Independent prognostic value of intravenous dipyridamole with technetium-99m sestamibi tomographic imaging in predicting cardiac events and cardiac-related hospital admissions.

OBJECTIVES: This study sought to establish the prognostic value of intravenous dipyridamole technetium-99m (Tc-99m) sestamibi single-photon emission computed tomographic (SPECT) myocardial perfusion imaging. BACKGROUND: Optimal management of patients with coronary artery disease involves strategies designed to reduce the risk of myocardial infarction and cardiac death. The role of myocardial perfusion imaging using newer clinical techniques to determine risk and possible benefit from therapy has not been evaluated. METHODS: Myocardial imaging results were classified as normal or abnormal (fixed or reversible defects; small, moderate or large). Follow-up evaluation of all patients included the occurrence of cardiac death or nonfatal myocardial infarction and other cardiac-related hospital admissions. RESULTS: During a mean (+/- SD) follow-up period of 12.8 +/- 6.8 months in 512 patients, 25 had a cardiac event. Patients with abnormal perfusion had significantly more cardiac events than those with normal perfusion (22 vs. 3, p < 0.01). Patients with reversible defects had the highest event rates (8.6%), and those with normal study results had a very low event rate (1.4%). Large defects were strongly associated with more cardiac events and hospital admissions than either normal scan results or abnormal results showing small defects. CONCLUSIONS: Patients with normal study results or a small defect after intravenous dipyridamole Tc-99m sestamibi SPECT imaging had an excellent short-term prognosis. Those with abnormal results (reversible or large defect) had an increased risk of subsequent cardiac death, nonfatal myocardial infarction and other cardiac-related hospital admissions.

Prognostic importance of scintigraphic left ventricular cavity dilation during intravenous dipyridamole technetium-99m sestamibi myocardial tomographic imaging in predicting coronary events.

Left ventricular (LV) cavity dilation during stress myocardial perfusion imaging has been associated with multivessel disease, and may be an independent prognostic marker in addition to perfusion defects. The present study examines the predictive value for future cardiac events of transient or fixed LV dilation during dipyridamole technetium-99m (Tc-99m) sestamibi single-photon emission computed tomography (SPECT) imaging. The study included 512 consecutive patients who underwent SPECT imaging with Tc-99m sestamibi after dipyridamole infusion. Transient LV dilation was seen in 70 patients (14%) and 74 had fixed cavity dilation (14%); cavity size was normal in 368 patients (72%). Each perfusion scan was classified as normal or abnormal, and if abnormal, defects were categorized as transient or fixed, and as small, medium, or large (depending upon the number of abnormal vascular territories). Events during a mean follow-up of 12.8 +/- 6.8 months were tabulated by direct review of hospital charts and death certificates. The cardiac event rate (cardiac death or nonfatal infarction) was 1.9% in patients with normal cavity size, 11.4% with transient LV dilation, and 13.5% with fixed LV dilation (p < 0.01). Compared with patients with normal cavity size, those with transient LV dilation were more likely to sustain a myocardial infarction (p < 0.01) and those with fixed dilation more frequently suffered cardiac death (p < 0.01) and hospitalization for heart failure (p < 0.01). The group with the highest risk had both a large perfusion defect and cavity dilation. By Cox proportional hazard regression analysis, both transient and fixed LV dilation were strong independent predictors of cardiac events. Transient or fixed LV dilation are commonly seen during dipyridamole Tc-99m sestamibi SPECT imaging (14% incidence for each) and are useful predictors of cardiac events.

Inherent resistance of HeLa cell derivatives to paromomycin.

The human tumor-derived cell line HeLa S3 and nuclear and mitochondrial gene mutants derived from it are resistant to the aminoglycoside antibiotic, paromomycin (PAR). Other carcinoma-derived cells, SV40-transformed cells, and four human diploid fibroblast cell lines are all sensitive to PAR. Sensitivity is dependent on cell density, and at cell numbers greater than 400/cm2 sensitive cells will proliferate in PAR. The resistance to PAR is inherited in a dominant manner in cell-to-cell fusion hybrids, but is not transferred in cytoplast-to-cell fusions. PAR resistance is therefore encoded by a nuclear gene(s). Resistance to PAR is not caused by changes in the response of mitochondrial or cytoplasmic protein synthesis to PAR in vitro. The uptake of PAR is similar in resistant and sensitive cells, and dimethyl sulfoxide does not render resistant cells more sensitive. Thus, HeLa cell PAR resistance is unlike previously reported ribosomal mutations and may derive from differences in the intracellular metabolism of PAR.

Interpretive reproducibility of stress Tc-99m sestamibi tomographic myocardial perfusion imaging.

BACKGROUND: Observer variability has been shown with interpretation of planar thallium-201 images. The interpretive reproducibility of technetium-99m sestamibi tomographic imaging is unknown. This study evaluated the interpretive reproducibility of interpretable Tc-99m sestamibi tomographic images among nuclear cardiologists with a wide range of training and experience. METHODS: Three experienced readers (EX) and 3 less-experienced readers (LEX) interpreted 138 exercise and rest Tc-99m sestamibi tomographic images (101 were abnormal in patients with coronary artery disease [CAD], 37 were normal in patients with <5% likelihood of CAD) twice in random sequence without clinical data. Images of good to excellent quality were randomly selected from a database at 2 nuclear cardiology laboratories. Intraobserver and interobserver agreement for global, left anterior descending (LAD) territory, non-LAD first (normal/abnormal) and second (normal/fixed/reversible) order, and defect extent (normal/single-vessel CAD/multi-vessel CAD) were assessed with percent agreement and Cohen's kappa (kappa) statistic. RESULTS: With regard to intraobserver agreement, first and second order ranged from 87% to 94% and 80% to 90% for global, 82% to 96% and 78% to 95% for LAD, and 88% to 91% and 80% to 90% for non-LAD, respectively. Defect extent ranged from 75% to 90%. There were no differences between EX and LEX for global and non-LAD first and second order, LAD first order, and defect extent. LAD second order was 93% for EX compared with 88% (P = .015) for LEX. With regard to interobserver agreement, first and second order ranged from 73% to 89% and 64% to 85% for global, 73% to 93% and 69% to 91% for LAD, and 76% to 88% and 68% to 84% for non-LAD, respectively. Defect extent ranged from 61% to 82%. Global first and second order ranged from 85% to 87% and 78% to 82% for EX compared with 73% to 84% and 64% to 79% for LEX. LAD first and second order ranged from 89% to 91% and 88% to 89% for EX compared with 73% to 91% and 69% to 70% for LEX. Non-LAD first and second order ranged from 82% to 86% and 76% to 77% for EX compared with 76% to 86% and 68% to 81% for LEX. Defect extent ranged from 69% to 75% for EX compared with 59% to 77% for LEX. CONCLUSIONS: There is moderate to excellent interpretive reproducibility with stress Tc-99m sestamibi SPECT imaging among nuclear cardiologists with a wide range of training and experience.

Effectiveness of nuclear cardiology training guidelines: a comparison of trainees with experienced readers.

BACKGROUND: To evaluate the effectiveness of published nuclear cardiology training guidelines, the diagnostic accuracy of image interpretation by nuclear cardiology trainees was compared with that of experienced nuclear cardiologists. METHODS AND RESULTS: The accuracy of three experienced nuclear cardiologists and three trainees with level II experience following Society of Nuclear Medicine/American College of Cardiology/American Society of Nuclear Cardiology guidelines in the interpretation of 114 exercise 99mTc-labeled sestamibi single-photon emission computed tomographic imaging studies was evaluated. Studies were selected randomly and included patients with less than 5% likelihood of coronary artery disease, as well as patients with angiographically demonstrated single and multivessel disease. Studies were interpreted by each reader without knowledge of clinical or exercise data. Each reader classified perfusion as normal or abnormal. Accuracy was assessed according to sensitivity, normalcy rate, and predictive accuracy. In addition, the ability of experienced readers and trainees to identify abnormal perfusion in patients with multivessel disease was compared. Trainees had high accuracy, comparable to experienced readers for sensitivity, normalcy rate, and predictive accuracy, as well as the ability to identify abnormal perfusion in patients with multivessel disease. In all categories, experienced interpretors demonstrated a trend toward greater accuracy with less observer variability than did trainees. CONCLUSION: Structured training in nuclear cardiology following Society of Nuclear Medicine/American College of Cardiology/American Society of Nuclear Cardiology guidelines during clinical cardiology fellowship is effective, and trainees possess the skills to interpret myocardial perfusion images accurately. Interpretive skills can be expected to improve further with experience.