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Funding Acknowledgements Type of funding sources: None. Background Two-Dimensional Strain for Diagnosing Chest Pain in the Emergency Room (2DSPER) was a prospective multicenter study designed to determine whether 2D longitudinal strain (2DLS) can assist in triage of patients with chest pain in the emergency department (ED). In that study 2DLS was not useful to rule out acute coronary syndromes (ACS) in the ED, partly because many patients without ACS had abnormal 2DLS. The prognostic significance of 2DLS in these patients is unclear. The aim of the current study was to determine whether global longitudinal strain (GLS), measured using 2D echocardiography in the ED, can predict long-term outcome. Methods Long-term (median 7.7 years [IQR 6.7-8.2]) major adverse cardiac events (MACE; cardiac death, ACS, revascularization, hospitalization for heart failure or atrial fibrillation) was available in 525 of 605 patients (87%) enrolled in the 2DSPER study. The study prospectively enrolled patients presenting to the ED with chest pain and suspected ACS but without a diagnostic ECG or elevated troponin. Global longitudinal strain (GLS) was computed from echocardiograms performed within 24 hours of chest pain using a dedicated 2DLS software (EchoPAC SW; GE Vingmed Ultrasound AS). MACE of patients with worse GLS (>median) was compared to those with better GLS (≤median). Results Median GLS was -18.8%. MACE occurred in 43/249 (17.3%) of patients with worse GLS (-16.8 ± 1.5) as compared with 49/276 (17.8%) with better GLS (-20.8 ± 1.6), HR 0.98 (95%CI 0.65-1.4, p = 0.9) (Figure). Similarly, there was no significant difference in total mortality (6% vs. 4.7%, p = 0.5), cardiac death (0.4% vs. 0.7%, p = 0.6), ACS (8% vs. 8.3%, p = 1), revascularization (10% vs. 10.9%, p = 0.8), hospitalization for heart failure (0.8% vs. 2.2%, p = 0.2) or atrial fibrillation (3.6% vs. 4.3%, p = 0.7) between groups. Predictors of MACE were male gender (HR 2.5, 1.4-4.3, p = 0.02), history of coronary artery disease (HR 3.3, 2-5.4, p Conclusions GLS did not predict long term outcome in patients presenting to the ED with chest pain. Long-term outcome was favorable in the group of patients with worse GLS, similar to better GLS. Abstract Figure.

Introduction Left ventricular (LV) relaxation time constant, Tau (τ), is one of the best indexes to evaluate left ventricular diastolic function and is usually assessed invasively. Tau is the time constant of the exponential regression Pt =(P0-P∞)e-t/τ+P∞ that expresses left ventricular isovolumic pressure decay, where Pt is LV pressure (LVP) at time t, P0 is LVP at dP/dtmin and P∞ is the asymptotic pressure, to which relaxation would lead if completed without LV filling. Several noninvasive methods were developed to calculate Tau, however, they are time-consuming and complicated. Recently, a simple method regional left ventricular pressure–strain loops and myocardial work was introduced and validated. We hypothesize that left ventricular relaxation time constant can be derived and calculated from the LV pressure–strain loops. Objective To calculate noninvasively Tau using LV pressure–strain loops and compare it to invasive Tau assessment. Methods The study includes patients with preserved LV systolic function without significant valvular disease that were scheduled to elective coronary catheterization. During catheterization, a fluid-filled catheter was placed in the LV to measure pressure. Echocardiography was performed simultaneously with LV pressure recording. Three standard apical views were acquired and subsequently 2D strain analysis was performed using commercially available GE software and LV pressure–strain loops were calculated. Doppler signal was used for timing of valvular events. Tau was calculated by the equation τ =P/(-dP/dt) that is a derivative of the ventricular pressure decline P = P0e-t/τ+PB with respect to time. The pressure between peak negative dP/dt and the lowest LV pressure shortly after mitral valve opening was used for this calculation. The study was approved by the institutional ethics committee. Results Forty patients, (mean age 65.1 ± 10.9 years, 27 male, BSA1.93 ± 0.18 m2) were included in the study. Heart rate and the mean blood pressure at the time of catheterization were 69.9 ± 11.8 min-1 and 85.2 ± 18.8 mmHg, respectively. The mean LV end diastolic diameter was 44 ± 4 mm, the LV mass was 86.7 ± 25.2 g/m2, LVEF 58.4 ± 6.6% and GLS 21.0 ± 3.2%. Tau, calculated noninvasively using derivative method was significantly lower than invasively derived measurement (40.1 ± 13.4 vs 49.8 ± 7.7 msec, p = 0.002). However, a significant positive correlation was observed between the two methods (r =0.67, p Conclusions This preliminary study demonstrates that Tau estimated by a noninvasive method using LV pressure–strain loops has a good correlation with Tau measured invasively. Therefore, Tau can be estimated noninvasively using novel left ventricular pressure–strain loop method. Abstract P1510 Figure.

Aims Assessing the quality of wall motion (WM) on echocardiograms remains a challenge. Previously, we validated an automated application used by experienced echocardiographers for WM classification based on longitudinal two-dimensional (2D) strain. The aim of this study was to show that the use of this automatic application was independent of the user's experience. Methods and results We compared the WM classifications obtained by the application when used by 12 highly experienced readers (Exp-R) vs. 11 inexperienced readers (InExp-R). Both classifications were compared with expert consensus classifications using the standard visual method. Digitized clips of cardiac cycles from three apical views in 105 patients were used for these analyses. Reproducibility of both groups was high (overall intra-class correlation coefficient: InExp-R = 0.89, Exp-R = 0.83); the lowest was noted for hypokinetic segments (InExp-R = 0.79, Exp-R = 0.72). InExp-R scores were concordant with Exp-R mode scores in 88.8% of segments; they were overestimated in 5.8% and underestimated in 3.2%. The sensitivity, specificity, and accuracy of InExp-R vs. Exp-R for classifying segments as normal/abnormal were identical (87, 85, and 86%, respectively). Conclusion Classification of WM from apical views with an automatic application based on longitudinal 2D strain by InExp-R vs. Exp-R was similar to visual classification by Exp-R. This application may be useful for inexperienced echocardiographers/technicians and may serve as an automated ‘second opinion’ for experienced echocardiographers.

This article explores the contribution of a multiple-method design to the study of classroom interaction. The theoretical and methodological frameworks of three constructivist discourse-oriented methods (i.e., Institutional Speech Event Analysis, The Four-World Method and Grounded Theory) are summarized and the same text is submitted to three independent text analyses. The article shows that a multiple-method design is conducive to the discovery of implicit meanings related to social, experiential and epistemological aspects of classroom interaction.

Introduction: Degenerative aortic stenosis (AS) is the most common valvular disease. Endothelial progenitor cells (EPCs) have a role in the repair of endothelial surfaces after injury. The aim of this study was to assess EPC number in pts with AS and to study the predictive value of circulating EPC levels on prognosis in pts with AS. Methods: The number of EPCs was determined by flow cytometry in 244 consecutive pts with AS and a control group of 75 pts. Thirty eight pts had mild AS, 52 pts had moderate AS and 154 pts presented with severe AS. We evaluated the association between baseline levels of EPCs and functional improvement after an intervention and death from cardiovascular causes. Results: The EPC number was significantly higher in pts with AS compared to the control group (p=0.026). There was no difference in EPC number among pts with mild, moderate or severe AS. Two hundred and six pts with moderate and severe AS were followed for a median of 20 months for the occurrence of cardiovascular events. One hundred and twenty pts underwent an intervention. Sixty-two percent showed improvement in functional class after the intervention and 38% did not improve. The EPC number was significantly higher in pts with functional improvement compared to those that did not improve (p=0.01). Forty one pts died during follow up, 21 pts died due to cardiac causes. Advanced age, the presence of CAD, high NYHA class, low aortic valve area, elevated pulmonary artery pressure and low EPC number were found to be predictors of cardiac death in the univariant analysis. Multivariant logistic regression model identified only low EPC number as associated with cardiac death during follow up (p= 0.025, Figure 1). Conclusions: EPC number is increased in pts with AS. However, in pts with moderate or severe AS a relatively low number of EPCs is associated with lack of functional improvement after intervention and with cardiac death at follow up. These results may help to identify AS pts at increased cardiovascular risk.

OBJECTIVES We sought to determine the feasibility and accuracy of real-time imaging of myocardial contrast echocardiography (MCE) in detecting myocardial perfusion defects during exercise echocardiography compared with radionuclide tomography. BACKGROUND Ultrasound imaging at a low mechanical index and frame rate (10 to 20 Hz) after intravenous injections of perfluorocarbon containing microbubbles has the potential to evaluate myocardial perfusion and wall motion (WM) simultaneously and in real time. METHODS One hundred consecutive patients with intermediate-to-high probability of coronary artery disease underwent treadmill (n = 50) or supine bicycle (n = 50) exercise echocardiography. Segmental perfusion with MCE and WM were assessed in real time before and at peak exercise using low mechanical index (0.3) and frame rates of 10 to 20 Hz after 0.3 ml bolus injections of intravenous Optison (Mallinckrodt Inc., San Diego, California). All patients had a dual isotope (rest thallium-201, stress sestamibi) study performed during the same exercise session, and 44 patients had subsequent quantitative coronary angiography. RESULTS In the 100 patients, agreement between MCE and single photon emission computed tomography (SPECT) was 76%, while it was 88% between MCE and WM assessment. Compared with quantitative angiography, sensitivity of MCE, SPECT and WM was comparable (75%), with a specificity ranging from 81% to 100%. The combination of MCE and WM had the best balance between sensitivity and specificity (86% and 88%, respectively) with the highest accuracy (86%). CONCLUSIONS The real-time assessment of myocardial perfusion during exercise stress echocardiography can be achieved with imaging at low mechanical index and frame rates. The combination of WM and MCE correlates well with SPECT and is a promising important addition to conventional stress echocardiography.

Background —Alterations in adrenergic receptor densities can potentially contribute to myocardial dysfunction. Their relevance to myocardial hibernation in humans is unknown. Methods and Results —Accordingly, 22 transmural myocardial biopsies were obtained in 11 patients with ischemic ventricular dysfunction during bypass surgery, guided by transesophageal echocardiography. Patients underwent dobutamine echocardiography (DE) and rest scintigraphic studies before revascularization and DE at 3 to 4 months. α- and β-receptor density (ARD and BRD) and extent of fibrosis were quantified from the myocardial biopsies. Of the 22 segments, 16 had abnormal rest function and 6 were normal. Severely hypokinetic or akinetic segments showed a 2.4-fold increase in ARD with a concomitant 50% decrease in BRD compared with normal segments. An increase in ARD, a decrease in BRD to a lesser extent, and thus an increase in ARD/BRD ratio were seen in dysfunctional segments with contractile reserve compared with normal segments and were most pronounced in those without contractile reserve ( P r =0.37 and −0.39, respectively). Conclusions —Thus, graded and reciprocal changes in α- and β-adrenergic receptor densities occur in viable, hibernating myocardium and may account in part for the observed depression in resting myocardial function and preserved contractile reserve in this entity.

OBJECTIVESWe sought to evaluate the relation of segmental tissue Doppler (TD) velocities to both the regional amount of interstitial fibrosis and the myocyte beta-adrenergic receptor density in humans.BACKGROUNDThe systolic myocardial velocity (Sm) and early diastolic myocardial velocity (Em) acquired by TD are promising new indexes of left ventricular function. However, their structural and functional correlates in humans are still unknown.METHODSTen patients with coronary artery disease underwent echocardiographic examination including TD imaging, along with transmural endomyocardial biopsy at the time of coronary bypass surgery (two biopsies per patient for a total of 20 specimens). The specimens were analyzed for percent interstitial fibrosis and beta-adrenergic receptor density.RESULTSNormal segments (n = 8) had a higher beta-adrenoceptor density (2,280 ± 738 vs. 1,373 ± 460, p = 0.03) and a lower amount of interstitial fibrosis (13 ± 3.3% vs. 28 ± 11.5%, p = 0.002) than dysfunctional segments (n = 12). Myocardial systolic velocity and Em were also significantly higher (9.5 ± 2.7 vs. 5.9 ± 1.8 cm/s, p = 0.025 and 11.3 ± 2.8 vs. 6.4 ± 2.1 cm/s, p = 0.002, respectively) in normal segments. A significant relationship was present between Em and the beta-adrenergic receptor density (r = 0.78, p < 0.001) and percent interstitial fibrosis (r = −0.7, p = 0.0026), which together accounted for 81% of the variance observed in Em. Likewise, a significant relationship was present between Sm and the beta-adrenergic receptor density (r = 0.68, p < 0.001) and the percent interstitial fibrosis (r = −0.66, p = 0.004) and together accounted for 62% of the variance observed in Sm.CONCLUSIONSSystolic myocardial velocity and Em are strongly dependent on both the number of myocytes and the myocardial beta-adrenergic receptor density.

Background— Identification and quantification of segmental left ventricular wall motion abnormalities on echocardiograms is of paramount clinical importance but is still performed by a subjective visual method. We constructed an automatic tool for assessment of wall motion based on longitudinal strain. Methods and Results— Echocardiograms of 105 patients (3 apical views) were blindly analyzed by 12 experienced readers. Visual segmental scores (VSS) and peak systolic longitudinal strain were assigned to each of 18 segments per patient. Ranges of peak systolic longitudinal strain that best fit VSS (by receiver operating characteristic analysis) were used to generate automatic segmental scores (ASS). Comparisons of ASS and VSS were performed on 1952 analyzable segments. There was agreement of wall motion scores between both methods in 89.6% of normal, 39.5% of hypokinetic, and 69.4% of akinetic segments. Correlation between methods was r =0.63 ( P Conclusions— Automatic quantification of wall motion on echocardiograms by this tool performs as well as visual analysis by experienced echocardiographers, with a greater reliability and similar agreement to angiographic findings.

Background— There are currently no data on the accuracy of intravenous myocardial contrast echocardiography (MCE) in detecting myocardial hibernation in man and its comparative accuracy to dobutamine echocardiography (DE) or thallium 201 (Tl 201 ) scintigraphy. Methods and Results— Twenty patients with coronary artery disease and ventricular dysfunction underwent MCE 1 to 5 days before bypass surgery and repeat echocardiography at 3 to 4 months. Patients also underwent DE (n=18) and rest-redistribution Tl 201 tomography (n=16) before revascularization. MCE was performed using continuous Optison infusion (12 to 16 cc/h) with intermittent pulse inversion harmonics and incremental triggering (1:1 to 1:8). Myocardial contrast intensity (MCI) replenishment curves were constructed to derive quantitative MCE indices of blood velocity and flow. Recovery of function occurred in 38% of dysfunctional segments. MCE parameters of perfusion in hibernating myocardium were similar to segments with normal function and higher than dysfunctional myocardium without recovery of function ( P 201 uptake ≥60% ( P 1.5 dB/s for recovery of function was 90% and was similar to Tl 201 scintigraphy (92%) and any contractile reserve (80%); specificity was higher than for Tl 201 and DE (63%, 45%, and 54%, respectively; P Conclusions— MCE with intravenous contrast identifies myocardial hibernation in humans. Prediction of viable myocardium with MCE is best using quantification of myocardial blood flow and provides improved accuracy compared with DE and Tl 201 scintigraphy.

Background— Myocardial contrast echocardiography (MCE) has been used to evaluate myocardial viability. There are no data, however, on the pathological determinants of myocardial perfusion by MCE in humans and the implications of such determinants. Methods and Results— MCE was performed in 20 patients with coronary artery disease and ventricular dysfunction within 24 hours before myocardial biopsy at surgery using a continuous Optison infusion (12 to 16 cc/h), with intermittent pulse inversion harmonics and incremental triggering. Peak myocardial contrast intensity (MCI) and the rate of increase in MCI (β) were quantitated. Thirty-six transmural myocardial biopsies (2 per patient) were obtained by transesophageal echocardiography. Total microvascular (r =0.59, P r =0.64, P r =−0.45, P =r =0.84 and 0.87, respectively; P Conclusions— Microvascular integrity is a significant determinant of maximal MCI in humans. MCE indices of blood velocity and flow are important parameters that predict recovery of function after revascularization.

ObjectivesThe purpose of this study is to investigate the morphologic characteristics of the cardiac interstitium in the hibernating human myocardium and evaluate whether active remodeling is present and is an important determinant of functional recovery.BackgroundMyocardial hibernation is associated with structural myocardial changes, which involve both the cardiomyocytes and the cardiac interstitium.MethodsWe evaluated 15 patients with coronary disease with two-dimensional echocardiography and thallium-201 (201Tl) tomography before coronary bypass surgery. During surgery, transmural myocardial biopsies were performed guided by transesophageal echocardiography. Myocardial biopsies were stained immunohistochemically to investigate fibroblast phenotype and examine evidence of active remodeling in the heart.ResultsAmong the 29 biopsied segments included in the study, 24 showed evidence of systolic dysfunction. The majority of dysfunctional segments (86.4%) were viable (201Tl uptake ≥60%). After revascularization, 12 dysfunctional segments recovered function as assessed with an echocardiogram three months after bypass surgery. Interstitial fibroblasts expressing the embryonal isoform of smooth muscle myosin heavy chain (SMemb) were noted in dysfunctional segments, predominantly located in border areas adjacent to viable myocardial tissue. Segments with recovery had higher SMemb expression (0.46 ± 0.16% [n = 12] vs. 0.10 ± 0.02% [n = 12]; p < 0.05) and a higher ratio of alpha-smooth muscle actin to collagen (0.14 ± 0.026 [n = 12] vs. 0.07 ± 0.01 [n = 12]; p < 0.05) compared with segments without recovery, indicating fibroblast activation and higher cellularity of the fibrotic areas. In addition, interstitial deposition of the matricellular protein tenascin, a marker of active remodeling, was higher in hibernating segments than in segments with persistent dysfunction (p < 0.05), suggesting an active continuous fibrotic process. Multiple logistic regression demonstrated a significant independent association between SMemb expression and functional recovery (p < 0.01).ConclusionsFibroblast activation and expression of SMemb and tenascin provide evidence of continuous remodeling in the cardiac interstitium of the hibernating myocardium, an important predictor of recovery of function after revascularization.

Myocardial hibernation refers to a state of prolonged impairment of left ventricular function in the presence of coronary artery disease, which may be reversed by revascularization. In this study we present evidence for a local inflammatory reaction in hibernating myocardial segments from patients undergoing coronary revascularization. We obtained transmural myocardial biopsies guided by transesophageal echocardiography from patients with ischemic ventricular dysfunction undergoing bypass surgery. Among the 28 biopsied segments included in the study, 23 showed evidence of systolic dysfunction. The majority of dysfunctional segments (85.7%) were viable ((201)Tl uptake/= 60%). The samples were stained with markers for mast cells, mature resident macrophages, and the monoclonal antibody Mac387 that labels newly recruited myeloid cells. Dysfunctional segments showed more extensive fibrosis and higher macrophage density than normal segments. Among the 23 dysfunctional segments, 12 recovered function as assessed with echocardiograms 3 months after revascularization. Segments with postoperative functional recovery had comparable macrophage and mast cell density with those showing persistent dysfunction. However, biopsied segments that subsequently recovered function contained significantly higher numbers of newly recruited Mac387-positive leukocytes (18.7 +/- 3.1 cells/mm(2), n = 12 versus 8.6 +/- 0.9 cells/mm(2), n = 11; P = 0.009). In addition, monocyte chemotactic protein-1, a potent mononuclear cell chemoattractant, was predominantly expressed in segments with recovery of function. Myocardial hibernation is associated with an inflammatory response leading to active leukocyte recruitment. Dysfunctional myocardial segments that show an active inflammatory reaction have a greater potential for recovery of function after revascularization. We postulate that revascularization may promote resolution of the ongoing inflammation, preventing further tissue injury and fibrosis.

Background —In patients with heart failure secondary to left ventricular (LV) systolic dysfunction, a short deceleration time (DT) successfully predicts clinical outcome. The impact of myocardial viability and revascularization on the mitral inflow velocities, however, is unknown. Methods and Results —Forty patients with ischemic cardiomyopathy underwent 201 Tl scintigraphy (SPECT) and 2D, Doppler, and dobutamine echocardiography (DE, to 40 μg · kg −1 · min −1 ) 2 days before CABG. Echocardiography was repeated 3 months after revascularization to determine recovery of function. Significant correlations were present between DT and LV contractile reserve by DE ( r =0.72), scar perfusion defect by SPECT ( r =−0.69), and the change in ejection fraction (ΔEF) after surgery ( r =0.77) (all P 150 ms effectively identified (sensitivity 79%, specificity 81%) patients with ΔEF ≥5%. The population was divided into 2 groups according to DT: group 1 (DT >150 ms, n=21) and group 2 (DT ≤150 ms, n=19). At baseline, NYHA class, LV EF, age, and use of cardiovascular drugs were similar between the 2 groups. The number of viable segments by both DE and SPECT, however, was higher in group 1 (both P P P =0.017). Conclusions —In patients with ischemic cardiomyopathy, the reduced amount of viable myocardium results in a restrictive mitral inflow pattern, which in turn predicts poor survival.