Stress Myocardial Contrast Echocardiography Research Articles

Cardiac Allograft Vasculopathy: Challenges and Advances in Invasive and Non-Invasive Diagnostic Modalities.

Cardiac allograft vasculopathy (CAV) is a distinct form of coronary artery disease that represents a major cause of death beyond the first year after heart transplantation. The pathophysiology of CAV is still not completely elucidated; it involves progressive circumferential wall thickening of both the epicardial and intramyocardial coronary arteries. Coronary angiography is still considered the gold-standard test for the diagnosis of CAV, and intravascular ultrasound (IVUS) can detect early intimal thickening with improved sensitivity. However, these tests are invasive and are unable to visualize and evaluate coronary microcirculation. Increasing evidence for non-invasive surveillance techniques assessing both epicardial and microvascular components of CAV may help improve early detection. These include computed tomography coronary angiography (CTCA), single-photon emission computed tomography (SPECT), positron emission tomography (PET), and vasodilator stress myocardial contrast echocardiography perfusion imaging. This review summarizes the current state of diagnostic modalities and their utility and prognostic value for CAV and also evaluates emerging tools that may improve the early detection of this complex disease.

Establishment of nonobstructive coronary microcirculatory disorders in rabbits using three established methods and a comparative study

To compare the merits and drawbacks of three approaches for establishing a rabbit model of nonobstructive coronary microcirculatory disease, namely, open thoracic subtotal ligation of coronary arteries, ultrasound-guided cardiac microsphere injection, and sodium laurate injection. New Zealand rabbits were allocated to four groups: a normal group (Blank group), an Open-chest group (Open-chest), a microsphere group (Echo-M), and a sodium laurate group (Echo-SL), each comprising 10 rabbits. The rabbits were sacrificed 24 h after the procedures, and their echocardiography, stress myocardial contrast echocardiography, pathology, and surgical times were compared. The results demonstrated varying degrees of reduced cardiac function in all three experimental groups, the Open-chest group exhibiting the most significant decline. The myocardial filling in the affected areas was visually analyzed by myocardial contrast echocardiography, revealing sparse filling at rest but more after stress. Quantitative analysis of perfusion parameters (β, A, MBF) in the affected myocardium showed reduced values, the Open-chest group having the most severe reductions. No differences were observed in stress myocardial acoustic imaging parameters between the Echo-M and Echo-SL groups. Among the pathological presentations, the Open-chest model predominantly exhibited localized ischemia, while the Echo-M model was characterized by mechanical physical embolism, and the Echo-SL model displayed in situ thrombosis as the primary pathological feature. Inflammatory responses and collagen deposition were observed in all groups, with the severity ranking of Open-chest > Echo-SL > Echo-M. The ultrasound-guided intracardiac injection method used in this experiment outperformed open-chest surgery in terms of procedural efficiency, invasiveness, and maneuverability. This study not only optimizes established cardiac injection techniques but also offers valuable evidence to support clinical investigations through a comparison of various modeling methods.

Association between Troponin Elevation and Decreased Myocardial Blood Flow Reserve in Patients without Obstructive Coronary Artery Disease

Introduction: To study the prognostic factors of patients with chest pain and without obstructive coronary artery disease is of great significance for the management of such patients. We assessed whether a high-sensitivity troponin I (hs-TnI) is associated with prognosis in patients with chest pain and without obstructive coronary artery disease. Methods: From 2011 to 2017, 489 consecutively hospitalized patients with chest pain and without significant coronary artery stenosis (<50%) were tested for hs-TnI and underwent stress myocardial contrast echocardiography (MCE). Myocardial blood flow reserve (MBFR) was measured by stress MCE. Patients were followed (median, 41 months) for composite endpoints, including cardiovascular death and non-fatal myocardial infarction. Cox proportional hazards models were performed to determine associations between hs-TnI and the composite endpoints. Results: Among 489 patients with chest pain and without significant coronary artery stenosis, 257 patients (52.6%) had elevated hs-TnI. Compared to patients with normal hs-TnI, patients with elevated hs-TnI were older (p = 0.013) and had a higher prevalence of atrial fibrillation (p = 0.003), higher left ventricular mass index (p = 0.002) and E/e’ septal (p < 0.001), and a lower MBFR (p < 0.001). After adjustment, there was still a significant association between hs-TnI and MBFR (odds ratio = 1.145; 95% confidence interval [CI], 1.079–1.214; p < 0.001). Compared with patients with normal hs-TnI, patients with elevated hs-TnI had a greater cumulative event rate (log-rank p = 0.002). Males (hazard ratio [HR], 4.770; 95% CI, 1.175–19.363; p = 0.029) and reduced MBFR (HR, 2.496; 95% CI, 1.446–4.311; p = 0.001) were risk factors associated with composite endpoints in patients with elevated hs-TnI. Conclusions: In patients with chest pain and without obstructive coronary artery disease, elevated hs-TnI is associated with decreased myocardial perfusion by contrast echocardiography as well as a higher incidence of cardiovascular events.

ATP Stress Myocardial Contrast Echocardiography Assessment of Coronary Microvascular Disease with Spasmodic Characteristics: A Case Report

Here, a patient with chest pain and &lt;50% stenosis on coronary angiography, where ATP stress myocardial contrast echocardiography (MCE) revealed that coronary flow reserve was reduced to 1.71 was presented. Perfusion delay occurred in the left ventricular wall of the apex of the heart before ATP stress, and the perfusion delay area was significantly reduced at peak stress. Similar to the characteristics of “reverse redistribution” of radionuclide myocardium perfusion in coronary vasospasm, the delayed perfusion area in the recovery period was larger than that detected before stress. Together with increased spectral resistance of the distal segment of left anterior descending coronary artery and chest pain, these findings indicated coronary microvascular disease with spasmodic characteristics in this patient. The perfusion characteristics on ATP stress determined by MCE and changes in coronary spectrum have value for the diagnosis and treatment of coronary microvascular disease with spasmodic characteristics.

Diagnostic significance of myocardial and multimodal contrast exercise stress echocardiography in the detection of hemodynamically significant coronary artery stenosis in stable angina pectoris

Aim. To evaluate the diagnostic significance of myocardial contrast stress echocardiography (MCSE) and multimodal contrast stress echocardiography (MMSE) with dosed exercise in detecting hemo­dynamically significant coronary artery stenosis in patients with stable coronary heart disease (CAD) without impaired regional left ventricular contractility at rest.Material and methods. MCSE and MMSE were performed in 61 pa­­tients with suspected or stable CAD (mean age, 62,9±8,9 years). All patients underwent coronary angiography. During MCSE, perfusion and regional contractility were assessed. With MMSE, regional contractility was assessed. Sensitivity, specificity, and positive (LR+) and negative (LR-) likelihood ratios for MCSE and MMSE were assessed in com­parison with coronary angiography.Results. The sensitivity of MCSE with perfusion assessment was 82% (CI, 67-92%) with specificity of 70% (35-92%), LR+ — 2,74, LR- — 0,26. Sensitivity of MCSE with assessment of perfusion and regional contractility was 67% (50-81%) with specificity of 90% (65-99%), LR+ — 6,67, LR- — 0,37. The sensitivity of MCSE with an estimate of regional contractility of 74% (58-87%) with a specificity of 90% (56-98%), LR+ — 7,4, LR- — 0,28. The sensitivity of MMSE in the mode of cavitary and myocardial contrasting was 72% (55-85%) with a specificity of 90% (56-99%), LR+ — 7,18, LR- — 0,31.Conclusion. MCSE with an assessment of regional contractility and MMSE are of diagnostic importance in the detection of CAD, a positive result of which increases the post-test probability of hemodynamically significant coronary artery stenosis. A positive result of MCSE with dosed exercise with isolated perfusion assessment does not have a diagnostically significant effect on the post-test probability of CAD.

Early diagnosis of coronary microvascular dysfunction by myocardial contrast stress echocardiography.

Coronary microvascular dysfunction (CMD) is one of the basic mechanisms of myocardial ischemia. Myocardial contrast echocardiography (MCE) is a bedside technique that utilises microbubbles which remain entirely within the intravascular space and denotes the status of microvascular perfusion within that region. Some pilot studies suggested that MCE may be used to diagnose CMD, but without further validation. This study is aimed to investigate the diagnostic performance of MCE for the evaluation of CMD. MCE was performed at rest and during adenosine triphosphate stress. ECG triggered real-time frames were acquired in the apical 4-chamber, 3-chamber, 2-chamber, and long-axis imaging planes. These images were imported into Narnar for further processing. Eighty-two participants with suspicion of coronary disease and absence of significant epicardial lesions were prospectively investigated. Thermodilution was used as the gold standard to diagnose CMD. CMD was present in 23 (28%) patients. Myocardial blood flow reserve (MBF) was assessed using MCE. CMD was defined as MBF reserve < 2. The MCE method had a high sensitivity (88.1%) and specificity (95.7%) in the diagnosis of CMD. There was strong agreement with thermodilution (Kappa coefficient was 0.727; 95% CI: 0.57-0.88, p < 0.001). However, the correlation coefficient (r = 0.376; p < 0.001) was not high.

Evaluation of left ventricular function in ischemia with non-obstructive coronary arteries: a research based on adenosine stress myocardial contrast echocardiography.

Patients with ischemia with non-obstructive coronary arteries (INOCA) have an increased risk of adverse cardiovascular events in the future, which is widespread but underdiagnosed. The purpose of this study is to explore the application value of adenosine stress myocardial contrast echocardiography (ASMCE) in INOCA disease, so that clinicians can early identify and intervene patients with left ventricular function subclinical impairment in INOCA. We enrolled 118 patients with INOCA by ASMCE and invasive coronary angiography (ICA), 97 of whom had complete data. The study population was divided into two subgroups depending on coronary flow velocity reserve (CFVR): impaired CFVR group (n = 34) and normal CFVR group (n = 63). Global longitudinal strain endocardial myocardial (GLSendo), mid-myocardial (GLSmid) and epicardial myocardial (GLSepi) increased after stress in both groups; transmural strain, wall motion scored index (WMSI) and myocardial perfusion scored index (MPSI) increased and FORCE decreased in impaired CFVR group after stress, but there was no difference in normal group before and after stress. There was no significant difference in left ventricular myocardial mechanical parameters, including ΔGLSendo, ΔGLSmid, ΔGLSepi, GLSendo-epi Reserve, Δpeak strain dispersion (PSD), PSD Reserve between the two groups, but ΔEF, strain reserve and left ventricular contractile reserve (LVCR) in the impaired CFVR group were lower than those in the normal CFVR group, while ΔWMSI and ΔMPSI were increased. CFVR can be a clinically valuable indicator in the ASMCE diagnosis of patients with microvascular angina pectoris in INOCA. In the evaluation of left ventricular function in INOCA patients, attention should be paid not only to myocardial deformation, but also to the dynamic changes of LVCR and myocardial perfusion during peak hyperemia.

Plasma hydroxyanthranilic acid as a predictor of stress induced myocardial ischemia in non-obstructive coronary artery disease

Abstract Background The tryptophan catabolite hydroxyanthranilic acid (HAA) has potent immunomodulatory and vasoactive effects. HAA is also a precursor in the synthesis of nicotinamide adenine dinucleotide (NAD), a crucial cofactor in energy-metabolism. We have previously demonstrated that elevated plasma HAA predicted risk of myocardial infarction. Purpose To explore if plasma HAA is associated with stress induced myocardial ischemia in non-obstructive coronary artery disease (CAD). Methods In 132 patients with chest pain and non-obstructive CAD by coronary computed tomography angiography (CCTA), plasma HAA was analyzed by gas chromatography tandem mass spectrometry. All participants underwent myocardial contrast stress echocardiography. Myocardial ischemia was assessed as delayed contrast replenishment at peak dobutamine stress during real-time low mechanical index imaging and destruction replenishment. The extent of ischemia was defined as the number of segments with delayed contrast enhancement using a 17-segment left ventricular model. Associations of plasma HAA with myocardial ischemia was evaluated in a multivariate adjusted linear regression model. Results Mean (SD) age at inclusion was 63 (8) years and 56% were women. At CCTA, the median (25th, 75th percentile) coronary artery calcium (CAC) score was 42 (13–107) Agatston units, whereas the mean (SD) segment involvement score (SIS) was 2.6 (1.6). Myocardial ischemia was found in 52% of patients with on average 5 (3) ischemic segments per patient. Serum HAA did not correlate with the CAC score or SIS (p&amp;gt;0.29). After multivariate adjustment including age, sex, body mass index, systolic blood pressure, diabetes, current smoking, and LDL cholesterol, the odds ratio and 95% confidence interval for myocardial ischemia was 1.55 (1.04–2.32), P=0.03, per SD increment of plasma HAA levels (log transformed). Plasma HAA was also associated with the extent of myocardial ischemia with a multivariate adjusted β of 0.26, P=0.004. Conclusion Plasma HAA is associated with the extent of myocardial ischemia in non-obstructive CAD. Potential roles of this metabolite in atherogenesis, vascular dysfunction and as a predictor of myocardial ischemia should be further elucidated. Funding Acknowledgement Type of funding sources: Public hospital(s). Main funding source(s): Western Norway Regional Health Authority

Myocardial contrast echocardiography assessment of perfusion abnormalities in hypertrophic cardiomyopathy

BackgroundPerfusion defects during stress can occur in hypertrophic cardiomyopathy (HCM) from either structural or functional abnormalities of the coronary microcirculation. In this study, vasodilator stress myocardial contrast echocardiography (MCE) was used to quantify and spatially characterize hyperemic myocardial blood flow (MBF) deficits in HCM.MethodsRegadenoson stress MCE was performed in patients with septal-variant HCM (n = 17) and healthy control subjects (n = 15). The presence and spatial distribution (transmural diffuse, patchy, subendocardial) of perfusion defects was determined by semiquantitative analysis. Kinetic analysis of time-intensity data was used to quantify MBF, microvascular flux rate (β), and microvascular blood volume. In patients undergoing septal myectomy (n = 3), MCE was repeated > 1 years after surgery. ResultsIn HCM subjects, perfusion defects during stress occurred in the septum in 80%, and in non-hypertrophied regions in 40%. The majority of septal defects (83%) were patchy or subendocardial, while 67% of non-hypertrophied defects were transmural and diffuse. On quantitative analysis, hyperemic MBF was approximately 50% lower (p < 0.001) in the hypertrophied and non-hypertrophied regions of those with HCM compared to controls, largely based on an inability to augment β, although hypertrophic regions also had blood volume deficits. There was no correlation between hyperemic MBF and either percent fibrosis on magnetic resonance imaging or outflow gradient, yet those with higher degrees of fibrosis (≥ 5%) or severe gradients all had low septal MBF during regadenoson. Substantial improvement in hyperemic MBF was observed in two of the three subjects undergoing myectomy, both of whom had severe pre-surgical outflow gradients at rest.ConclusionPerfusion defects on vasodilator MCE are common in HCM, particularly in those with extensive fibrosis, but have a different spatial pattern for the hypertrophied and non-hypertrophied segments, likely reflecting different contributions of functional and structural abnormalities. Improvement in hyperemic perfusion is possible in those undergoing septal myectomy to relieve obstruction. Trial registrationClinicalTrials.gov NCT02560467.Graphical

Surveillance of adenosine stress myocardial contrast echocardiography following percutaneous coronary intervention.

The ability of adenosine stress myocardial contrast echocardiography (AS-MCE) to reveal decreased coronary blood flow or perfusion defects (PDs) has not been explored for clinical implications after coronary revascularization. This study sought to identify the prognostic value of PDs in asymptomatic patients following percutaneous coronary intervention (PCI). We retrospectively analyzed 342 asymptomatic patients (67 years of mean age, 72% male) who underwent PCI with stents at least 9 months before AS-MCE between May 2019 and December 2020. Resting regional wall motion abnormality (rRWMA) and the patterns of PDs were assessed, and further PDs were classified as ischemic or fixed type. The primary endpoint was the composite of hospitalization for worsening heart failure, coronary revascularization, and cardiac death. In AS-MCE (median time interval following PCI: 17.4 months), PDs were present in 93 (27.2%) out of 342 patients; 70 of ischemic PD (75.3%), 58 of fixed PD (62.4%). Those with PD showed a higher frequency of rRWMA than those without PD (53.8 vs. 15.7%, p < 0.001). During the median follow-up of 22.6 months, 26 (7.6%) patients experienced more associated clinical outcomes with PD than rRWMA. Cox analysis revealed that the combined findings of rRWMA and PD, and specifically, ischemic PD of ≥ 2 segments were associated with a high increase in adverse outcomes. AS-MCE provided prognostic value in asymptomatic patients with prior PCI. PD might be complementary to rRWMA in risk stratification.

Total coronary atherosclerotic plaque burden is associated with myocardial ischemia in non-obstructive coronary artery disease.

AimWhether the total coronary atherosclerotic plaque burden is independently associated with myocardial ischemia in non-obstructive coronary artery disease (CAD) is not well established. We aimed to test the association of total plaque burden quantified by coronary computed tomography angiography (CCTA) with myocardial ischemia in patients with chronic coronary syndrome and non-obstructive CAD.MethodsWe included 125 patients (age 62 ± 9 years, 58% women) with chronic coronary syndrome and non-obstructive CAD (stenosis < 50%) by CCTA, who were grouped according to presence or absence of myocardial ischemia by myocardial contrast stress echocardiography. Total plaque burden was quantified by CCTA as the total plaque volume in the main coronary arteries, and positive remodelling was defined as remodelling index > 1.10.ResultsPatients with myocardial ischemia (n = 66) had higher total plaque burden (847 ± 245 mm3 vs. 758 ± 251 mm3, p = 0.049) and higher left ventricular (LV) mass index (42.1 ± 9.9 g/m2.7 vs. 37.3 ± 8.0 g/m2.7, p = 0.004), while age, sex, prevalence of hypertension, diabetes, calcium score and positive remodelling did not differ between the groups (all p > 0.05). In multivariable regression analysis, total plaque burden remained associated with presence of myocardial ischemia (OR 1.02, 95% CI 1.00–1.04, p = 0.045) independent of age, sex, hypertension, diabetes, LV mass index, coronary calcium score and positive remodelling.ConclusionTotal coronary artery plaque burden by CCTA was independently associated with myocardial ischemia in patients with non-obstructive CAD. Whether plaque quantification is useful for clinical management of patients with non-obstructive CAD should be tested in prospective studies.ClinicalTrials.gov: Identifier NCT01853527.

Regadenoson Mycardial Contrast Echocardiography Perfusion Imaging for Detection of Allograft Coronary Vasculopathy

<h3>Purpose</h3> Due to the often asymptomatic nature of cardiac allograft vasculopathy (CAV) serial surveillance is recommended for all cardiac transplant (OHT) recipients. Ideally, CAV surveillance should be non-invasive, not involve ionizing radiation, and discriminate diffuse CAV from focal obstructions. We hypothesized that vasodilator stress myocardial contrast echocardiography (MCE) perfusion imaging can non-invasively detect microvascular impact of diffuse or focal CAV. <h3>Methods</h3> The study was a retrospective, single center analysis of OHT recipients undergoing MCE between 1/20 and 10/20 (n=11). MCE at rest and after regadenoson was performed using a continuous infusion of lipid-shelled microbubbles. Images were analyzed by evaluating time-intensity after a destructive pulse sequence in all vascular territories. MCE data were correlated with wall motion assessment by conventional stress echocardiography and invasive coronary angiography (ICA). Grading of MCE as normal, mild, severe; and focal vs. diffuse was performed by one experienced reviewer in a blinded fashion. <h3>Results</h3> Mean age was 63 ± 3.3 years post OHT, at an average of 10.8 ± 3.3 years post OHT. Severe perfusion abnormalities during MCE were able to distinguish high grade CAV (2+) from low grade CAV (0-1) utilizing ICA as the gold standard. While stress echocardiographic wall motion assessment failed to indicate early CAV grade 1, abnormal MCE perfusion was found in 3 of 7 cases with angiographic CAV grade 1. <h3>Conclusion</h3> MCE is a practical, non-invasive perfusion imaging technique that may be useful for detecting significant CAV in OHT recipients. Perfusion deficits correlate with significant coronary artery stenosis identified by standard stress echocardiography and ICA, and may identify diffuse small vessel disease more effectively than current noninvasive techniques. Larger, prospective studies are needed to support this hypothesis and ultimately provide a rationale for routine use of MCE for CAV surveillance.

Myocardial energetic efficiency is depressed in ischemia with non-obstructive coronary arteries

Abstract Background Ischemia with non-obstructive coronary arteries (INOCA) is incompletely understood. Depressed myocardial energetic efficiency index (MEEi), the ratio between external work and myocardial oxygen consumption, has been shown in heart failure. However, MEEi in INOCA has not been explored. Purpose To test whether MEEi is associated with INOCA. Methods We included 125 patients (56% women, age 62±9 years) with exercise-induced chest pain and non-obstructive coronary arteries (stenosis &amp;lt;50%) by coronary computed tomography angiography (CCTA). Stroke volume (SV) and left ventricular (LV) mass were assessed by echocardiography. MEEi was calculated as (systolic blood pressure (SBP) x SV) / (SBP x heart rate) and normalized for LV mass. LV hypertrophy was defined as LV mass index &amp;gt;46.7 g/m2.7 in women and &amp;gt;49.2 g/m2.7 in men. Myocardial ischemia was detected by myocardial contrast stress echocardiography. Coronary artery plaque burden was measured as plaque volume by CCTA. Results In univariable regression analysis, stress-induced ischemia, male sex, diabetes, hypertension, LV hypertrophy, lower LV ejection fraction and higher SBP were associated with MEEi (all p&amp;lt;0.05). There were no associations with age, obesity or coronary artery plaque burden. MEEi was lower in patients with stress-induced ischemia (n=66) compared to patients without ischemia (0.47±0.16 vs. 0.54±0.21 ml/sec x g–1, p=0.026). In multivariable linear regression analysis, MEEi remained associated with stress-induced myocardial ischemia after adjustment for cardiovascular risk factors, SBP, LV hypertrophy, LV ejection fraction and coronary artery plaque burden (R2 0.26, p&amp;lt;0.001, Table). Conclusion MEEi is depressed in patients with INOCA. Our results suggest that myocardial ischemia negatively influences MEEi in patients with non-obstructive coronary arteries. Funding Acknowledgement Type of funding source: Public Institution(s). Main funding source(s): Western Norway Regional Health Authority, University of Bergen

Low-dose dobutamine stress myocardial contrast echocardiography for the evaluation of myocardial microcirculation and prediction of overall cardiac function recovery.

The study aimed to investigate the role of low-dose dobutamine stress myocardial contrast echocardiography (MCE) in evaluating myocardial local microcirculation and predicting cardiac function recovery in patients with myocardial infarction. A total of 50 patients with acute myocardial infarction (AMI) were enrolled in the present study. Positron emission tomography was used as a gold standard to determine viable/non-viable myocardial segments in infarcted myocardial region. MCE and dobutamine stress MCE were carried out 72 h after PCI. MCE was carried out again to evaluate myocardial condition at 6 months after PCI. As compared with normal myocardial segments, resting MCE revealed a significant decrease of the values of A (the peak intensity of the time-perfusion intensity curve, reflecting the myocardial blood volume), β (the slope of the curve, reflecting the myocardial blood flow (MBF) velocity) and A x β (reflecting MBF) of viable and non-viable myocardial segments. After being challenged by dobutamine, the values of A, β and A x β of normal coronary blood supply areas were significantly increased; while the segments A and A x β of viable myocardium were markedly decreased. Patients were further divided into two groups based on the changes in the contrast-enhanced index (CSI) following dobutamine loading. In the dobutamine stress echocardiography-positive group (the CSI increased or decreased by >0.2), the left ventricular ejection fraction was significantly increased and pro-B-type natriuretic peptide significantly decreased at 6 months following intervention. Low-dose dobutamine stress MCE was indicated to be an effective method to evaluate myocardial microcirculation perfusion in patients with AMI following PCI. In addition, CSI, as a simple semi-quantitative index, may predict left ventricular function in patients with AMI.

Comparison of myocardial contrast stress-echocardiography and standard stress-echocardiography in detecting myocardial ischemia in patients with different severity of coronary artery stenoses

To compare diagnostic value between standard stress-echocardiography and myocardial contrast stress echocardiography in detection of myocardial ischemia in patients with different severity of coronary artery stenoses. Myocardial contrast stress-echocardiography and standard stress-echocardiography were performed in 38 patients with coronary artery stenoses over 50% by angiography. Of all lesions 39 were intermediate (5075%) and 33 over 75% stenoses. Fractional flow reserve (FFR) was measured in 12 coronary arteries. During myocardial contrast stress-echocardiography wall motion and myocardial perfusion was assessed. Adequate visualisation increased from 81.6% in unenhanced segments to 96.1% in contrast-enhanced segments. The sensitivity, specificity, and diagnostic accuracy of standard stress-echocardiography and myocardial contrast stress-echocardiography in intermediate (5075%) coronary stenoses were 44%, 83%, 56% and 56%, 94% и 64% respectively compare to angiography. Taking into account the 12 arteries with evaluated FFR, these parameters increased to 52%, 93% и 65% in standard stress-echocardiography and to 68%, 100% and 75% in myocardial contrast stress-echocardiography. In coronary stenoses over 75% the sensitivity, specificity, and diagnostic accuracy of standard stress-echocardiography and myocardial contrast stress-echocardiography were 78%, 88%, 80% and 86%, 100%, 92% respectively Conclusion. Use of contrast-enhanced stress-echorardiography significantly increased the diagnostic value of this method by improving endocardial border visualization and possibilities of myocardial perfusion assessment.

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.

Left ventricular hypertrophy contributes to Myocardial Ischemia in Non-obstructive Coronary Artery Disease (the MicroCAD study)

BackgroundThe underlying mechanisms causing myocardial ischemia in non-obstructive coronary artery disease (CAD) are still unclear. We explored whether left ventricular hypertrophy (LVH) was associated with myocardial ischemia in patients with stable angina and non-obstructive CAD. Methods132 patients (mean age 63 ± 8 years, 56% women) with stable angina and non-obstructive CAD diagnosed as <50% stenosis by coronary computed tomography angiography (CCTA) underwent myocardial contrast stress echocardiography. Left ventricular (LV) hypertrophy (LVH) was identified by LV mass index >46.7 g/m2.7 in women and >49.2 g/m2.7 in men. Patients were grouped according to presence or absence of myocardial ischemia by myocardial contrast stress echocardiography. The number of LV segments with ischemia at peak stress was taken as a measure of the extent of myocardial ischemia. ResultsMyocardial ischemia was found in 52% of patients, with on average 5 ± 3 ischemic LV segments per patient. The group with myocardial ischemia had higher prevalence of LVH (23 vs. 10%, p = 0.035), while age, sex and prevalence of hypertension did not differ between groups (all p > 0.05). In multivariable regression analyses, LVH was associated with presence of myocardial ischemia (odds ratio 3.27, 95% confidence interval [1.11–9.60], p = 0.031), and larger extent of myocardial ischemia (β = 0.22, p = 0.012), independent of confounders including age, hypertension, obesity, hypercholesterolemia, calcium score and segment involvement score by CCTA. ConclusionsLVH was independently associated with both presence and extent of myocardial ischemia in patients with stable angina and non-obstructive CAD by CCTA. These results suggest LVH as an independent contributor to myocardial ischemia in non-obstructive CAD.Clinical trial registration number: ClinicalTrials.gov, identifier NCT018535271.

PO616 Clinical Profile and Risk Factors of In-Hospital Mortality Among Filipino Patients With Infective Endocarditis

The underlying mechanisms causing myocardial ischemia in non-obstructive coronary artery disease (CAD) are still unclear. We explored whether left ventricular hypertrophy (LVH) was associated with myocardial ischemia in patients with stable angina and non-obstructive CAD.132 patients (mean age 63 ± 8 years, 56% women) with stable angina and non-obstructive CAD diagnosed as <50% stenosis by coronary computed tomography angiography (CCTA) underwent myocardial contrast stress echocardiography. Left ventricular (LV) hypertrophy (LVH) was identified by LV mass index >46.7 g/m2.7 in women and >49.2 g/m2.7 in men. Patients were grouped according to presence or absence of myocardial ischemia by myocardial contrast stress echocardiography. The number of LV segments with ischemia at peak stress was taken as a measure of the extent of myocardial ischemia.Myocardial ischemia was found in 52% of patients, with on average 5 ± 3 ischemic LV segments per patient. The group with myocardial ischemia had higher prevalence of LVH (23 vs. 10%, p = 0.035), while age, sex and prevalence of hypertension did not differ between groups (all p > 0.05). In multivariable regression analyses, LVH was associated with presence of myocardial ischemia (odds ratio 3.27, 95% confidence interval [1.11–9.60], p = 0.031), and larger extent of myocardial ischemia (β = 0.22, p = 0.012), independent of confounders including age, hypertension, obesity, hypercholesterolemia, calcium score and segment involvement score by CCTA.LVH was independently associated with both presence and extent of myocardial ischemia in patients with stable angina and non-obstructive CAD by CCTA. These results suggest LVH as an independent contributor to myocardial ischemia in non-obstructive CAD.Clinical trial registration number: ClinicalTrials.gov, identifier NCT018535271.

Long-Term Association of Dipyridamole Stress Myocardial Contrast Echocardiography versus Single-Photon Emission Computed Tomography with Clinical Outcomes in Patients with Known or Suspected Coronary Artery Disease

Single-photon emission computed tomography (SPECT) is a well-established method to evaluate patients with coronary artery disease. Myocardial contrast echocardiography (MCE) is an imaging technique that allows the assessment of myocardial perfusion in real time. Previous research has shown that vasodilator MCE is superior to SPECT for the prediction of hard events. The aim of this study was to investigate the long-term association of SPECT and MCE with clinical outcomes in patients with known or suspected coronary artery disease. Accordingly, 258 patients who underwent MCE and SPECT as part of multicenter studies performed prospectively were followed up for hard events (all-cause mortality and nonfatal myocardial infarction). The mean age was 63.4±5.5years, 186 (72.1%) were men, and 32 (12.4%) had left ventricular systolic dysfunction. We calculated the ratio of the number of abnormal segments (at rest and/or stress) to the total number of segments expressed as MCE and SPECT indices. Over a mean follow-up period of 80.4±6.1months, 46 patients had hard events. MCE and SPECT indices were associated with all-cause mortality on univariate analysis (P=.008 and P=.035, respectively) but only MCE index was independently associated with hard events (hazard ratio, 4.24; 95% CI, 1.27-14.15; P=.019), beyond clinical data and left ventricular function, and independently associated with hard cardiac events (hazard ratio, 4.78; 95% CI, 1.06-21.59; P=.042). MCE but not SPECT showed a long-term association with outcome. These results thus favor the routine use of MCE in the long-term assessment of patients with known or suspected coronary artery disease.

Renin-Angiotensin System Inhibitors Can Prevent Intravenous Lipid Infusion-Induced Myocardial Microvascular Dysfunction and Leukocyte Activation.

Levels of triglycerides and free fatty acids (FFAs) are elevated in patients with diabetes and may contribute to endothelial dysfunction through renin-angiotensin system (RAS) activation and oxidative stress. The present study investigated how systemic FFA loading affected myocardial microcirculation during hyperemia via RAS.Methods and Results:Eight healthy men received candesartan, perindopril, or a placebo for 2 days in a double-blind crossover design, and then myocardial microcirculation during hyperemia induced by a 2-h infusion of lipid/heparin was assessed using dipyridamole stress-myocardial contrast echocardiography (MCE). Leukocyte activity and hemorheology were also assessed ex vivo using a microchannel flow analyzer, serum levels of oxidative stress markers, and IκB-α expression in mononuclear cells. Serum FFA elevation by the infusion of lipid/heparin significantly decreased myocardial capillary blood velocity and myocardial blood flow during hyperemia. Both candesartan and perindopril significantly prevented the FFA-induced decrease in capillary blood velocity and myocardial blood flow during hyperemia. Systemic FFA loading also caused an increase in the number of adherent leukocytes and prolonged the whole blood passage time. These effects were blocked completely by candesartan and partially by perindopril. Both agents prevented the FFA-induced enhancement of oxidative stress and IκB-α degradation in mononuclear cells. Both candesartan and perindopril can prevent FFA-induced myocardial microcirculatory dysfunction during hyperemia via modulation of leukocyte activation and microvascular endothelial function.