Gated myocardial perfusion single photon emission computed tomography in the clinical outcomes utilizing revascularization and aggressive drug evaluation (COURAGE) trial, Veterans Administration Cooperative study no. 424

Background  Stress gated myocardial perfusion single photon emission computed tomography (gSPECT) is increasingly used before and after intercurrent therapeutic intervention and is the basis for ongoing evaluation in the Department of Veterans Affairs clinical outcomes utilizing revascularization and aggressive drug evaluation (COURAGE) trial. Methods and Results  The COURAGE trial is a North American multicenter randomized clinical trial that enrolled 2287 patients to aggressive medical therapy vs percutaneous coronary intervention plus aggressive medical therapy. Three COURAGE nuclear substudies have been designed. The goals of substudy 0 are to examine the diagnostic accuracy of the extent and severity of inducible ischemia at baseline in COURAGE patients compared with patient symptoms and quantitative coronary angiography and to explore the relationship between inducible ischemia and the benefit from revascularization when added to medical therapy. Substudy 1 will correlate the extent and severity of provocative ischemia with the frequency, quality, and instability of recurrent symptoms in postcatheterization patients. Substudy 2 (n _ 300) will examine the usefulness of sequential gSPECT monitoring 6 to 18 months after therapeutic intervention. Together, these nuclear substudies will evaluate the role of gSPECT to determine the effectiveness of aggressive risk-factor modifications, lifestyle interventions, and anti-ischemic medical therapies with or without revascularization in reducing patients’ ischemic burdens. Conclusions  The unfolding of evidence on the application of gSPECT in trials such as COURAGE defines a new era for nuclear cardiology. We hope the evidence that emerges from the COURAGE trial will further establish the role of nuclear imaging in the evidence-based management of patients with stable coronary disease. The COURAGE trial was supported by the Cooperative Studies Program of the Department of Veterans Affairs Office of Research and Development in collaboration with the Canadian Institutes of Health Research. Unrestricted research grants were obtained from Merck & Co; Pfizer Pharmaceuticals; Bristol-Myers Squibb Medical Imaging; Astellas Pharma; Kos Pharmaceuticals; Data Scope; Astra Zeneca Pharmaceuticals; Astra-Zeneca-Canada; Schering-Plough Coorporation, Ltd; Sanofi-Aventis, Inc; First Horizon; and GE Healthcare. All industrial funding for this trial was directed through the Department of Veterans Affairs. Additional funding for this substudy was provided by grants to the Department of Veterans Affairs and Canadian Institutes of Health Research from Astellas Pharma and Bristol-Myers-Squibb Medical Imaging.     

Evaluation of left ventricular mechanical dyssynchrony as determined by phase analysis of ECG-gated SPECT myocardial perfusion imaging in patients with left ventricular dysfunction and conduction disturbances

Background  Cardiac resynchronization therapy (CRT) is approved for the treatment of patients with advanced systolic heart failure and evidence of dyssynchrony on electrocardiograms. However, a significant percentage of patients do not demonstrate improvement with CRT. Echocardiographic techniques have been used for more accurate determination of dyssynchrony. Single photon emission computed tomography (SPECT) myocardial perfusion imaging has not previously been used to evaluate cardiac dyssynchrony. The objective of this study is to evaluate mechanical dyssynchrony as described by phase analysis of gated SPECT images in patients with left ventricular dysfunction, conduction delays, and ventricular paced rhythms. Methods and Results  A novel count-based method is used to extract regional systolic wall thickening amplitude and phase from gated SPECT images. Five indices describing the phase dispersion of the onset of mechanical contraction are determined: peak phase, phase SD, bandwidth, skewness, and kurtosis. These indices were determined in consecutive patients with left ventricular dysfunction (n=120), left bundle branch block (n=33), right bundle branch block (n=19), and ventricular paced rhythms (n=23) and were compared with normal control subjects (n=157). Phase SD, bandwidth, skewness, and kurtosis were significantly different between patients with left ventricular dysfunction, left bundle branch block, right bundle branch block, and ventricular paced rhythms and normal control subjects (all P<.001) Peak phase was significantly different between patients with right ventricular paced rhythms and normal control subjects (P=.001). Conclusions  A novel SPECT technique for describing left ventricular mechanical dyssyn-chrony has been developed and may prove useful in the evaluation of patients for CRT. This study was funded in part by a research grant from the Medtronic-Duke Strategic Alliance, of which Dr Borges-Neto is the primary investigator.     

门控心肌显像结合GS Quant软件评价左室功能

目的:评价GS Quant软件结合99mTc-甲氧基异TN(MtBI)门控心肌断层显像(G-SPECT)测定左室射血分数(LVEF)的价值。方法:选择24例于同期2周内完成G-SPECT、门控心血池显像(RNA)和超声心动图检查(UCG)的患者,比较3种方法所测定的LVEF值。结果:99mTc-MIBI G-SPECT所测得的LVEF值与RNA和UCG法所测得的LVEF值均有较好的相关性,相关系数r分别为0.81(P<0.05)和0.76(P<0.05)。结论:99mTc-MIBI G-SPECT所测定的LVEF值有很好的准确性和可重复性,具有较高的临床应用价值,可进一步推广应用门控核素心肌断层显像这一技术。     

11项心功能指标的计算方法及微机处理

本文用OMEGA 500型Υ相机和MCS 560计算系统,即SPECT,R波门控采集心血池图象,在此基础上进行曲线分析,编制BASIC程序计算11项心功能指标。临床应用结果表明:PFR、LVFF、FFR是舒张期功能的优选指标,其它指标对心功能评价也都有显著意义。     

Radioisotope assessment of heart damage in hypertransfused thalassaemic patients

Twenty-five thalassaemic patients treated with repeated blood transfusion (BT) and intensive iron removal therapy were studied by echocardiography and rest/stress equilibrium gated radionuclide angiocardiography (EGNA). Stress left ventricular ejection fraction (LVEF) showed an important negative correlation with number of BTs (r = –0.75). Abnormal values of stress LVEF were measured after 200 BTs: these data demonstrate the effectiveness of stress LVEF in the follow-up of patients who have undergone repeated BTs and the clinical importance of intensive chelation therapy. Peak filling rate did not show diagnostic value in the early detection of iron cardiotoxicity. However, its inverse correlation with BT (r = –60) indicates that iron overload depresses the diastolic parameters.     

The interactions of phenytoin and its binding site in DI‐S6 segment of Na+ channel voltage‐gated peptide by NMR spectroscopy and molecular modeling study

Abstract: Nuclear magnetic resonance (NMR) spectra of a model peptide (BL‐DIS6), in the presence of anticonvulsant diphenyl drug, phenytoin (DPH), were measured to obtain the interactions between the selected drug and the model peptide. BL‐DIS6's sequence corresponds to the S6 segment in domain I of rat brain type IIA Na⁺‐channel. NMR studies have demonstrated that the magnitude of the chemical shifts of amide‐ and α‐protons can be used as a measurement of the complex stability and binding site of the peptide. Our NMR results propose a 3₁₀‐helical structure for BL‐DIS6, and suggest a binding cavity for DPH that involves the hydrophobic particles of residues Ans‐7, Leu‐8, Val‐11, and Val‐12. Furthermore, molecular modeling was performed to provide a possible complex conformation that the phenyl portion of DPH is accommodated in the proximity of the C‐terminal residues Ala‐11 and Val‐12, and simultaneously the heterocyclic amine ring of DPH is perching at the residue Asn‐7 periphery and stabilizing the phenyl portion deep insertion into the peptide.     

Additive value of low-dose dobutamine to technetium-99m sestamibi-gated single-photon emission computed tomography for prediction of wall motion improvement in patients undergoing coronary artery bypass graft

BACKGROUND: The two most useful methods for myocardial viability assessment are perfusion imaging and dobutamine echocardiography. HYPOTHESIS: The present study investigated the additive value of a new method, dobutamine technetium 99m (99mTc)-sestamibi-gated single-photon emission computed tomography (SPECT), which combines these two modalities, to the prediction of wall motion improvement after revascularization. METHODS: Fifty-five consecutive patients with ischemic cardiomyopathy, who were referred for viability evaluation, underwent resting and dobutamine (dose, 5-10 microkg/kg/min) gated SPECT with 99mTc-sestamibi. Of these patients, 36 underwent coronary artery bypass graft (CABG) within 1 month of the study and 32 had repeat resting gated SPECT within 1 year. Global and regional wall motion, wall thickness, and perfusion were simultaneously analyzed at rest and after dobutamine using the 20-segment model; the sestamibi uptake and wall motion response to dobutamine of each segment were rated quantitatively. Based on these findings, the segments were categorized as normal, viable, or nonviable. The predictive values for wall motion improvement were assessed by perfusion, using cutoffs of 50 and 60% of sestamibi uptake, and thereafter by the addition of dobutamine response in the segments that were rated nonviable. RESULTS: Of the 1,080 myocardial segments studied, 906 (84%) had abnormal wall motion and were analyzed for viability. Concordance between perfusion and wall motion response to dobutamine was 60% with the 50% cutoff of sestamibi uptake, and increased to 65% with the 60% sestamibi cutoff (p < 0.04). The respective predictive values of wall motion improvement using the 50 and 60% cutoff points were as follows: sensitivity 93 and 70%, respectively, (p < 0.01); specificity 59 and 86% (p < 0.001), respectively; accuracy 77% for both. The addition of the wall motion response to dobutamine to the assessment of the nonviable segments by perfusion (60% cutoff) increased the sensitivity from 70 to 85% (p = 0.001) and the negative predictive value from 70 to 81% (p = 0.009); the positive predictive value remained high (86 vs. 82%). No additive value of wall motion response to dobutamine was demonstrated for nonviable segments by perfusion with a 50% cutoff. CONCLUSION: Dobutamine sestamibi-gated SPECT is a feasible method for the analysis of myocardial perfusion, function, and contractile reserve of individual myocardial segments in patients with ischemic cardiomyopathy. Viability assessment based on a threshold of 60% uptake of sestamibi, with the addition of the wall motion response to dobutamine in the nonviable segments, seems to yield better predictive values for wall motion improvement after CABG.