Raymond Taillefer

Cardiac Outcomes After Screening for Asymptomatic Coronary Artery Disease in Patients With Type 2 Diabetes: The DIAD Study: A Randomized Controlled Trial

CONTEXT Coronary artery disease (CAD) is the major cause of mortality and morbidity in patients with type 2 diabetes. But the utility of screening patients with type 2 diabetes for asymptomatic CAD is controversial. OBJECTIVE To assess whether routine screening for CAD identifies patients with type 2 diabetes as being at high cardiac risk and whether it affects their cardiac outcomes. DESIGN, SETTING, AND PATIENTS The Detection of Ischemia in Asymptomatic Diabetics (DIAD) study is a randomized controlled trial in which 1123 participants with type 2 diabetes and no symptoms of CAD were randomly assigned to be screened with adenosine-stress radionuclide myocardial perfusion imaging (MPI) or not to be screened. Participants were recruited from diabetes clinics and practices and prospectively followed up from August 2000 to September 2007. MAIN OUTCOME MEASURE Cardiac death or nonfatal myocardial infarction (MI). RESULTS The cumulative cardiac event rate was 2.9% over a mean (SD) follow-up of 4.8 (0.9) years for an average of 0.6% per year. Seven nonfatal MIs and 8 cardiac deaths (2.7%) occurred among the screened group and 10 nonfatal MIs and 7 cardiac deaths (3.0%) among the not-screened group (hazard ratio [HR], 0.88; 95% confidence interval [CI], 0.44-1.88; P = .73). Of those in the screened group, 409 participants with normal results and 50 with small MPI defects had lower event rates than the 33 with moderate or large MPI defects; 0.4% per year vs 2.4% per year (HR, 6.3; 95% CI, 1.9-20.1; P = .001). Nevertheless, the positive predictive value of having moderate or large MPI defects was only 12%. The overall rate of coronary revascularization was low in both groups: 31 (5.5%) in the screened group and 44 (7.8%) in the unscreened group (HR, 0.71; 95% CI, 0.45-1.1; P = .14). During the course of study there was a significant and equivalent increase in primary medical prevention in both groups. CONCLUSION In this contemporary study population of patients with diabetes, the cardiac event rates were low and were not significantly reduced by MPI screening for myocardial ischemia over 4.8 years. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00769275.

The role of 99mTc-sestamibi and other conventional radiopharmaceuticals in breast cancer diagnosis

The wide availability and the extensive use of screening mammography have resulted in an earlier diagnosis of breast cancer and in a significant reduction in the relative risk of dying from this disease. Despite technical improvements and major advantages associated with the use of mammography (and breast ultrasound), this procedure has some limitations in clinical practice, especially in women with dense breast tissue, implants, severe dysplastic disease, or significant architectural distortion following breast surgery or radiation therapy. Different noninvasive imaging techniques have been evaluated to overcome these limitations. Nuclear medicine also has been actively involved in the detection of breast cancer, using various types of radiopharmaceuticals. Currently, there are three radiotracers commonly used for breast imaging or scintimammography in either clinical practice or research: 99mTc-sestamibi and 99mTc-tetrofosmin (two agents used for myocardial perfusion imaging) and 99mTc-MDP (methylene diphosphonate, used for bone scintigraphy). 99mTc-sestamibi was the first radiopharmaceutical to be approved by the FDA for scintimammography. Several prospective studies have shown that the overall sensitivity of 99mTc-sestamibi scintimammography in detection of breast cancer was 85%, the specificity was 89%, and the positive and negative predictive values were 89% and 84% respectively. Similar numbers have been demonstrated for 99mTc-tetrofosmin and 99mTc-MDP scintimammography. Although not indicated as a screening procedure for the detection of breast cancer, scintimammography may play a useful and significant role in various specific clinical indications such as nondiagnostic or difficult mammography, and evaluation of high-risk patients, tumor response to chemotherapy, and axillary lymph node metastatic involvement.

Long-term effect of total fundoplication on the myotomized esophagus.

From 1978 to 1983, 17 patients had an esophagocardiomyotomy with an added short total fundoplication as an antireflux procedure. Thirteen had achalasia and 4, diffuse esophageal spasm. All patients initially had the usual symptoms of these motor disorders. Early after the operation all became asymptomatic, but over the years of follow-up, symptoms reappeared in 14 of 17 patients, and 5 required reoperation. The distal esophageal transverse diameter showed progressive dilatation from 3.9 cm preoperatively to more than 6 cm after 10 years of evolution. Over the same period, deterioration in the esophageal emptying capacity caused esophageal stasis to increase from 32% to 75%. Manometric changes were significant after the operation: resting pressures in the esophageal body decreased from 10.5 to 4.4 mm Hg (p < 0.001) proximally and from 12.2 to 4.6 mm Hg distally (p < 0.001). Peak contraction pressures became significantly weaker: 38 to 30 mm Hg in the proximal esophagus (p < 0.001) and from 49.2 to 28.1 in the distal esophagus (p < 0.001). Tertiary contractions were unchanged distally, but peristalsis reappeared in more than 30% of all swallows in the proximal half of the esophageal body. The resting pressure gradient in the lower esophageal sphincter area was reduced from 25.5 to 7.4 mm Hg by the operation. This gradient remained stable over 10 years of follow-up. No significant acid exposure was documented in 8 patients undergoing 24-hour pH recordings after their operation. Endoscopy revealed dilatation and retention without evidence of reflux esophagitis damage. Total fundoplication when associated with esophageal myotomy results in improved symptoms in the early postoperative phase.(ABSTRACT TRUNCATED AT 250 WORDS)

Phase II safety and clinical comparison with single-photon emission computed tomography myocardial perfusion imaging for detection of coronary artery disease: flurpiridaz F 18 positron emission tomography.

OBJECTIVES This was a phase II trial to assess flurpiridaz F 18 for safety and compare its diagnostic performance for positron emission tomography (PET) myocardial perfusion imaging (MPI) with Tc-99m single-photon emission computed tomography (SPECT) MPI with regard to image quality, interpretative certainty, defect magnitude, and detection of coronary artery disease (CAD) (≥50% stenosis) on invasive coronary angiography (ICA). BACKGROUND In pre-clinical and phase I studies, flurpiridaz F 18 has shown characteristics of an essentially ideal MPI tracer. METHODS One hundred forty-three patients from 21 centers underwent rest-stress PET and Tc-99m SPECT MPI. Eighty-six patients underwent ICA, and 39 had low-likelihood of CAD. Images were scored by 3 independent, blinded readers. RESULTS A higher percentage of images were rated as excellent/good on PET versus SPECT on stress (99.2% vs. 88.5%, p < 0.01) and rest (96.9% vs. 66.4, p < 0.01) images. Diagnostic certainty of interpretation (percentage of cases with definitely abnormal/normal interpretation) was higher for PET versus SPECT (90.8% vs. 70.9%, p < 0.01). In 86 patients who underwent ICA, sensitivity of PET was higher than SPECT (78.8% vs. 61.5%, respectively, p = 0.02). Specificity was not significantly different (PET: 76.5% vs. SPECT: 73.5%). Receiver-operating characteristic curve area was 0.82 ± 0.05 for PET and 0.70 ± 0.06 for SPECT (p = 0.04). Normalcy rate was 89.7% with PET and 97.4% with SPECT (p = NS). In patients with CAD on ICA, the magnitude of reversible defects was greater with PET than SPECT (p = 0.008). Extensive safety assessment revealed that flurpiridaz F 18 was safe in this cohort. CONCLUSIONS In this phase 2 trial, PET MPI with flurpiridaz F 18 was safe and superior to SPECT MPI for image quality, interpretative certainty, and overall CAD diagnosis.

Thallium-201 myocardial imaging during pharmacologic coronary vasodilation: comparison of oral and intravenous administration of dipyridamole

Although the diagnostic utility of thallium-201 myocardial imaging after dipyridamole infusion is well established, the intravenous form of the drug is not yet commercially available in North America. Fifty patients referred for coronary angiography were prospectively studied. Within a 2 week period, each patient underwent cardiac catheterization and thallium-201 myocardial imaging after both oral and intravenous dipyridamole administration. For the oral protocol, patients were randomly assigned to treatment with either 200 or 400 mg of dipyridamole in tablet form. Coronary artery stenoses of 70% or greater were considered significant. For the 25 patients who received a 200 mg oral dose of dipyridamole, the scintigraphic study showed perfusion defects in 65% of patients with significant coronary artery disease after the oral dose and in 85% of patients after the intravenous dose. For the 25 patients who received a 400 mg oral dose, the sensitivity of the scintigram was 84% after the oral dose and 79% after the intravenous dose. Except for headache and nausea, side effects were less severe and less frequent with oral (either 200 or 400 mg) than with intravenous dipyridamole. Because of the delayed and variable absorption of dipyridamole tablets, the oral studies required a longer period of medical supervision (45 to 60 minutes), and aminophylline was empirically administered after completion of the first set of thallium-201 images. It is concluded from this study that thallium-201 myocardial imaging after coronary vasodilation with a 400 mg oral dose of dipyridamole is a safe, widely available and reliable alternative for the evaluation of coronary artery disease in patients unable to achieve an adequate exercise level on stress testing.

Acute beta-blockade reduces the extent and severity of myocardial perfusion defects with dipyridamole Tc-99m sestamibi SPECT imaging.

OBJECTIVES The goal of this study was to examine the effect of acute beta-blockade on dipyridamole Tc-99m sestamibi myocardial perfusion imaging (DMPI). BACKGROUND Studies suggest that antianginal drugs may reduce the presence and severity of myocardial perfusion defects with dipyridamole stress. However, there are no data regarding specific drugs. METHODS Patients with catheterization-proven coronary artery disease (CAD) were enrolled in this prospective, double-blind, placebo-controlled study and randomly assigned to DMPI after placebo, low-dose metoprolol (up to 10 mg), and high-dose metoprolol (up to 20 mg). Patients underwent one Tc-99m sestamibi study at rest on a separate day. The interval between DMPI studies was <or=14 days. Images were interpreted by three observers blinded to clinical data using a 17-segment, five-point model. For each image, a summed stress score (SSS), summed rest score (SRS), and summed difference score (SDS) were calculated (SDS = SSS - SRS). Images with an SSS <4 were considered normal. RESULTS Twenty-one patients completed all four Tc-99m sestamibi studies. The sensitivity of DMPI for detection of CAD was 85.7% with placebo versus 71.4% with low- and high-dose metoprolol. In comparison with placebo, the SSS was significantly lower (p < 0.05) with low- and high-dose metoprolol (12.0 +/- 10.1 vs. 8.7 +/- 9.0 and 9.3 +/- 10.6, respectively). The SDS also was significantly lower (8.4 +/- 8.8 with placebo vs. 5.0 +/- 6.7 [p < 0.001] and 5.4 +/- 7.9 [p < 0.01] with low- and high-dose metoprolol, respectively). CONCLUSIONS The presence and severity of CAD may be underestimated in patients receiving beta-blocker therapy undergoing dipyridamole stress myocardial perfusion imaging.

Same day injections of Tc-99m methoxy isobutyl isonitrile (hexamibi) for myocardial tomographic imaging: Comparison between rest-stress and stress-rest injection sequences

It has been shown that both rest and stress 99mTc-hexamibi myocardial perfusion imaging can be performed on the same day using two different doses injected within few hours (the first one at rest followed by a second at stress). In order to evaluate and compare 2 sequences (rest-stress and stress-rest) of 99mTc-hexamibi injections performed the same day, 18 patients with either abnormal 201Tl myocardial scan or abnormal coronary angiography were studied with 2 99mTc-hexamibi injections protocols. The rest-stress study was performed as follows: 7 mCi 99mTc-hexamibi was injected at rest. Single photon emission computed tomography (SPECT) was performed 60 min later. Immediately after the rest study, patients were injected at peak stress with 25 mCi 99mTc-hexamibi. Tomographic imaging was repeated 1 h later. Patients were submitted to the stress-rest protocol within 3 days. Tomographic imaging was done 1 h after a 7 mCi injection at stress. This study was followed by an injection of 25 mCi 99mTc-hexamibi at rest, a tomographic study was performed 60 min later. Myocardial sections were reconstructed in horizontal long, vertical long, and short axes. Data analysis also included polar map representation. A total of 324 segments were interpreted blind by 3 observers, there was an agreement in 283/324 (87.3%) segments between the 2 protocols. However, 24 segments (7.4%) judged ischemic on rest-stress were called scars on stress-rest. In three patients, myocardial segments were judged normal on the rest image of the rest-stress protocol while they were found abnormal (false positive images) on the stress-rest sequence. Stress images from both protocols were judged similar in 17 patients. In conclusion, when using a short time interval (less than 2 h) between two 99mTc-hexamibi injections, it is preferable to do a rest-stress sequence since the rest image performed initially represents a true rest study, which is not necessarily the case with the stress-rest sequence.

Clinical comparison between thallium-201 and Tc-99m-methoxy isobutyl isonitrile (hexamibi) myocardial perfusion imaging for detection of coronary artery disease.

Abstract99mTc-hexamibi (methoxy isobutyl isonitrile) is a new 99mTc-hexakis analog that can be used as a myocardial perfusion imaging agent. The purposes of this study were to compare 99mTc-hexamibi to 201Tl-thallous chloride myocardial stress scintigraphy in patients referred for investigation of chest pain and to evaluate the sensitivity of 99mTc-hexamibi in detection of coronary artery disease. One hundred patients were prospectively studied with both 201Tl and 99mTc-hexamibi planar imaging. Sixty five patients had a current coronary angiography. There was a total of 97 significantly (≤70%) stenosed major coronary arteries. 99mTc-hexamibi (25 mCi) study was done within a week of the 201Tl scan with similar double products upon standard treadmil stress testing. Rest studies with 99mTc-hexamibi were obtained 24–48 h after the stress test using the same acquisition parameters and dose. Analysis was performed blind by three observers. The left ventricle was divided into five segments in each image. Analysis of 201Tl and 99mTc-hexamibi results in 1500 left ventricle segments showed an overall agreement in 1326/1500 (88.4%) segments. Correlation between the patient diagnosis on the 201Tl and 99mTc-hexamibi studies showed an agreement in 89 patients (89%). 201Tl revealed myocardial uptake defects in 526 segments, detecting 72 out of 97 (74.2%) significantly stenosed coronary arteries and 99mTc-hexamibi detected 513 segments corresponding to 68 (70.1%) stenosed arteries (no significant statistical difference). In conclusion, these results show a good correlation between 201Tl and 99mTc-hexamibi myocardial imaging in the detection of significant coronary artery disease.

Enhanced detection of reversible perfusion defects by Tc-99m sestamibi compared to Tc-99m tetrofosmin during vasodilator stress SPECT imaging in mild-to-moderate coronary artery disease

OBJECTIVES We prospectively compared dipyridamole single-photon emission computed tomography (SPECT) imaging with Tc-99m sestamibi and Tc-99m tetrofosmin for the detection of reversible perfusion defects in patients with mild-to-moderate coronary artery disease. BACKGROUND Tc-99m tetrofosmin has a lower first-pass myocardial extraction fraction compared to Tc-99m sestamibi and thus could underestimate mild perfusion defects. METHODS Eighty-one patients with 50% to 90% stenosis in one or two major epicardial vessels without previous myocardial infarction, and seven with <5% probability of coronary artery disease underwent dipyridamole SPECT imaging with both agents. The SPECT data were analyzed quantitatively. RESULTS Tc-99m sestamibi detected reversible perfusion defects in a greater number of segments (total 363 and 285, p < 0.001, and mean +/- SD, 2.2 +/- 3.0 and 1.8 +/- 2.5 per patient, p = 0.008, for Tc-99m sestamibi and Tc-99m tetrofosmin, respectively), demonstrated a larger extent of perfusion defect (mean +/- SD, 15.8% +/- 12.3% and 12.0% +/- 11.4%, p < 0.03, for Tc-99m sestamibi and Tc-99m tetrofosmin, respectively) and more often correctly identified patients with disease in more than one coronary artery (p = 0.02). There was better defect contrast with Tc-99m sestamibi (defect/normal wall count ratios were 0.60 +/- 0.15 vs. 0.73 +/- 0.14 for Tc-99m sestamibi and Tc99m tetrofosmin, respectively, p = 0.01, for reversible defects seen in identical segments with both agents; and 0.73 +/- 0.16 vs 0.79 +/- 0.17, respectively, p <0.01, for reversible defects detected with either agent alone). There was no significant difference in diagnostic sensitivity or image quality. CONCLUSIONS These differences between two commonly used tracers may have significant diagnostic and prognostic implications.

Comparison between dipyridamole and adenosine as pharmacologic coronary vasodilators in detection of coronary artery disease with thallium 201 imaging

BackgroundBoth dipyridamole and adenosine are widely used as pharmacologic stressors with 201Tl imaging for detection of coronary artery disease. The purpose of this study was to compare dipyridamole and adenosine 201Tl imaging directly in patients with angiographically proved coronary artery disease.Methods and ResultsFifty-four patients were submitted to two planar 201Tl studies: one with dipyridamole and the other with adenosine. The interval between the two studies varied from 2 to 7 days and the order was assigned randomly. Three standard planar views were obtained 10 minutes and 4 hours after the injection of 3.0 mCi 201Tl. Administration of dipyridamole was as follows: 0.142 mg/kg/min during 4 minutes, followed by a slight exercise and 201Tl injection. The infusion of adenosine was as follows: 0.140 mg/kg/min during 6 minutes with injection of 201Tl after the third minute of infusion. Patients were asked to give their preference considering the number type, severity, and duration of side effects on a scale from 0 (worst) to 5 (best). Reading was done by two experienced observers. The heart was divided into three segments per view. The change in systolic blood pressure was-12±11 mm Hg for adenosine and-5±10 mm Hg for dipyridamole (p<0.001), and the change in heart rate was 18±10 beats/min for adenosine and 8±7 beats/min for dipyridamole (p<0.001). With regions of interest, ischemic/normal wall ratios were determined: 0.78 ± 0.06 for adenosine and 0.83±0.08 for dipyridamole (p<0.001). Adenosine detected 295 normal, 170 ischemic, and 21 scar segments, whereas dipyridamole detected 326, 135, and 25 segments, respectively. Patients preferred adenosine (4.3±1.0 for adenosine vs 3.8±1.5 for dipyridamole; p<0.04) mainly because of the short duration of side effects.ConclusionThis study shows that the use of adenosine with 201Tl imaging may have some advantages over dipyridamole.