Safety of granulocyte-colony-stimulating factor in acute myocardial infarction (the Rigenera study).
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Biomedical subjects
Publications and source records attributed to L Galiuto.
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OBJECTIVE: To test the hypothesis that impaired coronary and myocardial blood flow are linked with increased myocyte apoptosis, thus establishing a link between pressure overload and left ventricular (LV) remodelling. METHODS AND RESULTS: Peak diastolic coronary blood flow velocity (CBFV) was evaluated at transthoracic Doppler echocardiography, and signal intensity (SI) and the rate of SI rise (beta) were measured at myocardial contrast echocardiography in 11 patients with severe aortic stenosis and LV hypertrophy. In the same patients, biopsies were obtained from the anterolateral LV free wall during surgery and analysed for cardiomyocyte apoptosis. LV mass corrected CBFV (CBFVI) was significantly lower in patients than in controls (median 0.100 cm.g/s (interquartile range 0.07-0.115) v 0.130 cm.g/s (0.130-0.160), p = 0.002). Similarly, SI*beta was significantly lower in patients than in controls (11 1/s (8-66) v 83 1/s (73-95), p = 0.001). Apoptotic rate was increased in aortic stenosis more than 100-fold versus controls (1.2% (0.8-1.4) v 0.01% (0.01-0.01), p < 0.001) and inversely correlated with lower CBFVI and SI*beta (r = -0.77, p = 0.001 for both). CONCLUSIONS: Patients with severe aortic stenosis and LV hypertrophy have impaired myocardial perfusion, which is associated with enhanced cardiomyocyte apoptosis. Impaired myocardial perfusion and the ensuing oxygen demand-supply imbalance may, at least partially, be responsible for increased apoptosis and possible transition to heart failure, thus establishing a link between pressure overload, LV remodelling, and heart failure.
New technologies and the availability of new echo-contrast agents have resulted in advances of diagnostic and prognostic indications of left ventricular opacification (LVO) and myocardial perfusion. The clinical diagnostic value of ultrasound contrast media for LVO and its impact on the clinical decision-making process has been demonstrated in several studies. Recent research aims at developing new quantitative software to improve the delineation of the endocardial border, to assess 3D myocardial perfusion for more accurate regional/global LV function measurements, and to evaluate 4D intra-cardiac flow dynamics. Furthermore, a general consensus has been reached on the incremental value of myocardial contrast echocardiography (MCE) for obtaining additional information in both chronic and acute coronary artery disease (CAD) patients and on the possibility to make quantitative measurements of microvascular damage. Q-contrast is a new software system which provides quantitative measurements to generate parametric images of microcirculatory flow. In a research project including 120 patients, Q-contrast software has been tested to assess the role of contrast in AMI (Acute Myocardial Infarction Contrast Imaging (A.M.I.C.I. Study); good agreement between parametric MCE and SPECT has been found. Preliminary results further confirm that quantitative MCE may provide additional clinical value over qualitative information for the assessment of LV function and of the effects of coronary artery disease on the myocardial microcirculation (viability, ischemia or infarct).
There is a complex relation between what can be seen using perfusion imaging techniques, and what can be measured.
The myocardial performance index represents an easy and reproducible parameter of both systolic and diastolic left ventricular function for the risk stratification of patients following acute myocardial infarction.
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OBJECTIVE: To identify in humans the temporal patterns of no reflow and their functional implications. METHODS: 24 patients with first acute myocardial infarction and successful coronary recanalisation by recombinant tissue-type plasminogen activator (n = 15) or primary percutaneous transluminal coronary angioplasty (n = 9) were studied by myocardial contrast echocardiography within 24 hours of recanalisation and at one month's follow up. Myocardial contrast echocardiography was performed by intermittent harmonic power Doppler and intravenous Levovist. The regional contrast score index (CSI) was calculated within dysfunctioning myocardium. Videointensity was measured (dB) within risk and control areas and their ratio was calculated. RESULTS: In 8 patients reflow was observed at 24 hours and persisted at one month. Conversely in 16 patients areas of no reflow were detectable at 24 hours. At one month, no reflow was spontaneously reversible in 9 patients (mean (SD) CSI and videointensity ratio improved from 2.5 (0.5) to 1.4 (0.6) and from 0.6 (0.1) to 0.7 (0.1), respectively; p < 0.05) and was sustained in the remaining 7 patients (CSI and videointensity ratio remained unchanged from 2.6 (0.6) to 2.6 (0.5) and from 0.5 (0.2) to 0.5 (0.2), respectively; NS). Left ventricular function improved significantly in patients with reflow and reversible no reflow. Volumes were enlarged only in patients with sustained no reflow. CONCLUSIONS: No reflow detected at 24 hours may be sustained or spontaneously reversible at one month. Such reversibility of the phenomenon is associated with preserved left ventricular volumes and function. Clarification of the mechanisms of delayed reversibility may lead to tailored treatment of no reflow even in the subacute phase of myocardial infarction.
BACKGROUND: The purpose of this study was to verify whether endothelin A-antagonist administration at the time of coronary reperfusion preserves postischemic microvasculature and whether myocardial contrast echo (MCE) is able to detect pharmacologically induced changes in microvascular reflow. METHODS AND RESULTS: Twenty dogs underwent 90 minutes of LAD occlusion (OCC) followed by 180 minutes of reperfusion (RP). Five minutes before LAD reopening, an intravenous bolus (5 mg/kg) of LU 135252 was given in 10 dogs and vehicle in the remaining 10. At baseline (BSL), OCC, and 90 and 180 minutes of RP, microvascular flow (BF) was assessed by microspheres, and MCE was performed with intravenous echo contrast. MCE videointensity and BF were expressed as risk area/control ratio. Myocardial thickness of the risk area was calculated by 2D echo. No differences in BF between the 2 groups were observed at BSL, OCC, and 90 minutes of RP. At 180 minutes of RP, BF was decreased in controls (70+/-7.4% of BSL; P:<0.005 versus BSL) and preserved in LU 135252-treated animals (89+/-4% of BSL; P=NS versus BSL; P<0.05 versus controls). Videointensity at MCE closely followed the changes in BF observed in both groups throughout the protocol. Myocardial thickness at 180 minutes of RP increased to 138.6+/-9.9% of BSL in controls and remained at 108.9+/-7.4% of BSL in treated dogs (P<0.05). CONCLUSIONS: Endothelin A-antagonist treatment at the time of reperfusion significantly limited the progressive decrease in postischemic microvascular reflow and the increase in myocardial thickness. MCE allowed a reliable evaluation of pharmacologically induced changes in microvascular flow.
During myocardial ischemia produced by coronary occlusion, coronary microvessels and cardiac myocytes undergo progressive functional and structural changes. The prompt reopening of the epicardial vessel is the main therapeutic strategy to limit the vascular and cellular damage. However, the full benefit of reperfusion can be limited by progressive microvascular obstruction and cell death occurring after the reestablishment of flow. During ischemia-reperfusion, preservation of the integrity of the coronary microvasculature is a fundamental prerequisite to ensuring myocardial viability. Therefore, therapeutic approaches should be developed to prevent and treat microvascular impairment resulting from ischemia-reperfusion. Also, given the importance of the assessment and treatment of post-reperfusion disorders of coronary microvasculature, a diagnostic tool able to evaluate the structural and functional status of the microcirculation in vivo is needed. Myocardial contrast echocardiography has been demonstrated to be extremely useful in this setting. In this review, the anatomic and functional characteristics of the coronary microcirculation are described during normal conditions, as well as in the presence of ischemia-reperfusion injury. The role of myocardial contrast echocardiography in the assessment of microvascular dysfunction and specific potential therapeutic approaches to the treatment of microvascular damage during ischemia and after reperfusion are also discussed.
BACKGROUND: [corrected] Subendocardial thickening is greater than subepicardial thickening and acute myocardial ischemia mainly impairs the former. Integrated backscatter cyclic variations (IBScv) reflect regional myocardial contractility and are blunted during myocardial ischemia. We hypothesized that stress-induced myocardial ischemia mainly affects subendocardial IBScv. METHODS AND RESULTS: Multiplane transesophageal echocardiography and simultaneous atrial pacing were performed in 12 patients without coronary artery disease (CAD) and in 25 with significant CAD. In a transgastric 2-chamber view, we calculated IBScv in subendocardium and subepicardium and a heterogeneity index, both at rest and at peak-pacing. In 27 myocardial segments of patients with normal coronary arteries, and in 16 myocardial segments supplied by coronary artery without significant stenosis in patients with CAD, there was a transmural gradient of IBScv at rest and the heterogeneity index did not change during all the protocol steps. In the 53 myocardial segments related to a significantly narrowed coronary artery, the transmural gradient of IBScv, present at rest, significantly decreased at peak-pacing because of subendocardial blunting, but promptly recovered 5 seconds after pacing interruption. Moreover, the myocardial thickening at rest and peak pacing correlated with the subendocardial IBScv behavior and not with the subepicardial one. CONCLUSIONS: IBScv are greater in the subendocardium than in the subepicardium. Atrial pacing stress test does not affect IBScv in segments supplied by nonstenotic coronary arteries, whereas it affects segments supplied by diseased coronary arteries, blunting exclusively subendocardial IBScv. Heterogeneity of IBScv intramyocardial changes caused by stress-induced ischemia must be taken into account when using IBScv for investigating myocardial ischemia.
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Successfully reopening the infarct-related artery after acute myocardial infarction (MI) is currently achieved more frequently than before due to efficient therapeutic strategies, including new thrombolytic drugs and percutaneous transluminal coronary angioplasty. Successful reopening does not necessarily mean reperfusion; in fact the "no-reflow" phenomenon can occur. This phenomenon is due to functional and anatomic alterations, including microcirculation. Experimental and clinical studies have demonstrated that microvascular integrity is a fundamental prerequisite for ensuring viability after an acute MI. Often, studies have also shown that myocardial contrast echocardiography is a technique capable of detecting functional and anatomic conditions of microcirculation after ischemic reperfusion, and thus myocardial contrast echocardiography can be used for viability detection after acute MI.
We designed the present study (1) to investigate the velocities of longitudinal movement of the human left ventricle by pulsed-wave tissue Doppler (PWTD) imaging; (2) to test the hypothesis that a heterogeneous pattern of longitudinal systolic and diastolic velocities exists among individual left ventricular wall segments; (3) to establish the range of this heterogeneity, and (4) to correlate the function of individual segments with the known orientation of myocardial fibers. PWTD is a novel ultrasound method to quantify myocardial contraction and relaxation velocities. In 27 young normal subjects, PWTD peak values of longitudinal systolic and diastolic velocities were measured for 12 left ventricular segments visualized from the apical window. The PWTD sampling of each myocardial segment resulted in a triphasic velocity curve during each cardiac cycle: a systolic velocity wave (S) directed toward the transducer, and an early diastolic (E) and a late diastolic (A) velocity wave away from the transducer. A heterogeneous pattern of systolic and diastolic myocardial velocities was observed between individual wall segments as well as for the basal and midsegments of each myocardial wall. The difference between the highest and lowest values for S was 38.4% in the basal segments and 56.3% in the midwall segments. The difference between low and high velocities for E was 61.4% in the basal and 38.2% in the midsegments; for A the difference was 29.5% in the basal and 32.6% in the midsegments. In general, lower velocity values were found in the septum with higher basal to midwall difference. The lateral and posterior walls had higher, but more uniform, velocities. PWTD enables the quantitative assessment of regional systolic and diastolic myocardial velocities. Substantial heterogeneity of velocities exists within individual myocardial segments, and must be taken into account in any clinical application. The observed heterogeneity in longitudinal function is consistent with the known spatial distribution of myocardial fibers.
BACKGROUND: Infective endocarditis remains a life-threatening disease, and its optimal management is of paramount importance. Transesophageal echocardiography (TEE) is useful for the diagnosis of endocarditis-induced lesions, but the prognostic significance of the method remains controversial. HYPOTHESIS: The purpose of this study was to relate clinical and TEE characteristics to the occurrence of mortality and/or systemic embolization in a consecutive series of 45 patients with a diagnosis of infective endocarditis. METHODS: All patients underwent at least one monoplane TEE. Clinical data, episodes of embolization, and echocardiographic characteristics were prospectively recorded. Stepwise logistic discriminant analysis was performed to identify the independent variables that best predicted three binary outcomes: systemic embolization, death, and systemic embolization and/or death. RESULTS: Twelve of the 45 patients (27%) died from the endocarditis. Significant univariate predictors of death were the presence of paravalvular abscess (p = 0.025), number of vegetations (p = 0.021), Staphylococcus aureus isolated in blood cultures (p = 0.002), medical treatment alone (p < 0.002), and systemic embolism (p < 0.001). In multivariate analysis, systemic embolism (chi 2 = 29.3; p < 0.01), echocardiographic evidence of paravalvular abscess (chi 2 = 5.6; p = 0.018), Staphylococcus aureus endocarditis (chi 2 = 5.5; p = 0.016), and medical treatment alone (chi 2 = 5.11; p = 0.024) emerged as optimal predictors of death. Systemic embolization occurred in 12 patients. Independent variables predicting systemic embolization were a total length of vegetations > 14 mm (p = 0.01), greater age (p = 0.02), and medical treatment alone (p = 0.03). When two or more vegetations were observed, the total length is the sum of the individual sizes. Independent risk factors for the development of systemic emboli and/or death as a combined end point were total length of vegetations on TEE (chi 2 = 6.4; p = 0.003) and medical treatment alone (chi 2 = 4.1; p = 0.047). CONCLUSIONS: High-risk patients may be identified by the combination of clinical variables and TEE characteristics.
BACKGROUND: Dynamic changes of myocardial blood flow have been observed after reperfusion of an occluded coronary artery. MCE performed by intracoronary contrast injection can provide an estimate of microvascular flow. We hypothesized that MCE performed using intravenous infusion of a new generation contrast agent and electrocardiogram-gated harmonic imaging would be able to assess serial changes of microvascular perfusion. OBJECTIVE: To study the potential of myocardial contrast echocardiography (MCE) to assess serial changes of microvascular flow during ischemia-reperfusion. METHODS: Sixteen dogs underwent 90 or 180 min of left anterior descending coronary occlusion, followed by 180 min of reperfusion. Regional blood flow (RBF) was measured with fluorescent microspheres at baseline, during coronary occlusion, and at 5, 30, 90, and 180 min during reperfusion. At the same time points, MCE was performed with intravenous infusion of AF0150 (4 mg/min). Gated end-systolic images in short axis were acquired in harmonic mode and digitized on-line. Background-subtracted videointensity measured from MCE and RBF obtained from fluorescent microspheres were calculated for the risk area and for a control area, and were expressed as the ratio of the two areas. RESULTS: After initial hyperemia, a progressive reduction in flow was observed during reperfusion. MCE correctly detected the time course of changes in flow during occlusion-reperfusion. Videointensity ratio significantly correlated with RBF data (r=0.79; p < 0.0001). CONCLUSIONS: The progressive reduction in blood flow occurring within the postischemic microcirculation was accurately detected by MCE. This approach has potential application in the evaluation and management of postischemic reperfusion in humans.
AIMS: To evaluate the effects of acute, atrial pacing-induced, reversible myocardial ischaemia on myocardial thickening and integrated backscatter cyclic variations in patients with or without coronary artery disease. METHODS AND RESULTS: Thirty-six patients with suspected coronary artery disease underwent transoesophageal echocardiography with simultaneous atrial pacing, and coronary angiography. In myocardial segments not related to a significantly narrowed coronary artery, both from patients with and without coronary artery disease, thickening and integrated backscatter cyclic variations were not reduced at peak pacing. In segments related to a significantly narrowed coronary artery, thickening decreased at peak pacing, was still reduced at pacing interruption and recovered at 2 min, while backscatter cyclic variations, blunted at peak pacing, immediately recovered after pacing interruption. CONCLUSION: During stress-induced myocardial ischaemia, backscatter cyclic variations are blunted and thickening reduced. Returning to baseline, pre-atrial pacing values occur more rapidly in backscatter cyclic variations than when thickening takes place. Evaluation of stress-induced alterations in backscatter cyclic variations may aid in the identification of ischaemia-induced regional left ventricular functional impairment and, hence, in coronary artery disease diagnosis.
AIMS: The study was set up to evaluate the functional role of post-infarct preserved microvascular integrity. Low dose dobutamine echocardiography and myocardial contrast echocardiography were used to study patients before hospital discharge who had suffered a recent myocardial infarction and had a patent infarct-related artery (TIMI flow grade 3). METHOD: In the dysfunctioning infarct area, the wall motion score index was calculated at baseline, during the dobutamine infusion and at the 3 month follow-up echocardiogram; contrast echocardiography was performed at the time of coronary angiography, before hospital discharge. RESULTS: In patients with more than 50% of the dysfunctioning infarct area opacified at contrast echocardiography (group A), regional wall motion score index decreased, compared to baseline, during the dobutamine infusion (1.97 +/- 0.78 vs 2.5 +/- 0.35 at baseline; P < 0.001) and at follow-up echocardiography (1.83 +/- 0.63 vs 2.5 +/- 0.35 at baseline; P < 0.001). In patients with less extensive microvascular integrity as revealed by contrast echocardiography (group B), regional wall motion score index did not decrease from baseline during either the dobutamine infusion (2.73 +/- 0.21 vs 2.81 +/- 0.20 at baseline; P = ns), or at follow-up (2.81 +/- 0.20 vs 2.81 +/- 0.20 at baseline; P = ns). CONCLUSION: In patients with post-infarct dysfunctioning myocardium but a patent infarct-related artery, microvascular integrity, as assessed by myocardial contrast echocardiography, is an indicator of myocardial viability in terms of preserved contractile reserve, as demonstrated by dobutamine infusion and functional recovery at follow-up.