Positron emission tomography using(18)F-fluoro-deoxyglucose and euglycaemic hyperinsulinaemic glucose clamp: optimal criteria for the prediction of recovery of post-ischaemic left ventricular dysfunction. Results from the European Community Concerted Action Multicenter study on use of(18)F-fluoro-deoxyglucose Positron Emission Tomography for the Detection of Myocardial Viability.

AIMS: To assess the accuracy of positron emission tomography to predict recovery of global cardiac function after revascularization in patients with coronary artery disease. METHODS AND RESULTS: One hundred and seventy-eight patients (157 male, 58+/-10 years) with coronary artery disease and left ventricular dysfunction (mean ejection fraction 39+/-14%) were enrolled in six European centres. They underwent a common protocol for the assessment of viability using(18)F-fluoro-2-deoxyglucose (FDG) positron emission tomography during a standardized euglycaemic hyperinsulinaemic glucose clamp before revascularization by either surgery (n=140) or angioplasty (n=38). Seven patients were excluded because of incomplete revascularization of a dysfunctional region. Based on the recovery of global ejection fraction 2-6 months after revascularization, patients were classified into two groups: 82 patients who had a >5% improvement in ejection fraction postoperatively, and 89 patients without postoperative ejection fraction improvement. Optimal cut-off points for postoperative improvement of global cardiac function were computed, using receiver operating curve analysis. The highest sensitivity (79%) and specificity (55%) for predicting postoperative ejection fraction improvement by positron emission tomography was found when three or more dysfunctional segments had a relative FDG uptake >45% of normal remote myocardium (overall accuracy 67%). CONCLUSIONS: In a large cohort of coronary patients with impaired ejection fraction, FDG positron emission tomography demonstrated high sensitivity and moderate specificity to predict improvement of cardiac function after coronary revascularization.

Exaggerated chronotropic and energetic response to dobutamine after orthotopic cardiac transplantation.

BACKGROUND: After heart transplantation, the transplanted denervated heart displays both an exaggerated chronotropic and an exaggerated inotropic response to circulating catecholamines. This study assessed whether denervated transplanted hearts also display an exaggerated energetic response when challenged with dobutamine. METHODS AND RESULTS: A total of 18 heart transplant recipients and 14 normal volunteers underwent measurements of myocardial oxygen consumption (MVO2), external work (EW), and pressure-volume area (PVA), at rest and during infusion of dobutamine. At rest, calculated myocardial (PVA/MVO2) and mechanical (EW/MVO2) efficiencies were similar among transplant recipients and normal volunteers. During low-dose dobutamine infusion (8 microg/kg/min), transplant recipients exhibited a larger increase in heart rate (to 126 +/- 14 vs 87 +/- 26 beats/min, p < 0.001) and MVO2 (to 269 +/- 43 vs 233 +/- 19 J/min/100g, p < 0.05) and a smaller increase in EW (64 +/- 18 vs 72 +/- 13 J/min/100g, p < 0.05) and PVA (70 +/- 16 vs 81 +/- 13 J/min/100g, p < 0.05) than did normal volunteers. As a result, both myocardial (26 +/- 4 vs 35 +/- 4%, p < 0.05) and mechanical (23 +/- 4 vs 30 +/- 4%, p < 0.001) efficiencies were lower during dobutamine infusion in transplant recipients than in normal volunteers. During the infusion of a higher dose of dobutamine (19 microg/kg/min), the chronotropic and inotropic responses of heart transplant recipients were even more exaggerated. The fall in myocardial efficiency induced by dobutamine correlated with the increase in heart rate (r = -0.58) and could be reproduced in normal volunteers by coadministration of atropine. CONCLUSIONS: Transplant recipients exhibit a larger fall in contractile efficiency and a larger oxygen-wasting effect during dobutamine infusion than do normal volunteers. Because normal volunteers pre-medicated with atropine presented with a similar increase in heart rate and a similar fall in efficiency, the exaggerated energetic response of transplanted hearts to dobutamine likely resulted from the same mechanisms as their chronotropic supersensitivity, i.e., the loss of inhibitory parasympathetic innervation.

Relation between Gd-DTPA contrast enhancement and regional inotropic response in the periphery and center of myocardial infarction.

BACKGROUND: Gd-DTPA contrast-enhanced (CE) MRI identifies patterns of early hypoenhancement and delayed hyperenhancement in acute myocardial infarction, but their clinical significance for the prediction of myocardial viability remains controversial. Therefore, we closely examined the relationship between these CE patterns and regional inotropic response to low-dose dobutamine infusion at a regional level. METHODS AND RESULTS: Thirteen dogs underwent CE and tagged MRI at rest and during 5 microg. kg(-1). min(-1) dobutamine 48 hours after MI. CE patterns and 3D regional strains were measured in 96 segments per animal. Segments were categorized as being normofunctional (n=828) if resting circumferential shortening was within the range of remote myocardium, or dysfunctional (n=420) if not. Inotropic response in resting dysfunctional segments was assessed according to CE patterns. Significant improvement of radial thickening (from +12+/-1% [mean+/-SEM] to +22+/-2%, P<0.05) and circumferential shortening (from +1+/-1% to -5+/-1%, P<0.05) strains occurred in dysfunctional myocardium with normal CE pattern but not in myocardium with early hypoenhancement. Delayed hyperenhanced myocardium displayed a more complex behavior. Circumferential stretching improved in the peripheral regions (from +4+/-1% to -2+/-2%, P<0.05), where the infarct was nontransmural (38+/-3% transmurality), but not in centrally hyperenhanced regions (from +4+/-1% to +1+/-1% P=NS), where the infarct was 66+/-3% transmural. CONCLUSIONS: Inotropic reserve was confined to dysfunctional myocardium with normal contrast enhancement but not to myocardium with early hypoenhancement. Inotropic response in delayed hyperenhanced myocardium is influenced by transmurality of necrosis. These observations support the use of CE MRI for the clinical detection of myocardial viability.

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.

The pathophysiology of myocardial hibernation: current controversies and future directions.

It is now widely accepted that patients with chronic coronary artery disease can experience prolonged regional ischemic dysfunction that does not necessarily arise from irreversible tissue damage and, to some extent, can be reversed by restoration of blood flow. Recent clinical and experimental data suggest that this form of chronic but reversible left ventricular dysfunction represents a complex, progressive, and dynamic phenomenon. The initial stages of dysfunction are probably caused by chronic stunning. They are characterized by normal resting perfusion but reduced flow reserve, mild myocyte alterations, maintained membrane integrity (allowing the transport of both thallium and glucose), preserved capacity to respond to an inotropic stimulus, and no or little tissue fibrosis. After revascularization, functional recovery will probably be rapid and complete. On the other hand, the more advanced stages of dysfunction likely correspond to chronic hibernation. They usually are associated with reduced rest perfusion; increased tissue fibrosis; more severe myocyte alterations (degeneration[?], apoptosis); and a decreased ability to respond to inotropic stimuli. Nonetheless, membrane function and glucose metabolism may long remain preserved. After revascularization, functional recovery, if any, will probably be quite delayed and mostly incomplete.

Effect of naratriptan on myocardial blood flow and coronary vasodilator reserve in migraineurs.

BACKGROUND: Migraine drugs can produce adverse cardiac effects. The authors have demonstrated previously that ergotamine can lead to a significant reduction of hyperemic myocardial blood flow, but little is known about the effect of the newer serotonin analogues. Coronary artery constriction caused by serotonin or its analogues is mediated mainly by 5HT2 receptors. The selective 5HT1B/1D agonist naratriptan has no significant activity at 5HT2 receptors; however, like all 5HT1B/1D agonists developed for the acute treatment of migraine, naratriptan could potentially constrict coronary arteries by activation of 5HT1B receptors. METHODS: The effects on myocardial blood flow of subcutaneous naratriptan 1.5 mg compared with placebo were assessed under resting and hyperemic conditions with PET using oxygen-15 labeled water during two separate visits. This study was a randomized, double-blind, placebo-controlled crossover trial in 34 migraine subjects with no evidence of ischemic heart disease, studied outside a migraine attack. RESULTS: Naratriptan did not differ significantly from placebo in its effects on resting myocardial blood flow, but did evoke a small, significant fall in hyperemic myocardial blood flow (-13% versus placebo) and an increase in hyperemic coronary resistance (+19% versus placebo) without any signs or symptoms suggestive of myocardial ischemia. Naratriptan did not significantly affect the coronary vasodilator reserve (hyperemic/resting blood flow) compared with placebo. CONCLUSIONS: These results show that at therapeutic doses, naratriptan exerts only a minor effect on myocardial blood flow, coronary vasodilator reserve, or coronary resistance among subjects with no evidence of ischemic heart disease. These results should not be extrapolated to patients with coronary artery disease, in whom all 5HT1 agonists for migraine are contraindicated.

Time course of functional recovery after coronary artery bypass graft surgery in patients with chronic left ventricular ischemic dysfunction.

Chronic left ventricular (LV) ischemic dysfunction, a condition often referred to as myocardial hibernation, is associated in humans with ultrastructural alterations of the myocytes, including the loss of myofilaments and the accumulation of glycogen. Given the severity of these structural changes, contractile function is unlikely to resume immediately upon revascularization. Therefore, the aim of the present study was to assess the time course of functional improvement after successful revascularization as well as its potential structural correlates. We studied 32 patients with coronary disease and chronic LV ischemic dysfunction who underwent bypass surgery. Dynamic positron emission tomography with N-13 ammonia and F-18 deoxyglucose to assess myocardial perfusion and glucose metabolism was performed in 29 patients. In all patients, a transmural biopsy was harvested from the center of the dysfunctional area, to quantify the increase in extracellular matrix and the presence of structurally altered cardiomyocytes. LV function was serially measured by digitized 2-dimensional echocardiography before and at 10 days, 2 months, and 6 months after revascularization. The time course of recovery of regional function was estimated from the monoexponential decrease in dysfunctional wall motion score. At follow-up, 19 patients had improved LV function, whereas 13 patients showed persistent dysfunction. Before revascularization, reversibly dysfunctional segments had higher myocardial blood flow (82 +/- 29 vs 53 +/- 21 ml. (min. 100 g)(-1), p = 0.044), higher glucose uptake (40 +/- 16 vs 21 +/- 9 micromol. (min. 100 g)(-1), p = 0.001), and less increase in extracellular matrix (25 +/- 15% vs 46 +/- 17%, p = 0.0008) than segments with persistent dysfunction. The extent to which function recovered was positively correlated with myocardial blood flow and negatively correlated with the increase in the extracellular matrix. In patients with reversible dysfunction, the return of segmental function was progressive and followed a monoexponential time course with a median time constant of 23 days (range 6 to 78). The rate of recovery correlated best with the proportion of altered cardiomyocytes in the biopsy. The present study thus indicates that the recovery of regional and global LV function after successful revascularization is progressive and follows a monoexponential time course that is influenced by the extent of the structural changes affecting cardiomyocytes.

Microvascular obstruction and left ventricular remodeling early after acute myocardial infarction.

BACKGROUND: The presence of microvascular obstruction (MO) within infarcted regions may adversely influence left ventricular (LV) remodeling after acute myocardial infarction. This study examined whether the extent of MO directly alters the mechanical properties of the infarcted myocardium. METHODS AND RESULTS: Seventeen dogs underwent 90 minutes of balloon occlusion of the left anterior descending coronary artery, followed by reperfusion. Gadolinium-enhanced perfusion MRI and 3D-tagging were performed 4 to 6 and 48 hours (8 animals) and 10 days (9 animals) after reperfusion. Early increase in LV end-diastolic volume (from 42+/-9 to 54+/-14 mL, P<0.05) between 4 to 6 and 48 hours after reperfusion was predicted by both extent of MO (r=0.89, P<0.01) and infarct size (r=0.83, P<0.01), defined as MRI hypoenhanced and hyperenhanced regions, respectively. Multivariate analysis demonstrated that extent of MO had better and independent value to predict LV volume than overall infarct size. A strong inverse relationship existed between magnitude of first principal strain (r=-0.80, P<0.001) and relative extent of MO within infarcted myocardium. Also, infarcted myocardium involved by extensive areas of MO demonstrated reductions of circumferential (r=-0.61, P<0.01) and longitudinal (r=-0.53, P<0. 05) stretching. Furthermore, significant reductions of radial thickening (9+/-6% versus 14+/-3%, P<0.01) occurred in noninfarcted regions adjacent to infarcts that had increased (>35%) amounts of MO. CONCLUSIONS: In the early healing phase of acute myocardial infarction, the extent of MO in infarcted tissue relates to reduced local myocardial deformation and dysfunction of noninfarcted adjacent myocardium. Such strain alterations might explain the increased remodeling observed in patients with large regions of MO.

Comparison of myocardial contrast echocardiography with NC100100 and (99m)Tc sestamibi SPECT for detection of resting myocardial perfusion abnormalities in patients with previous myocardial infarction.

OBJECTIVE: To determine whether myocardial contrast echocardiography (MCE) following intravenous injection of perfluorocarbon microbubbles permits identification of resting myocardial perfusion abnormalities in patients who have had a previous myocardial infarction. PATIENTS AND INTERVENTIONS: 22 patients (mean (SD) age 66 (11) years) underwent MCE after intravenous injection of NC100100, a novel perfluorocarbon containing contrast agent, and resting (99m)Tc sestamibi single photon emission computed tomography (SPECT). With both methods, myocardial perfusion was graded semiquantitatively as 1 = normal, 0.5 = mild defect, and 0 = severe defect. RESULTS: Among the 203 normally contracting segments, 151 (74%) were normally perfused by SPECT and 145 (71%) by MCE. With SPECT, abnormal tracer uptake was mainly found among normally contracting segments from the inferior wall. By contrast, with MCE poor myocardial opacification was noted essentially among the normally contracting segments from the anterior and lateral walls. Of the 142 dysfunctional segments, 87 (61%) showed perfusion defects by SPECT, and 94 (66%) by MCE. With both methods, perfusion abnormalities were seen more frequently among akinetic than hypokinetic segments. MCE correctly identified 81/139 segments that exhibited a perfusion defect by SPECT (58%), and 135/206 segments that were normally perfused by SPECT (66%). Exclusion of segments with attenuation artefacts (defined as abnormal myocardial opacification or sestamibi uptake but normal contraction) by either MCE or SPECT improved both the sensitivity (76%) and the specificity (83%) of the detection of SPECT perfusion defects by MCE. CONCLUSIONS: The data suggest that MCE allows identification of myocardial perfusion abnormalities in patients who have had a previous myocardial infarction, provided that regional wall motion is simultaneously taken into account.

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.

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.

Relation of exercise capacity to left ventricular systolic function and diastolic filling in idiopathic or ischemic dilated cardiomyopathy.

Although exercise intolerance is a cardinal symptom of patients with dilated cardiomyopathy (DC) and heart failure, the factors that limit exercise capacity in these patients remain a matter of debate. To assess the contribution of left ventricular (LV) diastolic filling to the variable exercise capacity of patients with DC, we studied 47 patients (60 +/- 12 years) with DC in stable mild-to-moderate heart failure with a mean LV ejection fraction of 28%. Exercise capacity was measured as total body peak oxygen consumption (VO2) during symptom-limited bicycle (10 W/min) and treadmill (modified Bruce protocol) exercise. LV systolic function and diastolic filling were assessed at rest before each exercise by M-mode, Doppler echocardiography, and radionuclide ventriculography. As expected, treadmill exercise always yielded higher peak VO2 than bicycle exercise (21 +/- 6 vs 18 +/- 5 ml/kg/min, range 12 to 35 and 7 to 30 ml/kg/min, respectively, p <0.001). Both of these VO2 measurements were highly reproducible (R = 0.98). With univariate analysis, close correlations were found between peak VO2 (with either exercise modalities) and Doppler indexes of LV diastolic filling, as well as with the radionuclide LV ejection fraction. Stepwise multiple regression analysis identified 3 nonexercise variables as independent correlates of peak VO2, of which the most powerful was the E/A ratio (multiple r2 = 0.38, p <0.0001), followed by peak A velocity (r2 = 0.54, p <0.0001) and mitral regurgitation grade (r2 = 0.58, p = 0.024). In conclusion, our data indicate that in patients with DC, peak VO2 is better correlated to diastolic filling rather than systolic LV function.

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.

Risk stratification in patients with dilated cardiomyopathy: contribution of Doppler-derived left ventricular filling.

Dilated cardiomyopathy (DCM) is a major cause of mortality among patients with heart failure. The aim of the present study was to investigate the independent contribution of Doppler-derived left ventricular (LV) filling to the prediction of survival in patients with DCM, of either ischemic or nonischemic origin, and to derive a simple risk stratification score based on easily available clinical and echocardiographic parameters. We followed 197 consecutive patients (159 men, mean age 60+/-13 years) with an echocardiographic diagnosis of DCM (LV end-diastolic dimension >60 mm, fractional shortening <25%) over an average period of 62+/-13 months. The presumed etiology of DCM was ischemic in 52% of the patients. During follow up, 69 patients died of cardiac causes and 41 required transplantation. At 5 years, overall cardiac event-free survival was 55% and freedom from death or heart transplantation was 43% (compared with 86% for the 5-year age- and sex-adjusted survival rate in our country). Kaplan-Meier survival curves generated for different thresholds of the peak E velocity and the E/A ratio indicated significant worsening of prognosis with increasing values of these parameters in both ischemic and nonischemic patients. Using Cox stepwise regression analyses, age (chi-square to remove 24.4; p <0.001), peak E velocity (chi-square to remove=18.9; p <0.001), LV ejection fraction (chi-square to remove 6.4; p <0.011), and systolic blood pressure (chi-square to remove 4.5; p=0.034) independently predicted cardiac deaths, whereas New York Heart Association (NYHA) functional class (chi-square to remove 48.5; p < 0.001), LV ejection fraction (chi-square to remove 19.1; p <0.001), E/A ratio (chi-square to remove 10.8; p <0.001), and systolic blood pressure (chi-square to remove 5.8; p <0.016) were independently associated with cardiac death or need for transplantation. Based on these parameters, a risk score was elaborated, which allowed appropriate classification of each individual patient into low- (5-year survival rate of 72%), intermediate- (46% survival rate), and high-risk groups (11% survival rate). In conclusion, our data show that among the noninvasive parameters commonly available in patients with either ischemic or nonischemic DCM, age, the NYHA functional class, the LV ejection fraction, the systolic blood pressure, the peak E velocity, and the E/A ratio provide relevant and independent information regarding the risk of cardiac death or the need for heart transplantation.

Magnitude and time course of microvascular obstruction and tissue injury after acute myocardial infarction.

BACKGROUND: Microvascular obstruction within an area of myocardial infarction indicates worse functional recovery and a higher risk of postinfarction complications. After prolonged coronary occlusion, contrast-enhanced MRI identifies myocardial infarction as a hyperenhanced region containing a hypoenhanced core. Because the time course of microvascular obstruction after infarction/reperfusion is unknown, we examined whether microvascular obstruction reaches its full extent shortly after reperfusion or shows significant progression over the following 2 days. METHODS AND RESULTS: Seven dogs underwent 90-minute balloon occlusion of the left anterior descending coronary artery (LAD) followed by reflow. Gadolinium-DTPA-enhanced MRI performed at 2, 6, and 48 hours after reperfusion was compared with radioactive microsphere blood flow (MBF) measurements and myocardial staining to define microvascular obstruction (thioflavin S) and infarct size (triphenyltetrazolium chloride, TTC). The MRI hypoenhanced region increased 3-fold during 48 hours after reperfusion (3.2+/-1.8%, 6.7+/-4.4%, and 9.9+/-3.2% of left ventricular mass at 2, 6, and 48 hours, respectively, P<0.03) and correlated well with microvascular obstruction (MBF <50% of remote region, r=0.99 and thioflavin S, r=0.93). MRI hyperenhancement also increased (21.7+/-4.0%, 24.3+/-4.6%, and 28.8+/-5.1% at 2, 6, and 48 hours, P<0.006) and correlated well with infarct size by TTC (r=0.92). The microvascular obstruction/infarct size ratio increased from 13.0+/-4.8% to 22.6+/-8.9% and to 30.4+/-4.2% over 48 hours (P=0.024). CONCLUSION: The extent of microvascular obstruction and the infarct size increase significantly over the first 48 hours after myocardial infarction. These results are consistent with progressive microvascular and myocardial injury well beyond coronary occlusion and reflow.

Relation of ultrasonic tissue characterization with integrated backscatter to contractile reserve in chronic left ventricular ischemic dysfunction.

Previous studies have shown that viable but stunned myocardium displays contractile reserve and exhibits cardiac cycle-dependent variations of integrated backscatter, whereas infarcted myocardium does not. The present study was designed to evaluate whether integrated backscatter imaging could be useful in identifying segments with recruitable inotropic reserve in patients with chronic left ventricular (LV) ischemic dysfunction. We studied 15 patients (mean age 59 +/- 10 years) with chronic coronary artery disease, anterior or inferior wall dysfunction, and depressed LV ejection fraction (35 +/- 12%), and 6 noncardiac control subjects (mean age 49 +/- 18 years). Cardiac cycle-dependent variations of integrated backscatter were measured in anterior and inferior segments during transesophageal echocardiography and compared with the contractile response (% wall thickening) of these segments to low doses of dobutamine (5 to 10 microg/kg/min). The average magnitude of cardiac cycle-dependent variations of integrated backscatter was greater among normally contracting segments of both patients and controls (5.67 +/- 0.88 and 5.64 +/- 2.26 dB, respectively, p = NS) than among dysfunctional segments (2.77 +/- 3.05 dB, p <0.01 vs control and remote segments). Dysfunctional segments were further categorized into those with and without dobutamine-induced contractile reserve. At baseline, systolic wall thickening was similar among segments responding to dobutamine than among those that did not (3.6 +/- 2.3% vs 2.9 +/- 1.6%, p = NS). During dobutamine, systolic wall thickening increased only in segments showing improvement in wall motion score (to 24.5 +/- 4.7%), whereas it remained unchanged in segments not responding to dobutamine (to 2.0 +/- 3.7%, p <0.01). The magnitude of resting cardiac cycle-dependent variations of integrated backscatter was larger in segments responding to dobutamine than in those with persistent dysfunction (5.31 +/- 2.06 vs 0.23 +/- 0.94 dB, p <0.01) and correlated significantly (r = 0.74, p <0.01) with systolic wall thickening during dobutamine. Our data demonstrate that resting cardiac cycle-dependent variations of integrated backscatter closely parallel contractile reserve in patients with chronic LV ischemic dysfunction. This suggests that tissue characterization with integrated backscatter could be a useful adjunct to the delineation of myocardial viability in these patients.

[Role of isotopic techniques in the evaluation of myocardial viability in man]. / Place des techniques isotopiques dans l'évaluation de la viabilité myocardique chez l'homme.

Modern management of coronary artery disease is increasingly based on techniques of myocardial revascularisation. The introduction of coronary bypass surgery, percutaneous coronary angioplasty and thrombolysis has radically changed the prognosis, reducing the morbidity and mortality related to myocardial infarction and chronic ischaemic heart disease (when associated with left ventricular dysfunction). In this case, the beneficial effects of revascularisation are probably due to improved contractility of dysfunctional tough viable myocardium in response to improved perfusion. Several methods are available for predicting the reversible character of segmental dysfunction after revascularisation. Most are based on fundamental cellular mechanisms thought to contribute to cellular viability and postoperative contractile recovery. These include adequate tissue perfusion for providing energetic substrate and the elimination of metabolic waste; the maintenance of essential membrane functions, the conservation of metabolic pathways for the aerobic use of glucose and fatty acids, and the maintenance of a contractile function capable of ensuring efficacious mechanical activity after surgery. Thallium or MIBI myocardial scintigraphy and position emission tomography (PET) allow the non-invasive evaluation of some of these mechanisms. These techniques are capable of detecting viable myocardium with a high sensitivity (> 80%). They are limited by a lack of specificity (+/- 55% for thallium and +/- 75% for PET). However, all have an additive prognostic value with respect to usual functional (ejection fraction) and anatomical (coronary angiography) parameters.