Quantitative Myocardial Contrast Echocardiography Research Articles

Mental Stress-Induced Myocardial Ischemia Detected by Global Longitudinal Strain and Quantitative Myocardial Contrast Echocardiography in Women With Nonobstructive Coronary Artery Disease

The utility of radionuclide myocardial perfusion imaging including positron emission tomography (PET) for diagnosing mental stress-induced myocardial ischemia (MSIMI) is clinically restricted. This study aims to assess the diagnostic performance of novel echocardiographic techniques, including automated strain and quantitative myocardial contrast echocardiography (MCE) with dedicated software and deep neural network model, for MSIMI detection. The secondary objective was to explore the correlation between changes in myocardial blood flow and MSIMI. Seventy-two female patients ages 18 to 75 with angina and nonobstructive coronary artery disease (ANOCA) and 23 healthy controls were prospectively recruited. Both echocardiography with contrast agent and PET imaging were performed during structured mental stress testing. Mental stress-induced myocardial ischemia was defined as a summed difference score ≥3 on PET. Echocardiographic parameters including left ventricular global longitudinal strain, β, and A×β were obtained, and their trends during mental stress testing were observed. ΔGLS was defined as the ratio of difference between global longitudinal strain values at stress and rest to the rest data. β reserve and A×β reserve were respectively calculated. Thirty-two ANOCA patients (44%) and 1 control (4%) were diagnosed with MSIMI (P<.01). For ANOCA patients with MSIMI, left ventricular GLS, β, and A×β declined to varied extents during mental stress testing compared with those without MSIMI and the controls (P<.05). Bland-Altman plots demonstrated good consistency between β reserve and A×β reserve output by the deep neural network model and iMCE software. Receiver operating characteristic curve analyses showed that ΔGLS, β reserve, and A×β reserve demonstrated favorable ability to predict MSIMI, especially the combination of A×β reserve using iMCE analysis and ΔGLS (area under the curve, 0.94; sensitivity, 83%; specificity, 97%). Novel technologies in echocardiography exhibit the potential to be a clinical alternative to cardiac PET for effectively detecting MSIMI. Attenuated myocardial blood flow response during structured mental stress testing was correlated with MSIMI, providing a reasonable explanation for the chest discomfort persisting in ANOCA women.

Contrast Echocardiography for Assessing Myocardial Perfusion.

Improvements in ultrasound methods for detecting microbubble ultrasound enhancing agents have led to an increase in the use of perfusion imaging with myocardial contrast echocardiography (MCE). This technique is now beginning to play an important role in specific clinical scenarios, which is the focus of this review. MCE was originally conceived as a technique for detecting resting perfusion abnormalities related to ischemia at rest or during stress from coronary artery disease. More recently, MCE has increasingly been used in circumstances where the technique's ability to provide rapid, quantitative, or bedside assessment of perfusion is advantageous. Quantitative MCE is also increasingly being used as a research technique for evaluating pathobiology and therapy that involve changes in the myocardial microcirculation. While MCE was developed and validated decades ago, it is only now beginning to be used by an increasing number of clinicians due to improvements in imaging technology and recognition of specific situations where the technique is impactful.

Comparative analysis of instantaneous wave-free ratio and quantitative real-time myocardial contrast echocardiography for the assessment of myocardial perfusion.

The field of coronary artery physiology is developing rapidly and changing the practice of interventional cardiology. A new functional evaluation technique using the instantaneous wave-free ratio (iFR) has become an alternative to fractional flow reserve. Future research studies need to determine whether physiological indicators play a role in evaluating myocardial perfusion in the catheter room. Thirty-eight patients scheduled for coronary angiography and iFR evaluation underwent a real-time myocardial contrast echocardiography (RT-MCE) examination at rest. The myocardial perfusion parameters (A, β, and A × β) on the myocardial perfusion curve were quantitatively analyzed using Q-Lab software. Coronary angiography and iFR assessment were completed within 1 week after the RT-MCE examination in all patients. Correlation analysis was used to identify iFR- and MCE-related indicators. The sensitivity and specificity of iFR in the quantitative detection of coronary microcirculation were obtained. The correlation coefficients between iFR and A, β, and A × β were 0.81, 0.66, and 0.82, respectively. The cut-off value for iFR was 0.85 for microvascular ischemia detection, while the sensitivity and specificity for the diagnosis of myocardial perfusion were 90.7 and 89.9%, respectively. The receiver operating characteristic (ROC) curve area for iFR was 0.946 in the segments related to myocardial blood flow. The iFR is an effective tool for detecting myocardial microcirculation perfusion, with satisfactory diagnostic performance and a demonstrated role in physiological indices used for the perfusion assessment.

Prognostic value of myocardial contrast echocardiography in acute anterior wall ST-segment elevation myocardial infarction with successful epicardial recanalization.

Although myocardial contrast echocardiography (MCE) can evaluate microvascular perfusion abnormalities, its prognostic value is uncertain in acute anterior wall ST-Segment elevation myocardial infarction (STEMI) with successful epicardial recanalization. Therefore, the study aims to investigate the prognostic role of qualitative and quantitative MCE in acute anterior wall STEMI with successful epicardial recanalization. 153 STEMI patients were assessed by MCE within 7days after successful epicardial recanalization. Qualitative perfusion parameters (microvascular perfusion score index, MPSI) and quantitative perfusion parameters (A, β, and Aβ) were acquired using a 17-segment model. And corrected A and Aβ were calculated. Patients were all followed for major adverse cardiovascular events (MACEs). During median follow-up of 27 (4) months, 39 (25.49%) patients experienced MACEs, while 114 (74.51%) were free from MACEs. Patients with MACEs had higher MPSI (1.65 ± 0.13 vs. No-MACEs 1.35 ± 0.20, P < 0.001), lower β (1.09 ± 0.19s-1 vs. No-MACEs 1.34 ± 0.30s-1, P < 0.001), corrected A (0.17 ± 0.03dB vs. No-MACEs 0.19 ± 0.04dB, P = 0.039) and lower corrected Aβ (0.19 ± 0.06dB/s vs. No-MACEs 0.25 ± 0.08dB/s, P < 0.001). MPSI of 1.44 provided an area under the curve (AUC) of 0.872, while β of 1.18s-1 and corrected Aβ of 0.22dB/s provided AUCs of 0.759 and 0.724, respectively. The combination of MPSI, β and corrected Aβ provided an increased AUC of 0.964 (all P < 0.05). Time-dependent ROC analysis showed that the AUCs of the MPSI, β, corrected Aβ and the combination at 1, 1.5 and 2years indicated a strong predictive power for MACEs (AUC = 0.900/0.894/0.881 for MPSI, 0.648/0.704/0.732 for β, 0.674/0.686/0.722 for corrected Aβ, and 0.947/0.962/0.967 for the combination, respectively). Patients with MPSI < 1.44, β > 1.18s-1, or corrected Aβ > 0.22dB/s had lower event rate (all Log Rank P ≤ 0.001). MPSI, β, corrected Aβ, GLS and WBC were independent predictors of MACEs with adjusted hazard ratio of 34.41 (8.18-144.87), P < 0.001 for MPSI; 39.29 (27.46-65.44), P < 0.001 for β; 8.93 (1.46-54.55), P = 0.018 for corrected Aβ; 10.88 (2.83-41.86), P = 0.001 for GLS; and 1.43 (1.16-1.75), P = 0.001 for WBC. Qualitative and quantitative MCE can accurately predict MACEs in acute anterior wall STEMI with successful epicardial recanalization, and their combined predictive value is higher.

Plasma Lipidomic Patterns in Patients with Symptomatic Coronary Microvascular Dysfunction.

Coronary microvascular dysfunction (MVD) is a syndrome of abnormal regulation of vascular tone, particularly during increased metabolic demand. While there are several risk factors for MVD, some of which are similar to those for coronary artery disease (CAD), the cause of MVD is not understood. We hypothesized that MVD in symptomatic non-elderly subjects would be characterized by specific lipidomic profiles. Subjects (n = 20) aged 35–60 years and referred for computed tomography coronary angiography (CTA) for chest pain but who lacked obstructive CAD (>50% stenosis), underwent quantitative regadenoson stress-rest myocardial contrast echocardiography (MCE) perfusion imaging for MVD assessment. The presence of MVD defined by kinetic analysis of MCE data was correlated with lipidomic profiles in plasma measured by liquid chromatography and high-resolution mass spectrometry. Nine of twenty subjects had evidence of MVD, defined by reduced hyperemic perfusion versus other subjects (beta-value 1.62 ± 0.44 vs. 2.63 ± 0.99 s−1, p = 0.009). Neither the presence of high-risk but non-obstructive CAD on CTA, nor CAD risk factors were different for those with versus without MVD. Lipidomic analysis revealed that patients with MVD had lower concentrations of long-carbon chain triacylglycerols and diacylglycerols, and higher concentrations of short-chain triacylglycerols. The diacylglycerol containing stearic and linoleic acid classified all participants correctly. We conclude that specific lipidomic plasma profiles occur in MVD involving saturated long-chain fatty acid-containing acylglycerols that are distinctly different from those in non-obstructive CAD. These patterns could be used to better characterize the pathobiology and potential treatments for this condition.

A deep learning approach with temporal consistency for automatic myocardial segmentation of quantitative myocardial contrast echocardiography.

Quantitative myocardial contrast echocardiography (MCE) has been proved to be valuable in detecting myocardial ischemia. During quantitative MCE analysis, myocardial segmentation is a critical step in determining accurate region of interests (ROIs). However, traditional myocardial segmentation mainly relies on manual tracing of myocardial contours, which is time-consuming and laborious. To solve this problem, we propose a fully automatic myocardial segmentation framework that can segment myocardial regions in MCE accurately without human intervention. A total of 100 patients' MCE sequences were divided into a training set and a test set according to a 7: 3 proportion for analysis. We proposed a bi-directional training schema, which incorporated temporal information of forward and backward direction among frames in MCE sequences to ensure temporal consistency by combining convolutional neural network with recurrent neural network. Experiment results demonstrated that compared with a traditional segmentation model (U-net) and the model considering only forward temporal information (U-net + forward), our framework achieved the highest segmentation precision in Dice coefficient (U-net vs U-net + forward vs our framework: 0.78 ± 0.07 vs 0.79 ± 0.07 vs 0.81 ± 0.07, p < 0.01), Intersection over Union (0.65 ± 0.09 vs 0.66 ± 0.09 vs 0.68 ± 0.09, p < 0.01), and lowest Hausdorff Distance (32.68 ± 14.6 vs 28.69 ± 13.18 vs 27.59 ± 12.82 pixel point, p < 0.01). In the visual grading study, the performance of our framework was the best among these three models (52.47 ± 4.29 vs 54.53 ± 5.10 vs 57.30 ± 4.73, p < 0.01). A case report on a randomly selected subject for perfusion analysis showed that the perfusion parameters generated by using myocardial segmentation of our proposed framework were similar to that of the expert annotation. The proposed framework could generate more precise myocardial segmentation when compared with traditional methods. The perfusion parameters generated by these myocardial segmentations have a good similarity to that of manual annotation, suggesting that it has the potential to be utilized in routine clinical practice.

Coronary flow velocity reserve and inflammatory markers in living kidney donors

BackgroundCoronary microvascular dysfunction is prevalent in chronic kidney disease (CKD), and may contribute to the development of myocardial dysfunction in CKD. Coronary flow velocity reserve (CFVR) is a marker of coronary microvascular function and falls with increasing CKD stage. Living kidney donors have renal function consistent with early stage CKD and concern has been raised about their cardiovascular risk. No studies to date have investigated the presence of coronary microvascular dysfunction in living kidney donors. Methods25 healthy controls and 23 living kidney donors were recruited and underwent assessment with transthoracic echocardiography, Doppler CFVR, myocardial contrast echocardiography and serum multiplex immunoassay panels. ResultsDoppler CFVR was significantly reduced in living kidney donors compared to controls (mean CFVR 3.4 ± 0.7 vs 3.8 ± 0.6, mean difference 0.4 95% confidence interval 0.03–0.8, p =.036). Quantitative myocardial contrast echocardiography showed a trend towards reduced coronary flow reserve in living kidney donors. Compared to controls, living kidney donors had higher serum high sensitivity C reactive peptide (hsCRP) and lower levels of uromodulin. ConclusionsThis is the first study of CFVR in living kidney donors. We have shown that the modest drop in estimated glomerular filtration rate in living kidney donors is associated with lower values of Doppler CFVR compared to controls, suggesting that isolated reductions in renal function may lead to altered microvascular function. The increase in hsCRP and reduction in uromodulin suggests that chronic subclinical inflammation may contribute to altered microvascular function in this population.

Flow Augmentation in the Myocardium by Ultrasound Cavitation of Microbubbles: Role of Shear-Mediated Purinergic Signaling

Ultrasound-mediated cavitation of microbubble contrast agents produces high intravascular shear. We hypothesized that microbubble cavitation increases myocardial microvascular perfusion through shear-dependent purinergic pathways downstream from ATP release that is immediate and sustained through cellular ATP channels such as Pannexin-1. Quantitative myocardial contrast echocardiography perfusion imaging and invivo optical imaging of ATP was performed in wild-type and Pannexin-1-deficient (Panx1-/-) mice before and 5 and 30minutes after 10minutes of ultrasound-mediated (1.3MHz, mechanical index 1.3) myocardial microbubble cavitation. Flow augmentation in a preclinical model closer to humans was evaluated in rhesus macaques undergoing myocardial contrast echocardiography perfusion imaging after high-power cavitation in the apical four-chamber plane for 10minutes. Microbubble cavitation in wild-type mice (n=7) increased myocardial perfusion by 64%±25% at 5minutes and 95%±55% at 30minutes compared with baseline (P<.05). In Panx1-/- mice (n=5), perfusion increased by 28%±26% at 5minutes (P=.04) but returned to baseline at 30minutes. Myocardial ATP signal in wild-type (n=7) mice undergoing cavitation compared with sham-treated controls (n=3) was 450-fold higher at 5minutes and 90-fold higher at 30minutes after cavitation (P<.001). The ATP signal in Panx1-/- mice (n=4) was consistently 10-fold lower than that in wild-type mice and was similar to sham controls at 30minutes. In macaques (n=8), myocardial perfusion increased twofold in the cavitation-exposed four-chamber plane, similar in degree to that produced by adenosine, but did not increase in the control two-chamber plane. Cavitation of microbubbles in the myocardial microcirculation produces an immediate release of ATP, likely from cell microporation, as well as sustained release, which is channel dependent and responsible for persistent flow augmentation. These findings provide mechanistic insight by which cavitation improves perfusion and reduces infarct size in patients with myocardial infarction.

Coronary Microvascular Dysfunction by Myocardial Contrast Echocardiography in Nonelderly Patients Referred for Computed Tomographic Coronary Angiography

Microvascular dysfunction (MVD) is a potential cause of chest pain in younger individuals. The authors hypothesized that nonelderly patients referred for computed tomographic angiography (CTA) but without significant stenosis would have a high prevalence of MVD by myocardial contrast echocardiography (MCE). Secondary aims were to test whether the presence of nonobstructive coronary artery disease (CAD) or reduced brachial flow-mediated dilation (FMD) predicted MVD. Subjects ≤60years of age undergoing CTA were recruited if they had either no evidence of coronary plaque or evidence of mild CAD (<50% stenosis) and at least one high-risk plaque feature. Subjects underwent quantitative perfusion imaging using MCE at rest and during regadenoson vasodilator stress. MVD was defined as global or segmental delay of microvascular refill (≥2sec) during regadenoson. FMD of the brachial artery was also performed. Of the 29 patients in whom MCE could be performed, 12 (41%) had MVD. These subjects, compared with those with normal microvascular function, had lower hyperemic perfusion (mean, 236±68 vs 354±161 intensity units/sec; P=.02) and microvascular flux rate (mean, 1.6±0.4 vs 2.5±0.9sec-1; P=.002) on quantitative MCE. The degree of FMD was not significantly different in those with or without MVD (mean, 11±4% vs 9±4%; P=.32), and there was a poor correlation between results on stress MCE and FMD. Only eight of the 29 subjects were classified as having nonobstructive CAD. There were no groupwise differences in the prevalence of MVD function in those with versus without CAD (43% vs 38% for negative and positive findings on CTA, respectively, P=.79). MVD is a common finding in the nonelderly population referred for CTA for evaluation of possible CAD but without obstructive stenosis. Neither the presence of noncritical atherosclerotic disease nor abnormal FMD increases the likelihood for detecting MVD in this population.

Coronary Microcirculation in Heart Failure with Preserved Systolic Function

The Heart Failure with Preserved Ejection Fraction (HFpEF) is defined as the preserved left ventricular ejection fraction (LVEF) with the signs of heart failure, elevated natriuretic peptides, and either the evidence of the structural heart disease or diastolic dysfunction. The importance of this form of heart failure was increased after studies where the mortality rates and readmission to the hospital were founded similar as in patients with HF and reduced EF (HFrEF). Coronary microvascular ischemia, cardiomyocyte injury and stiffness could be important factors in the pathophysiology of HFpEF. The goal of this work is to analyse the relationship of HFpEF and coronary microcirculation in previous studies. The useful diagnostic marker of coronary microcirculation in HFpEF may be the parameters measured by transthoracic echocardiography (TTE), the coronary flow reserve (CFR), as well as fractional flow reserve (FFR) and quantitative myocardial contrast echocardiography (MCE). Cardiac magnetic resonance (CMR) imaging represents the diagnostic gold standard in HFpEF. Coronary microvascular dysfunction in the absence of obstructive coronary artery disease (CAD) is poorly understood and may be more prevalent amongst women than men. Troponin level may be important in risk stratification of HEpEF patients. There are no precise answers with respect to the pathophysiological mechanism, nor are there any precise practical clinical assessment of and diagnostic method for coronary microvascular dysfunction and diastolic dysfunction. In accordance with that, there is no well-established treatment for HFpEF.

A novel method for quantitative myocardial contrast echocardiography in mice.

The small size of the mouse heart frequently imparts technical challenges when applying conventional in vivo imaging methods for assessing heart function. Here, we describe the use of high-frequency ultrasound imaging in conjunction with a size-tuned blood pool contrast agent for quantitatively assessing myocardial perfusion in living mice. A perflurocarbon microbubble formulation exhibiting a narrow size distribution was developed, and echogenicity was assessed at 18 MHz in vitro. Adult mice were subjected to permanent ligation of the left anterior descending artery. Ultrasound imaging was performed on day 7, and a cohort of intact mice was used as a control. Parasternal long-axis cine clips were acquired at 18 MHz before and after contrast administration. Reduced ejection fraction and increased end-systolic volume were observed in infarcted compared with control mice. In control animals, washin of the contrast agent was visible in all myocardial segments. Reduced contrast enhancement was observed in apical-posterolateral regions of all infarcted mice. A novel method for reslicing of the imaging data through the time domain provided a two-dimensional presentation of regional contrast agent washin, enabling convenient identification of locations exhibiting altered perfusion. Myocardial segments exhibiting diminished contractility were observed to have correspondingly low relative myocardial perfusion. The contrast agent formulation and methods demonstrated here provide the basis for simplifying routine in vivo estimation of infarct size in mice and may be particularly useful in longitudinal evaluation of revascularization interventions and assessment of peri-infarct ischemia. NEW & NOTEWORTHY Murine myocardial contrast echocardiography frequently suffers from poor sensitivity to contrast. Here, we formulated a novel size-tuned microbubble contrast agent and validated it for use with ultra-high-frequency ultrasound. A novel data method for evaluating myocardial perfusion based on reslicing the imaging data through the time domain is presented.

Myocardial perfusion echocardiography and coronary microvascular dysfunction.

Our understanding of coronary syndromes has evolved in the last two decades out of the obstructive atherosclerosis of epicardial coronary arteries paradigm to include anatomo-functional abnormalities of coronary microcirculation. No current diagnostic technique allows direct visualization of coronary microcirculation, but functional assessments of this circulation are possible. This represents a challenge in cardiology. Myocardial contrast echocardiography (MCE) was a breakthrough in echocardiography several years ago that claimed the capability to detect myocardial perfusion abnormalities and quantify coronary blood flow. Research demonstrated that the integration of quantitative MCE and fractional flow reserve improved the definition of ischemic burden and the relative contribution of collaterals in non-critical coronary stenosis. MCE identified no-reflow and low-flow within and around myocardial infarction, respectively, and predicted the potential functional recovery of stunned myocardium using appropriate interventions. MCE exhibited diagnostic performances that were comparable to positron emission tomography in microvascular reserve and microvascular dysfunction in angina patients. Overall, MCE improved echocardiographic evaluations of ischemic heart disease in daily clinical practice, but the approval of regulatory authorities is lacking.

Usefulness of the parameters of quantitative myocardial perfusion contrast echocardiography in patients with chronic total occlusion and collateral flow.

Microvascular obstruction becomes more severe with longer duration of ischemia, such as chronic total occlusion (CTO) which used to have collateral flow. In this study, we explored the correlation between parameters measured using quantitative myocardial perfusion contrast echocardiography (MCE) and the angiographic collateral flow grades in patients with CTO. Furthermore, we investigated the usefulness of the parameters of quantitative MCE for the measurement of microvasculature changes after revascularization of CTO lesions. Between January 2011 and January 2013, 44 patients who had undergone coronary angiography (CAG) due to chest pain and had confirmed CTO lesions were enrolled in this prospective observational study. All patients had baseline MCE within 24 hours after diagnostic CAG. Patients were then assigned to one of two groups: a medical therapy group (Group I, n = 20) or a reperfusion group with percutaneous coronary intervention (PCI) (Group II, n = 24). All patients had follow-up MCE 3 months later. Consistent with the CAG results in both groups, on baseline MCE, the myocardial blood flow (AI × β) values were higher in Grade III collateral flow than in Grade I or II collateral flow (AI of collateral flow Grade I vs. Grade II vs. Grade III: 2.34 ± 2.65 vs. 2.52 ± 2.67 vs. 3.87 ± 4.57, P = 0.038). The plateau acoustic intensity (AI) and wall-motion score index (WMSI) were significantly improved at the 3-month follow-up after successful reperfusion with PCI (5.75 ± 3.52 before vs. 8.11 ± 6.02 after, P = 0.004) and (1.76 ± 0.83 before vs. 1.43 ± 0.64 after, P ≤ 0.001), respectively. However, the AI and WMSI values were not improved in the medical treatment group, (6.04 ± 4.64 before vs. 6.01 ± 5.52 after, P = 0.966) and (1.61 ± 0.82 before vs. 1.66 ± 0.67 after, P = 0.616), respectively. MCE is a useful tool for estimating microvascularity in patients with CTO lesions and correlates well with angiographic collateral flow.

QUANTITATIVE ASSESSMENT OF MYOCARDIAL BLOOD FLOW RESERVE USING DEFINITY DURING REGADENOSON VASODILATOR STRESS REAL-TIME MYOCARDIAL CONTRAST ECHOCARDIOGRAPHY FOR DETECTION OF LEFT ANTERIOR DESCENDING CORONARY ARTERY STENOSIS

To assess the feasibility and diagnostic accuracy of quantitative real-time myocardial contrast echocardiography (RTMCE) during regadenoson (Reg) (Astellas Pharma Inc) vasodilator stress for detection of significant Left anterior descending (LAD) stenosis (≥ 50% or ≥ 70% by quantitative coronary

Resting qualitative and quantitative myocardial contrast echocardiography to predict cardiac events in patients with acute myocardial infarction and percutaneous revascularization

Successful restoration of patency of the infarct-related artery is important in management of acute ST-segment elevation myocardial infarction (STEMI); however, it does not necessarily translate into the restoration of perfusion at the tissue level. In this study, we evaluate the prognostic role of qualitative and quantitative myocardial contrast echocardiography (MCE) in predicting cardiac events (after adjustment for cardiovascular risk factors) in STEMI patients undergoing reperfusion. Bedside resting real-time MCE using continuous infusion of diluted contrast agent (Definity) was performed within a median of 21.4 h from revascularization in STEMI. Myocardial perfusion on qualitative MCE was graded 1 = homogenous; 2 = partial/patchy; and 3 = absent. Perfusion score index (PSI) was calculated by adding the perfusion score in all segments divided by the total number of evaluable segments. Quantitative perfusion parameters [A, dB; β, sec(-1); and Aβ] were analyzed using a 17-segment model. Patients were followed for cardiac events including death; nonfatal myocardial infarction (MI); hospitalization for cardiac symptoms; coronary revascularization; or heart failure. Thirty-seven reperfused STEMI patients with a mean age of 64 years (range, 40-86 years) were enrolled and followed for a median of 1.4 years. Cardiac events occurred in 22 patients. Patients with cardiac events had a higher perfusion score index (PSI), and lower A, β and Aβ parameters compared to patients without events [1.84 ± 0.36 vs 1.39 ± 0.17 for PSI, P < 0.001; 0.57 ± 0.24 vs 0.85 ± 0.30 for A, P = 0.03; 0.34 ± 0.15 vs. 0.53 ± 0.17 for β, P = 0.002; and 0.21 ± 0.12 vs. 0.49 ± 0.32, for Aβ, P = 0.003; respectively]. A PSI value of 1.58 provided an area under the curve (AUC) of 0.873, while β of 0.423 and Aβ of 0.323 provided an AUC of 0.858 and 0.842, respectively. PSI and Aβ were independent predictors of cardiac events with an adjusted hazard ratio of 3.41 (1.19-12.27); and 4.19 (1.3-19.09), respectively. No contrast-related side effects were reported. Evaluation of perfusion in reperfused STEMI patients by qualitative and quantitative MCE (myocardial blood flow, Aβ) provides independent prediction of cardiac events.

Myocardial Contrast Echocardiography for the Detection of Coronary Artery Disease in Patients with Global Hypokinesis Admitted for First-Onset Acute Heart Failure: Pilot Study

BackgroundThe non-invasive differentiation of ischemic and nonischemic acute heart failure (AHF) not resulting from acute myocardial infarction is difficult and has therapeutic and prognostic implications. The aim of this study was to assess whether resting myocardial contrast echocardiography (MCE) can detect coronary artery disease (CAD) in patients with decreased left ventricular (LV) systolic function and global hypokinesis presenting with AHF.MethodsTwenty-one consecutive patients underwent low-power real-time MCE based on color-coded pulse inversion Doppler. Standard apical LV views were acquired during contrast IV infusion of Definity®. Following transient microbubbles destruction, the contrast replenishment rate (β), reflecting myocardial blood flow velocity, was derived by plotting signal intensity vs. time and fitting data to the exponential function: y (t) = A (1 - e-β(t-t0)) + C.ResultsOf the 21 (mean age 56.6 ± 13.6 years) patients, 5 (23.8%) demonstrated flow-limiting CAD (> 70% of luminal diameter narrowing). The mean ± standard deviation of LV ejection fraction was 29.6 ± 8.6%. Quantitative MCE analysis was feasible in 258 of 378 segments (68.3%). There were no significant difference in "β" and "Aβ" in patients without and with CAD (0.48 ± 0.27 vs. 0.45 ± 0.25, p = 0.453 for β and 2.99 ± 2.23 vs. 3.68 ± 3.13, p = 0.059 for Aβ, respectively). No contrast-related side effects were reported.ConclusionResting quantitative MCE analysis in patients with AHF was feasible, however, the parameters did not aid in detecting of CAD.

Impaired right ventricular myocardial perfusion and right ventricular dysfunction in patients with pulmonary arterial hypertension: a study of contrast echocardiography and strain imaging

Background: Little is known about right ventricular (RV) dysfunction in patient with pulmonary arterial hypertension (PAH). Recently, RV ischemia has been reported to be a contributory factor in the development of RV dysfunction. The aim of this study is to evaluate RV myocardial perfusion and assess its relationship with RV dysfunction. Methods: This prospective study consisted of 10 consecutive patients (7 female, 51±17 years) with PAH (6 idiopathic PAH (IPAH), and 4 chronic thromboembolic pulmonary hypertension (CTEPH)), and 6 healthy controls (3 females, 37±6 years). Quantitative myocardial contrast echocardiography (MCE) was performed using Philips iE33 imaging system with an S5-1 probe. We depicted the apical four chamber view. A solution of Levovist (300mg/ml) was inravenously administered at a rate of 3ml/min with a volumetric pump. End-systolic images were obtained every four heart beats. The MCE images were analyzed off-line using VoluMap-445 system. The RV myocardium was divided into six segments, at each myocardial segment, calibrated contrast intensity (CI) was determined as the difference (dB) between the mean myocardial CI and cavity CI. 2D speckle tracking echocardiographic study was also performed using Vivid E9 ultrasound system. Results: Among 96 RV myocardial segments, quantitative CI analysis was possible in 86 segments (90%). RV fractional area change was 46% (healthy), 34% (CTEPH) and 25% (IPAH). Mean calibrated CI of RV free wall was -13.4dB, -19.3dB and -22.8dB, respectively (p=0.01). We found good inverse correlation between calibrated CI and longitudinal strain of RV free wall (r=-0.5, p=0.0013). ![Figure][1] Conclusion: Quantitative MCE revealed patients with PAH have impaired RV myocardial perfusion, and this correlated well with the RV longitudinal myocardial dysfunction. [1]: pending:yes

099 MYOCARDIAL CONTRAST ECHOCARDIOGRAPHY DISTINGUISHES PHYSIOLOGICAL FROM PATHOLOGICAL GREY-ZONE LEFT VENTRICULAR HYPERTROPHY

Background It remains difficult to distinguish an athlete9s heart (physiological left ventricular hypertrophy (LVH) from hypertrophic cardiomyopathy (HCM) (pathological LVH) especially when subjects fall into Maron9s grey zone ventricular wall thickness of 12–15 mm. Pathological LVH is one of the common causes of sudden death in young athletes. We hypothesised that pathological LVH due to HCM will have more fibrosis and reduced myocardial blood flow reserve (MBFR) compared to athletes. Capillary blood volume (CBV) which is reduced in fibrosis and MBFR can be assessed at the bedside by flash-replenishment myocardial contrast echocardiography (MCE). Methods 25 subjects with genetically proven septal HCM and 25 athletes all with grey zone septal hypertrophy (13.7±1.2 mm) were recruited. There were no significant differences in age (p=0.57, 33±8 years/32±8 years), gender(males-HCM:21, Atheletes:25) and degree of septal LVH (p=0.71, 14±0.89 vs 13.7±1.03) between HCM and athletes. All subjects underwent rest and stress vasodilator myocardial contrast echocardiography and quantitative analysis of CBV (dâ), blood velocity (dâ/s), myocardial blood flow (db/s 2 ) and MBFR(stress MBF/rest MBF) of the septum and apex was performed. Results Patients with HCM had significantly lower CBV (15.56±12.45 vs 18.30±12.6; p value=0.01) at rest and significantly lower resting MBF (14.10±15 vs 36.1±14.7; p=0.032) compared to athletes. MBFR was also significantly reduced compared to athletes (2.49 vs 5.67; p value=0.027). The receiver-operator characteristics(ROC) curve for CBV and MBFR demonstrated areas under the curve of 0.65 and 0.84 respectively. A cut-off of MBFR of 4.8 provides a sensitivity and specificity of 99% and 81% respectively for the detection of pathological LVH. The positive predictive value for predicting pathological LVH was 88% with a negative predictive value of 92%. Conclusions Quantitative MCE reliably distingisuishes physiological from pathological LVH in patients with grey zone hypertrophy who pose a diagnostic dilemma.

Quantitative myocardial contrast echocardiography: a new method for the non-invasive detection of chronic heart transplant rejection

Chronic heart transplant rejection, i.e. cardiac allograft vasculopathy (CAV) is a major adverse prognostic factor after heart transplantation (HTx). This study tested the hypothesis that the relative myocardial blood volume (rBV) as quantified by myocardial contrast echocardiography accurately detects severe CAV as defined by coronary intravascular ultrasound (IVUS). Forty-five HTx patients underwent a total of 50 quantitative IVUS measurements for intima thickness assessment (>1 mm = severe CAV; the reference method). Simultaneously, the two factors constituting myocardial perfusion (mL/min/g) were obtained by transthoracic contrast echocardiography at rest: rBV (the test method), a measure of microvascular density (mL/mL), and its exchange rate β (1/s; a measure of coronary conductance) after mechanical contrast bubble disruption.Sixty-nine per cent (31 of 45) of the HTx patients showed severe CAV. rBV at rest was equal to 0.17 ± 0.05 in the group without severe CAV, and it was equal to 0.12 ± 0.07 in the group with severe CAV (P = 0.0157). Conversely, β amounted to 6.4 ± 4.5 in the former and to 10.3 ± 6.2 in the latter group (P = 0.0410), thus, maintaining normal resting myocardial perfusion at 1 mL/min/g. IVUS determined intima thickness correlated significantly and inversely with rBV at rest. An rBV value at rest <0.14 accurately detected severe CAV (intima thickness >1 mm): area under the receiver operating characteristics curve = 0.844, P = 0.004, sensitivity = 0.90, specificity = 0.75. Severe CAV can be detected using the non-invasive method of quantitative myocardial contrast echocardiography. rBV at rest amounting to <14% of the surrounding tissue accurately detects coronary intima thickness >1 mm as determined invasively by IVUS. NCT00414895.

Quantitative Myocardial Contrast Supine Bicycle Stress Echocardiography for Detection of Coronary Artery Disease

If compared with two-dimensional echocardiography (2DE), quantitative myocardial contrast echocardiography (MCE) improves detection of coronary artery disease (CAD) during pharmacological stress, but there is paucity of data regarding quantitative MCE performed during supine bicycle stress. To determine the feasibility and accuracy of quantitative MCE and assess its incremental benefit over 2DE for detection of CAD during supine bicycle stress. Sixty-one consecutive patients (47 males, 14 females, mean age 57 ± 12 years) with suspected CAD, who were scheduled for coronary angiography, underwent 2DE and MCE supine bicycle stress. The diagnosis of obstructive CAD (≥50% stenosis) was based on inducible wall-motion and myocardial perfusion abnormalities. For quantitative myocardial perfusion analysis, A, β, and Aβ reserve were derived from myocardial contrast replenishment curves. Quantitative coronary angiography revealed ≥50% stenosis in 41, ≥70% stenosis in 18, single vessel disease in 24, and multivessel disease in 17 patients. If compared with 2DE, quantitative MCE was more sensitive (71% vs. 93%; P < 0.05) and more accurate (74% vs. 89%; P < 0.05) to detect obstructive CAD. The sensitivity of 2DE and quantitative MCE was 61% and 91% (P < 0.05) in 50-69% stenosis, and 63% and 92% (P < 0.05) in single vessel disease. No difference in sensitivity between 2DE and quantitative MCE was found in subjects with ≥70% stenosis (83% vs. 94%, P = NS) and multivessel disease (82% vs. 94%, P = NS). Quantitative MCE enhances sensitivity and accuracy of supine bicycle stress 2DE for detection of obstructive CAD, and this incremental benefit is especially present in less severe disease.