146 resultados para Ventricular Ejection Fraction
em Université de Lausanne, Switzerland
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AIMS: Patients with well-tolerated sustained monomorphic ventricular tachycardia (SMVT) and left ventricular ejection fraction (LVEF) over 30% may benefit from a primary strategy of VT ablation without immediate need for a 'back-up' implantable cardioverter-defibrillator (ICD). METHODS AND RESULTS: One hundred and sixty-six patients with structural heart disease (SHD), LVEF over 30%, and well-tolerated SMVT (no syncope) underwent primary radiofrequency ablation without ICD implantation at eight European centres. There were 139 men (84%) with mean age 62 ± 15 years and mean LVEF of 50 ± 10%. Fifty-five percent had ischaemic heart disease, 19% non-ischaemic cardiomyopathy, and 12% arrhythmogenic right ventricular cardiomyopathy. Three hundred seventy-eight similar patients were implanted with an ICD during the same period and serve as a control group. All-cause mortality was 12% (20 patients) over a mean follow-up of 32 ± 27 months. Eight patients (40%) died from non-cardiovascular causes, 8 (40%) died from non-arrhythmic cardiovascular causes, and 4 (20%) died suddenly (SD) (2.4% of the population). All-cause mortality in the control group was 12%. Twenty-seven patients (16%) had a non-fatal recurrence at a median time of 5 months, while 20 patients (12%) required an ICD, of whom 4 died (20%). CONCLUSION: Patients with well-tolerated SMVT, SHD, and LVEF > 30% undergoing primary VT ablation without a back-up ICD had a very low rate of arrhythmic death and recurrences were generally non-fatal. These data would support a randomized clinical trial comparing this approach with others incorporating implantation of an ICD as a primary strategy.
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AIMS: Estimates of the left ventricular ejection fraction (LVEF) in patients with life-threatening ventricular arrhythmias related to coronary artery disease (CAD) have rarely been reported despite it has become the basis for determining patient's eligibility for prophylactic defibrillator. We aimed to determine the extent and distribution of reduced LVEF in patients with sustained ventricular tachycardia or ventricular fibrillation. METHODS AND RESULTS: 252 patients admitted for ventricular arrhythmia related to CAD were included: 149 had acute myocardial infarction (MI) (Group I, 59%), 54 had significant chronic obstructive CAD suggestive of an ischaemic arrhythmic trigger (Group II, 21%) and 49 patients had an old MI without residual ischaemia (Group III, 19%). 34% of the patients with scar-related arrhythmias had an LVEF > or =40%. Based on pre-event LVEF evaluation, it can be estimated that less than one quarter of the whole study population had a known chronic MI with severely reduced LVEF. In Group III, the proportion of inferior MI was significantly higher than anterior MI (81 vs. 19%; absolute difference, -62; 95% confidence interval, -45 to -79; P < or = 0.0001), though median LVEF was higher in inferior MI (0.37 +/- 10 vs. 0.29 +/- 10; P = 0.0499). CONCLUSION: Patients included in defibrillator trials represent only a minority of the patients at risk of sudden cardiac death. By applying the current risk stratification strategy based on LVEF, more than one third of the patients with old MI would not have qualified for a prophylactic defibrillator. Our study also suggests that inferior scars may be more prone to ventricular arrhythmia compared to anterior scars.
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BACKGROUND: Improved survival after prophylactic implantation of a defibrillator in patients with reduced left ventricular ejection fraction (EF) after myocardial infarction (MI) has been demonstrated in patients who experienced remote MIs in the 1990s. The absolute survival benefit conferred by this recommended strategy must be related to the current risk of arrhythmic death, which is evolving. This study evaluates the mortality rate in survivors of MI with impaired left ventricular function and its relation to pre-hospital discharge baseline characteristics. METHODS: The clinical records of patients who had sustained an acute MI between 1999 and 2000 and had been discharged from the hospital with an EF of < or = 40% were included. Baseline characteristics, drug prescriptions, and invasive procedures were recorded. Bivariate and multivariate analyses were performed using a primary end point of total mortality. RESULTS: One hundred sixty-five patients were included. During a median follow-up period of 30 months (interquartile range, 22 to 36 months) 18 patients died. The 1-year and 2-year mortality rates were 6.7% and 8.6%, respectively. Variables reflecting coronary artery disease and its management (ie, prior MI, acute reperfusion, and complete revascularization) had a greater impact on mortality than variables reflecting mechanical dysfunction (ie, EF and Killip class). CONCLUSIONS: The mortality rate among survivors of MIs with reduced EF was substantially lower than that reported in the 1990s. The strong decrease in the arrhythmic risk implies a proportional increase in the number of patients needed to treat with a prophylactic defibrillator to prevent one adverse event. The risk of an event may even be sufficiently low to limit the detectable benefit of defibrillators in patients with the prognostic features identified in our study. This argues for additional risk stratification prior to the prophylactic implantation of a defibrillator.
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OBJECTIVES: We assessed the clinical characteristics of patients with acute ischemic stroke (AIS) with left ventricular ejection fraction (EF) ≤ 35% and investigated the association of low EF with early and long-term outcome. METHODS: A total of 2439 patients of the Acute Stroke Registry and Analysis of Lausanne (ASTRAL) were selected. Demographics, risk factors, pre-stroke treatment, and clinical, radiological and metabolic variables in patients with and without low EF were compared. Functional independence (modified Rankin Score ≤ 2) and mortality were recorded 1 week up to 12 months from admission. RESULTS: Low EF patients (n=119) were more commonly men, older, had higher rates of coronary artery disease and atrial fibrillation (AF), and more frequent pretreatment with anticoagulants, antiplatelets and antihypertensive agents. On admission, they presented with higher stroke severity and had lower values of systolic blood pressure, higher heart rate, and worse estimated glomerular filtration rate. Stroke-related disability and death rates were higher in low EF patients during follow-up (19.5% vs. 7.8% at 1 week, and 36.1% vs. 16.5% at 12 months). Increasing age, stroke severity, and AF were independent predictors of one-year mortality in these patients while prior use of statins had a favorable effect on early mortality. CONCLUSIONS: AIS in patients with low EF is associated with older age, cardiac comorbidities, and more severe clinical presentation. Low EF can identify a subset of AIS patients at high risk of early and long-term functional disability and mortality.
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BACKGROUND: Intracoronary injection of autologous bone marrow-derived mononucleated cells (BM-MNC) may improve LV function shortly after acute ST elevation myocardial infarction (STEMI), but little is known about the long-term durability of the treatment effect. METHODS: In a single-centre trial a total of 60 patients with acute anterior STEMI, successful reperfusion therapy and a left ventricular ejection fraction (LVEF) of <50% were screened for the study. 23 patients were actively treated with intracoronary infusion of BM-MNC within a median of 3 days. The open-label control group consisted of 19 patients who did not consent to undergo BM-MNC treatment but agreed to undergo regular clinical and echocardiographic follow-up for up to 5 years after AMI. RESULTS: Whereas at 4 months there was no significant difference between the increase in LVEF in the BM-MNC group and the control group (+7.0%, 95%CI 3.6; 10.4) vs. +3.9%, 95%CI -2.1; 10), the absolute increase at 5 years remained stable in the BM-MNC but not in the control group (+7.95%, 95%CI 3.5; 12.4 vs. -0.5%, 95%CI -5.4; 4.4; p for interaction between groups = 0.035). DISCUSSION: In this single-centre, open-labelled study, intracoronary administration of BM-MNC is feasible and safe in the short term. It is also associated with sustained improvement of left ventricular function in patients with acute myocardial infarction, encouraging phase III studies to examine the potential BM-MNC effect on clinical outcome.
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Introduction : La diminution de la fraction d'éjection après infarctus du myocarde est-elle suffisante pour justifier l'implantation prophylactique de défibrillateur ? Introduction: La diminution de la fraction d'éjection (FE) est un facteur prédictif majeur de mortalité cardiaque chez les patients avec ancien infarctus du myocarde (IM). Les plus récentes études, pour la plupart conduites à la fin des années 90, montrent une diminution de la mortalité post-hospitalière à 10 à 20% par année. Une amélioration de la survie par implantation prophylactique de défibrillateurs a été démontrée chez les patients avec dysfonction myocardique avancée après ancien IM dans la cadre de l'étude MADIT II (Multicenter Automatic Defibrillator Implantation Trial) et est depuis lors, considérée comme une thérapie recommandée. Le bénéfice de l'implantation prophylactique de défibrillateurs en terme de nombre nécessaire de patients à traiter pour prévenir un évènement est d'un intérêt primordial en raison des complications potentielles liées à la procédure et l'appareillage, des implications psychologiques ainsi qu'en raison de l'analyse coût-efficacité. Le nombre de patients à traiter est corrélé au risque actuel de mortalité rythmique, probablement influencé par les récentes avancées thérapeutiques dans la prise en charge aigue de l'IM (notamment par angioplastie primaire) et de l'insuffisance cardiaque. Or, dans '' l'étude MADIT II, le recrutement des patients était effectué entre 1997 et 2001 et l'intervalle moyen entre l'IM et le recrutement était de plus de 6 ans. Le but de l'étude était donc d'évaluer, dans la pratique générale, la mortalité actuelle de patients ayant survécu à un IM avec diminution consécutive significative de la FE. La stratification du risque sur la base des variables hospitalières a de même été explorée. Méthode: Une analyse de cohorte de patients avec infarctus aigu du myocarde admis de 1999 à 2000 a été effectuée dans 2 centres hospitaliers (un universitaire et un cantonal). Tous les dossiers cliniques des patients sortis d'hôpital avec FE documentée ≤ 0.40 ont été inclus. Les caractéristiques des patients, les procédures diagnostiques et thérapeutiques ainsi que la médication étaient reportées. La période de suivi débutait à la sortie d'hôpital. Les end-points primaires étaient la mortalité globale, la mortalité cardiaque et les morts subites. Une analyse bivariée et multivariée a été effectuée. Résultats: 165 patients ont été inclus. Durant un suivi médian de 30 mois (interquartile range 22-36), 18 patients sont décédés (5 morts classifiées comme cardiaques, 8 comme subites, 5 de causes non cardiaques). Les taux de mortalité à un et deux ans selon analyse de Kaplan-Meier étaient de 6.7 et 8.6%, respectivement. Les variables reflétant l'atteinte coronarienne et sa prise en charge (antécédent d'IM, reperfusion aigue, revascularisation complète) étaient plus significativement associées à la mortalité comparées aux variables reflétant la dysfonction myocardique (FE, classe Killip à l'admission). Conclusion : La mortalité des patients ayant survécu à un IM avec dysfonction myocardique avancée a diminué de façon substantielle depuis la fin des années 90. La diminution de la mortalité rythmique implique une augmentation proportionnelle du nombre de patients à traiter par implantation de défibrillateur pour prévenir un évènement. Par ailleurs, une stratification du risque après IM basée uniquement sur la FE semble être inappropriée au vu de son impact mineur sur la mortalité comparé aux autres facteurs de risque identifiés dans notre étude. Les patients sans antécédents d'infarctus et ceux ayant bénéficié d'une revascularisation aigue ou complète avait une mortalité cumulée à 2 ans de, respectivement, 2.5%, 3.9% et 2.3%. Pour ce type de patients à bas risque le bénéfice de l'implantation prophylactique de défibrillateur doit être remis en question. Au vu de cette étude, une stratification additionnelle du risque avant implantation de défibrillateur est à considérer.
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BACKGROUND: The impact of preoperative impaired left ventricular ejection fraction (EF) in octogenarians following coronary bypass surgery on short-term survival was evaluated in this study. METHODS: A total of 147 octogenarians (mean age 82.1 ± 1.9 years) with coronary artery diseases underwent elective coronary artery bypass graft between January 2000 and December 2009. Patients were stratified into: Group I (n = 59) with EF >50%, Group II (n = 59) with 50% > EF >30% and in Group III (n = 29) with 30% > EF. RESULTS: There was no difference among the three groups regarding incidence of COPD, renal failure, congestive heart failure, diabetes, and preoperative cerebrovascular events. Postoperative atrial fibrillation was the sole independent predictive factor for in-hospital mortality (odds ratio (OR), 18.1); this was 8.5% in Group I, 15.3% in Group II and 10.3% in Group III. Independent predictive factors for mortality during follow up were: decrease of EF during follow-up for more that 5% (OR, 5.2), usage of left internal mammary artery as free graft (OR, 18.1), and EF in follow-up lower than 40% (OR, 4.8). CONCLUSIONS: The results herein suggest acceptable in-hospital as well short-term mortality in octogenarians with impaired EF following coronary artery bypass grafting (CABG) and are comparable to recent literature where the mortality of younger patients was up to 15% and short-term mortality up to 40%, respectively. Accordingly, we can also state that in an octogenarian cohort with impaired EF, CABG is a viable treatment with acceptable mortality.
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While the lesions produced by transmyocardial laser revascularisation (TMLR) induce scar formation, it is important to determine whether this procedure can be deleterious for the left-ventricular function, which is already impaired by the underlying ischaemic process in some patients. Ten channels were drilled in the left lateral wall of the hearts of ten pigs (mean weight, 61 +/- 8.2kg) with a Holmium:YAG laser. Haemodynamic measurements and echocardiographic assessment of left-ventricular function were performed before the TMLR procedure, 5 and 30 min after, and lastly after 5 min of pacing at a rate increased by 30% of the baseline value. Echocardiographic assessment was in the short axis at the level of the laser channels, and included left-ventricular ejection fraction and segmental wall motility of the lasered area (scale 0-3:0 = normal 1 = hypokinesia, 2 = akinesia, 3 = dyskinesia). Values at 5 and 30 min were compared with baseline values; the difference was considered significant if p < 0.05. Haemodynamical values were stable throughout all the procedures. The ejection fraction showed a slight but significant decrease 5 min after the creation of the channels (60.4 +/- 6.8% vs 54 +/- 7.6%, p=0.02) and recovered at 30min. The segmental motility score of the involved areas increased to 1 after 5 min in five animals, and came back to 0 at 30 min except in one animal. Even with pacing no segmental dysfunction occurred. The reversibility of the segmental hypokinesia induced by TMLR, as well as the absence of pace-induced dysfunction 30 min after the procedure strongly suggest the inocuity of TMLR in this experimental set-up.
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A crucial method for investigating patients with coronary artery disease (CAD) is the calculation of the left ventricular ejection fraction (LVEF). It is, consequently, imperative to precisely estimate the value of LVEF--a process that can be done with myocardial perfusion scintigraphy. Therefore, the present study aimed to establish and compare the estimation performance of the quantitative parameters of the reconstruction methods filtered backprojection (FBP) and ordered-subset expectation maximization (OSEM). METHODS: A beating-heart phantom with known values of end-diastolic volume, end-systolic volume, and LVEF was used. Quantitative gated SPECT/quantitative perfusion SPECT software was used to obtain these quantitative parameters in a semiautomatic mode. The Butterworth filter was used in FBP, with the cutoff frequencies between 0.2 and 0.8 cycles per pixel combined with the orders of 5, 10, 15, and 20. Sixty-three reconstructions were performed using 2, 4, 6, 8, 10, 12, and 16 OSEM subsets, combined with several iterations: 2, 4, 6, 8, 10, 12, 16, 32, and 64. RESULTS: With FBP, the values of end-diastolic, end-systolic, and the stroke volumes rise as the cutoff frequency increases, whereas the value of LVEF diminishes. This same pattern is verified with the OSEM reconstruction. However, with OSEM there is a more precise estimation of the quantitative parameters, especially with the combinations 2 iterations × 10 subsets and 2 iterations × 12 subsets. CONCLUSION: The OSEM reconstruction presents better estimations of the quantitative parameters than does FBP. This study recommends the use of 2 iterations with 10 or 12 subsets for OSEM and a cutoff frequency of 0.5 cycles per pixel with the orders 5, 10, or 15 for FBP as the best estimations for the left ventricular volumes and ejection fraction quantification in myocardial perfusion scintigraphy.
Compressed Sensing Single-Breath-Hold CMR for Fast Quantification of LV Function, Volumes, and Mass.
Resumo:
OBJECTIVES: The purpose of this study was to compare a novel compressed sensing (CS)-based single-breath-hold multislice magnetic resonance cine technique with the standard multi-breath-hold technique for the assessment of left ventricular (LV) volumes and function. BACKGROUND: Cardiac magnetic resonance is generally accepted as the gold standard for LV volume and function assessment. LV function is 1 of the most important cardiac parameters for diagnosis and the monitoring of treatment effects. Recently, CS techniques have emerged as a means to accelerate data acquisition. METHODS: The prototype CS cine sequence acquires 3 long-axis and 4 short-axis cine loops in 1 single breath-hold (temporal/spatial resolution: 30 ms/1.5 × 1.5 mm(2); acceleration factor 11.0) to measure left ventricular ejection fraction (LVEFCS) as well as LV volumes and LV mass using LV model-based 4D software. For comparison, a conventional stack of multi-breath-hold cine images was acquired (temporal/spatial resolution 40 ms/1.2 × 1.6 mm(2)). As a reference for the left ventricular stroke volume (LVSV), aortic flow was measured by phase-contrast acquisition. RESULTS: In 94% of the 33 participants (12 volunteers: mean age 33 ± 7 years; 21 patients: mean age 63 ± 13 years with different LV pathologies), the image quality of the CS acquisitions was excellent. LVEFCS and LVEFstandard were similar (48.5 ± 15.9% vs. 49.8 ± 15.8%; p = 0.11; r = 0.96; slope 0.97; p < 0.00001). Agreement of LVSVCS with aortic flow was superior to that of LVSVstandard (overestimation vs. aortic flow: 5.6 ± 6.5 ml vs. 16.2 ± 11.7 ml, respectively; p = 0.012) with less variability (r = 0.91; p < 0.00001 for the CS technique vs. r = 0.71; p < 0.01 for the standard technique). The intraobserver and interobserver agreement for all CS parameters was good (slopes 0.93 to 1.06; r = 0.90 to 0.99). CONCLUSIONS: The results demonstrated the feasibility of applying the CS strategy to evaluate LV function and volumes with high accuracy in patients. The single-breath-hold CS strategy has the potential to replace the multi-breath-hold standard cardiac magnetic resonance technique.
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Morphological and functional effects of transmyocardial laser revascularization (TMLR) are analyzed in an acute setting on a porcine model. Ten channels were drilled in the left lateral wall of the heart of 15 pigs (mean weight, 73 +/- 4 kg) with a Holmium-YAG laser (wavelength: 2.1 mu, probe diameter: 1.75 mm). Echocardiographic control was performed before the TMLR procedure as well as 5 min and 30 min thereafter. Echocardiographic parameters were recorded in short-axis at the level of the laser channels, and included left ventricular ejection fraction, fractional shortening and segmental wall motility of the channels' area (scale 0-3: 0 = normal, 1 = hypokinesia, 2 = akinesia, 3 = dyskinesia). After sacrifice the lased region was sliced perpendicularly to the channels for histological and morphometrical analysis. Five minutes after the drilling of the channels, all the echocardiographic index worsened significantly in comparison with baseline values (p < 0.01). All recovered after 30 min and showed no difference with baseline values. Cross-section of the channel lesions measured 8.8 +/- 2.4 mm2 which is more than three times that of the probe (p < 0.01). In acute conditions, the lesions due to the TMLR probe are significantly larger than the probe itself and cause a transient drop of the segmental wall motility on a healthy myocardium. These results suggest that TMLR should be used cautiously in the clinical setting for patients with an impaired ventricular function.
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The importance of the right ventricle as a determinant of clinical symptoms, exercise capacity, peri-operative survival and postoperative outcome has been underestimated for a long time. Right ventricular ejection fraction has been used as a measure of right ventricular function but has been found to be dependent on loading conditions, ventricular interaction as well as on myocardial structure. Altered left ventricular function in patients with valvular disease influences right ventricular performance mainly by changes in afterload but also by ventricular interaction. Right ventricular function and regional wall motion can be determined with right ventricular angiography, radionuclide ventriculography, two-dimensional echocardiography or magnetic resonance imaging. However, the complex structure of the right ventricle and its pronounced translational movements render quantification difficult. True regional wall motion analysis is, however, possible with myocardial tagging based on magnetic resonance techniques. With this technique a baso-apical shear motion of the right ventricle was observed which was enhanced in patients with aortic stenosis.
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OBJECTIVE. The purpose of our study was to evaluate hepatic, gastrointestinal, and cardiac toxicity after PRECISION transarterial chemoembolization (TACE) with drug-eluting beads (DEB) versus conventional TACE with doxorubicin in the treatment of intermediate-stage hepatocellular carcinoma (HCC).SUBJECTS AND METHODS. Two hundred twelve patients (185 men and 27 women; mean age, 67 years) were randomized to TACE with DEB or conventional TACE. The majority of patients (67% in both groups) presented in a more advanced stage. Safety was measured by rate of adverse events (Southwest Oncology Group criteria) and changes in laboratory parameters. Cardiotoxicity was assessed with left ventricular ejection fraction (LVEF) mainly on MRI or echocardiography.RESULTS. The mean maximum postchemoembolization alanine transaminase increase in the DEB group was 50% less than in the conventional TACE group (p < 0.001) and 41% less in respect to aspartate transaminase (p < 0.001). End-of-study values returned to approximately baseline levels but with greater variability in conventional TACE patients. Treatment-emergent adverse events in the hepatobiliary system organ class occurred in 16.1% of DEB group patients compared with 25% of conventional TACE patients. There were fewer liver toxicity events in the DEB group. There was a small but statistically significant difference in mean change from baseline in LVEF between the two groups of 4 percentage points for the conventional TACE group (95% CI, 0.71-7.3; p = 0.018).CONCLUSION. PRECISION TACE with DEB loaded with doxorubicin offers a safe therapy option for intermediate-stage HCC, even in patients with more advanced liver disease.
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The goal of this follow-up study was to assess the long-term survival of all patients having undergone a first PTCA between 1981 and 1990 and to relate the outcome to the baseline clinical and angiographic state. Although PTCA has become a widely accepted therapeutic choice for revascularization, the authors lacked information on long-term outcome. Data was collected by questionnaire, the end points being a second PTCA, MI, CABG, death or any of these events. The survival curves were constructed using the Kaplan-Meier method. Multivariate analysis was performed by a Cox proportional hazards model. Complete follow-up data were collected for 1,071 patients for a mean period of 7.4 years (SEM +/- 1.98 months) with a range of 0 to 14 years. Mean age was 57 years. PTCA was successful in 85% of patients. In-hospital event rates were death 1.3%, MI 4.4%, and emergency CABG 2.9%. Overall survival at 14 years was 69% (SEM +/- 9.6%) and event-free survival was 47% (SEM +/- 5.8%). MI rate was 11%, CABG 15%, and 20% of patients underwent repeat PTCA. Presence of cardiovascular risk factors, poor left ventricular ejection fraction, and prior CABG were significantly associated with poorer event-free survival. The short-term observations are consistent with results reported by the other follow-up studies. In addition, the study found a total survival rate 14 years after a first PTCA of 69% and 47% of the cohort remained event free.
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PURPOSE: The aim of the study was to determine whether glucose uptake in viable myocardium of ischemic cardiomyopathy patients depends on rest myocardial blood flow (MBF) and the residual myocardial flow reserve (MFR). METHODS: Thirty-six patients with ischemic cardiomyopathy (left ventricular ejection fraction 25 ± 10 %) were studied with N-ammonia and F-fluorodeoxyglucose (FDG) positron emission tomography (PET). Twenty age-matched normals served as controls. Regional MBF was determined at rest and during dipyridamole hyperemia and regional FDG extraction was estimated from regional FDG to N-ammonia activity ratios. RESULTS: Rest MBF was reduced in viable (0.42 ± 0.18 ml/min per g) and nonviable regions (0.32 ± 0.09 ml/min per g) relative to remote regions (0.68 ± 0.23 ml/min per g, p < 0.001) and to normals (0.63 ± 0.13 ml/min per g). Dipyridamole raised MBFs in controls, remote, viable, and nonviable regions. MBFs at rest (p < 0.05) and stress (p < 0.05) in viable regions were significantly higher than that in nonviable regions, while MFRs did not differ significantly (p > 0.05). Compared to MFR in remote myocardium, MFRs in viable regions were similar (1.39 ± 0.56 vs 1.70 ± 0.45, p > 0.05) but were significantly lower in nonviable regions (1.23 ± 0.43, p < 0.001). Moreover, the FDG and thus glucose extraction was higher in viable than in remote (1.40 ± 0.14 vs 0.90 ± 0.20, p < 0.001) and in nonviable regions (1.13 ± 0.21, p < 0.001). The extraction of FDG in viable regions was independent of rest MBF but correlated inversely with MFRs (r =-0.424, p < 0.05). No correlation between the FDG extraction and MFR was observed in nonviable regions. CONCLUSION: As in the animal model, decreasing MFRs in viable myocardium are associated with increasing glucose extraction that likely reflects a metabolic adaptation of remodeling hibernating myocytes.