Biomedical subjects

Stephan G Nekolla

Publications and source records attributed to Stephan G Nekolla.

At least 19 recordsLinked to original sources

PubMed2006

Diagnostic value of contrast-enhanced magnetic resonance imaging and single-photon emission computed tomography for detection of myocardial necrosis early after acute myocardial infarction.

OBJECTIVES: This study sought to evaluate the diagnostic value of contrast-enhanced magnetic resonance imaging (CMR) and single-photon emission computed tomography (SPECT) for detection of myocardial necrosis after acute myocardial infarction (AMI). BACKGROUND: Single-photon emission computed tomography is widely accepted in the clinical setting for detection and estimation of myocardial infarction. Contrast-enhanced magnetic resonance imaging offers technical advantages and is therefore a promising new method for identification of infarcted tissue. METHODS: Seventy-eight patients with AMI were examined by CMR and SPECT 7 days after percutaneous coronary intervention. Contrast-enhanced magnetic resonance imaging and SPECT images were scored for presence and location of infarction using a 17-segment model. Results were compared with the peak troponin T level, electrocardiographic, and angiographic findings. RESULTS: Acute myocardial infarction was detected significantly more often by CMR than SPECT (overall sensitivity: 97% vs. 87%; p = 0.008). Sensitivity of CMR was superior to SPECT in detecting small infarction as assessed by the peak troponin T level <3.0 ng/ml (92 vs. 69%; p = 0.03), and infarction in non-anterior location (98% vs. 84%; p = 0.03). Non-Q-wave infarctions were more likely to be detected by CMR (sensitivity 85% vs. 46%; p = 0.06). While CMR offered high sensitivity for detection of AMI irrespective of the infarct-related artery, SPECT was less sensitive, particularly within the left circumflex artery territory. CONCLUSIONS: Contrast-enhanced magnetic resonance imaging is superior to SPECT in detecting myocardial necrosis after reperfused AMI because CMR detects small infarcts that were missed by SPECT independent of the infarct location. Thus, CMR is attractive for accurate detection and assessment of the myocardial infarct region in patients early after AMI.

Aged↗

PubMed2006

Noninvasive characterization of myocardial molecular interventions by integrated positron emission tomography and computed tomography.

OBJECTIVES: We sought to investigate the usefulness of integrated positron emission tomography (PET) and computed tomography (CT) for in vivo characterization of an angiogenesis-directed molecular intervention. BACKGROUND: Controversies about the effectiveness of molecular therapies for cardiovascular disease have prompted the need for more powerful noninvasive imaging techniques. METHODS: In a model of regional adenoviral transfer of the VEGF(121) gene to myocardium of healthy pigs, PET-CT using multiple molecular-directed radiotracers was employed. RESULTS: Two days after gene transfer, successful transgene expression was noninvasively confirmed by a reporter probe targeting co-expressed HSV1-sr39tk reporter gene. The CT-derived ventricular function and morphology remained unaltered (left ventricular ejection fraction 57 +/- 5% in adenovirus-injected animals vs. 53 +/- 5% in controls; p = 0.36). Increased regional perfusion was identified in areas overexpressing VEGF (myocardial blood flow during adenosine-induced vasodilation 1.47 +/- 0.49 vs. 1.14 +/- 0.27 ml/g/min in remote areas; p = 0.01), corroborating in vivo effects on microvascular tone and permeability. Finally, regional angiogenesis-associated alpha(v)beta3 integrin expression was not enhanced, suggesting little contribution to the perfusion increase. Fusion of CT morphology and tracer-derived molecular signals allowed for accurate regional localization of biologic signals. Findings were validated by control vectors, sham-operated animals, and ex vivo tissue analysis. CONCLUSIONS: Integrated PET-CT has the potential to dissect cardiovascular biologic mechanisms from gene expression to physiologic function and morphology. The VEGF overexpression in healthy myocardium increases myocardial perfusion without significant up-regulation of alpha(v)beta3 integrin adhesion molecules early after the intervention.

Animals↗

PubMed2006

Quantitation of cardiac sympathetic innervation in rabbits using 11C-hydroxyephedrine PET: relation to 123I-MIBG uptake.

PURPOSE: Although (11)C-hydroxyephedrine ((11)C-HED) PET is used to map cardiac sympathetic innervation, no studies have shown the feasibility of quantitation of (11)C-HED PET in small- to medium-sized animals. Furthermore, its relation to (123)I-MIBG uptake, the most widely used sympathetic nervous tracer, is unknown. The aims of this study were to establish in vivo sympathetic nerve imaging in rabbits using (11)C-HED PET, and to compare the retention of (11)C-HED with that of (123)I-MIBG. METHODS: Twelve rabbits were assigned to three groups; control (n=4), chemical denervation by 6-hydroxydopamine (6-OHDA) (n=4) and reserpine treated to inhibit vesicular uptake (n=4). After simultaneous injection of (11)C-HED and (123)I-MIBG, all animals underwent dynamic (11)C-HED PET for 40 min with arterial blood sampling. The (11)C-HED retention fraction and normalised (11)C-HED activity measured by tissue sampling were compared with those measured by PET. RESULTS: Both the (11)C-HED retention fraction and the normalised (11)C-HED activity measured by PET correlated closely with those measured by tissue sampling (R=0.96027, p<0.001 and R=0.97282, p<0.001, respectively). Inhibition study by 6-OHDA resulted in a significant reduction in retention (90%) for both (11)C-HED and (123)I-MIBG. Reserpine pretreatment reduced (11)C-HED retention by 50%, but did not reduce (123)I-MIBG retention at 40 min after injection. CONCLUSION: Non-invasive quantitation of cardiac sympathetic innervation using (11)C-HED PET is feasible and gives reliable estimates of cardiac sympathetic innervation in rabbits. Additionally, although both (11)C-HED and (123)I-MIBG are specific for sympathetic neurons, (11)C-HED may be more specific for intravesicular uptake than (123)I-MIBG in some situations, such as that seen in reserpine pretreatment.

3-Iodobenzylguanidine↗

PubMed2006

Effect of left ventricular function on diagnostic accuracy of FDG SPECT.

OBJECTIVES: Fluorine-18 fluorodeoxyglucose (FDG) SPECT has emerged as an alternative to dedicated PET imaging. However, it remains uncertain whether FDG SPECT is an as accurate for viability assessment as FDG PET in patients with severely reduced left ventricular function. The aim of the study was to assess the diagnostic accuracy of FDG SPECT in a head-to-head comparison with FDG PET, and divide the patients according to the severity of left ventricular dysfunction. METHODS: A total of 47 patients, with a history of myocardial infarction underwent FDG/perfusion (99mTc-sestamibi or 201Tl) SPECT as well as FDG/13N-ammonia PET. The patients were divided into 2 subgroups based on the left ventricular ejection fraction (LVEF) (35% cutoff). The left ventricular myocardium was divided into 13 segments, and each segment was classified as viable or scar using a semi-quantitative scoring system based on defect severity and the presence or absence of perfusion-FDG mismatch. RESULTS: Of the 47 patients studied, 23 had LVEF < 35% (low LVEF group; mean 25 +/- 7%), whereas the remaining 24 had LVEF > or = 35% (high LVEF group; mean 47 +/- 6%). In the low LVEF group, 213 segments (71%) were dysfunctional, as compared to 102 (33%) in the high LVEF group. The agreement for detection of viability between PET and SPECT in the low LVEF group was 82% (kappa 0.63), which was not different from the agreement in the high LVEF group (85%, kappa 0.66, p = 0.42 versus low LVEF group). CONCLUSIONS: The results indicate that FDG SPECT can be used for tissue viability assessment regardless of the severity of left ventricular dysfunction.

Female↗

PubMed2006

Effect of diabetes mellitus on sympathetic neuronal regeneration studied in the model of transplant reinnervation.

UNLABELLED: The transplanted heart is initially denervated but undergoes subsequent sympathetic reinnervation. It thus provides a unique model for studying regeneration as a specific component of autonomic nerve biology. The aim of this study was to determine the effect of diabetes mellitus on the regenerational capacity of sympathetic neurons using molecule-targeted PET. METHODS: Twenty-two nonrejecting, otherwise healthy cardiac transplant recipients underwent PET with the (11)C-labeled physiologic neurotransmitter epinephrine at 4.0 +/- 3.3 y after surgery. Sympathetic reinnervation was defined as regional restoration of epinephrine retention to values within normal limits. RESULTS: Reinnervation was observed in 8 of 12 patients with no evidence of diabetes and in 6 of 10 patients with a long-term history of diabetes mellitus. The regional extent of reinnervation (4.7% +/- 5.3% of left ventricle vs. 19.1% +/- 20.6% for nondiabetic recipients, P = 0.04) and the regeneration rate (0.8% +/- 1.0% of left ventricle per year vs. 8.0% +/- 10.1% for nondiabetic recipients, P = 0.04) were significantly reduced in diabetic subjects. In a multivariate model, diabetes mellitus was an independent determinant of allograft reinnervation. Finally, the reappearance of innervation was found to correlate with an improved chronotropic and inotropic response to stress in a standardized, symptom-limited exercise test including radionuclide angiography. CONCLUSION: The regenerational capacity of the sympathetic nervous system of the heart is reduced, but not abolished, by diabetes mellitus. This study on cardiac transplant recipients further supports a general link between impaired glucose handling and cardiac autonomic nerve function.

Catecholamines↗

PubMed2005

Mechanical reperfusion in patients with acute myocardial infarction presenting more than 12 hours from symptom onset: a randomized controlled trial.

CONTEXT: No specifically designed studies have addressed the role of primary percutaneous coronary intervention in patients with acute ST-segment elevation myocardial infarction (STEMI) presenting more than 12 hours after symptom onset. Current guidelines do not recommend reperfusion treatment in these patients. OBJECTIVE: To assess whether an immediate invasive treatment strategy is associated with a reduction of infarct size in patients with acute STEMI, presenting between 12 and 48 hours after symptom onset, vs a conventional conservative strategy. DESIGN, SETTING, AND PATIENTS: International, multicenter, open-label, randomized controlled trial conducted from May 23, 2001, to December 15, 2004, of 365 patients aged 18 to 80 years without persistent symptoms admitted with the diagnosis of acute STEMI between 12 and 48 hours after symptom onset. INTERVENTIONS: Random assignment to either an invasive strategy (n=182) based predominantly on coronary stenting with abciximab or a conventional conservative treatment strategy (n=183). MAIN OUTCOME MEASURES: The primary end point was final left ventricular infarct size according to single-photon emission computed tomography study with technetium Tc 99m sestamibi performed between 5 and 10 days after randomization in 347 patients (95.1%). Secondary end points included composite of death, recurrent MI, or stroke at 30 days. RESULTS: The final left ventricular infarct size was significantly smaller in patients assigned to the invasive group (median, 8.0%; interquartile range [IQR], 2.0%-15.8%) vs those assigned to the conservative group (median, 13.0%; IQR, 3.0%-27.0%; P<.001). The mean difference in final left ventricular infarct size between the invasive and conservative groups was -6.8% (95% confidence interval [CI], -10.2% to -3.5%). The secondary end points of death, recurrent MI, or stroke at 30 days occurred in 8 patients in the invasive group (4.4%) and 12 patients in the conservative group (6.6%) (relative risk, 0.67; 95% CI, 0.27-1.62; P = .37). CONCLUSION: An invasive strategy based on coronary stenting with adjunctive use of abciximab reduces infarct size in patients with acute STEMI without persistent symptoms presenting 12 to 48 hours after symptom onset.

Abciximab↗

PubMed2005

Gender and myocardial salvage after reperfusion treatment in acute myocardial infarction.

OBJECTIVES: The aim of this study was to investigate whether there are gender-associated differences in the amount of myocardial salvage after primary percutaneous coronary intervention (PCI) in patients with acute myocardial infarction (AMI). BACKGROUND: Despite having a more adverse cardiovascular risk profile, women with AMI have similar or even better outcomes after primary PCI compared with men. The reasons for these findings are unclear. METHODS: In this study we included 202 women and 561 men with AMI who underwent primary PCI in the setting of three randomized trials. The primary end point of the study was myocardial salvage index (proportion of initial perfusion defect salvaged by reperfusion therapy), obtained by paired scintigraphic studies performed 7 to 10 days apart. RESULTS: The amount of myocardium at risk or initial perfusion defect (median [25th, 75th percentiles]) did not differ significantly between women and men (22.0% [12.0, 40.0] vs. 24.0% [14.0, 39.0] of the left ventricle [LV], p = 0.26). Final infarct size, measured in the follow-up scintigraphy, was significantly smaller in women than in men (6.0% [0.71, 18.7] vs. 10.0% [3.9, 21.8] of the LV, p = 0.001). Myocardial salvage index was 0.64 (0.35, 0.95) in women versus 0.50 (0.26, 0.77) in men (p < 0.001). After adjustment for baseline characteristics, female gender was an independent predictor of greater myocardial salvage after PCI (p = 0.002). CONCLUSIONS: The efficacy of primary PCI in patients with AMI appears to be gender-dependent. Myocardial salvage achieved by primary PCI is greater in women than in men.

Aged↗

PubMed2005

Quantitative measurement of infarct size by contrast-enhanced magnetic resonance imaging early after acute myocardial infarction: comparison with single-photon emission tomography using Tc99m-sestamibi.

OBJECTIVES: The aim of this research was to evaluate kinetics and extent of myocardial contrast enhancement (CE) in comparison with single-photon emission computed tomography (SPECT) early after acute myocardial infarction (AMI). BACKGROUND: Quantification of infarct size serves as a surrogate end point in evaluating new therapies of AMI. Contrast-enhanced magnetic resonance imaging (CeMRI) of the myocardium is a promising new method for identification of irreversible tissue injury. METHODS: A total of 33 patients were examined by CeMRI and SPECT 7 +/- 2 days after AMI and successful coronary intervention. After gadolinium-diethylenetraimine pentaacetic acid injection (0.2 mmol/kg), continuous short-axis slices of the left ventricle (LV) were acquired every 7 min up to 42 min using different inversion times (TI). Myocardial CE at each imaging time point was quantified and compared with corresponding SPECT perfusion defect. RESULTS: All patients showed myocardial CE in the infarct region. A constant TI for CeMRI resulted in a decrease of signal intensity and extent of CE on late acquisitions. With TI adjustment, infarct image intensity peaked at 21 min with a contrast of 478% of remote myocardium and remained at this level up to 42 min after contrast injection (437%); CE extent was stable over time and agreed well with SPECT within an average difference of 3% of the LV myocardium, yielding the best correlation at 28 min (r = 0.86). CONCLUSIONS: In patients after AMI and successful reperfusion, CE is stable over time and matches well with SPECT perfusion defect; CeMRI under standardized conditions can accurately assess myocardial infarct size in vivo and may be attractive for serving as a surrogate end point early after AMI.

Adult↗

PubMed2005

Accuracy of cardiac PET imaging using post-injection transmission scan.

UNLABELLED: The purpose of this study was to investigate the accuracy of cardiac PET with post-injection transmission scans. METHODS: We performed a phantom study using 18F solution as well as 13N-ammonia PET study of ten patients. The average activities of no myocardial defect phantom model were estimated, and myocardial defect sizes of 12 phantom models were measured by pre- and post-injection transmission methods at various 18F activities. In 13N-ammonia PET at rest and during adenosine triphosphate (ATP) stress studies, measured defect sizes were compared between both methods. RESULTS: The ratios of average activity estimated by both methods (post/pre value) were almost 1.00 at each 18F activity and segment. Measured defect sizes by both methods showed an excellent correlation with true defect sizes (r = 0.98, p < 0.01 for pre vs. true value: r = 0.98, p < 0.01 for post vs. true value). The mean absolute errors of measurements were minimal up to 3.5% LV, and were similar between both methods. In 13N-ammonia PET, measured defect sizes by both methods also showed a good correlation (r = 0.97, p < 0.01). CONCLUSION: The results indicate that cardiac PET imaging with post-injection transmission scan provides information on myocardial tracer activity as well as myocardial defect size as does conventional pre-injection transmission method.

Adult↗

PubMed2005

Assessment of global and regional left ventricular function by electrocardiographic gated N-13 ammonia positron emission tomography in patients with coronary artery disease.

BACKGROUND: Electrocardiographic gated 13N-ammonia positron emission tomography (PET) enables simultaneous assessment of myocardial blood flow and left ventricular (LV) function. The aim of this study was to assess the accuracy of gated 13N-ammonia PET for evaluating global and regional LV function in patients with coronary artery disease (CAD) in comparison with conventional left ventriculography (LVG). METHODS AND RESULTS: Fifty-four patients with CAD underwent gated 13N-ammonia PET and LVG. The LV end-diastolic and end-systolic volumes (LVEDV, LVESV) and ejection fraction (LVEF) by gated 13N-ammonia PET were calculated using Cedars-Sinai automated quantitative gated single photon emission computed tomography (QGS) and compared with those obtained by LVG. The regional wall motion (RWM) was visually scored, and compared with that on LVG. There were good correlations between the 2 methods for LVEF, LVEDV and LVESV (R=0.828, R=0.821 and R=0.874 respectively). The RWM assessed by gated 13N-ammonia PET also agreed well with that by LVG (complete agreement was 70.4%, kappa=0.58). CONCLUSIONS: Gated 13N-ammonia PET combined with QGS works reasonably well for the assessment of both global and regional LV function in CAD patients, although additional calibration may be necessary.

Adult↗

PubMed2005

PET/CT: challenge for nuclear cardiology.

This review focuses on the clinical potential of PET/CT for the characterization of coronary artery disease. We describe the technical challenges of combining instrumentation with very different imaging performances and speculate on future clinical applications in the field of cardiology.

Cardiology↗

PubMed2004

Electrocardiographic-gated dual-isotope simultaneous acquisition SPECT using 18F-FDG and 99mTc-sestamibi to assess myocardial viability and function in a single study.

PURPOSE: Dual-isotope simultaneous acquisition single-photon emission computed tomography (DISA SPECT) with 18F-fluorodeoxyglucose (FDG) and (99m)Tc-sestamibi appears attractive for the detection of viable myocardium because it permits simultaneous assessment of glucose utilisation and perfusion. Another potential benefit of this approach is that the measurement of left ventricular (LV) function may be possible by ECG gating. The aim of this study was to test the hypothesis that both myocardial viability and LV function can be assessed by a single ECG-gated 18F-FDG/(99m)Tc-sestamibi DISA SPECT study, based on comparison with 18F-FDG/13N-ammonia positron emission tomography (PET) and magnetic resonance imaging (MRI) as reference techniques. METHODS: Thirty-three patients with prior myocardial infarction underwent ECG-gated 18F-FDG/(99m)Tc-sestamibi DISA SPECT and 18F-FDG/13N-ammonia PET on a single day. Of these, 25 patients also underwent cine-MRI to assess LV function. The LV myocardium was divided into nine regions, and each region was classified as viable or scar using a semiquantitative visual scoring system as well as quantitative analysis. The global and regional LV function measured by gated SPECT was compared with the results of MRI. RESULTS: There was good agreement in respect of viability (90-96%, kappa 0.74-0.85) between DISA SPECT and PET by either visual or quantitative analysis. Furthermore, although both global and regional LV function measured by gated SPECT agreed with those by MRI, (99m)Tc-sestamibi showed a closer correlation with MRI than did 18F-FDG. CONCLUSION: In conclusion, ECG-gated DISA SPECT provides information on myocardial viability, as well as global and regional LV function, similar to that obtained by PET and MRI.

Adult↗

PubMed2004

Assessment of right ventricular oxidative metabolism by PET in patients with idiopathic dilated cardiomyopathy undergoing cardiac resynchronization therapy.

PURPOSE: Right ventricular (RV) performance is known to have prognostic value in patients with congestive heart failure (CHF). Cardiac resynchronization therapy (CRT) has been found to enhance left ventricular (LV) energetics and metabolic reserve in patients with heart failure. The interplay between the LV and RV may play an important role in CRT response. The purpose of the study was to investigate RV oxidative metabolism, metabolic reserve and the effects of CRT in patients with CHF and left bundle brach block. In addition, the role of the RV in the response to CRT was evaluated. METHODS: Ten patients with idiopathic dilated cardiomyopathy who had undergone implantation of a biventricular pacemaker 8+/-5 months earlier were studied under two conditions: CRT ON and after CRT had been switched OFF for 24 h. Oxidative metabolism was measured using [11C]acetate positron emission tomography (Kmono). The measurements were performed at rest and during dobutamine-induced stress (5 microg/kg per minute). LV performance and interventricular mechanical delay (interventricular asynchrony) were measured using echocardiography. RESULTS: CRT had no effect on RV Kmono at rest (ON: 0.052+/-0.014, OFF: 0.047+/-0.018, NS). Dobutamine-induced stress increased RV Kmono significantly under both conditions but oxidative metabolism was more enhanced when CRT was ON (0.076+/-0.026 vs 0.065+/-0.027, p=0.003). CRT shortened interventricular delay significantly (45+/-33 vs 19+/-35 ms, p=0.05). In five patients the response to CRT was striking (32% increase in mean LV stroke volume, range 18-36%), while in the other five patients no response was observed (mean change +2%, range -6% to +4%). RV Kmono and LV stroke volume response to CRT correlated inversely (r=-0.66, p=0.034). None of the other measured parameters, including all LV parameters and electromechanical parameters, were associated with the response to CRT. In responders, RV Kmono with CRT OFF was significantly lower than in non-responders (0.036+/-0.01 vs 0.058+/-0.02, p=0.047). CONCLUSION: CRT appears to enhance RV oxidative metabolism and metabolic reserve during stress. Patients responding to CRT appear to have lower RV oxidative metabolism at rest, suggesting that the RV plays a significant role in the response to CRT.

Acetates↗

PubMed2004

The effects of cardiac resynchronization therapy on left ventricular function, myocardial energetics, and metabolic reserve in patients with dilated cardiomyopathy and heart failure.

OBJECTIVES: The effects of long-term cardiac resynchronization therapy (CRT) on left ventricular (LV) energetics and metabolic reserve were evaluated. BACKGROUND: Cardiac resynchronization therapy is a new therapy for patients with drug-refractory severe heart failure (HF). METHODS: Ten patients with idiopathic dilated cardiomyopathy who had undergone implantation of biventricular pacemaker 8 +/- 5 months earlier were studied during two conditions: CRT switched on, and after CRT was switched off for 24 h. Left ventricular function was measured using echocardiography and oxidative metabolism using [(11)C]acetate positron emission tomography. Both measurements were performed at rest and during dobutamine-induced stress (5 microg/kg/min). Basal- and adenosine-stimulated (140 microg/kg/min) myocardial blood flow were quantitated using [(15)O]water. RESULTS: During CRT off, LV stroke volume was significantly reduced at rest (72 +/- 18 ml vs. 63 +/- 15 ml, p < 0.05), but LV oxidative metabolism (K(mono)) remained unchanged (0.046 +/- 0.008 vs. 0.054 +/- 0.016 min(-1)) leading to a significant deterioration of myocardial efficiency of forward work (from 48.2 +/- 16.7 to 36.6 +/- 11.7 mm Hg.l/g, p < 0.05). During dobutamine-induced stress, stroke volume and K(mono) values were not different whether CRT was on or off. However, myocardial efficiency (56.1 +/- 16.1 vs. 49.8 +/- 18.0 mm Hg.ml.g(-1).min(-1), p = 0.099) and metabolic reserve, the response of K(mono) to dobutamine (0.023 +/- 0.014 vs. 0.013 +/- 0.014 min(-1), p = 0.09), tended to reduce when CRT was switched off. Cardiac resynchronization therapy had no effects on myocardial perfusion. Natriuretic peptides increased significantly during CRT-off period. CONCLUSIONS: Long-term CRT has beneficial effects on LV function and myocardial efficiency at rest in patients with HF. These effects are not associated with changes in myocardial perfusion or oxygen consumption. During dobutamine-induced stress, CRT does not affect functional parameters, but myocardial efficiency and metabolic reserve may be increased.

Carbon Radioisotopes↗

PubMed2004

Early administration of reteplase plus abciximab vs abciximab alone in patients with acute myocardial infarction referred for percutaneous coronary intervention: a randomized controlled trial.

CONTEXT: The optimal pharmacological strategy for bridging the delay between admission and performance of percutaneous coronary intervention (PCI) in patients with acute myocardial infarction (MI) is not known. OBJECTIVE: To assess whether early administration of reteplase plus abciximab produces better results compared with abciximab alone in patients with acute MI referred for PCI. DESIGN, SETTING, AND PATIENTS: Open-label, randomized controlled study conducted from May 3, 2001, through June 2, 2003, of 253 patients who were admitted to 13 community hospitals without catheterization facilities (n = 186) and to 5 hospitals with catheterization facilities (n = 67), with the diagnosis of an ST-segment elevation acute MI within 12 hours from onset of symptoms. INTERVENTIONS: Patients received intravenously either the combination of a half-dose reteplase (two 5-U boluses, 30 minutes apart) with a standard dose of abciximab (0.25 mg/kg bolus, 0.125 microg/kg per minute infusion [maximum 10 microg/min for 12 hours]) or the standard dose of abciximab alone; all patients were then transferred for PCI. MAIN OUTCOME MEASURE: Final infarct size according to a single-photon emission computed tomography study with technetium Tc 99m sestamibi performed between 5 and 10 days after randomization in 228 patients (90.1% of entire sample). RESULTS: Of the 253 patients enrolled, 125 were assigned to reteplase plus abciximab and 128 to abciximab alone. The median (interquartile range) of the final infarct size of the left ventricle was 13.0% (3.0%-28.0%) in the reteplase plus abciximab group and 11.5% (3.0%-26.3%) in the abciximab-alone group (P =.81). The mean difference in final infarct size of left ventricle between the reteplase plus abciximab group and the abciximab group was 1.3% (95% confidence interval [CI], -3.1% to 5.7%). Within 6 months after randomization, the composite secondary end point of death, recurrent MI, or stroke occurred in 8 patients (6.4%) in the reteplase plus abciximab group and 6 patients (4.7%) in the abciximab group (relative risk, 1.4; 95% CI, 0.5-3.9; log-rank P =.56). Major bleeding complications were observed in 7 patients (5.6%) in the reteplase plus abciximab group and 2 patients (1.6%) in the abciximab group (P =.16). CONCLUSION: Early administration of reteplase plus abciximab does not lead to a reduction of infarct size compared with abciximab alone in patients with acute MI referred for PCI.

Abciximab↗

PubMed2004

Relation of coronary vasoreactivity and coronary calcification in asymptomatic subjects with a family history of premature coronary artery disease.

Electron-beam computed tomography (EBCT) allows non-invasive imaging of coronary calcification and has been promoted as a screening tool for coronary artery disease (CAD) in asymptomatic high-risk subjects. This study assessed the relation of coronary calcifications to alterations in coronary vascular reactivity by means of positron emission tomography (PET) in asymptomatic subjects with a familial history of premature CAD. Twenty-one subjects (mean age 51+/-10 years) underwent EBCT imaging for coronary calcifications expressed as the coronary calcium score (CCS according to Agatston) and rest/adenosine-stress nitrogen-13 ammonia PET with quantification of myocardial blood flow (MBF) and coronary flow reserve (CFR). The mean CCS was 237+/-256 (median 146, range 0-915). The CCS was <100 in eight subjects and >100 units in 13. As defined by age-related thresholds, 15 subjects had an increased CCS (>75th percentile). Overall mean resting and stress MBF and CFR were 71+/-16 ml 100 g(-1) min(-1), 218+/-54 ml 100 g(-1) min(-1) and 3.20+/-0.77, respectively. Three subjects with CCS ranging from 114 to 451 units had an abnormal CFR (<2.5). There was no relation between CCS and resting or stress MBF or CFR ( r=0.17, 0.18 and 0.10, respectively). In asymptomatic subjects a pathological CCS was five times more prevalent than an abnormal CFR. The absence of any close relationship between CCS and CFR reflects the fact that quantitative myocardial perfusion imaging with PET characterises the dynamic process of vascular reactivity while EBCT is a measure of more stable calcified lesions in the arterial wall whose presence is closely related to age.

Age Factors↗

PubMed2004

The influence of myocardial blood flow and volume of distribution on late Gd-DTPA kinetics in ischemic heart failure.

PURPOSE: To determine the mechanism of enhancement of contrast-enhanced MRI (ceMRI) in chronic ischemic myocardium. While ceMRI can identify scar tissue in chronic ischemic myocardium, the mechanism of enhancement is not completely understood. MATERIALS AND METHODS: A total of 11 patients with ischemic heart failure (ejection fraction [EF] 28 +/- 9%) were imaged with ceMRI and positron emission tomography (PET) to measure myocardial blood flow (MBF). Longitudinal relaxation rate (T1) of blood, normal tissue, and scar tissue defined by ceMRI was determined before and two to 50 minutes after contrast (Look Locker technique), and the partition coefficient (lambda) and volume of distribution (VD) were calculated. RESULTS: In scar and viable tissue, T1 was significantly different over the whole period after contrast, but not before contrast. However, T1 of scar and blood were similar five to 15 minutes post contrast, making the detection of subendocardial defects difficult. lambda reached an initial steady state in viable tissue, but was delayed (20 minutes) in scar tissue. VD in scar was double that of viable tissue (0.54 +/- 0.01 vs. 0.29 +/- 0.02, respectively) indicating an increased interstitial space. Contrast wash-in kinetics correlated moderately with MBF (r = -0.36), but well with the combination of MBF and VD (r = 0.59). CONCLUSION: Late myocardial contrast kinetics depend on both MBF and VD; however the increased VD seems to be the main mechanism for the late enhancement effect.

Blood Volume↗

PubMed2004

Presence of sympathetically denervated but viable myocardium and its electrophysiologic correlates after early revascularised, acute myocardial infarction.

AIMS: After acute myocardial infarction (AMI), regional denervation exceeding the scar area has been described. We sought to define the electrophysiologic correlates of denervated, but viable, myocardium by combining scintigraphic imaging with extensive electrocardiographic evaluation in AMI patients treated with early reperfusion therapy. METHODS AND RESULTS: Within 14 days after AMI, 67 consecutive patients underwent radionuclide imaging of myocardial resting perfusion using (201)thallium and of presynaptic sympathetic innervation using (123)I-metaiodobenzylguanidine (MIBG). The mean left ventricular ejection fraction was 58+/-15%. Electrophysiologic studies included evaluation of ventricular repolarisation (resting ECG), depolarisation (signal-averaged ECG), and 24-h Holter monitoring. The perfusion defect, innervation defect, and perfusion/innervation mismatch size of the left ventricle were 14+/-15%, 39+/-22%, and 26+/-16%, respectively. Mismatch was present in 60/67 patients (90%) and correlated with prolonged repolarisation defined by QTc interval (r = 0.40; P < 0.001), and with indexes of delayed depolarisation from signal-averaged ECG (r = -0.32; P = 0.014). Other electrophysiologic parameters did not correlate. During follow-up (4.3+/-1 years) event rates were low, with two cardiac deaths and no severe ventricular arrhythmia causing hospitalisation. CONCLUSIONS: After early reperfusion for myocardial infarction, viable but denervated myocardium is frequent and correlates with slow depolarisation and repolarisation. However, in patients with small infarct size and preserved left ventricular function, these findings seem to have little influence on outcome.

3-Iodobenzylguanidine↗