Patient Management After Noninvasive Cardiac Imaging – Results From SPARC (Study of Myocardial Perfusion and Coronary Anatomy Imaging Roles in Coronary Artery Disease)

OBJECTIVES: This study examined short-term cardiac catheterization rates and medication changes after cardiac imaging. Noninvasive cardiac imaging is widely used in coronary artery disease, but its effects on subsequent patient management are unclear.

METHODS: We assessed the 90-day post-test rates of catheterization and medication changes in a prospective registry of 1,703 patients without a documented history of coronary artery disease and an intermediate to high likelihood of coronary artery disease undergoing cardiac single-photon emission computed tomography, positron emission tomography, or 64-slice coronary computed tomography angiography.

RESULTS: Baseline medication use was relatively infrequent. At 90 days, 9.6% of patients underwent catheterization. The rates of catheterization and medication changes increased in proportion to test abnormality findings. Among patients with the most severe test result findings, 38% to 61% were not referred to catheterization, 20% to 30% were not receiving aspirin, 35% to 44% were not receiving a beta-blocker, and 20% to 25% were not receiving a lipid-lowering agent at 90 days after the index test. Risk-adjusted analyses revealed that compared with stress single-photon emission computed tomography or positron emission tomography, changes in aspirin and lipid-lowering agent use was greater after computed tomography angiography, as was the 90-day catheterization referral rate in the setting of normal/nonobstructive and mildly abnormal test results.

CONCLUSIONS: Overall, noninvasive testing had only a modest impact on clinical management of patients referred for clinical testing. Although post-imaging use of cardiac catheterization and medical therapy increased in proportion to the degree of abnormality findings, the frequency of catheterization and medication change suggests possible undertreatment of higher risk patients. Patients were more likely to undergo cardiac catheterization after computed tomography angiography than after single-photon emission computed tomography or positron emission tomography after normal/nonobstructive and mildly abnormal study findings.

PMID:

Assessment of Valvular Calcification and Inflammation by Positron Emission Tomography in Patients With Aortic Stenosis

OBJECTIVES: The pathophysiology of aortic stenosis is incompletely understood and the relative contributions of valvular calcification and inflammation to disease progression are unknown.

METHODS: Patients with aortic sclerosis and mild, moderate and severe stenosis were prospectively compared to age and sex-matched control subjects. Aortic valve severity was determined by echocardiography. Calcification and inflammation in the aortic valve were assessed by sodium 18-fluoride (18F-NaF) and 18-fluorodeoxyglucose (18F-FDG) uptake using positron emission tomography. One hundred and twenty one subjects (20 controls; 20 aortic sclerosis; 25 mild, 33 moderate and 23 severe aortic stenosis) were administered both 18F-NaF and 18F-FDG.

RESULTS: Quantification of tracer uptake within the valve demonstrated excellent inter-observer repeatability with no fixed or proportional biases and limits of agreement of ±0.21 (18F-NaF) and ±0.13 (18F-FDG) for maximum tissue-to-background ratios (TBR). Activity of both tracers was higher in patients with aortic stenosis than control subjects (18F-NaF:2.87±0.82 vs 1.55±0.17; 18F-FDG: 1.58±0.21 vs 1.30±0.13; both P1.97) and 35% increased 18F-FDG (>1.63) uptake. A weak correlation between the activities of these tracers was observed (r(2)= 0.174, P

CONCLUSIONS: Positron emission tomography is a novel, feasible and repeatable approach to thee valuation of valvular calcification and inflammation in patients with aortic stenosis. The frequency and magnitude of increased tracer activity correlates with disease severity, and is strongest for 18F-NaF.

PMID: 22090163

Cardiovascular Magnetic Resonance and Single-Photon Emission Computed Tomography for Diagnosis of Coronary Heart Disease (CE-MARC): A Prospective Trial

PMID:

Quantitative Relationship Between the Extent and Morphology of Coronary Atherosclerotic Plaque and Downstream Myocardial Perfusion

OBJECTIVES: Although the relationship between coronary stenosis and myocardial perfusion is well established, little is known about the contribution of other anatomic descriptors of atherosclerosis burden to this relationship. The purpose of this study was to quantify the effects of coronary atherosclerosis morphology and extent on myocardial flow reserve (MFR).

METHODS: We evaluated the relationship between atherosclerosis plaque burden, morphology, and composition and regional MFR (MFR_regional) in 73 consecutive patients undergoing Rubidium-82 positron emission tomography and coronary computed tomography angiography for the evaluation of known or suspected coronary artery disease.

RESULTS: Atherosclerosis was seen in 51 of 73 patients and in 107 of 209 assessable coronary arteries. On a per-vessel basis, the percentage diameter stenosis (p = 0.02) or summed stenosis score (p = 0.002), integrating stenoses in series, was the best predictor of MFR_regional. Importantly, MFR_regional varied widely within each coronary stenosis category, even in vessels with nonobstructive plaques (n = 169), 38% of which had abnormal MFR_regional (<2.0). Total plaque length, composition, and remodeling index were not associated with lower MFR. On a per-patient basis, the modified Duke CAD (coronary artery disease) index (p = 0.04) and the number of segments with mixed plaque (p = 0.01) were the best predictors of low MFR_global.

CONCLUSIONS: Computed tomography angiography descriptors of atherosclerosis had only a modest effect on downstream MFR. On a per-patient basis, the extent and severity of atherosclerosis as assessed by the modified Duke CAD index and the number of coronary segments with mixed plaque were associated with decreased MFR.

PMID:

Imaging Intraplaque Inflammation in Carotid Atherosclerosis With 11C-PK11195 Positron Emission Tomography/Computed Tomography

OBJECTIVES: We sought to determine whether intraplaque inflammation could be measured with positron emission tomography/computed tomography angiography (PET/CTA) using (11)C-PK11195, a selective ligand of the translocator protein (18 kDa) (TSPO) which is highly expressed by activated macrophages.

METHODS: (n = 32; mean age 70 ± 9 years) with carotid stenoses (n = 36; 9 symptomatic and 27 asymptomatic) underwent (11)C-PK11195 PET/CTA imaging. (11)C-PK11195 uptake into carotid plaques was measured using target-to-background ratios (TBR). On CTA images, plaque composition was assessed by measuring CT attenuation of the carotid plaque. Eight patients underwent carotid endarterectomy and ultrathin contiguous sections were processed for TSPO and CD68 (using immunohistochemical staining, (3)H-PK11195 autoradiography, and confocal fluorescence microscopy).

RESULTS: Carotid plaques associated with ipsilateral symptoms (stroke or transient ischaemic attack) had higher TBR (1.06 ± 0.20 vs. 0.86 ± 0.11, P = 0.001) and lower CT attenuation [(median, inter-quartile range) 37, 24-40 vs. 71, 56-125 HU, P = 0.01] than those without. On immunohistochemistry and confocal fluorescence microscopy, CD68 and PBR co-localized with (3)H-PK11195 uptake at autoradiography. There was a significant correlation between (11)C-PK11195 TBR and autoradiographic percentage-specific binding (r = 0.77, P = 0.025). Both TBR and CT plaque attenuation had high negative predictive values (91 and 92%, respectively) for detecting symptomatic patients. However, the best positive predictive value (100%) was achieved when TBR and CT attenuation were combined.

CONCLUSIONS: Imaging intraplaque inflammation in vivo with (11)C-PK11195 PET/CTA is feasible and can distinguish between recently symptomatic and asymptomatic plaques. Patients with a recent ischaemic event had ipsilateral plaques with lower CT attenuation and increased (11)C-PK11195 uptake.

PMID:

Cardiac PET/CT for the Evaluation of Known or Suspected Coronary Artery Disease

Positron emission tomography (PET) is increasingly being applied in the evaluation of myocardial perfusion. Cardiac PET can be performed with an increasing variety of cyclotron- and generator-produced radiotracers. Compared with single photon emission computed tomography, PET offers lower radiation exposure, fewer artifacts, improved spatial resolution, and, most important, improved diagnostic performance. With its capacity to quantify rest-peak stress left ventricular systolic function as well as coronary flow reserve, PET is superior to other methods for the detection of multivessel coronary artery disease and, potentially, for risk stratification. Coronary artery calcium scoring may be included for further risk stratification in patients with normal perfusion imaging findings. Furthermore, PET allows quantification of absolute myocardial perfusion, which also carries substantial prognostic value. Hybrid PET-computed tomography scanners allow functional evaluation of myocardial perfusion combined with anatomic characterization of the epicardial coronary arteries, thereby offering great potential for both diagnosis and management. Additional studies to further validate the prognostic value and cost effectiveness of PET are warranted.

PMID: 21918042

Rates of Downstream Invasive Coronary Angiography and Revascularization: Computed Tomographic Coronary Angiography vs. Tc-99m Single Photon Emission Computed Tomography

OBJECTIVES: Computed tomographic coronary angiography (CTA) appears to be a useful modality for the detection of obstructive coronary artery disease (CAD). Recent data suggest that CTA may reduce the frequency of normal invasive coronary angiograms. However, there remains concern that the implementation of CTA could increase referrals to invasive coronary angiography (ICA). To further support the clinical acceptance of CTA, it is important to compare CTA to another accepted modality such as single photon emission computed tomography (SPECT). We followed a cohort of 64-slice CTA patients and a matched cohort of Tc-99m SPECT patients to determine downstream referrals for ICA and revascularization.

METHODS: Consecutive CTA patients (without history of revascularization or cardiac transplantation) were prospectively enrolled and compared with a Tc-99m SPECT cohort (matched for age, gender, and Morise score). Each CTA and SPECT was evaluated for obstructive CAD and patients were followed for downstream ICA and revascularization.

RESULTS: Of the 1221 patients in each cohort, 129 (10.6%) CTA patients and 125 (10.2%) SPECT patients were referred to ICA. Of those referred to ICA, obstructive CAD was confirmed in 105 (81.4%) CTA patients and in 88 (70.4%) SPECT patients. Differences in false positive rates were significantly lower in the CTA than the SPECT cohort (9.7 and 25.8%, respectively, P = 0.009). Rates of revascularization were similar in the CTA and SPECT cohorts (6.2 vs. 5.9%, respectively).

CONCLUSIONS: Compared with SPECT, CTA had similar referrals for ICA and revascularization rates but lower false positive rates. Computed tomographic coronary angiography appears to be a viable non-invasive diagnostic modality and does not appear to negatively impact upon ICA resources.

PMID: 21893487

Pharmacology in Nuclear Cardiology

Although exercise remains the preferred method of cardiac stress testing, pharmacological stress plays an important role in nuclear cardiology. The globally ageing population will see an expansion of the application of pharmacological stress testing, and with this, comes the need to understand the pharmacological basis, mechanisms of action, potential interactions and adverse effects to inform usage in less-than-ideal circumstances. This study aims to enhance the decision-making process in day-to-day clinical nuclear cardiology practice through a better understanding of nuances relevant to the pharmacological agents used for cardiac stress testing.

PMID: 21471849

Hypoxia But Not Inflammation Augments Glucose Uptake in Human Macrophages Implications For Imaging Atherosclerosis With (18)Fluorine-Labeled 2-Deoxy-D-Glucose Positron Emission Tomography

OBJECTIVES: Patient studies suggest that positron emission tomography (PET) using  (18)fluorine-labeled 2-deoxy-D-glucose FdG can detect “active” atherosclerotic plaques, yet the mechanism giving rise to FdG signals remains unknown. This study investigated the regulation of glucose uptake in cells that participate in atherogenesis by stimuli relevant to this process, to gain mechanistic insight into the origin of the FdG uptake signals observed clinically.

METHODS: We exposed cells to conditions thought to operate in atheroma and determined rates of glucose uptake.

RESULTS: Hypoxia, but not pro-inflammatory cytokines, potently stimulated glucose uptake in human macrophages and foam cells. Statins attenuated this process in vitro, suggesting that these agents have a direct effect on human macrophages. Immunohistochemical study of human plaques revealed abundant expression of proteins regulating glucose utilization, predominantly in macrophage-rich regions of the plaques-regions previously proved hypoxic. Smooth-muscle cells and endothelial cells markedly increased rates of glucose uptake when exposed to pro-inflammatory cytokines.

CONCLUSIONS: Glucose uptake and, probably, FdG uptake signals in atheroma may reflect hypoxia-stimulated macrophages rather than mere inflammatory burden. Cytokine-activated smooth-muscle cells also may contribute to the FdG signal.

PMID: 21798423

Environmental Impact of Cardiac Imaging Tests For the Diagnosis of Coronary Artery Disease

OBJECTIVES: The use of cardiovascular imaging is growing inexorably and concerns have been expressed about its cost and radiation safety.

METHODS: In this study, the relative environmental impact of MRI, single photon emission tomography and cardiac ultrasound (echo) for the diagnosis of coronary artery disease were examined.

RESULTS: The results emphasise that echo causes the least environmental impact at each stage of its life cycle. The effect of one echo on human health, ecosystem effects and resource use was of the order of 1-20% of those of the alternative methods.

CONCLUSIONS: Although there are circumstances in which one imaging modality is preferred on clinical grounds, when everything else is equal, these results support the selection of echocardiography as the preferred test on environmental grounds.

PMID: 21685481

Integrated SPECT/CT for Assessment of Haemodynamically Significant Coronary Artery Lesions in Patients With Acute Coronary Syndrome

OBJECTIVES: Early risk stratification in patients with non-ST elevation acute coronary syndromes (NSTE-ACS) is important since the benefit from more aggressive and costly treatment strategies is proportional to the risk of adverse clinical events. In the present study we assessed whether hybrid single photon emission computed tomography (SPECT)/coronary computed tomography angiography (CCTA) technology could be an appropriate tool in stratifying patients with NSTE-ACS.

METHODS: SPECT/CCTA was performed in 90 consecutive patients with NSTE-ACS. The Thrombolysis in Myocardial Infarction risk score (TIMI-RS) was used to classify patients as low- or high-risk. Imaging was performed using SPECT/CCTA to identify haemodynamically significant lesions defined as >50% stenosis on CCTA with a reversible perfusion defect on SPECT in the corresponding territory.

RESULTS: CCTA demonstrated at least one lesion with >50% stenosis in 35 of 40 high-risk patients (87%) as compared to 14 of 50 low-risk patients (35%; TIMI-RS <3; p <0.0001). Of the 40 high-risk and 50 (16%) low-risk TIMI-RS patients, 16 (40%) and 8 (16%), respectively, had haemodynamically significant lesions (p = 0.01). Patients defined as high-risk by a high TIMI-RS, a positive CCTA scan or both (n = 45) resulted in a sensitivity of 95%, specificity of 49%, PPV of 35% and NPV of 97% for having haemodynamically significant coronary lesions. Those with normal perfusion were spared revascularization procedures, regardless of their TIMI-RS.

CONCLUSIONS: Noninvasive assessment of coronary artery disease by SPECT/CCTA may play an important role in risk stratification of patients with NSTE-ACS by better identifying the subgroup requiring intervention.

PMID: 21688049

Cost-Effectiveness of Coronary Computed Tomography and Cardiac Stress Imaging in the Emergency Department a Decision Analytic Model Comparing Diagnostic Strategies for Chest Pain in Patients at Low Risk of Acute Coronary Syndromes

OBJECTIVES: Emergency department presentations with chest pain are expensive and often unrelated to coronary artery disease (CAD). Coronary computed tomographic angiography (CTA) may allow earlier discharge of low-risk patients, resulting in cost savings.

METHODS: We modeled clinical and economic outcomes of diagnostic strategies in patients with chest pain and at low risk of CAD: exercise electrocardiography (ECG), stress single-photon emission computed tomography (SPECT), stress echocardiography, and a CTA strategy comprising an initial CTA scan with confirmatory SPECT for indeterminate results.

RESULTS: Our results suggest that a 2-step diagnostic strategy of CTA with SPECT for intermediate scans is likely to be less costly and more effective for the diagnosis of a patient group at low risk of CAD and a prevalence of 2% to 30%. The CTA strategies were cost saving (lower costs, higher quality-adjusted life-years) compared with stress ECG, echocardiography, and SPECT.

CONCLUSIONS: Confirming intermediate/indeterminate CTA scans with SPECT results in cost savings and quality-adjusted life-year gains due to reduced hospitalization of patients who returned false-positive initial CTA test. However, CTA may be associated with a higher event rate in negative patients than SPECT, and the diagnostic and prognostic information for the use of CTA in the emergency department is evolving. Large comparative, randomized, controlled trials of the different diagnostic strategies are needed to compare the long-term costs and consequences of each strategy in a population of defined low-risk patients in the emergency department.

PMID: 21565744

Troponin T Levels and Infarct Size by SPECT Myocardial Perfusion Imaging

OBJECTIVES: To evaluate the relationship between serial cardiac troponin T (cTnT) levels with infarct size and left ventricular ejection fraction by gated single-photon emission computed tomography myocardial perfusion imaging (SPECT-MPI) in patients with acute myocardial infarction (AMI). Current guidelines recommend the use of cTnT as the biomarker of choice for the diagnosis of AMI. Data relating cTnT to SPECT-MPI in patients with AMI are limited.

METHODS: A subset of patients with their first AMI participating in a community-based cohort of AMI in Olmsted County, Minnesota, were prospectively studied. Serial cTnT levels were evaluated at presentation, <12 h and 1, 2, and 3 days after onset of pain. Peak cTnT was defined as the maximum cTnT value.

RESULTS: A total of 121 patients (age, 61 ± 13 years; 31% women) with AMI underwent gated SPECT-MPI at a median (25th percentile, 75th percentile) of 10 (5, 15) days post-AMI. The type of infarct was non-ST-segment elevation myocardial infarction in 61%, and 13% were anterior in location. The median infarct size was 1% (0%, 11%) and the median gated left ventricular ejection fraction was 54% (47%, 60%). Fifty-nine patients (49% of the population) had no measurable infarction by SPECT-MPI. Independent predictors of measurable SPECT-MPI infarct size included cTnT at days 1, 2, and 3 and peak cTnT, but not at presentation or <12 h. In receiver-operator characteristic analysis, the area under the curve was highest at day 3. Receiver-operator characteristic analysis demonstrated a cutoff of 1.5 ng/ml for peak cTnT for the detection of measurable infarct size.

CONCLUSIONS: In a community-based cohort of patients with their first AMI, independent predictors of measurable SPECT-MPI infarct size included cTnT at days 1, 2, and 3 and peak cTnT. In contrast, cTnT level at presentation and <12 h was not an independent predictor of myocardial infarction size as assessed by SPECT-MPI. Receiver-operator characteristic analysis demonstrated a cutoff value peak cTnT of 1.5 ng/ml for the detection of measurable infarct.

PMID: 21565741

Heterogeneous Myocardial FDG Uptake and the Disease Activity in Cardiac Sarcoidosis

OBJECTIVES: This study evaluated the usefulness of fasting (18)F-fluorodeoxyglucose (FDG)-positron emission tomography (PET) in the diagnosis and management of cardiac sarcoidosis (CS) and compared it with FDG uptake in dilated cardiomyopathy (DCM).  Cardiac sarcoidosis may clinically present as DCM but is amenable to systemic corticosteroid therapy if disease activity is high. Although alterations of FDG uptake have been reported in CS, limited information is available on the quantitative estimates of FDG uptake.

METHODS: Fasting FDG-PET was performed in 24 systemic sarcoidosis patients and was compared with 8 age-matched DCM patients. FDG-PET was also performed in 15 age-matched healthy control subjects. Twelve of the 24 sarcoidosis patients had cardiac involvement based on criteria established by the Japanese Ministry of Health and Welfare; the remaining 12 of 24 patients revealed no evidence of cardiac involvement. The myocardial FDG uptake was quantified by measuring the standardized uptake value in 17 myocardial segments in each subject. Coefficient of variation (COV), which equals the standard deviation of uptake divided by the average uptake of 17 segments, was calculated as an index of heterogeneity in the heart.

RESULTS: The FDG uptake was distinctly heterogeneous in CS patients. The COV value was significantly greater in CS patients (0.25 ± 0.05) than control subjects (0.14 ± 0.03, p < 0.01), sarcoidosis patients without cardiac involvement (0.14 ± 0.03, p < 0.01), or DCM patients (0.15 ± 0.02, p < 0.01). The COV value in DCM patients was similar to control subjects or sarcoidosis patients without cardiac involvement. The cutoff COV value for the diagnosis of CS was 0.18 (sensitivity: 100%; specificity: 97%). After corticosteroid therapy in CS patients, the COV value was decreased to 0.14 ± 0.06 (p < 0.05) and became essentially similar to the other groups.

CONCLUSIONS: Heterogeneous myocardial FDG uptake may be a useful diagnostic marker of disease activity for CS.

PMID: 21163450

Incremental Value of Dual-Energy CT to Coronary CT Angiography for the Detection of Significant Coronary Stenosis: Comparison with Quantitative Coronary Angiography and Single Photon Emission Computed Tomography

PMID: 21547377