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Background: Radiation exposure during nuclear cardiology procedures has received much attention and has prompted citations for radiation reduction. In 2010, the American Society of Nuclear Cardiology recommended reducing the average patient study radiation exposure to Methods and Results: This was an analysis of nuclear cardiology studies submitted to the Intersocietal Accreditation Commission for either or both cardiac PET and SPECT accreditation. Cardiac SPECT data represented year 2015 while PET data combined years 2013 to 2015. Data was analyzed with χ 2 and Mann-Whitney U tests (reported as median, 25th percentile, and 75th percentile). Reported PET MPI radiation exposure for 111 laboratories (532 patient cases) was 3.7 (3.2–4.1) mSv per study with no geographic variation. Reported SPECT MPI radiation exposure for 665 laboratories (3067 patient studies) was 12.8 (12.2–14.3) mSv. Highest radiation exposure was found in the South region. Technetium-only studies resulted in a median of 12.2 mSv per study. Conclusions: Radiation exposure from cardiac PET MPI in US laboratories applying for Intersocietal Accreditation Commission accreditation is low (111 laboratories, 3.7 mSv) and substantially lower than cardiac SPECT (665 laboratories, 12.8 mSv).

Background— Positron emission tomography (PET) myocardial perfusion imaging (MPI) offers technical benefits compared with single photon emission computed tomography (SPECT) MPI, but there has been no systematic comparison of their diagnostic accuracy for coronary artery disease. We performed a bivariate meta-analysis of the published literature to compare the sensitivity and specificity of PET versus SPECT stress MPI for ≥50% stenosis of any epicardial coronary artery in patients with known or suspected coronary artery disease. Methods and Results— We searched MEDLINE and EMBASE from inception through January 2012 and the references of identified studies for prospective, English language studies that evaluated the sensitivity and specificity of PET and/or SPECT MPI with coronary angiography as the reference standard and reported sufficient data to calculate patient-level true and false positives and negatives. Two investigators independently extracted patient and study characteristics; a third investigator resolved any disagreements. We identified 117 studies, including 108 evaluating SPECT MPI, 4 evaluating PET MPI, and 5 evaluating both modalities. Bivariate meta-analysis demonstrated a significantly higher pooled mean sensitivity with PET (92.6% [95% Confidence Interval, 88.3% to 95.5%]) compared with SPECT (88.3% [95% confidence interval, 86.4% to 90.0%]) ( P =0.035). No significant difference in specificity was observed between PET (81.3% [95% confidence interval, 66.6% to 90.4%]) and SPECT (75.8% [95% confidence interval, 72.1% to 79.1%]) ( P =0.39). Few studies investigated coronary angiography with PET. Only 5 studies directly compared SPECT and PET. Conclusions— In a meta-analysis of 11,862 patients, PET MPI demonstrated a higher sensitivity for coronary artery disease than SPECT MPI. No difference in specificity was detected in the pooled analysis of PET and SPECT MPI.

Background: Coronary artery disease (CAD) is under-diagnosed in women. Flurpiridaz F 18 injection (flurpiridaz) is a PET myocardial perfusion imaging (MPI) tracer in clinical development. We hypothesized flurpiridaz would result in improved CAD detection in women in comparison to SPECT. Methods: This Phase 3 study was designed to assess the diagnostic efficacy of flurpiridaz and SPECT with Tc99m-labeled agents for CAD detection in the same patients. Patients with known or suspected CAD who were either scheduled for or had completed invasive coronary angiography (without intervention) were included. Each patient was studied using both rest/stress flurpiridaz PET MPI and rest/stress Tc-99m labeled SPECT MPI. Images were interpreted by 3 expert readers blinded to all clinical information. Quantitative coronary angiography (QCA) was used with patients considered CAD positive with a stenosis ≥50% in at least one major vessel. Results: 795 subjects were enrolled at 72 clinical sites in US, Canada and Finland. The study included 235 (30%) evaluable female subjects with a mean age of 62.4±10.1 years, body weight of 85.0±21.6 kg, and a BMI of 32.3±7.8 (58.7% with a BMI≥30). The agent was safe and well tolerated. A statistically significant greater sensitivity was seen for flurpiridaz (67.8%) vs SPECT (37.3%, p Conclusions: The results of this Phase 3 trial demonstrate the superiority of flurpiridaz over standard SPECT MPI for the assessment of CAD in women, with lower radiation exposure than standard SPECT.

A preliminary report on medical radiation exposures to the US population based on publicly available sources of data estimated that the collective dose received from medical uses of radiation has increased by >700% between 1980 and 2006.1 Computed tomography (CT) has had an annual growth rate of >10% per year and accounted for ≈50% of the collective dose in 2006. Approximately 65% of the collective CT dose is from studies of chest, abdomen, and pelvis. In 2006, cardiac CT accounted for 1.5% of the collective CT dose; however, utilization of cardiac CT is expected to rise, with the potential to further increase exposure to the population.1 Nuclear medicine studies in the United States have increased by 5% annually to 20 million in 2006 and accounted for ≈25% of the 2006 collective medical radiation dose. Among nuclear medicine studies, cardiac imaging represented 57% of the number of studies and ≈85% of the radiation dose.1 A number of publications on imaging with CT, fluoroscopy, or radioisotopes have emphasized the risks that may be associated with exposure to ionizing radiation.2–4 To make informed decisions concerning the use of medical radiation in imaging procedures, the following are important components: (1) A working knowledge of the principles and uncertainties of the estimation of patient dose and biological risk; (2) a comparison of the risks of radiation exposure with the risks of activities in daily life; and (3) recognition of the potential risk of failing to make important diagnoses or treatment decisions if imaging is not performed because of safety concerns. There is no federal regulation of patient radiation dose, with the exception of mammography. Most federal and state regulations are aimed at equipment performance or the handling of nuclear materials. Therefore, appropriate utilization of the equipment or nuclear material in cardiac …

OBJECTIVE: Accreditation of cerebrovascular ultrasound laboratories by the Intersocietal Accreditation Commission (IAC) or equivalent bodies is supported by The Joint Commission certification of stroke centers. Limited information exists on the accreditation status and geographic distribution of these testing facilities in the US. The aims were to: (1) Identify the proportion of IAC accredited vascular testing facilities used by Medicare beneficiaries for outpatient cerebrovascular testing services; (2) Describe the geographical distribution of these facilities; and (3) Identify variation in the types and volumes of cerebrovascular testing procedures by accreditation status. METHODS: As a part of the VALUE (Vascular Accreditation, Location & Utilization Evaluation) Study, we examined the proportion of IAC accredited facilities that conducted cerebrovascular testing in a 5% CMS random Outpatient Limited Data Set (LDS) for the US in 2011 and investigated their geographical distribution using the Medicare Provider of Services (POS) file. RESULTS: Of the 7,864 total facilities billing Medicare for cerebrovascular testing procedures, only 22% (n=1,723) were IAC accredited. The percentage of facilities conducting cerebrovascular testing that were IAC accredited varied by region (Χ2[3]=400.4, p CONCLUSIONS: The proportion of IAC accredited facilities conducting outpatient cerebrovascular testing is low and varies by region. The growing number of certified stroke centers should be accompanied by more accredited vascular testing facilities that could potentially improve quality of stroke care.

Stress myocardial perfusion imaging (MPI) has become an important tool in risk stratification of patients with known coronary artery disease. A normal myocardial perfusion scan has a high negative predictive value and is associated with low annual mortality rate (1%). Patients with extensive ischemia (20% of the left ventricle), defects in more than 1 coronary vascular territory, transient or persistent left ventricular cavity dilation, and ejection fraction less than 45% have a high annual mortality rate (3%). Those patients should undergo coronary revascularization whenever feasible, as the cardiac event rate increases in proportion to the magnitude of the jeopardized myocardium. Stress MPI can be used to demonstrate ischemia in patients with symptoms early after coronary artery bypass surgery (5 years) or in those without symptoms late (/= 5 years) after coronary artery bypass surgery. With respect to patients who underwent percutaneous interventions, stress MPI can help detect in-stent restenosis early after the intervention (3-6 months) or assess the progression of native coronary disease afterward. Since preliminary data suggest that a reduction in the perfusion defect size may translate to a reduction of coronary events, stress MPI can help assess the efficacy of medical management of coronary disease. Finally, stress MPI is indicated for perioperative cardiac risk stratification for noncardiac surgery in patients with intermediate risk predictors (mild angina, prior myocardial infarction or heart failure symptoms, diabetes mellitus, renal insufficiency) and poor functional capacity or in those who undergo high-risk surgery with significant implications in further preoperative management.

Background — Coronary artery disease can develop prematurely and is the leading cause of death among diabetics, making noninvasive risk stratification desirable. Methods and Results — Patients with symptoms of coronary artery disease who were undergoing stress myocardial perfusion imaging (MPI) from 5 centers were prospectively followed (2.5±1.5 years) for the subsequent occurrence of cardiac death, myocardial infarction (MI), and revascularization. Stress MPI results were categorized as normal or abnormal (fixed or ischemic defects and 1, 2, or 3 vessel distribution). Of 4755 patients, 929 (19.5%) were diabetic. Patients with diabetes, despite an increased revascularization rate, had 80 cardiac events (8.6%; 39 deaths and 41 MIs) compared with 172 cardiac events (4.5%; 69 deaths and 103 MIs) in the nondiabetic cohort ( P P P Conclusions — In this large cohort of diabetics undergoing stress MPI, the presence and the extent of abnormal stress MPI independently predicted subsequent cardiac events. Using stress MPI in conjunction with clinical information can provide risk stratification of diabetic patients.

Background —A diagnostic test that could distinguish between stable and unstable coronary atherosclerotic plaques would be useful. We tested the ability of a new glycoprotein IIb/IIIa platelet inhibitor DMP-444, labeled with technetium (Tc)-99 m, to identify platelet-rich thrombus by nuclear imaging in a canine model. Methods and Results —Combinations of a flow-limiting stenosis and 0 to 15 minutes of endothelial electrical stimulation at a site in the left anterior descending coronary artery were used to induce varying amounts of thrombus formation. In 10 animals with markedly positive nuclear images after the injection of Tc-99m DMP-444, the presence of platelet-rich thrombus was confirmed postmortem by gross appearance, high nuclear counts, and abundant platelets on electron microscopy. The 10 animals with negative images had lower counts, smaller thrombus weights ( P Conclusions —Activated platelets participating in acute thrombus formation can be accurately detected by nuclear imaging using Tc-99 m DMP-444.

Background —Because of its brief hemodynamic effects and minor effect on determinants of myocardial oxygen demand, vasodilator stress myocardial perfusion imaging (MPI) can be applied very early after acute myocardial infarction (AMI) for risk stratification, allowing management decisions to be made earlier and thus potentially shortening hospitalization stays, reducing costs, and preventing early cardiac events. This multicenter randomized trial compared the prognostic value of early dipyridamole MPI and standard predischarge submaximal exercise MPI in patients who presented with AMI. Methods and Results —Patients who presented with their first AMI (n=451) were randomized in a 3:1 ratio to undergo either both an early (day 2 to 4) dipyridamole 99m Tc-sestamibi MPI study and a predischarge (day 6 to 12) submaximal exercise 99m Tc-sestamibi MPI study or only the predischarge study. Multivariate predictors of in-hospital cardiac events included nuclear imaging summed stress and summed reversibility scores and peak creatine kinase. For postdischarge cardiac events, multivariate predictors in patients undergoing dipyridamole MPI included only the summed stress, reversibility, and rest imaging scores and anterior MI. For a given summed stress score, the interaction of reversibility score further improved the predictive value. Dipyridamole MPI showed better risk stratification than submaximal exercise MPI. Conclusions —Dipyridamole MPI very early after MI predicts early and late cardiac events, with superior prognostic value compared with submaximal exercise imaging. The extent and severity of the stress defect and reversibility of the defect were the most important predictors of cardiac death and recurrent MI. This technique can allow management decisions to be made earlier with regard to AMI patients and could have important economic impact if applied widely.

Background —Soft tissue attenuation is a prominent cause of single-photon emission computed tomography (SPECT) imaging artifacts, which may result in reduced diagnostic accuracy of myocardial perfusion imaging. A method incorporating simultaneously acquired transmission data permits nonuniform attenuation correction and when incorporating scatter correction and resolution compensation may substantially reduce interpretive errors. Methods and Results —A prospective multicenter trial was performed recruiting patients with angiographically documented coronary disease (n=96) and group of subjects with a low likelihood of disease (n=88). The uncorrected and attenuation/scatter corrected images were read independently, without knowledge of the patient’s clinical data. The detection of ≥50% stenosis was similar using uncorrected perfusion data or with attenuation/scatter correction and resolution compensation (visual or visual plus quantitative analysis), 76% versus 75% versus 78%, respectively ( P =NS). The normalcy rate, however, was significantly improved with this new methodology, using either the corrected images (86% vs 96%; P =0.011) or with the corrected data and quantitative analysis (86% vs 97%; P =0.007). The receiver operator characteristic curves were also found to be marginally but not significantly higher with attenuation/scatter correction than with tradition SPECT imaging. However, the ability to detect multivessel disease was reduced with attenuation/scatter correction. Regional differences were also noted, with reduced sensitivity but improved specificity for right coronary lesions using attenuation/scatter correction methodology. Conclusions —This multicenter trial demonstrates the initial clinical results of a new SPECT perfusion imaging modality incorporating attenuation and scatter correction in conjunction with 99m Tc sestamibi perfusion imaging. Significant improvements in the normalcy rate were noted without a decline in overall sensitivity but with a reduction in detection of extensive coronary disease.

Acute chest pain syndromes are common, with over 6 million patients in the United States presenting to emergency departments with suggestive symptoms. This review concentrates on the previous models and new diagnostic testing procedures. The different modalities emphasized are computer-generated models, serum markers, echocardiography, and nuclear imaging in the emergency department. The use of new markers and imaging may help to risk-stratify patients earlier for potential treatment and triage decisions.

On behalf of the Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation (COURAGE) Investigators, we wish to thank Drs Joshi, Tarantini, and colleagues for their letters to the editor regarding our article.1 Many excellent comments were made that serve to clarify the COURAGE nuclear substudy. It is important to note that this study was devised to compare treatment effectiveness using nuclear quantification of ischemia as a surrogate outcome. The design of the substudy was based on the prognostic findings from observational registries of tens of thousands of patients undergoing stress myocardial perfusion single photon emission computed tomography (SPECT).2–4 Importantly, no published data were available previously to suggest that significant relative risk reduction would be seen in patients with ischemia reduction. Therefore, this study was not powered to examine differences in prognosis but was designed to determine whether percutaneous coronary intervention (PCI) resulted in a greater reduction of objective ischemia than did optimal medical therapy alone, extending prior, small series that found serial changes in …

In order to study acute changes in perfusion with intracoronary thrombolytic therapy, the authors have used ten times the pretherapy intracoronary thallium-201 dose for the posttherapy study. Because of the larger posttherapy dose, the posttherapy images had ten times as many counts as the pretherapy images. Since the change in image quality between the pretherapy and posttherapy studies might affect interpretation, they studied the effect of image statistics on interpretation of perfusion scintigraphy. The pretherapy and posttherapy images were scored on a four-point scale in five segments on each of three views. In 31 patients, Poisson-distributed pseudorandom noise was added to the posttherapy study in order to match the statistical accuracy of the pretherapy study. A blinded interpretation of the pretherapy and posttherapy noise-added images was performed in the same way as the initial unblinded interpretation. The mean difference between the unblinded pretherapy and posttherapy scores (the improvement in thallium distribution with therapy) was 2.5 +/- 0.8 (standard error) compared with the difference between the blinded pretherapy and posttherapy noise-added scores which was 2.6 +/- 1.0. The correlation between readings of similar pairs of data was higher than the correlation between pretherapy and posttherapy studies. Thus, the difference in statisticmore » quality of the pretherapy and posttherapy studies did not affect the interpretation of these studies. Therefore, the evaluation of pretherapy and posttherapy studies using a ten-fold increase in thallium-201 dosage is valid.« less

Both systolic and diastolic dysfunction have been described during pacing-induced ischemia, but the temporal sequence of systolic and diastolic impairment has not been established. Accordingly, 22 patients with coronary artery disease were paced at increasing heart rates and studied with simultaneous hemodynamic monitoring, electrocardiographic recording, and radionuclide ventriculography. In addition, with synchronized left ventricular pressure tracings and radionuclide volume curves, three sequential pressure-volume diagrams were constructed for each patient corresponding to baseline, intermediate, and maximum pacing levels. Eleven patients (group I) demonstrated a nonischemic response to pacing tachycardia without chest pain, significant electrocardiographic changes, or significant rise in left ventricular end-diastolic pressure (LVEDP) in the immediate postpacing period. These patients demonstrated a progressive decrease in LVEDP, end-diastolic volume, and end-systolic volume, no change in cardiac output or left ventricular ejection fraction, and a progressive increase in left ventricular diastolic peak filling rate and the end-systolic pressure-volume ratio. Pressure-volume diagrams shifted progressively leftward and slightly downward, suggesting both an increase in contractility and a mild increase in left ventricular distensibility. The remaining 11 patients (group II) exhibited an ischemic response to pacing tachycardia, with each patient experiencing angina pectoris, demonstrating greater than 1 mm ST segment depression on the electrocardiogram, and exhibiting greater than 5 mm Hg rise in LVEDP immediately after pacing. LVEDP, end-diastolic volume, and end-systolic volume in these patients initially decreased and then subsequently increased during angina, with no change in cardiac output but a decrease in ejection fraction. Left ventricular peak diastolic filling rate and the left ventricular end-systolic pressure-volume ratio both increased at the intermediate pacing rate but fell at maximum pacing. Pressure-volume diagrams for these patients shifted leftward initially, then back to the right, during intermediate and peak pacing levels, often with an upward shift in the diastolic pressure-volume relationship. LVEDP in group II was significantly higher than that in group I at the intermediate pacing level with no difference in end-diastolic or end-systolic volumes, suggesting decreased left ventricular distensibility in these patients before the onset of systolic dysfunction at the maximum pacing level.(ABSTRACT TRUNCATED AT 400 WORDS)

To elucidate the mechanisms by which the new bipyridine inotropic agent milrinone improves cardiac function, we examined multiple indexes of left ventricular diastolic function before and after administration of milrinone to patients with advanced (NYHA class III or IV) congestive heart failure. In 13 patients left ventricular pressure measurements were made with a micromanometer to permit assessment of peak negative dP/dt and the time constant of left ventricular isovolumic relaxation, T, before and after milrinone. In nine patients radionuclide ventriculographic studies were performed during left heart catheterization, allowing calculation of left ventricular peak filling rate, volumes, and the diastolic pressure-volume relationship before and after milrinone. After intravenous administration of milrinone, peak negative dP/dt increased (+ 18%; p less than .01) and T decreased (-30%; p less than .01), while heart rate increased by only 8% (87 +/- 12 to 94 +/- 15 beats/min; p less than .01), left ventricular systolic pressure did not change, and mean aortic pressure fell by 11% (p less than .01). Left ventricular peak filling rate increased (1.2 +/- 0.6 to 1.7 +/- 0.7 end-diastolic volumes/sec; p less than or equal to .02) despite a decrease in left ventricular filling pressure (mean pulmonary wedge pressure 27 +/- 7 to 18 +/- 9 mm Hg; p less than .01). There was a fall in left ventricular end-diastolic pressure (28.6 +/- 6 to 19 +/- 7 mm Hg; p less than or equal to .01), with no significant change in left ventricular end-diastolic volume. This was associated with a downward shift in the left ventricular diastolic pressure-volume relationship in most cases.(ABSTRACT TRUNCATED AT 250 WORDS)

Clomiphene citrate, 50–400 rag/day for 2–12 months (median 7 months), stimulated the pituitary-gonadal axis in 13 normal men as evidenced by increased urinary excretion of hormones. Urinary total gonadotropins were increased by 80–400%, urinary ICSH 160–1200%, urinary estrogens by 150–680%, and urinary testosterone by 140–250%. In each individual the increase in ICSH was greater than the increase in total gonadotropins. No dose relationship was observed in any of these hormonal parameters. Sperm concentration was dosage related: low dosages of clomiphene (50 mg/day) caused an increase; intermediate dosages (100 and 200 mg/day) caused an increase, decrease, or no change; and high doses caused precipitous decreases. One subject given 3 doses showed 3 responses in sperm counts from an increase with a low dosage to azoospermia with a high dosage. It is inferred that the effect of the increase in gonadotropins and testosterone stimulates spermatogenesis at the spermatogonial level, causing an increase...