Myocardial strain imaging: review of general principles, validation, and sources of discrepancies.

Myocardial tissue tracking imaging techniques have been developed for a more accurate evaluation of myocardial deformation (i.e. strain), with the potential to overcome the limitations of ejection fraction (EF) and to contribute, incremental to EF, to the diagnosis and prognosis in cardiac diseases. While most of the deformation imaging techniques are based on the similar principles of detecting and tracking specific patterns within an image, there are intra- and inter-imaging modality inconsistencies limiting the wide clinical applicability of strain. In this review, we aimed to describe the particularities of the echocardiographic and cardiac magnetic resonance deformation techniques, in order to understand the discrepancies in strain measurement, focusing on the potential sources of variation: related to the software used to analyse the data, to the different physics of image acquisition and the different principles of 2D vs. 3D approaches. As strain measurements are not interchangeable, it is highly desirable to work with validated strain assessment tools, in order to derive information from evidence-based data. There is, however, a lack of solid validation of the current tissue tracking techniques, as only a few of the commercial deformation imaging softwares have been properly investigated. We have, therefore, addressed in this review the neglected issue of suboptimal validation of tissue tracking techniques, in order to advocate for this matter.

Coronary in-stent restenosis in diabetic patients after implantation of sirolimus or paclitaxel drug-eluting coronary stents.

It is now emerging that, in patients who are at high risk for cardiovascular complications and, in particular, those with diabetes, the occurrence of late restenosis and thrombosis after treatment of coronary artery disease with drug-eluting stents is higher than earlier reports have suggested. Therefore, the aim of this study was to assess the prevalence of in-stent restenosis in a cohort of consecutive patients with diabetes treated for coronary disease in 2005 with drug-eluting stents [either sirolimus (58%) or paclitaxel (42%)]. The duration of follow-up was 9.0+/-3.4 months [mean+/-1 standard deviation (S.D.)]. A total of 154 patients (type 2 diabetes: 91%) were included in the study (age: 66+/-10 years), and the total number of implanted stents was 184. Two subjects died from cardiac causes, while myocardial infarction and (un)stable angina were observed in 3 (2%) and 39 (25%) patients, respectively. In-stent restenosis, appraised by angiography, was observed in 17 individuals (11%) after a mean follow-up of five months. Mean HbA(1c) in patients with restenosis was 7.6+/-1.8%. There was no difference in the rate of restenosis with sirolimus-(n=8) compared with paclitaxel-(n=9) eluting stents. Male gender, oral therapy for diabetes and stent diameter were predictors of in-stent restenosis. In conclusion, even over a medium-term period, in-stent restenosis remains a potential risk for coronary diabetic patients treated with drug-eluting devices.

No-flow ischemia inhibits insulin signaling in heart by decreasing intracellular pH.

Glucose-insulin-potassium solutions exert beneficial effects on the ischemic heart by reducing infarct size and mortality and improving postischemic left ventricular function. Insulin could be the critical protective component of this mixture, although the insulin response of the ischemic and postischemic myocardium has not been systematically investigated. The aim of this work was to study the insulin response during ischemia by analyzing insulin signaling. This was evaluated by measuring changes in activity and/or phosphorylation state of insulin signaling elements in isolated perfused rat hearts submitted to no-flow ischemia. Intracellular pH (pH(i)) was measured by NMR. No-flow ischemia antagonized insulin signaling including insulin receptor, insulin receptor substrate-1, phosphatidylinositol 3-kinase, protein kinase B, p70 ribosomal S6 kinase, and glycogen synthase kinase-3. These changes were concomitant with intracellular acidosis. Perfusing hearts with ouabain and amiloride in normoxic conditions decreased pH(i) and insulin signaling, whereas perfusing at pH 8.2 counteracted the drop in pH(i) and the inhibition of insulin signaling by ischemia. Incubation of cardiomyocytes in normoxic conditions, but at pH values below 6.75, mimicked the effect of ischemia and also inhibited insulin-stimulated glucose uptake. Finally, the in vitro insulin receptor tyrosine kinase activity was progressively inhibited at pH values below physiological pH(i), being abolished at pH 6.0. Therefore, ischemic acidosis decreases kinase activity and tyrosine phosphorylation of the insulin receptor thereby preventing activation of the downstream components of the signaling pathway. We conclude that severe ischemia inhibits insulin signaling by decreasing pH(i).

Prognostic value of myocardial ischemia and viability in patients with chronic left ventricular ischemic dysfunction.

BACKGROUND: Previous studies showed that thallium scintigraphy and dobutamine echocardiography were accurate, noninvasive ways of predicting contractile recovery after revascularization in patients with left ventricular (LV) dysfunction. However, the prognostic impact of such methods remains uncertain. METHODS AND RESULTS: We prospectively studied 137 consecutive patients with coronary disease and LV dysfunction who underwent exercise-redistribution-reinjection thallium scintigraphy and dobutamine echocardiography to identify myocardial ischemia and viability. A total of 94 patients subsequently underwent revascularization, and 43 underwent medical treatment. The primary endpoint was cardiac mortality, and mean follow-up was 33+/-10 months. Twenty-four patients died of cardiac causes. By Cox's regression analysis, long-term survival was related to the extent of coronary disease, the presence of diabetes, type of treatment, the presence of ischemic myocardium as determined by thallium scintigraphy, and the presence of viable myocardium as determined by both tests. Three-year survival was greater in patients with ischemic myocardium (as determined by thallium scintigraphy) or viable myocardium (as determined by both tests) who underwent revascularization than in the other groups (P=0.018 with thallium; P<0.001 with dobutamine). Subgroup analyses indicated that among patients with 1- or 2-vessel disease, only those with ischemic or viable myocardium improved survival after revascularization, whereas in patients with 3-vessel or left main diseases, revascularization always improved survival, albeit more in the presence of ischemic or viable myocardium. CONCLUSIONS: Among the parameters commonly available in patients with LV ischemic dysfunction, the presence of ischemic myocardium (as determined by thallium scintigraphy) and that of viable myocardium (as determined by dobutamine echocardiography) are independent predictors of subsequent mortality. These observations may be useful in the preoperative selection of patients for revascularization.

Destruction of contrast microbubbles by ultrasound: effects on myocardial function, coronary perfusion pressure, and microvascular integrity.

BACKGROUND: Recent experimental data indicate that ultrasound-induced destruction of ultrasound contrast microbubbles can cause immediate rupture of the microvessels in which these microbubbles are located. METHODS AND RESULTS: To examine the functional and morphological significance of these findings in the heart, isolated rabbit hearts were perfused retrogradely with buffer containing ultrasound contrast agents and were insolated at increasing levels of acoustic energy with a broadband transducer emitting at 1.8 MHz and receiving at 3.6 MHz and operated in the triggered mode (1 Hz). At the end of each experiment, the hearts were fixed in glutaraldehyde and examined with light microscopy. Neither exposure to ultrasound alone or to contrast alone affected left ventricular developed pressure. By contrast, simultaneous exposure to contrast and ultrasound resulted in a reversible, transient mechanical index (MI)-dependent decrease in left ventricular developed pressure (to 83+/-5% of baseline at an MI of 1.6) and a transient MI-dependent increase in coronary perfusion pressure (to 120+/-6% of baseline at an MI of 1.6). Myocardial lactate release also showed significant increases with increasing MIs. Macroscopically, areas of intramural hemorrhage were identified over the beam elevation in hearts exposed to both contrast and high-MI ultrasound. Light microscopy revealed the presence of capillary ruptures, erythrocyte extravasation, and endothelial cell damage. The mean percentage of capillaries ruptured at an MI of 1.6 was 3.6+/-1.4%. CONCLUSIONS: Simultaneous exposure of isolated rabbit hearts to ultrasound and contrast agents results in an MI-dependent, transient depression of left ventricular contractile function, a rise in coronary perfusion pressure, an increase in lactate production, and limited capillary ruptures.

Left ventricular filling in dilated cardiomyopathy: relation to functional class and hemodynamics.

Left ventricular systolic function does not correlate well with functional class in patients with dilated cardiomyopathy. To determine whether the correlation is better with Doppler indexes of left ventricular diastolic function, 34 patients with dilated cardiomyopathy (M-mode echocardiographic end-diastolic dimension greater than 60 mm, fractional shortening less than 25%, increased E point-septal separation) were studied. Patients were classified into two groups according to functional class. Group 1 consisted of 16 patients in New York Heart Association functional class I or II; group 2 included 18 patients in functional class III or IV. Left ventricular dimensions, fractional shortening, left ventricular mass, meridional end-systolic wall stress, peak early and late transmitral filling velocities and their ratio, isovolumetric relaxation period and time to peak filling rate were computed from pulsed wave Doppler and M-mode echocardiograms and calibrated carotid pulse tracings. Right heart catheterization was performed in 20 of 34 patients. No differences were observed between groups with regard to age, gender distribution, heart rate, blood pressure and M-mode echocardiographic-derived indexes of systolic function. Peak early filling velocity (72 +/- 13 versus 40 +/- 10 cm/s, p less than 0.001) was higher and atrial filling fraction (27 +/- 4% versus 46 +/- 8%, p less than 0.001) was lower in group 2 than in group 1. The ratio of early to late transmitral filling velocities was higher in group 2 patients (2.3 +/- 0.5 versus 0.7 +/- 0.2, p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Asynchronous (segmental early) relaxation impairs left ventricular filling in patients with coronary artery disease and normal systolic function.

Asynchronous segmental early relaxation, defined as a localized early segmental outward motion of the left ventricular endocardium during isovolumetric relaxation, has been associated with an altered left ventricular relaxation rate. To determine whether asynchronous segmental early relaxation also results in impaired left ventricular filling, early diastolic ventricular wall motion and Doppler-derived left ventricular filling indexes were examined in 25 patients with documented coronary artery disease and normal systolic function. Patients were further classified into two groups according to the presence (n = 15, group 1) or absence (n = 10, group 2) of asynchronous early relaxation at left ventriculography. A third group of 10 age-matched normal subjects served as a control group. No differences were observed between the two patient groups with coronary artery disease with respect to age, gender distribution, heart rate, left ventricular systolic and diastolic pressures or extent and severity of coronary artery disease. No differences in transmitral filling dynamics were observed between group 2 patients and age-matched control subjects. Conversely, group 1 patients had significantly lower peak early filling velocities (44 +/- 11 vs. 58 +/- 11 cm/s, p less than 0.01), larger atrial filling fraction (45 +/- 4% vs. 38 +/- 4%, p less than 0.001), lower ratio of early to late transmitral filling velocities (0.6 +/- 0.08 vs. 0.99 +/- 0.18, p less than 0.001) and a longer isovolumetric relaxation period (114 +/- 12 vs. 90 +/- 6 ms, p less than 0.001) compared with group 2 patients and control subjects.(ABSTRACT TRUNCATED AT 250 WORDS)

Hemodynamic and volume correlates of left ventricular diastolic relaxation and filling in patients with aortic stenosis.

OBJECTIVE: The aim of the present study was to evaluate the hemodynamic and volume correlates of early diastolic filling and isovolumetric relaxation in patients with aortic stenosis. BACKGROUND: Left ventricular diastolic relaxation and filling have been found to be heterogeneous in patients with aortic stenosis. Potential mechanisms underlying this heterogeneity include individual differences in the severity of muscle hypertrophy or systolic dysfunction, or both, in the presence and severity of mitral regurgitation and in the level of left atrial pressure. METHODS: Right (fluid-filled) and left (high fidelity micromanometer) ventricular pressures, left ventricular volumes (contrast angiography) and transmitral inflow dynamics (Doppler echocardiography) were measured in 17 patients with isolated severe aortic stenosis (valve area less than 0.75 cm2). Measurements included left ventricular end-diastolic and end-systolic volumes, left ventricular ejection fraction, peak positive and negative first derivative of left ventricular pressure (dP/dt), the time constant of isovolumetric relaxation (tau), left ventricular end-diastolic pressure, left ventricular mass, left ventricular end-systolic stress, mean capillary wedge pressure and peak early (E) and late (A) transmitral filling velocities. Patients were subclassified according to left ventricular ejection performance at rest and mean capillary wedge pressure. RESULTS: Patients with normal ejection performance and normal mean capillary wedge pressure had a normal rate of isovolumetric left ventricular pressure decay and an abnormal diastolic filling pattern, with diastolic filling occurring primarily during atrial systole. In contrast, in patients with systolic dysfunction and elevated mean capillary wedge pressure, isovolumetric pressure decay was prolonged and diastolic filling occurred essentially during the rapid filling period, with reduced atrial contribution to left ventricular filling and a short isovolumetric relaxation period. Stepwise multiple linear regression analysis identified two variables as independent predictors of transmitral velocity profile and three variables independently predictive of the rate of left ventricular pressure decay. The single most important predictor of transmitral filling pattern was the pulmonary capillary wedge pressure (p less than 0.0001), followed by the left ventricular peak negative dP/dt (p = 0.002). The single most powerful predictor of the rate of reduction in left ventricular pressure was left ventricular mass index (p less than 0.0001), followed by end-systolic volume index (p = 0.0002) and left ventricular peak negative dP/dt (p = 0.0029). CONCLUSIONS: In patients with aortic stenosis, left ventricular filling is essentially determined by left atrial pressure, whereas isovolumetric relaxation more closely depends on the severity of muscle hypertrophy and chamber dilation.

Head-to-head comparison of exercise-redistribution-reinjection thallium single-photon emission computed tomography and low dose dobutamine echocardiography for prediction of reversibility of chronic left ventricular ischemic dysfunction.

OBJECTIVES: We sought to directly compare the diagnostic value of exercise-redistribution-reinjection thallium single-photon emission computed tomography (SPECT) and low dose dobutamine echocardiography for prediction of contractile recovery after revascularization. BACKGROUND: Both thallium SPECT and dobutamine echocardiography have been proposed to predict the reversibility of left ventricular dysfunction after revascularization. Although both techniques permit differentiation of viable from nonviable myocardium, few studies have directly compared their accuracy in the same patients. METHODS: Seventy-three consecutive patients (mean [+/- SD] age 59 +/- 9 years) with coronary disease and regional left ventricular dysfunction underwent exercise-redistribution-reinjection thallium SPECT and dobutamine echocardiography before revascularization. Recovery of function was evaluated with echocardiography 5.5 +/- 2.5 months after revascularization. For analysis, the left ventricle was divided into 16 segments, in which percent thallium uptake was quantitated using circumferential profiles, and regional wall motion was graded semiquantitatively (normal = 1; akinetic = 3). RESULTS: The diagnostic performance of the two tests was investigated both for individual patients and for individual segments. Individual patient analysis showed that left ventricular ejection fraction improved > 5% after revascularization in 43 patients, whereas 30 showed no change. Receiver operating characteristic curves were used to select optimal criteria for prediction of functional recovery after revascularization. According to a mean thallium uptake > 54% at reinjection, SPECT had a sensitivity of 72%, a specificity of 73% and an overall accuracy of 73%. Similarly, according to an improvement in wall motion score > 3.5 grades during doubutamine echocardiography, echocardiography had a sensitivity of 88%, a specificity of 77% and an overall accuracy of 84% (p = NS vs. thallium). Segmental analysis showed that SPECT and dobutamine echocardiography had similar sensitivity (77% and 75%, respectively), but SPECT had lower specificity (56% vs. 86%, p < 0.01). CONCLUSIONS: Quantitative exercise-redistribution-reinjection thallium SPECT and dobutamine echocardiography have comparable accuracy for prediction of reversibility of global left ventricular dysfunction after revascularization. However, dobutamine echocardiography has greater specificity than thallium imaging for prediction of functional recovery on a segmental basis.

How accurate is dobutamine stress electrocardiography for detection of coronary artery disease? Comparison with two-dimensional echocardiography and technetium-99m methoxyl isobutyl isonitrile (mibi) perfusion scintigraphy.

OBJECTIVES: This study was designed to establish the appropriate diagnostic criteria for positive dobutamine electrocardiographic (ECG) stress test results and to compare their accuracy with those of dobutamine two-dimensional echocardiography and perfusion scintigraphy. BACKGROUND: Conventional criteria for positive findings on ECG exercise testing may not be appropriate for use with dobutamine ECG stress testing. METHODS: One hundred twenty-nine consecutive patients with an interpretable ECG and without previous myocardial infarction were prospectively studied at the time of coronary arteriography. All completed a standard dobutamine protocol (5 to 40 micrograms/kg body weight per min in 3-min dose increments) without side effects. Significant coronary artery disease, defined as > 50% lumen diameter stenosis of a major epicardial coronary artery on coronary angiography, was present in 83 patients. Empiric receiver operating curves were generated for various ECG criteria derived from computer-averaged signals. RESULTS: The best ECG criterion, with a sensitivity of 42% and a specificity of 83%, was an ST segment shift, relative to baseline, of 0.5 mm 80 ms after the J point. The sensitivity of this criterion was greater than that of the conventional criterion of 1-mm ST segment depression 60 (23%) or 80 (18%) ms after the J point, was comparable to that of chest pain occurring during the test (44%, p = NS) but remained inferior to the sensitivities of technetium-99m methoxyl isobutyl isonitrile (mibi) perfusion (76%) or stress echocardiography (76%, p < 0.001, for both). The specificity of this criterion was not significantly different from that of technetium-99m mibi perfusion tomography (65%) or stress echocardiography (89%) but was superior to that of chest pain (59%, p < 0.025). CONCLUSIONS: We conclude that this new criterion for dobutamine electrocardiography is specific but that an imaging technique is still required to accurately predict coronary artery disease.

Myocardial perfusion and oxygen consumption in reperfused noninfarcted dysfunctional myocardium after unstable angina: direct evidence for myocardial stunning in humans.

OBJECTIVES: To positively establish the diagnosis of myocardial stunning in patients with unstable angina and persistent wall motion abnormalities after reperfusion by coronary angioplasty. BACKGROUND: Although myocardial stunning is thought to occur in several clinical conditions, definite proof of its existence in humans is still lacking, owing to the difficulty of measuring myocardial blood flow (MBF) in absolute terms. METHODS: We studied 14 patients with unstable angina due to proximal left anterior descending coronary artery disease who presented persistent anterior wall motion abnormalities despite revascularization of the culprit lesion by percutaneous coronary angioplasty (PTCA) and who did not have clinical evidence of necrosis. Dynamic positron emission tomography (PET) with [13N]-ammonia and [11C]-acetate was performed 48 h after PTCA to determine absolute MBF and oxygen consumption (MVO2). Regional wall thickening and regional cardiac work were determined using two-dimensional echocardiography. Improvement of segmental wall motion abnormalities was followed for a median of 4 months (1.5 to 14 months). RESULTS: As judged from the changes in segmental wall motion score, regional dysfunction was spontaneously reversible in 12/14 patients and improved from 2.2 +/- 0.3 to 1.2 +/- 0.3 at late follow-up (p < 0.001). With PET, [13N]-ammonia MBF was similar among dysfunctional and remote normally contracting segments (85 +/- 29 vs. 99 +/- 20 ml x min (-1) x 100g(-1), p = not significant [n.s.]), thus demonstrating a perfusion-contraction mismatch. Despite the reduced contractile function, dysfunctional myocardium presented near normal levels of MVO2 (6.5 +/- 4.2 vs. 8.0 +/- 1.9 ml x min (-1)x 100g(-1), p = n.s.). Consequently, the regional myocardial efficiency (regional work divided by MVO2) of the dysfunctional myocardium was found to be markedly decreased as compared with normally contracting myocardium (6 +/- 6% vs. 26 +/- 6%, p < 0.001). CONCLUSIONS: This study demonstrates that human dysfunctional myocardium capable of spontaneously recovering contractile function after unstable angina endures a state of perfusion-contraction mismatch. These data for the first time provide unequivocal direct evidence for the existence of acute myocardial stunning in humans.

Accuracy and feasibility of contrast echocardiography for detection of perfusion defects in routine practice: comparison with wall motion and technetium-99m sestamibi single-photon emission computed tomography. The Nycomed NC100100 Investigators.

OBJECTIVES: We sought to assess the feasibility and accuracy of myocardial contrast echocardiography (MCE) using standard imaging approaches for the detection of perfusion defects in patients who had a myocardial infarction (MI). BACKGROUND: Myocardial contrast echocardiography may be more versatile than perfusion scintigraphy for identifying the presence and extent of perfusion defects after MI. However, its reliability in routine practice is unclear. METHODS: Fundamental or harmonic MCE was performed with continuous or triggered imaging in 203 patients with a previous MI using bolus doses of a perfluorocarbon-filled contrast agent (NC100100). All patients underwent single-photon emission computed tomography (SPECT) after the injection of technetium-99m (Tc-99m) sestamibi at rest. Quantitative and semiquantitative SPECT, wall motion and digitized echocardiographic data were interpreted independently. The accuracy of MCE was assessed for detection of segments and patients with moderate and severe sestamibi-SPECT defects, as well as for detection of patients with extensive perfusion defects (>12% of left ventricle). RESULTS: In segments with diagnostic MCE, the segmental sensitivity ranged from 14% to 65%, and the specificity varied from 78% to 95%, depending on the dose of contrast agent. Using both segment- and patient-based analysis, the greatest accuracy and proportion of interpretable images were obtained using harmonic imaging in the triggered mode. For the detection of extensive defects, the sensitivity varied from 13% to 48%, with specificity from 63% to 100%. Harmonic imaging remained the most accurate approach. Time since MI and SPECT defect location and intensity were all determinants of the MCE response. The extent of defects on MCE was less than the extent of either abnormal wall motion or SPECT abnormalities. The combination of wall motion and MCE assessment gave the best balance of sensitivity (46% to 55%) and specificity (82% to 83%). CONCLUSIONS: Although MCE is specific, it has limited sensitivity for detection of moderate or severe perfusion defects, and it underestimates the extent of SPECT defects. The best results are obtained by integration with wall motion. More sophisticated methods of acquisition and interpretation are needed to enhance the feasibility of this technique in routine practice.

Expression of inducible nitric oxide synthase in human coronary atherosclerotic plaque.

OBJECTIVE: Macrophages in atherosclerotic plaque may express the inducible isoform of NO synthase (iNOS), which produces large amounts of NO. On one hand, the production of NO can be protective by its vasodilatory, antiaggregant and antiproliferative effects. On the other hand, the formation of peroxynitrite from NO may favour vasospasm and thrombogenesis. In this study, we investigated whether iNOS is present in human coronary atherosclerotic plaque, and we correlated these data with the clinical instability of the patients. METHODS: Fragments were retrieved by coronary atherectomy from 24 patients with unstable angina and 12 patients with stable angina. The presence of macrophages, and the production of TNF alpha, iNOS and nitrotyrosine were detected by immunocytochemistry. RESULTS: Macrophage clusters were found in 67% of stable patients and 87% of patients with unstable angina (NS). TNF alpha was expressed in about 50% of cases in both groups. iNOS was not expressed in fragments from stable patients but was found in macrophages from 58% of unstable patients (P < 0.001). The expression of iNOS was associated with the presence of nitrotyrosine residues, a marker of peroxynitrite formation. Expression of iNOS was correlated both with complaints of angina at rest (P < 0.05) and with the presence of thrombus at morphological examination (P < 0.001). CONCLUSION: The expression of iNOS may be induced in human coronary atherosclerotic plaque and is associated with different factors of instability.

Cardiomyocyte remodelling during myocardial hibernation and atrial fibrillation: prelude to apoptosis.

OBJECTIVE: Similar structural changes in the myocardium can be observed in chronic hibernating myocardium and in myocardium taken from hearts suffering chronic atrial fibrillation. We investigated whether or not these changes are indicative of apoptosis. METHODS: Myocardial biopsies from 28 strictly selected patients with chronic hibernating myocardium and heart samples from 13 goats with pacing-induced chronic atrial fibrillation were used. Special attention was paid to processing the tissues immediately (fixation/freezing) in order to prevent artificial degenerative changes, thereby excluding false positive identification of apoptosis. Infarcted areas or infarcted border zones were excluded from our study. Apoptosis was detected with light and electron microscopy and terminal deoxynucleotidyl transferase nick end-labelling. Immunohistochemistry was used for detecting Bcl-2, P53 and PCNA-proteins associated with apoptosis/DNA damage. RESULTS: The results obtained for chronic hibernating left ventricular myocardium were similar to those for chronic fibrillating atrial myocardium. No apoptotic nuclei, as characterised by extensive chromatin clumping, could be observed in normal or dedifferentiated cardiomyocytes under the electron microscope. The end-labelling assay did not reveal any cardiomyocytes with damaged DNA. Nor could we find any evidence of substantial expression of Bcl-2, P53 or PCNA, a result indicative of the absence of apoptotic threat or DNA damage. CONCLUSION: Cardiomyocyte dedifferentiation, but not extensive degeneration through apoptosis, can be observed in chronic hibernating myocardium and chronic fibrillating atrium. Dedifferentiation may be the best way to survive prolonged exposure to the unfavourable conditions imposed by increased wall stress, a relative lowered oxygen environment, or both.

Insulin antagonizes AMP-activated protein kinase activation by ischemia or anoxia in rat hearts, without affecting total adenine nucleotides.

AMP-activated protein kinase (AMPK) is known to be activated by phosphorylation on Thr172 in response to an increased AMP/ATP ratio. We report here that such an activation indeed occurred in anaerobic rat hearts and that it was antagonized (40-50%) when the hearts were pre-treated with 100 nM insulin. The effect of insulin (1) was blocked by wortmannin, an inhibitor of phosphatidylinositol-3-kinase; (2) only occurred when insulin was added before anoxia, suggesting a hierarchical control; (3) resulted in a decreased phosphorylation state of Thr172 in AMPK and (4) was unrelated to changes in the AMP/ATP ratio. This is the first demonstration that AMPK activity could be changed without a detectable change in the AMP/ATP ratio of the cardiac cell.

Delineation of myocardial viability with PET.

UNLABELLED: Relative flow and metabolic imaging (the "mismatch pattern") with PET have been proposed to identify the presence of viable myocardium in patients with ischemic left ventricular dysfunction. Yet, optimal criteria to identify dysfunctional but viable myocardium and predict significant functional improvement have not been fully defined. METHODS: Dynamic PET imaging with 13N-ammonia and 18F-deoxyglucose to assess absolute myocardial perfusion and glucose uptake was performed in 25 patients (20 men, 5 women; mean age 57 +/- 12 yr, range 30-72 yr) scheduled for coronary revascularization because of coronary artery disease, anterior wall dysfunction and mildly depressed left ventricular ejection fraction (49% +/- 11%). Global and regional left ventricular function was evaluated by contrast left ventriculography at baseline and after revascularization. RESULTS: As judged from the changes in end-systolic volume and resting anterior wall motion before and after revascularization, 17 patients with improved wall motion score and decreased end-systolic volume were considered to have viable myocardium, whereas 8 patients with either no change in regional wall motion or increased end-systolic volume were considered to have nonviable myocardium. Before revascularization, viable myocardium showed higher absolute myocardial blood flow (77 +/- 20 versus 51 +/- 9 ml (min.100 g)-1, p = 0.004) and absolute regional myocardial glucose uptake (36 +/- 14 versus 24 +/- 11 mumole (min.100 g)-1, p = 0.04) than nonviable myocardium. CONCLUSION: This study identified absolute myocardial blood flow and normalized glucose extraction as the most powerful predictors of the return of contractile function after coronary revascularization in patients with ischemic anterior wall dysfunction.

Nitrogen-13-ammonia and oxygen-15-water estimates of absolute myocardial perfusion in left ventricular ischemic dysfunction.

UNLABELLED: Measurements of resting myocardial blood flow (MBF) in patients with chronic left ventricular ischemic dysfunction by 15O-water with 13N-ammonia and PET have yielded conflicting results. The aim of this study was to perform a head-to-head comparison of both tracers in the same patient population and to answer the question of whether distinctive tracer properties account for differences in estimates of MBF in chronically dysfunctional myocardium by both tracers. METHODS: A total of 30 patients with chronic dysfunction of the anterior myocardial wall due to significant left anterior descending coronary artery disease underwent PET measurements of absolute MBF in the anterior wall by use of 15O-water and 13N-ammonia before coronary revascularization by either coronary artery bypass graft (n = 24) or percutaneous transluminal coronary angioplasty (n = 6). Improvement of regional contractile function was assessed by two-dimensional echocardiography at a mean of 7.5 +/- 2.1 mo after revascularization. As judged from the changes in anterior myocardial wall motion after revascularization, patients were considered to have either reversibly (n = 16) or persistently (n = 14) dysfunctional myocardium. Estimates of MBF by 15O-water and 13N-ammonia, obtained in every patient before revascularization, were compared among the two patient groups by use of previously validated methods. RESULTS: With 13N-ammonia, resting regional MBF was significantly higher in reversibly as opposed to persistently dysfunctional segments [84 +/- 8 versus 48 +/- 6 ml (min x 100 g)(-1), mean +/- s.e.m., p < 0.01]. By contrast, no such difference was found when using 15O-water to measure MBF [74 +/- 6 versus 86 +/- 9 ml (min x 100 g)(-1), p = ns]. This was mainly due to the fact that the perfusable tissue fraction (PTF), a fitted parameter of the 15O-water model, was significantly higher in reversibly as opposed to persistently dysfunctional segments (0.63 +/- 0.03 versus 0.50 +/- 0.03, p < 0.05). As a consequence, the 15O-water perfusable tissue index (PTI), which is the ratio of the PTF to the anatomical tissue fraction, was greater in reversibly dysfunctional as opposed to persistently dysfunctional segments (1.07 +/- 0.07 versus 0.79 +/- 0.05, p < 0.01). CONCLUSION: This study demonstrates significant differences in MBF estimates between 15O-water and 13N-ammonia in chronically dysfunctional ischemic myocardium. Our results indicate that the 15O-water method yields higher absolute MBF values than the 13N-ammonia approach. Our results also support the use of PTI as a marker of myocardial tissue viability.

Influence of transmitral filling dynamics on continuous-wave Doppler assessment of aortic regurgitation by half-time methods.

The influence of transmitral filling dynamics on the evaluation of aortic regurgitation (AR) by continuous-wave Doppler pressure half-time was assessed in 30 consecutive patients in sinus rhythm with chronic moderate to severe AR. Pulsed-wave Doppler-derived regurgitant fraction (obtained from aortic and pulmonary stroke volumes) and color flow mapping relative regurgitant area (obtained from the parasternal short-axis view) were chosen as reference standards for the severity of AR. An excellent correlation was found between these 2 parameters (r = 0.98), while correlations were poor between pressure half-time and either regurgitant fraction (r = -0.74) or relative regurgitant jet area (r = -0.69). The ratio of early (E) to late (A) transmitral peak velocities was used to divide the study population into 2 groups: group A (n = 16) with E/A less than 1 and group B (n = 14) with E/A greater than 1. In patients with a similar degree of AR (estimated from Doppler regurgitant fraction or relative regurgitant jet area), the pressure half-time was found to be significantly shorter. Thus, the severity of AR in group A patients was overestimated (p less than 0.01). Compared to group B, group A patients were significantly shorter. Thus, the severity of AR in group A patients was overestimated (p less than 0.01). Compared to group B, group A patients were significantly older (p less than 0.02) and had a larger left ventricular mass (p less than 0.005).(ABSTRACT TRUNCATED AT 250 WORDS)

Predictive accuracy of echocardiographic response of mildly dyssynergic myocardial segments to low-dose dobutamine.

Low-dose dobutamine echocardiography has a high sensitivity for predicting functional recovery after revascularization. In segments with mild wall motion abnormalities, the specificity of the technique is rather low, suggesting overestimation of functional recovery in these segments.

Comparison of dipyridamole stress echocardiography and perfusion scintigraphy for cardiac risk stratification in vascular surgery patients.

Dipyridamole single-photon emission computed tomography (SPECT) has a high negative predictive value for perioperative cardiac events, but events are infrequent in patients with a positive test. In contrast, dipyridamole echocardiography is more selective for detection of multivessel disease and thus may have a greater specificity for cardiac events. We therefore compared the ability of dipyridamole SPECT and echocardiography to predict perioperative and long-term cardiac events in 133 patients referred for vascular surgery. The group was also evaluated based on clinical features and ejection fraction. Four patients had surgery cancelled because of high risk and were excluded from further analysis. Among the 129 remaining patients, 21 had coronary revascularization (n=12) or an early cardiac end point (n=9). The sensitivity of SPECT for the prediction of early events (90%) was not significantly different from that of echocardiography (66%, p=NS). The specificity of SPECT (68%) was less than that of echocardiography (88%, p <0.001%), as was the accuracy (72% vs 84%, p=0.02). These findings were replicated after exclusion of patients with treatment end points. During long-term follow-up, 12 patients experienced > or = 1 event: 6 died from cardiac causes, 4 underwent revascularization, and 3 had myocardial infarction. Thus, the specificity of SPECT and echocardiography for late events were 58% and 80%, respectively (p <0.001). The 3-year survival of patients without ischemia during echocardiography or at SPECT was not different (93% vs 94%, p=NS).