An Australian comparison of specialist care of acute myocardial infarction

Objective. To determine whether patients hospitalized with acute myocardial infarction (AMI) in an Australian setting receive better pharmacological care if managed by cardiologists than by non-cardiologists. Design. Retrospective chart review of patients hospitalized between 1 January 1997 and 30 June 1998, undertaken by abstractors blind to study objectives. Setting. One tertiary and two community hospitals in south-east Queensland, Australia, in which all patients admitted with AMI were cared for by cardiologists and general physicians, respectively. Study participants. Two cohorts of consecutive patients satisfying diagnostic criteria for AMI: 184 in the tertiary hospital and 207 in the community hospitals. Main outcome measures. Frequency of use, in highly eligible patients, of thrombolysis, P-blockers, aspirin, angiotensin-converting enzyme (ACE) inhibitors, lipid-lowering agents, nitrates, and calcium antagonists. Cohorts were compared for differences in prognostic factors or illness severity. Results. In community hospital patients, there was greater use of thrombolysis [100% versus 83% in the tertiary hospital; difference 17%, 95% confidence interval (CI) 11-26%; P < 0.001] and of ACE inhibitors (84% versus 66%; difference 18%, 95% CI 3-34%; P = 0.02), and lower median length of stay (6.0 days versus 7.0 days; P = 0.001) compared with tertiary hospital patients. Frequency of use of other drugs, and adjusted rates of death and re-infarction were the same for both cohorts. Conclusions. With respect to pharmacological management of patients hospitalized with AMI, cardiologists and general physicians appear to provide care of similar quality and achieve equivalent outcomes. Further studies are required to confirm the generalizability of these results to Australian practice as a whole.

Eosinophilic heart: Marked left ventricular wall thickening and myocardial dysfunction improving with corticosteroid therapy

We report a case of a 34-year-old male with acute severe heart failure associated with marked concentric left ventricular wall thickening and biopsy evidence of eosinophilic myocardial infiltrate. This appears to be an unusual description of this degree of concentric myocardial thickening in eosinophilic myocarditis coupled with Doppler tissue echocardiography. Following high-dose corticosteroid treatment, wall thickness, systolic and diastolic left ventricular function normalized and the patient experienced a dramatic clinical improvement. (ECHOCARDIOGRAPHY, Volume 20, May 2003).

A clinical and echocardiographic score for assigning risk of major events after dobutamine echocardiograms

OBJECTIVES We sought to develop and validate a risk score combining both clinical and dobutamine echocardiographic (DbE) features in 4,890 patients who underwent DbE at three expert laboratories and were followed for death or myocardial infarction for up to five years. BACKGROUND In contrast to exercise scores, no score exists to combine clinical, stress, and echocardiographic findings with DbE. METHODS Dobutamine echocardiography was performed for evaluation of known or suspected coronary artery disease in 3,156 patients at two sites in the U.S. After exclusion of patients with incomplete follow-up, 1,456 DbEs were randomly selected to develop a multivariate model for prediction of events. After simplification of each model for clinical use, the models were internally validated in the remaining DbE patients in the same series and externally validated in 1,733 patients in an independent series. RESULTS The following score was derived from regression models in the modeling group (160 events): DbE risk = (age (.) 0.02) + (heart failure + rate-pressure product <15,000) (.) 0.4 + (ischemia + scar) (.) 0.6. The presence of each variable was scored as 1 and its absence scored as 0, except for age (continuous variable). Using cutoff values of 1.2 and 2.6, patients were classified into groups with five-year event-free survivals >95%, 75% to 95%, and <75%. Application of the score in the internal validation group (265 events) gave equivalent results, as did its application in the external validation group (494 events, C index = 0.72). CONCLUSIONS A risk score based on clinical and echocardiographic data may be used to quantify the risk of events in patients undergoing DbE. (C) 2004 by the American College of Cardiology Foundation.

Alterations of left ventricular myocardial characteristics associated with obesity

Background-Obesity is associated with heart failure, but an effect of weight, independent of comorbidities, on cardiac structure and function is not well established. We sought whether body mass index (BMI) and insulin levels were associated with subclinical myocardial disturbances. Methods and Results-Transthoracic echocardiography, myocardial Doppler-derived systolic (sm) and early diastolic velocity ( em), strain and strain rate imaging and tissue characterization with cyclic variation (CVIB), and calibrated integrated backscatter (cIB) were obtained in 109 overweight or obese subjects and 33 referents (BMI35) and the referent patients (P

Echocardiographic detection of early diabetic myocardial disease

OBJECTIVES We sought to determine whether disturbances of myocardial contractility and reflectivity could be detected in diabetic patients without overt heart disease and whether these changes were independent and incremental to left ventricular hypertrophy (LVH). BACKGROUND Left ventricular (LV) dysfunction is associated with diabetes mellitus, but LVH is common in this population and the relationship between diabetic LV dysfunction and LVH is unclear. METHODS We studied 186 patients with normal ejection fraction and no evidence of CAD: 48 with diabetes mellitus only (DM group), 45 with LVH only (LVH group), 45 with both diabetes and LVH (DH group), and 48 normal controls. Peak strain and strain rate of six walls in apical four-chamber, long-axis, and two-chamber views were evaluated and averaged for each patient. Calibrated integrated backscatter (113) was assessed by comparison of the septal or posterior wall with pericardial IB intensity. RESULTS All patient groups (DM, DH, LVH) showed reduced systolic function compared with controls, evidenced by lower peak strain (p < 0.001) and strain rate (p = 0.005). Calibrated 113, signifying myocardial reflectivity, was greater in each patient group than in controls (p < 0.05). Peak strain and strain rate were significantly lower in the DH group than in those in the DM alone (p < 0.03) or LVH alone (p = 0.01) groups. CONCLUSIONS Diabetic patients without overt heart disease demonstrate evidence of systolic dysfunction and increased myocardial reflectivity. Although these changes are similar to those caused by LVH, they are independent and incremental to the effects of LVH. (C) 2003 by the American College of Cardiology Foundation.

Is quantitative interpretation likely to increase sensitivity of dobutamine stress echocardiography? A study of false-negative results

Background: False-negative interpretations of do-butamine stress echocardiography (DSE) may be associated with reduced wall stress. using measurements of contraction, we sought whether these segments were actually ischemic but unrecognized or showed normal contraction. Methods. We studied 48 patients (29 men; mean age 60 +/- 10 years) with normal regional function on the basis of standard qualitative interpretation of DSE. At coronary angiography within. 6 months of DSE, 32 were identified as having true-negative and 16 as having false-negative results of DSE. Three apical views were used to measure regional function with color Doppler tissue, integrated backscatter, and strain rate imaging. Cyclic variation of integrated backscatter was measured in 16 segments, and strain rate and peak systolic strain was calculated in 6 walls at rest and peak stress. Results. Segments with false-negative results of DSE were divided into 2 groups with and without low wall stress according to previously published cut-off values. Age, sex, left ventricular mass, left ventricular geometric pattern, and peak workload were not significantly different between patients with true and false-negative results of DSE. Importantly, no significant differences in cyclic variation and strain parameters at rest and peak stress were found among segments with true-and false-negative results of DSE with and without low wall stress. Stenosis severity had no influence on cyclic variation and strain parameters at peak stress. Conclusions: False-negative results of DSE reflect lack of ischemia rather than underinterpretation of regional left ventricular function. Quantitative markers are unlikely to increase the sensitivity of DSE.

Local thrombolysis or rapid transfer for primary angioplasty for patients presenting with ST segment elevation myocardial infarction to hospitals without angioplasty facilities

No Abstract

Quantitative myocardial contrast echocardiography for prediction of thrombolysis in myocardial infarction flow in acute myocardial infarction

Clinical evaluation of arterial potency in acute ST-elevation myocardial infarction (STEMI) is unreliable. We sought to identify infarction and predict infarct-related artery potency measured by the Thrombolysis In Myocardial Infarction (TIMI) score with qualitative and quantitative intravenous myocardial contrast echocardiography (MCE). Thirty-four patients with suspected STEMI underwent MCE before emergency angiography and planned angioplasty. MCE was performed with harmonic imaging and variable triggering intervals during intravenous administration of Optison. Myocardial perfusion was quantified offline, fitting an exponential function to contrast intensity at various pulsing intervals. Plateau myocardial contrast intensity (A), rate of rise (beta), and myocardial flow (Q = A x beta) were assessed in 6 segments. Qualitative assessment of perfusion defects was sensitive for the diagnosis of infarction (sensitivity 93%) and did not differ between anterior and inferior infarctions. However, qualitative assessment had only moderate specificity (50%), and perfusion defects were unrelated to TIMI flow. In patients with STEMI, quantitatively derived myocardial blood flow Q (A x beta) was significantly lower in territories subtended by an artery with impaired (TIMI 0 to 2) flow than those territories supplied by a reperfused artery with TIMI 3 flow (10.2 +/- 9.1 vs 44.3 +/- 50.4, p = 0.03). Quantitative flow was also lower in segments with impaired flow in the subtending artery compared with normal patients with TIMI 3 flow (42.8 +/- 36.6, p = 0.006) and all segments with TIMI 3 flow (35.3 +/- 32.9, p = 0.018). An receiver-operator characteristic curve derived cut-off Q value of

Use of tissue Doppler imaging to facilitate the prediction of events in patients with abnormal left ventricular function dobutamine echocardiography

The extent of abnormality in patients with positive do-butamine echocardiography (DE) is predictive of risk, but the wall motion score (WMS) has low concordance among observers. We sought whether quantifying the extent of abnormal wall motion using tissue Doppler (TD) could guide risk assessment in patients with abnormal DE in 576 patients with known or suspected coronary artery disease; standard DE was combined with color TD imaging at peak dose. WMS was assessed by an expert observer and studies were identified as abnormal in the presence of 2:1 segments with resting or stress-induced wall motion abnormalities. Patients with abnormal DE had peak systolic velocity measured in each segment. Tissue tracking was used to measure myocardial displacement. Follow-up for death or infarction was per-formed after. 16 +/- 12 months. Of 251 patients with abnormal DE, 22 patients died (20 from cardiac causes) and 7 had nonfatal myocardial infarctionis. The average WMS in patients with events was 1.8 +/- 0.5, compared with 1.7 +/- 0.5 in patients without events (p = NS). The average systolic velocity in patients with events was 4.9 +/- 1.7 cm/s and 6.4 +/- 6.5 cm/s in the patients without events (p <0.001). The average tissue tracking in patients with events was 4.5 +/- 1.5 mm and was significant. (5.7 +/- 3.1 mm),in those,without events (p <0.001). Thus, TD is an alternative to WMS for quantifying the total extent of abnormal left ventricular function-at DE, and appears to be superior for predicting adverse outcomes. (C) 2004 by Excerpta Medica, Inc.

Glutamate transporter localization does not correspond to the temporary functional recovery and late degeneration after acute ocular ischemia in rats

Purpose: To determine whether the localization of retinal glutamate transporters is affected by retinal ischaemia and whether their ability to transport glutamate decreases with the progression of ischemic retinal and optic nerve degeneration. Methods: Retinal ischemia was induced in rats by acutely increasing the intraocular pressure (IOP, 110 mmHg/60 min). Reperfusion was permitted for periods up to 60 days post-ischemia. Functional evaluation was performed by monitoring the pupil light reflexes (PLRs) and electroretinograms (flash, flicker ERG and oscillatory potentials). Glutamate transporter localization and D-aspartate (glutamate analogue) uptake were assessed by immunohistochemistry. Results: Intense immunoreactivity for the retinal glutamate transporters (GLAST, GLT1, EAAC1 and EAAT5) was observed at all time points after the insult, despite severe retinal degeneration. D-aspartate was also normally accumulated in the ischemic retinas. Ten days post-operatively the PLR ratio (ratio = indirect/direct PLR = 34 +/- 7(.)5%) was significantly less than the pre-operative value (pre-op = 76(.)7 +/- 2 (.)6%, p < 0(.)05). However, 25 and 35 days post-operatively PLR ratios did not differ significantly from pre-operative values (44(.)4 +/- 6(.)9 and 53(.)8 +/- 9(.)6%, p > 0(.)05). Forty-five and 60 days post-operatively the PLR ratio declined again and was significantly lower than the pre-operative value (33(.)8 + 8(.)7 and 26(.)2 + 8(.)9%, p < 0(.)05). Statistical analysis revealed that all tested ERG components had significantly higher values at 32, but not at 42 and 58 days post-operatively when compared to the first time point recorded post-operatively (10 days). Conclusions: While retinal glutamate transport is compromised during an acute ischemic insult, consequent retinal recovery and degeneration are not due to a change in the excitatory amino acid transporter localization or D-aspartate (glutamate analogue) uptake. Rat retina and optic nerve are capable of spontaneous, but temporary, functional recovery after an acute ischemic insult. (C) 2004 Elsevier Ltd. All rights reserved.

Design of artificial myocardial microtissues

Cultivation technologies promoting organization of mammalian cells in three dimensions are essential for gene-function analyses as well as drug testing and represent the first step toward the design of tissue replacements and bioartificial organs. Embedded in a three-dimensional environment, cells are expected to develop tissue-like higher order intercellular structures (cell-cell contacts, extracellular matrix) that orchestrate cellular functions including proliferation, differentiation, apoptosis, and angiogenesis with unmatched quality. We have refined the hanging drop cultivation technology to pioneer beating heart microtissues derived from pure primary rat and mouse cardiomyocyte cultures as well as mixed populations reflecting the cell type composition of rodent hearts. Phenotypic characterization combined with detailed analysis of muscle-specific cell traits, extracellular matrix components, as well as endogenous vascular endothelial growth factor (VEGF) expression profiles of heart microtissues revealed (1) a linear cell number-microtissue size correlation, (2) intermicrotissue superstructures, (3) retention of key cardiomyocyte-specific cell qualities, (4) a sophisticated extracellular matrix, and (5) a high degree of self-organization exemplified by the tendency of muscle structures to assemble at the periphery of these myocardial spheroids. Furthermore (6), myocardial spheroids support endogenous VEGF expression in a size-dependent manner that will likely promote vascularization of heart microtissues produced from defined cell mixtures as well as support connection to the host vascular system after implantation. As cardiomyocytes are known to be refractory to current transfection technologies we have designed lentivirus-based transduction strategies to lead the way for genetic engineering of myocardial microtissues in a clinical setting.

Clinical decision-making and myocardial viability: current perspectives

Not all myocardium involved in a myocardial infarction is dead or irreversibly damaged. The balance between the amount of scar and live tissue, and the nature of the live tissue, determine the likelihood that contractile function will improve after revascularisation. This improvement (which defines viability) may be predicted with about 80% accuracy using several techniques. This review examines the determinants of functional recovery and how they may be integrated in making decisions regarding revascularisation. (Intern Med J 2005; 35: 118–125)

Myocardial blood volume and perfusion reserve responses to combined dipyridamole and exercise stress: A quantitative approach to contrast stress echocardiography

Background: Qualitative interpretation of myocardial contrast echocardiography (MCE) improves the accuracy of wall-motion analysis for assessment of coronary artery disease (CAD). We examined the feasibility and accuracy of quantitative MCE for diagnosis of CAD. Methods: Dipyridamole/exercise stress MCE (destruction-replenishment protocol with real-time imaging) was performed in 90 patients undergoing quantitative coronary angiography, 48 of whom had significant (> 50%) stenoses. MCE was repeated with exercise alone in 18 patients. Myocardial blood flow (A*beta) was obtained from blood volume (A) and time to refill (beta). Results: Quantification of flow reserve was feasible in 88%. The mean A*beta reserve in the anterior wall was significantly impaired for patients with left anterior descending coronary artery disease (n = 28) compared with those with no disease (1.6 +/- 1.2 vs; 4.0 +/- 2.5, P <=.001). This reflected impaired beta reserve, with no difference in the A reserve. Applying a receiver operating characteristic curve derived cutoff of 2.0 for A*beta reserve, quantitative MCE was 76% sensitive and 71% specific for the diagnosis of significant left anterior descending coronary artery stenosis. Posterior circulation results were similar, with 78% sensitivity and 59% specificity for detection of posterior CAD. Overall, quantitative MCE was similarly sensitive to qualitative approach for diagnosis of CAD (88% vs 93%), but with lower specificity (52% vs 65%, P =.07). In 18 patients restudied with pure exercise stress, the mean myocardial blood flow reserve was less than after combined stress (2.1 +/- 1.6 vs 3.7 +/- 1.9, P =.01). Conclusion: Quantitative MCE is feasible for the diagnosis of CAD with dipyridamole/exercise stress. Dipyridamole prolongs postexercise hyperemia, augmenting the degree of hyperemia at the time of imaging.