Severe regional ischemia alters coronary flow reserve in the remote perfusion area

BACKGROUND: Clinical and experimental studies suggest that coronary flow reserve (CFR) may be abnormal in regions remote from myocardial infarction. We sought to determine the possible relation among stenosis severity, ischemic dysfunction, and impairment of CFR in remote regions. METHODS AND RESULTS: In 7 open-chest dogs, acute graded left circumflex (LCX) ischemia was created and maintained based on measurement of the transstenotic (aortic-distal LCX) pressure gradient (measured in millimeters of mercury). Regional thickening was assessed with sonomicrometers. Regional myocardial flow was assessed at rest with radiolabeled microspheres. Doppler flow probes were placed on proximal LCX and left anterior descending (LAD) arteries to measure resting flow and CFR in response to intracoronary injection of adenosine (36 microg). These parameters were assessed under baseline conditions and during transstenotic gradients of 10, 20, 30, and 40 mm Hg. Increasing LCX stenosis severity caused progressive impairment of LCX CFR: baseline (2.22+/-0.10), stenosis 10 (1.80+/-0.06), stenosis 20 (1.56+/-0.08), stenosis 30 (1.30+/-0.04), and stenosis 40 (1.17+/-0.06) (P<.01 vs. baseline). Remote LAD CFR was not altered by mild to moderate LCX stenosis (baseline [2.33+/-0.19]; stenosis 10 [2.30+/-0.25]; stenosis 20 [2.15+/-0.26]). However, critical LCX stenosis producing mild to moderate reduction in thickening in the ischemic region was associated with a significant impairment of LAD CFR: stenosis 30 (1.90+/-0.26) and stenosis 40 (1.80+/-0.22) (P<.01 vs. baseline). These changes in remote CFR persisted after correction for changes in the rate-pressure product. CONCLUSION: In an acute canine model of progressive LCX coronary stenosis, CFR was impaired in both ischemic and remote nonischemic regions in association with mild to moderate ischemic-induced regional myocardial dysfunction. Thus pharmacologic vasodilation provoked only mild heterogeneity in CFR in the presence of a critical LCX stenosis as a result of concurrent reduction of LAD CFR. This phenomenon warrants further clinical and experimental investigation because it may affect detection of flow heterogeneity during acute ischemia (which induced myocardial dysfunction).     

Resolution of perfusion defects with antiischemic medical therapy

Conclusion  Myocardial ischemia has been clearly associated with an increased risk of cardiac events. Traditionally, patients showing evidence of ischemia have been treated with revascularization in an attempt to reduce this risk. However, recent studies have shown that antiischemic medications can reduce the extent of stress-induced scintigraphic ischemia and that this reduction may actually reduce risk and improve long-term outcome^1,2. Our report illustrates the effectiveness of medical therapy insuppressing myocardial ischemia and demonstrates the value of nuclear myocardial perfusion imaging in the management and observation of patients with underlying coronary artery disease.     

Incremental prognostic value of coronary flow reserve assessed with single-photon emission computed tomography

Background  

We assessed the prognostic value of coronary flow reserve (CFR) estimated by single-photon emission computed tomography (SPECT) in patients with suspected myocardial ischemia.     

Sex differences in myocardial oxygen and glucose metabolism

Background  Both physiologic and pathophysiologic conditions affect the myocardium’s substrate use and, consequently, its structure, function, and adaptability. The effect of sex on myocardial oxygen, glucose, and fatty acid metabolism in humans is unknown. Methods and Results  We studied 25 young subjects (13 women and 12 men) using positron emission tomography, quantifying myocardial blood flow, myocardial oxygen consumption (MVO₂), and glucose and fatty acid extraction and metabolism. MVO₂ was higher in women than in men (5.74±1.08 μmol·g⁻¹·min⁻¹ vs 4.26±0.69 μmol·g⁻¹·min⁻¹,P<.005). Myocardial glucose extraction fraction and utilization were lower in women than in men (0.025±0.019 vs 0.062±0.028 [P<.001] and 133±96 nmol·g⁻¹·min⁻¹ vs 287±164 nmol·g⁻¹·min⁻¹ [P<.01], respectively). There were no sex differences in myocardial blood flow, fatty acid metabolism, or plasma glucose, fatty acid, or insulin levels. Female sex was an independent predictor of increased MVO₂ (P=.01) and decreased myocardial glucose extraction fraction and utilization (P<.005 andP<.05, respectively). Insulin sensitivity was an independent predictor of increased myocardial glucose extraction fraction and utilization (P<.01 andP=.01, respectively). Conclusions  Further studies are necessary to elucidate the mechanisms responsible for sex-associated differences in myocardial metabolism. However, the presence of such differences may provide a partial explanation for the observed sex-related differences in the prevalence and manifestation of a variety of cardiac disorders. This work was supported by grants HD145902 (Building Interdisciplinary Research in Women’s Health), RR00036 (General Clinical Research Center), DK56341 (Clinical Nutrition Research Unit), K23-HL077179, RO1-AG15466, PO1-HL13581, and HL73120 from the National Institutes of Health (Bethesda, Md) and grant 051893 (AHA02255732) from the Robert Wood Johnson Foundation (Princeton, NJ).     

MRI detection of myocardial perfusion defects due to coronary artery stenosis with MS-325

PURPOSE: To assess the value of an intravascular, albumin-targeted contrast agent, MS-325, in visualizing myocardial ischemia with magnetic resonance imaging (MRI). MATERIALS and METHODS: Left anterior descending coronary artery (LAD) stenosis was created in 19 pigs using a closed-chest modified angioplasty technique. Myocardial ischemia was detected by first-pass, contrast-enhanced MRI at peak dipyridamole stress and was compared to Technetium-99m (Tc-99m) sestamibi single photon emission computed tomography (SPECT). Regional coronary blood flow was determined using microspheres. RESULTS: Inducible myocardial ischemia with >40% reduction in stress myocardial blood flow was created in eight animals. An MRI defect, classified as > or=75% reduction in peak myocardial signal intensity in the affected territory, was detected in 92.3% of these animals. In the presence of mild coronary stenosis, there was uniform enhancement with MRI and tracer uptake by SPECT. Concordance of MRI and SPECT for detecting perfusion defects was 85%. CONCLUSION: The pattern of prolonged and persistent MR hypoenhancement of the ischemic myocardial bed using MS-325, which is retained primarily in the vascular bed due to its albumin-binding properties, facilitates the detection of myocardial perfusion defects.     

Myocardial perfusion reserve and contractile pattern after beta-blocker therapy in patients with idiopathic dilated cardiomyopathy

Background  

In Idiopathic Dilated Cardiomyopathy (IDC) an imbalance between myocardial oxygen consumption and supply has been postulated. The ensuing subclinical myocardial ischemia may contribute to progressive deterioration of LV function. β-blocker is the therapy of choice in these patients. However, not all patients respond to the same extent. The aim of this study was to elucidate whether differences between responders and non-responders can be identified with respect to regional myocardial perfusion reserve (MPR) and contractile performance.     

激光心肌孔道内控制释放bFGF对急性心肌梗死犬心脏形态与收缩功能的影响

目的 探讨在激光打孔的心肌孔道内埋植含有控制释放碱性成纤维细胞生长因子(bFGF)的纤维蛋白胶(FG)对急性心肌梗死(AMI)犬心脏形态和功能的影响。方法 18只成年健康杂种犬于开胸后结扎左前降支(LAD)，制作AMI模型。随机分为3组，每组6只。单纯心肌梗死(MI)组，直接关胸；激光心肌血运重建(TMR)组，于AMI30min后行透壁心肌打孔；bFGF组，则于AMI30min后行非透壁心肌打孔，并随即向孔道内注射含有bFGF的FG以封闭激光孔道。8周后行超声心动图和核素心肌显像，评价心脏形态和左心室收缩功能。结果 MI组与TMR组于术后第22d和34d各有1只死亡，bFGF组无死亡。超声心动图检查，MI组和TMR组分别有2只和1只发生室壁瘤，bFGF组未见室壁瘤；与MI组和TMR组相比，bFGF组的左室前壁舒张期厚度(LVAW)更大；bFGF组和TMR组的射血分数(EF)均高于MI组；bFGF组每搏出量(SV)和心输出量(CO)均高于MI组和TMR组；3组之间室壁运动指数(WMI)差异均有显著意义。核素心肌显像心功能检测也显示，bFGF组的EF和SV均高于MI组与TMR组。结论 在TMR孔道内使用FG控释bFGF安全可行，能减轻AMI后的心室重构，防止室壁瘤形成，改善左心室收缩功能，其疗效明显优于单纯TMR。     

Stunned myocardium

BACKGROUND: Stunned myocardium is a state of delayed recovery of regional contractility after a transient period of ischemia followed by reperfusion. CASE REPORT: A 67-year-old patient was admitted to our hospital with acute anterior myocardial infarction, and treated using percutaneous transluminal coronary angioplasty (PTCA) within acute disease stage. Reversible myocardial dysfunction persisted after ischemia following the return of normal perfusion. Abnormal resting wall motion with augmentation of contractility at low and high doses of dobutamine characterizes the stunned myocardium and reflects the normal blood flow reserve, characteristic for these postischemic, reperfused segments. SPECT (Single Photon Emission Computerized Tomography) with Tc 99 and dipyradamole showed normalization of perfusion defects in the apical region. There months after the infarction and PTCA, contractility was almost completely recovered. CONCLUSION: Stunned myocardium recovery lasted from few weeks to few months. Control ultrasonography as well as SPECT showed normalization of systolic function of the left ventricle in the viable segments registered at previous examinations.     

碱性成纤维细胞生长因子治疗猪心肌梗死的心肌SPECT显像

目的评价心肌SPECT显像对碱性成纤维细胞生长因子（b-FGF）缓释可降解支架治疗中国实验用小型猪急性心肌梗死的价值。方法选择中国实验用小型猪12头,体质量25～35kg,按完全随机法分为打孔＋空白支架（模型组）和打孔＋b-FGF支架（实验组）2组。所有猪左前降支均被结扎造成心肌梗死模型。2组均在梗死区及梗死周边区使用机械打孔器间断打孔并分别埋入空白支架和b-FGF缓释可降解支架。术后使用心肌^99Tc^m-甲氧基异丁基异腈（MIBI）SPECT显像、超声心动图、免疫组织化学检测心肌血流改变、短轴缩短率变化、新生血管密度。采用SPSS11．5软件,组间比较行成组资料的t检验。结果术后6周,实验组梗死心肌质量减少程度高于模型组[（34．33±4．18）g与（24．33±2．16）g,t=5．03,P〈0．05];实验组心肌缺血总分值差值（SDS）高于模型组[（13．83±2．86）分与（8．33±1．37）分,t=5．06,P〈0．05]。术后6周,实验组短轴缩短率[FS,（31．13±0．99）％]和新生血管密度[（6201±443）像豸影高倍视野]均高于模型组[（27．11±0．71）％和（2654±373）像素／高倍视野,t=8．12,15．01,P均〈0．05]。结论b-FGF缓释可降解支架植入可以改善心肌梗死区血流和心肌活力;心肌SPECT显像是一种评估b-FGF缓释可降解支架治疗急性心肌梗死效果有价值的方法。     

Clinical significance of diastolic function as an indicator of myocardial ischemia assessed by 16-frame gated myocardial perfusion SPECT

Objective  Studies have suggested that ischemia-induced diastolic dysfunction persists longer than systolic dysfunction. We examined whether global left ventricular (LV) diastolic function during stress testing assessed by 16-frame gated myocardial perfusion single-photon emission computed tomography (SPECT) is useful as an indicator of myocardial ischemia. Methods  Thirty-nine patients underwent 16-frame technetium-99m (Tc-99m) quantitative gated SPECT (QGS), including treadmill exercise testing for suspected ischemic heart disease. Diastolic parameters of the first-third filling fraction (1/3FF), and the peak filling rate (PFR) were calculated by a time-volume curve from the QGS data. Results  The patients were divided into four groups, namely, IS, NL, DN, and DD, on the basis of tracer accumulation and the LV ejection fraction (LVEF) at rest. In the IS group (reversible tracer uptake reduction suggesting ischemia; n = 11), LVEF, 1/3FF, and PFR after stress were significantly lower than those at rest, whereas in the NL group (normal perfusion; n = 10) and DN group (fixed tracer uptake reduction with normal systolic function; EF ≥ 60% at rest; n = 10), LVEF, 1/3FF, and PFR after stress did not differ from those at rest. However, in the DD group (fixed tracer uptake reduction with cardiac dysfunction; EF < 60%, average 47.1%; n = 8), LVEF, 1/3FF, and PFR were significantly altered after stress. Conclusions  Altered global LV diastolic function during stress assessed by 16-frame gated myocardial perfusion SPECT is useful for the detection of myocardial ischemia. However, similar findings are observed in patients with cardiac dysfunction but without detectable ischemia. Our findings do suggest that tests should be performed with caution to determine whether ischemia exists on the basis of altered global LV function after stress in patients with cardiac dysfunction.     

Impaired myocardial oxidative metabolism in the remote normal region in patients in the chronic phase of myocardial infarction and left ventricular remodeling

Background  Left ventricular (LV) remodeling occurs in the remote normal region in the LVs after myocardial infarction (MI) and is closely involved in heart failure. Methods  We assessed myocardial oxygen consumption using a clearance rate constant K _mono for the time activity curves of ¹¹C-acetate in 15 patients with a prior anterior wall MI, 8 with a prior inferior wall MI, and 10 age-matched normal control subjects. LV end-systolic volume index (ESVI) was determined by echocardiography. Results  The LVESVI was significantly greater in patients with an anterior and inferior MI than in control subjects. The heart rate systolic pressure product did not differ among the groups. K _mono in the remote normal region in patients with an anterior MI was significantly less than that in the corresponding area in control subjects (0.055 ± 0.005 vs 0.065 ± 0.008 min⁻¹, P < .001). K _mono in the remote normal region in those with an inferior MI was also significantly less compared with controls (0.054 ± 0.007 vs 0.069 ± 0.010 min⁻¹, P < .01). Conclusion  In patients with a prior MI and LV remodeling, myocardial oxidative metabolism is apparently impaired in the remote normal region where augmented myocardial energy production is needed against the increased end-systolic wall stress caused by LV dilatation.     

Severe coronary artery calcifications are associated with ischemia in patients undergoing medical therapy

Background  The role of coronary artery calcification (CAC) detection in individuals undergoing medical therapy is controversial. These patients frequently exhibit an artificially low clinical suspicion for obstructive heart disease. Whether detection of CAC adds value to their assessment is unknown. Methods and Results  We conducted a cross-sectional analysis of 703 adequately treated individuals who had CAC scoring with electron beam computed tomography and myocardial perfusion imaging within 6 months. We assessed the association of risk factor analysis and CAC scoring with myocardial perfusion imaging abnormalities. Univariate associations between ischemia and male gender, low high-density lipoprotein, high body mass index, diabetes, and CAC score were noted. Despite reasonable control of blood pressure and low-density lipoprotein, the prevalence of inducible ischemia was 0.8%, 4.8%, 5.7%, 8.0%, and 15.1% across CAC scores of 0 to 10, 11 to 100, 101 to 400, 401 to 1000, and greater than 1000, respectively (P<.001 for trend). Logistic regression analysis demonstrated that, after adjustment for risk factors the odds of ischemia was 3.0 (95% confidence interval, 1.5–5.7) in individuals with CAC scores greater than 400 compared with those with CAC scores of 400 or less. Conclusions  The presence of a CAC score greater than 400 is associated with ischemia in a population receiving good medical therapy. The detection of significant CAC in these individuals warrants additional evaluation for ischemia.     

家兔挤压伤后心脏节段旋转功能评价的实验研究

目的应用超声斑点追踪技术评价家兔挤压伤后的心脏收缩期节段旋转功能,评估挤压伤后心肌继发受损的情况。方法 42只新西兰家兔按标准制作挤压伤模型,随机分为对照组,解压即刻,解压后6、12、24、48、72 h共7组,每组6只,分别检测挤压前及解压后不同时间段左室收缩期节段旋转功能等情况。结果左室感兴趣区域的收缩期节段旋转功能在解压后12～24 h降至最低（P〈0.01）,72 h后逐渐恢复并相对稳定在一定水平。结论挤压伤后由于缺血再灌注等多种因素可导致心肌正性变力及变时效应减低,以致心肌纤维收缩性能及节段旋转功能明显降低,伤后12～24 h为心肌受损达峰时间段。     

Insights into the assessment of myocardial perfusion offered by different cardiac imaging modalities

Myocardial perfusion may be very broadly defined as the tightly regulated nutrient delivery to cardiac tissue. The different components of perfusion are myocardial blood flow, oxygen delivery, myocardial oxygen consumption, and myocardial blood volume. Historically, focus has been placed mostly on the assessment of blood flow. In many instances, knowledge of flow without information about these other aspects is inadequate. This review discusses the various cardiac imaging techniques used for the assessment of myocardial perfusion that represent diverse physiologic measures of “perfusion.” Their strengths and limitations are discussed as is their relevance to specific clinicopathologic conditions. Significant work still needs to be performed before all the aspects of myocardial perfusion can be precisely measured in human beings. Supported in part by a grant (R01-HL48890) from the National Institutes of Health, Bethesda, Md. Dr. Lindner is the recipient of a Fellowship Training Grant from the Virginia Affiliate of the American Heart Association, Glen Allen, Va. Dr. Kaul is an Established Investigator of the National Center of the American Heart Association, Dallas, Texas.     

Prognostic value of myocardial perfusion scintigraphy in type 2 diabetic patients with mild, stable angina pectoris

Aim  To determine the prognostic value of reversible myocardial perfusion defects on myocardial perfusion scintigraphy (MPS) in patients with type 2 diabetes mellitus and mild anginal complaints. Methods and results  In the MERIDIAN trial, patients with diabetes mellitus type 2, stable, mild anginal symptoms (Canadian Cardiovascular Society classification (CCS) I-II/IV) and reversible perfusion defects were randomized to either continued pharmacological treatment or early invasive treatment. In this sub analysis, the severity of the myocardial perfusion defect was related to the occurrence of cardiac death and non-fatal myocardial infarction, in 319 patients (63% male, 65 ± 9 years). During follow-up (2.2 ± 0.6 years), 14 patients had a cardiac event: 3 in 171 patients without myocardial ischemia and 11 in 148 patients with myocardial ischemia. Annual event rates rose from 0.8% to 5.8% with increasing severity of myocardial ischemia. Multivariable analysis identified the presence of severe myocardial ischemia (hazard ratio (HR) 5.45, 95%CI 1.89-15.71) and insulin use (HR 4.00, 95%CI 1.25-12.75) as independent predictors of cardiac events. Conclusions  Type 2 diabetics with mild anginal symptoms with no or moderate myocardial ischemia have a low annual cardiac event rate. In patients with severe myocardial ischemia event rate increased 3-6 fold. See related editorial, doi:.     

Stress dynamic myocardial CT perfusion for symptomatic patients with intermediate- or high-risk of coronary artery disease: Optimization and incremental improvement between the absolute and relative myocardial blood flow analysis

BackgroundThe optimization of myocardial CT perfusion (CTP) assessment remains inconsistent and uncertain. Our aim was to explore the superior analysis selection and incremental improvement of myocardial blood flow (MBF) assessment on CTP in diagnosing hemodynamically significant coronary artery disease (CAD).MethodsSixty patients (43 men and 17 women; 61.38 ± 8.01 years) were prospectively recruited and underwent stress dynamic myocardial CTP examinations. Absolute and relative MBF was used for ischemia evaluation with the invasive coronary angiography and fractional flow reserve were used as the reference standard. Areas under the receiver operating characteristic curves (AUCs) and cutoff values were calculated and compared.ResultsThere were 151 vessels in 60 patients finally enrolled for analysis. The sensitivity, specificity, PPV, NPV and diagnostic accuracy for the absolute MBF value and relative MBF ratio were 82.76%, 98.92%, 97.96%, 90.20%, and 92.72% and 74.14%, 93.56%, 87.76%, 85.29%, and 86.09%, respectively. The absolute MBF value was superior than the relative MBF ratio in detecting ischemia (AUC, 0.955 [95%CI: 0.919–0.990] vs.0.906 [95%CI:0.857–0.954])(P = 0.02). For territories with both sensitivity and specificity ≤90%, the diagnostic accuracy increased from 79.1% to 88.4% when the specific data were assessed using the absolute MBF value instead of the relative MBF ratio.ConclusionsThe absolute MBF value from the endocardial myocardium on stress dynamic myocardial CTP showed superior diagnostic performance compared to the relative MBF ratio for the detection of myocardial ischemia in intermediate-to-high risk patients. The absolute MBF value provides an incremental benefit toward diagnostic performance for the relative MBF ratio evaluation.     

Continuous intravenous infusion of prostaglandin E1 improves myocardial perfusion reserve in patients with ischemic heart disease assessed by positron emission tomography: a pilot study

Objective  

Recent investigation has demonstrated that prostaglandin E₁ (PGE₁) therapy increased capillary density in explanted hearts. Dynamic ¹³N-ammonia positron emission tomography (PET) is reliable for non-invasive measurement of myocardial blood flow and myocardial perfusion reserve (MPR). The aim of this study was to investigate the effects of PGE₁ therapy during 4 weeks on reduction of myocardial perfusion abnormalities and increase of MPR in the patients with ischemic heart disease.     

PET detection of the impact of dobutamine on myocardial glucose metabolism in women with type 1 diabetes mellitus

Background. Our objective was to determine, in the hearts of women with type 1 diabetes mellitus (T1DM), whether the fate of extracted glucose is altered and, if so, what the impact of dobutamine is on myocardial substrate metabolism. In experimental models of T1DM, myocardial glycolysis and glucose oxidation are reduced with the impairment becoming more pronounced with dobutamine. Whether similar changes occur in humans with T1DM is unclear. Methods and Results. Myocardial perfusion, oxygen consumption, and glucose and fatty acid metabolism were measured with positron emission tomography in 19 women, 7 normal volunteers (NVs) and 12 with T1DM. The NVs and 6 T1DM (DM1) patients were studied under baseline metabolic conditions and 6 T1DM patients were studied during hyperinsulinemic-euglycemic clamp (DM1-C), both at rest and during dobutamine. At rest, myocardial glucose uptake, glycolysis, glycogen storage, and oxidation were reduced by similar levels in DM1 patients compared with NVs (P<.05). During dobutamine, although myocardial glucose uptake was not different from DM1 patients at rest, fractional glycolysis was lower compared with NVs or DM1-C patients and reflected a lower glucose oxidation rate (P<.001). Measurements of myocardial glucose metabolism at rest and during dobutamine were comparable between NVs and DM1-C patients. During dobutamine, myocardial fatty acid uptake and oxidation increased in all 3 groups. Conclusions. In women with T1DM, (1) myocardial glucose metabolism is impaired downstream from initial uptake, (2) these abnormalities become more pronounced with dobutamine and are paralleled by an increase in myocardial fatty acid metabolism, and (3) insulin restores glucose metabolism to levels observed in normal control subjects. This work was supported by grants PO1-HL-13851, R01-HL69100, and M01-RR00036 from the National Institutes of Health (Bethesda, Md).     

Value of cardiac nuclear imaging in clinical care of patients with ischemic heart disease

Coronary revascularization with PTCA or by means of CABG surgery is frequently used in the care of patients with ischemic heart disease. Before revascularization is performed, stress myocardial perfusion imaging may assist in management decisions by demonstrating the presence of myocardial ischemia and viability, and delineating the severity and extent of coronary artery disease. The presence of myocardial ischemia may provide an indication for revascularization, even in asymptomatic persons. The significance of equivocal lesions may be determined and the culprit vessel may be successfully defined by this radionuclide technique. Recently, the quantitative estimation of myocardial flow reserve with N-13 ammonia PET and the precise detection of myocardial viability with F-18 FDG PET have been introduced to support the limitations of conventional SPECT imaging. After revascularization, these radionuclide techniques are useful to demonstrate improvement of myocardial perfusion or flow reserve, and are also very important to determine restenosis after PCI and graft disease after CABG surgery.     

Prognosis in patients with spontaneous chest pain, a nondiagnostic electrocardiogram, normal cardiac enzymes, and no evidence of severe resting ischemia by quantitative technetium 99m sestamibi tomographic imaging

Background  There are limited data addressing the outcome of patients with normal or near normal myocardial perfusion during chest pain at rest. The purpose of this study was to determine the prognosis of patients with spontaneous chest pain, a normal or nondiagnostic electrocardiogram, no enzymatic evidence of myocardial infarction, and no evidence of severe resting ischemia by quantitative technetium 99m (^99mTc) sestamibi imaging. Methods  In the study, 111 patients who fulfilled the above criteria were injected with ^99mTc sestamibi during resting chest pain and were followed for a median 2.7 years. Of the patients in the study group, 58% had coronary artery disease that was documented by clinical history or coronary angiography. Tomographic ^99mTc perfusion images were interpreted with a quantitative threshold technique initially developed to detect severely hypoperfused myocardium. The images were also interpreted qualitatively to detect patients with milder degrees of hypoperfused myocardium. Results  During follow-up 3 patients had cardiac deaths, 5 had nonfatal myocardial infarctions, and 21 underwent revascularization procedures (13 within 3 months and 8 more than 3 months after the sestamibi study). At 3 years, survival free of cardiac death was 97%, survival free of cardiac death or myocardial infarction was 91%, and survival of cardiac death, myocardial infarction, or late revascularization was 82%. Quantitative analysis of the scans revealed that 100% of patients without fixed defects had 3-year survival free of cardiac death versus 76% of patients who had fixed defects (p<0.001). Mild to moderate resting ischemia by qualitative interpretation of the scans was present in 20% of patients, but this did not predict outcome. Conclusions  Patients with spontaneous chest pain and nonischemic quantitative ^99mTc sestamibi images were at reasonably low risk for hard cardiac events although some patients (18%) required revascularization. Supported in part by the DuPont Merck Pharmaceutical Company, N. Billerica, Mass.