography was performed at rest and during vasodilator stress in consecutive patients (N = 120) undergoing SPECT imaging for known or suspected CAD. Myocardial opacification, wall motion, and tracer uptake were visually analyzed in 12 myocardial segments by 2 pairs of blinded observers. Concordance between the 2 methods was assessed using the kappa statistic. RESULTS: Of 1356 segments, 1025 (76%) were interpretable by MCE, wall motion, and SPECT. Sensitivity of wall motion was 75%, specificity 83%, and accuracy 81% for detecting abnormal myocardial perfusion by SPECT (kappa = 0.53). Myocardial contrast echocardiography and wall motion together yielded significantly higher sensitivity (85% vs 74%, P < .05), specificity of 83%, and accuracy of 85% (kappa = 0.64) for the detection of abnormal myocardial perfusion. In 89 patients who underwent coronary angiography, MCE and wall motion together yielded higher sensitivity (83% vs 64%, P < .05) and accuracy (77% vs 68%, P < .05) but similar specificity (72%) compared with SPECT for the detection of high-grade, stenotic (> or = 75%) coronary lesions. CONCLUSION: Assessment of myocardial perfusion adds value to conventional stress echocardiography by increasing its sensitivity for the detection of functionally abnormal myocardial perfusion. Myocardial contrast echocardiography and wall motion together provide higher sensitivity and accuracy for detection of CAD compared with SPECT.

Evidence of left ventricular contractile asynchrony by echocardiographic phase imaging in patients with type 2 diabetes mellitus and without clinically evident heart disease.

Left ventricular electromechanical asynchrony has been shown to predict cardiac events in patients with heart failure. This study investigated whether left ventricular asynchrony is present in patients with type 2 diabetes mellitus (DM) with no clinically evident heart disease and normal QRS durations. Asynchrony was evaluated in 24 patients with DM, 15 nondiabetic control subjects, and 20 patients with left bundle branch block (LBBB) due to cardiomyopathy serving as positive controls by conventional tissue Doppler imaging and by a novel method, echocardiographic phase imaging. Asynchrony was significantly higher in patients with DM than in controls and significantly lower than in patients with LBBB. This was shown by tissue Doppler imaging: the SD of time to peak myocardial velocity was 13 +/- 10 ms in controls, compared with 30 +/- 19 ms in patients with DM (p <0.01) and 68 +/- 28 ms in those with LBBB (p <0.001). Similar data were obtained using echocardiographic phase imaging: the SD of phase degrees was 25 degrees +/- 8 degrees in controls, compared with 44 degrees +/- 21 degrees in patients with DM (p = 0.02) and 76 degrees +/- 25 degrees in those with LBBB (p <0.001). Tissue Doppler imaging correlated with echocardiographic phase imaging (r = 0.79, p <0.0001) but was more time consuming (15.5 +/- 4.5 vs 4.5 +/- 2.2 min/patient, p <0.05) and showed higher intraobserver variability (5.6% vs 3.2%, p <0.05). In conclusion, this is the first study showing increased left ventricular asynchrony in patients with DM and no clinical evidence of heart disease.

Ultrasound exposure can increase the membrane permeability of human neutrophil granulocytes containing microbubbles without causing complete cell destruction.

Activated polymorphonuclear neutrophil (PMN) granulocytes can bind and subsequently phagocytose microbubbles used as ultrasound (US) contrast agents. The purpose of the present study was to assess insonation effects on cell membrane integrity and metabolic activity of activated PMN. Furthermore, we investigated whether or not there is an acoustic threshold at which insonation of PMN results in increase of membrane permeability without causing complete cell destruction. PMN isolated from healthy volunteers were activated with phorbol myristate acetate (PMA) for 15 min to allow phagocytosis of albumin and lipid microbubbles and were subsequently exposed to US with a mechanical index between 0.15 and 1.8. Apoptosis, loss of membrane integrity and formation of cell fragments were evaluated by measurement of lactate dehydrogenase leakage and by double staining with annexin V and propidium iodide, using flow cytometry. Neutrophil superoxide anion generation was measured photometrically. Insonation of activated PMN in the presence of microbubbles amplified apoptosis and lactate dehydrogenase leakage and induced loss of membrane integrity and complete cell destruction with increasing acoustic pressures. The bioeffects observed by insonation with high mechanical indices (1.0 to 1.8), and particularly the formation of cell fragments, were significantly more pronounced in the presence of albumin microbubbles. Insonation in the presence of lipid microbubbles increased cell membrane permeability, but caused significantly less cell destruction and left the metabolic activity of activated PMN uninfluenced. Thus, both albumin and lipid microbubbles induce apoptosis and membrane injury during insonation of activated PMN. However, insonation in the presence of lipid microbubbles seems to influence cell viability to a smaller extent. This could be of advantage in the setting of US-guided local drug delivery. In this setting, increase of membrane permeability may allow bioactive substances to enter into cells, which survive the US treatment, and specifically modify their function.

The potential of a new stable ultrasound contrast agent for site-specific targeting. An in vitro experiment.

Microbubble-based ultrasound contrast agents can be used for specific site targeting, but demonstrate time-limited opacification. We have previously demonstrated the potential of gold-bound microtubules to provide a stable ultrasound contrast effect. Aim of the present study was to test the feasibility of gold-bound microtubules specifically to bind to human thrombi and to inflammatory activated human umbilical vein endothelial cells (HUVEC) in vitro. HUVEC were incubated with tumor necrosis factor, to induce expression of adhesion molecules. Human clots and HUVEC were incubated with biotinylated monoclonal antifibrin and anti-E-selectin antibodies, respectively. Probes were incubated with excess avidin followed by biotinylated gold-bound microtubules and by secondary Cy3-anti-beta-tubulin antibody and processed for immune fluorescence microscopy. Clots were transferred in copolymer foils filled with buffer and were ultrasonographically imaged before and after their treatment with the antifibrin antibody and with biotinylated microtubules, using a broadband harmonic transducer, transmitting and receiving at a mean frequency of 1.7 MHz and 3.2 MHz. The feasibility of specific gold-bound microtubules conjugation to antibody treated clots and HUVEC was confirmed using immune fluorescence analysis. Contrast intensities of the clots significantly increased after their treatment with antifibrin antibody and incubation with gold-bound microtubules (39 +/- 2 dB versus 26 +/- 2 dB, p < 0.001) and remained high after 20 min of ultrasound exposure (37 +/- 2 dB versus 39 +/- 2 dB, p = NS). Thus, gold-bound microtubules can specifically bind to human thrombi and to endothelial cells, providing a significant contrast effect which remains stable in the ultrasound field. This may be a promising approach to target thrombi and inflammatory active atherosclerotic plaques.

Evaluation of cardioprotective effects of recombinant soluble P-selectin glycoprotein ligand-immunoglobulin in myocardial ischemia-reperfusion injury by real-time myocardial contrast echocardiography.

OBJECTIVES: The purpose was to examine the cardioprotective effects of recombinant P-selectin glycoprotein ligand-immunoglobulin (rPSGL-Ig) in ischemia-reperfusion injury by real-time myocardial contrast echocardiography (MCE). BACKGROUND: P-selectin mediates leukocyte recruitment into areas of inflammation. METHODS: Sixteen pigs underwent 45 min of left anterior descending coronary artery occlusion followed by reperfusion and received rPSGL-Ig or vehicle. To assess changes in myocardial perfusion (A x beta), MCE was performed. RESULTS: After 120 min of reperfusion, A x beta in the risk area was higher (0.84 +/- 0.15 dB/s vs. 0.28 +/- 0.1 dB/s, p < 0.0001), and the infarct size was lower (30.3 +/- 12% vs. 57 +/- 14%, p = 0.002) in the rPSGL-Ig group compared with the vehicle group. CONCLUSIONS: Recombinant PSGL-Ig improved postischemic reflow accurately detected by real-time MCE.

Usefulness of real-time myocardial perfusion imaging to evaluate alterations of myocardial blood flow in patients with stable angina pectoris undergoing elective percutaneous coronary interventions.

Release of cardiac enzymes has been reported in patients with stable angina who undergo elective percutaneous coronary intervention (PCI) and has been associated with adverse clinical outcomes. The aim of the present study was to investigate whether impaired microvascular integrity can be detected using myocardial contrast echocardiography in patients undergoing elective PCI, and whether it is related to the extent of postprocedural troponin T elevation. We investigated consecutive patients with stable angina (n = 19) who were scheduled for elective angioplasty with stent placement. Myocardial contrast echocardiography was performed before and 2 to 4 hours and 24 hours after coronary intervention. Contrast images were analyzed visually and quantitatively measuring the peak signal intensity (A) and the slope of the signal intensity rise (beta) in 16 myocardial segments. The product of A x beta was calculated in each segment to estimate the regional myocardial blood flow. Troponin T was collected serially before and 2 to 4 hours and 24 hours after PCI. Five patients (26%) had elevated troponin T 24 hours after PCI (range 0.03 to 0.46 microg/L). Eight patients (42%), including all 5 patients with elevated troponin T levels, demonstrated impaired microvascular integrity 2 to 4 hours after PCI in >or=2 myocardial segments (range 2 to 4) within the perfusion territory of the target vessel. Of the 11 patients without evidence of impaired myocardial perfusion by myocardial contrast echocardiography, none had elevated troponin T levels at follow-up. Quantitative analysis of myocardial blood flow showed that impaired perfusion after PCI was partially reversible. Thus, A x beta had decreased significantly at 2 to 4 hours after PCI (3.4 +/- 1.6 vs 8.8 +/- 3.4 dB/s baseline, p <0.01), reincreased after 24 hours (6.4 +/- 2.3 dB/s at 24 hours vs 3.4 +/- 1.6 dB/s at 2 to 4 hours, p <0.01), but did not return to baseline (8.8 +/- 3.4 dB/s at baseline vs 6.4 +/- 2.3 dB/s at 24 hours, p <0.01). The perfusion defect size 2 to 4 hours after PCI was closely related to the troponin T levels after 24 hours (r(2) = 0.80, p <0.0001). In conclusion, impaired microvascular integrity is partially present in patients with stable angina who undergo elective PCI, is partially reversible, and is closely related to the release of troponin T. Because judgment of interventional success has shifted downstream to tissue level perfusion, myocardial contrast echocardiography may be useful to monitor such alterations in myocardial tissue perfusion.

Usefulness of real-time myocardial perfusion imaging to evaluate tissue level reperfusion in patients with non-ST-elevation myocardial infarction.

Microvascular integrity is a prequisite for functional recovery in patients who have myocardial infarction after recanalization of the infarct-related coronary artery. In this study, we investigated whether impaired myocardial perfusion is present in patients who have non-ST-elevation myocardial infarction and whether the extent and time course of myocardial tissue reperfusion as assessed by myocardial contrast echocardiography (MCE) are related to functional recovery. Consecutive patients (n = 32) who presented with a first non-ST-elevation myocardial infarction were included in our study. MCE was performed on admission, 1 to 4 hours after angioplasty, and at 24 hours, 4 days, and 4 weeks of follow-up. Contrast images were analyzed visually and quantitatively. Myocardial blood flow was estimated by calculating the product of peak signal intensity and the slope of signal intensity increase. Improvement of wall motion on follow-up echocardiograms after 4 weeks served as a reference for functional recovery of impaired left ventricular function. Of 496 segments available for analysis, 128 (26%) were initially dysfunctional and 96 (75%) recovered at 4 weeks of follow-up. Myocardial tissue reperfusion occurred gradually, expanding over the first 24 hours after percutaneous coronary intervention (myocardial blood flow of 0.4 +/- 0.3 initially, 0.6 +/- 0.4 at 24 hours, and 1.6 +/- 0.7 dB/s at 4 weeks of follow-up, p <0.001). Extent of tissue reperfusion was closely related to grade of improvement of global ejection fraction (r2 = 0.76, p <0.001). MCE predicted functional recovery with a sensitivity of 81%, a specificity of 88%, and accuracy of 83% on a segmental level. Thus, impaired microvascular integrity is suggested by MCE in patients who present with non-ST-elevation myocardial infarction. Improvement of regional tissue perfusion after revascularization is closely related to functional recovery. This information may aid risk stratification and allow monitoring of the effectiveness of reperfusion therapy in these patients.

Usefulness of real-time myocardial perfusion imaging in the evaluation of patients with first time chest pain.

In patients who have acute coronary syndrome (ACS), rapid and accurate risk stratification is crucial. Real-time myocardial contrast echocardiography (MCE) extends the evaluation of wall motion abnormalities by assessing myocardial perfusion. We investigated whether MCE could contribute to clinical and biochemical markers in identifying patients who have ACS when presenting to the emergency department. Consecutive patients (n = 100) who presented with first occurrence of chest pain underwent MCE to evaluate myocardial perfusion. Contrast images were also analyzed quantitatively off-line by measuring peak signal intensity (A) and slope of signal intensity increase (beta) in 16 myocardial segments. Thirty-seven of 100 patients had ACS. MCE showed perfusion defects in 9 of 12 patients (75%) who had unstable angina and had high-grade stenotic lesions on an angiogram that were missed by assessment of troponin T. MCE identified all 6 patients who had non-ST-elevation myocardial infarction and no initial increase in troponin T and 17 of 19 patients who had non-ST-elevation myocardial infarction and an initial increase in troponin T. In 2 patients who had chest pain and increased troponin T, MCE excluded ACS by identifying perimyocarditis as the underlying cause. Multivariate logistic regression analysis showed that MCE was the strongest predictor of ACS, thus adding significant diagnostic value to conventional tests. Initial perfusion defect size correlated strongly with increased troponin T at 96 hours (r = 0.73, p <0.001) and with ejection fraction at 4 weeks of follow-up (r = -0.79, p <0.001). Thus, our data suggest that MCE can accurately identify patients who have ACS.

Comparison of real-time myocardial contrast echocardiography for the assessment of myocardial viability with fluorodeoxyglucose-18 positron emission tomography and dobutamine stress echocardiography.

Little is known about the diagnostic value of real-time myocardial contrast echocardiography (MCE) for the assessment of myocardial viability. We compared the diagnostic accuracy of MCE with that of low-dose dobutamine stress echocardiography (DSE) and of combined technetium-99 sestamibi single-photon emission computed tomography and fluorodeoxyglucose-18 positron emission tomography and investigated whether quantitative assessment of myocardial blood flow could increase its diagnostic value. Cardiac imaging was performed with these 3 methods in 41 patients who had ischemic heart disease (ejection fraction < 40%) and were being considered for revascularization. Follow-up echocardiograms were obtained after 3 to 6 months in revascularized patients, and increased regional function served as a standard reference for assessment of myocardial viability. A control group of 25 patients who had no coronary artery disease underwent MCE to assess normal values of myocardial perfusion parameters. Recovery of myocardial function was predicted by MCE with a sensitivity of 86% and a specificity of 43%. Nuclear imaging was comparably sensitive (90%) and specific (44%), whereas low-dose DSE was similarly sensitive (83%) but more specific (76%). Normalization of myocardial signal intensity to that of the control group significantly increased the specificity of MCE from 43% to 64% and the accuracy from 73% to 81%. A combination of quantitative MCE and DSE provided the best diagnostic characteristics, with a sensitivity of 96%, a specificity of 63%, and an accuracy of 83%. Thus, MCE is useful for assessing myocardial viability. Normalization of contrast intensity to that of a reference control group is a valid approach for detection of myocardial viability and expands on information obtained from visual MCE and DSE.

Cyclic variation of myocardial signal intensity in real-time myocardial perfusion imaging.

BACKGROUND: The presence of cyclic intensity variation during real-time myocardial perfusion imaging (RTPI) has been controversially discussed. We investigated whether cyclic intensity variation is systematically found during RTPI and whether such variations are related to regional functional parameters. METHODS: Intraoperative RTPI were obtained in 12 pigs before, during, and after left descending coronary artery occlusion with 60 mL/h SonoVue infusion. Furthermore, RTPI was performed in 14 patients after slow bolus injection of 0.7 mL of Optison. Instantaneous regional systolic to diastolic (S/D) myocardial intensity ratios were calculated after high mechanical index bubble destruction. S/D ratios were correlated with A- and beta-values, and fractional area shortening. RESULTS: Systematic cyclic S/D changes were present in both experimental settings showing significantly higher systolic values (animals, S/D 1.28 +/- 0.44; patients, S/D 1.25 +/- 0.7). Cyclic S/D variation was not related to fractional area shortening, or A- or beta-values (all r < 0.3, not significant). CONCLUSION: Consistent cyclic changes in myocardial contrast intensity can be measured both in intraoperative animals and in patients, showing higher systolic values. S/D ratios are not related to regional functional parameters.

Real-time myocardial contrast echocardiography for pharmacologic stress testing: is quantitative estimation of myocardial blood flow reserve necessary?

BACKGROUND: Little is known about the diagnostic accuracy of quantitative real-time myocardial contrast echocardiography (MCE) as an adjunct to stress testing. This study was performed to evaluate the agreement between MCE and technetium 99m-sestamibi single photon emission computed tomography (SPECT) for detection of perfusion defects and to investigate whether quantitative assessment of myocardial perfusion can increase the diagnostic value of MCE. METHODS: MCE was performed at rest and during peak adenosine stress in 50 unselected patients undergoing SPECT imaging. Concordance between the 2 methods was assessed using kappa statistics. MCE images were analyzed quantitatively, measuring peak intensity (A) and maximal rise of signal intensity (beta). Myocardial blood flow reserve was estimated by calculating the ratios of A(adenosine)/A(baseline) (A reserve), beta(adenosine)/beta(baseline) (beta reserve), and A x beta(adenosine)/A x beta(baseline) (A x beta reserve). RESULTS: Visual analysis of MCE agreed well with SPECT (kappa = 0.67) with sensitivity of 64%, specificity of 97%, and overall accuracy of 87%. Quantitative analysis showed that peak signal intensity A significantly increased under adenosine stress in SPECT-normal segments (2.6 +/- 1.9 vs 3.0 +/- 1.6 dB, P <.0001), tendencially decreased in reversible (3.0 +/- 2.0 vs 2.4 +/- 1.2 dB, P =.07) and remained unchanged in fixed (0.9 +/- 0.9 vs 0.8 +/- 0.9 dB) defects. beta Increased markedly under adenosine in normal segments (0.4 +/- 0.4 vs 1.4 +/- 1.3, P <.0001) but not in segments with reversible or fixed defects. Receiver operating characteristic showed that beta reserve and A x beta reserve, but not A reserve, are sensitive parameters for detecting perfusion defects with areas under the curve of 0.84, 0.85, and 0.61, respectively. Cut-off values of 1.9 and 2.3, respectively, for beta and A x beta reserve yielded sensitivity rates of 79% and 80%, specificity rates of 75% and 78%, and overall accuracy rates of 76% and 79%, respectively. CONCLUSION: Quantitative estimation of myocardial blood flow reserve by MCE parameters corresponds to the evaluation of myocardial perfusion by nuclear imaging and can increase the sensitivity but not the overall accuracy of contrast echocardiography.

Contribution of stress echocardiography to clinical decision making in unselected ambulatory patients with known or suspected coronary artery disease.

BACKGROUND: Due to its higher diagnostic accuracy stress echocardiography (SE) has been advocated as a substitute for stress ECG to detect coronary heart disease (CAD). However, its contribution to clinical decision-making in unselected patients presenting to the ambulatory care centre for known or suspected coronary artery disease is unclear. METHODS: To evaluate the clinical value of SE in unselected patients, we prospectively obtained SE and stress ECG in 221 consecutive patients (142 males; mean age 58+/-12 years) presenting to the ambulatory care centre with known or suspected CAD. Patients with acute coronary syndrome were not included. RESULTS: Results of stress ECG and SE were concordant in 181 (82%) and discordant in 40 patients (18%). The clinical decision to recommend or to currently withhold coronary angiography was possible solely on the basis of clinical criteria and stress ECG findings in 191 (86.4%) patients but was guided by the results of SE in 30 patients (13.6%). Left heart catheterization and coronary angiography were conducted in 61 patients. In this population SE was more accurate (82.6%) than stress ECG (65.6%) in indicating significant coronary artery stenosis. CONCLUSION: Despite its higher accuracy, SE adds little to the information derived from dynamic stress ECG and symptom evaluation in unselected outpatients with known or suspected CAD. Thus, SE should not in general replace stress ECG as a screening method for detecting significant coronary artery disease, for both clinical and economic reasons.

Potential of gold-bound microtubules as a new ultrasound contrast agent.

Contrast agents based on gas-filled microspheres share the problem of time limited opacification due to low stability of microbubbles. The aim of this study was to test if gold-bound microtubules provide backscattering that allows microtubules to be potentially useful as an ultrasound (US) contrast agent. Gold colloids were immobilized on protein microtubule walls. Latex balloons were filled with gold-bound microtubules or conventional left heart contrast agent and were ultrasonographically imaged in fundamental and harmonic modes. Feasibility of anti-beta-tubulin antibody conjugation to gold-bound microtubules was confirmed using immune fluorescence analysis. Gold particles were successfully bound to microtubules. Contrast intensities in latex balloons filled with gold-bound microtubules (141 +/- 35) were comparable to those with Levovist (180 +/- 35) and did not decrease significantly during continuous US imaging for 20 min (135 +/- 34 vs. Levovist 5.0 +/- 2.0). Anti-beta-tubulin antibodies were successfully conjugated to gold-bound microtubules. Gold-bound microtubules provide a persistent contrast effect, suggesting their use as an ultrasonic contrast agent with the feasibility of antibody conjugation.

Ultrasound contrast agents can influence the respiratory burst activity of human neutrophil granulocytes.

Activated leucocytes can bind and, subsequently, phagocytose microbubbles that are used as ultrasound (US) contrast agents. The purpose of this study was to investigate whether or not microbubbles can influence the inflammatory response of human neutrophil granulocytes. Granulocytes isolated from healthy volunteers were activated with various stimuli, for example, the bacterial peptide N-formyl-methyonyl-leucyl-phenylalanine (fMLP), the calcium ionophore A23187, the protein kinase C activator phorbol myristate acetate (PMA) and the cytokine tumor necrosis factor alpha (TNF-alpha), and incubated with albumin or phospholipid microbubbles. Neutrophil respiratory burst activity and elastase release were quantified. Albumin (Optison) and phospholipid (SonoVue) contrast agents induced an extensive oxidative response of human granulocytes to all the stimuli used, and these effects could be significantly impaired by preincubation of the cells with cytochalasin B. Left heart contrast agents used for contrast-enhanced US assessment can activate human neutrophil granulocytes, inducing an extensive respiratory burst to secondary stimuli. The potential clinical relevance of this effect needs to be elucidated.