Balaji Tamarappoo

Pericardial Fat Burden on ECG-Gated Noncontrast CT in Asymptomatic Patients Who Subsequently Experience Adverse Cardiovascular Events

OBJECTIVES We aimed to evaluate whether pericardial fat has value in predicting the risk of future adverse cardiovascular outcomes. BACKGROUND Pericardial fat volume (PFV) and thoracic fat volume (TFV) can be routinely measured from noncontrast computed tomography (NCT) performed for calculating coronary calcium score (CCS) and may predict major adverse cardiac event (MACE) risk. METHODS From a registry of 2,751 asymptomatic patients without known cardiac artery disease and 4-year follow-up for MACE (cardiac death, myocardial infarction, stroke, late revascularization) after NCT, we compared 58 patients with MACE with 174 same-sex, event-free control subjects matched by a propensity score to account for age, risk factors, and CCS. The TFV was automatically calculated, and PFV was calculated with manual assistance in defining the pericardial contour, within which fat voxels were automatically identified. Independent relationships of PFV and TFV to MACE were evaluated using conditional multivariable logistic regression. RESULTS Patients experiencing MACE had higher mean PFV (101.8 +/- 49.2 cm(3) vs. 84.9 +/- 37.7 cm(3), p = 0.007) and TFV (204.7 +/- 90.3 cm(3) vs. 177 +/- 80.3 cm(3), p = 0.029) and higher frequencies of PFV >125 cm(3) (33% vs. 14%, p = 0.002) and TFV >250 cm(3) (31% vs. 17%, p = 0.025). After adjustment for Framingham risk score (FRS), CCS, and body mass index, PFV and TFV were significantly associated with MACE (odds ratio [OR]: 1.74, 95% confidence interval [CI]: 1.03 to 2.95 for each doubling of PFV; OR: 1.78, 95% CI: 1.01 to 3.14 for TFV). The area under the curve from receiver-operator characteristic analyses showed a trend of improved MACE prediction when PFV was added to FRS and CCS (0.73 vs. 0.68, p = 0.058). Addition of PFV, but not TFV, to FRS and CCS improved estimated specificity (0.72 vs. 0.66, p = 0.008) and overall accuracy (0.70 vs. 0.65, p = 0.009) in predicting MACE. CONCLUSIONS Asymptomatic patients who experience MACE exhibit greater PFV on pre-MACE NCT when they are compared with event-free control subjects with similar cardiovascular risk profiles. Our preliminary findings suggest that PFV may help improve prediction of MACE.

Stress Thallium-201/Rest Technetium-99m Sequential Dual Isotope High-Speed Myocardial Perfusion Imaging

OBJECTIVES Our purpose was to describe a novel, rapid stress thallium-201 (Tl-201)/rest technetium-99m (Tc-99m) agent myocardial perfusion imaging (MPI) protocol (Tl/Tc) with a high-speed MPI scanner and to compare this protocol with a standard rest/stress Tc-99m agent protocol (Tc/Tc) with respect to image quality and radiation dosimetry. BACKGROUND Recent advances in gamma camera technology have provided opportunity for improved SPECT MPI protocols. A rapid Tl/Tc protocol that could improve image information while maintaining a low radiation burden for the patient would be desirable. METHODS We compared high-speed SPECT MPI studies in 374 consecutive patients undergoing exercise or pharmacologic Tl/Tc protocol to those of 262 patients undergoing rest/stress Tc/Tc protocol. RESULTS Tl/Tc imaging was accomplished in <20 min. Overall image quality was good to excellent in 96% and 98% of patients with the Tl/Tc and the Tc/Tc protocols, respectively (p = ns). Beginning rest imaging within 2 min after rest injection with the Tl/Tc protocol did not result in reduced confidence in image interpretation. Early rest Tc images of the Tl/Tc protocol showed less extracardiac activity than was observed on standard rest imaging used in the Tc/Tc protocol (84% vs. 61%), respectively (p < 0.01). The normalcy rate was high in both groups (100% vs. 92%). Radiation burden was similar between the Tl/Tc and Tc/Tc protocols. CONCLUSIONS A rapid stress Tl-201/rest Tc-99m protocol for use with high-speed SPECT MPI has image quality and radiation dosimetry similar to those observed with a conventional rest/stress Tc-99m protocol. The Tl/Tc protocol offers promise as an efficient and relatively low radiation dose method, in which the superior qualities of Tl-201 for stress imaging and of the Tc-99m agents for rest imaging can be preserved. The findings also suggest that with rapid imaging rest MPI immediately after Tc-99m agent injection may be superior to standard delayed image initiation.

Increased Pericardial Fat Volume Measured From Noncontrast CT Predicts Myocardial Ischemia by SPECT

OBJECTIVES We evaluated the association between pericardial fat and myocardial ischemia for risk stratification. BACKGROUND Pericardial fat volume (PFV) and thoracic fat volume (TFV) measured from noncontrast computed tomography (CT) performed for calculating coronary calcium score (CCS) are associated with increased CCS and risk for major adverse cardiovascular events. METHODS From a cohort of 1,777 consecutive patients without previously known coronary artery disease (CAD) with noncontrast CT performed within 6 months of single photon emission computed tomography (SPECT), we compared 73 patients with ischemia by SPECT (cases) with 146 patients with normal SPECT (controls) matched by age, gender, CCS category, and symptoms and risk factors for CAD. TFV was automatically measured. Pericardial contours were manually defined within which fat voxels were automatically identified to compute PFV. Computer-assisted visual interpretation of SPECT was performed using standard 17-segment and 5-point score model; perfusion defect was quantified as summed stress score (SSS) and summed rest score (SRS). Ischemia was defined by: SSS - SRS ≥4. Independent relationships of PFV and TFV to ischemia were examined. RESULTS Cases had higher mean PFV (99.1 ± 42.9 cm(3) vs. 80.1 ± 31.8 cm(3), p = 0.0003) and TFV (196.1 ± 82.7 cm(3) vs. 160.8 ± 72.1 cm(3), p = 0.001) and higher frequencies of PFV >125 cm(3) (22% vs. 8%, p = 0.004) and TFV >200 cm(3) (40% vs. 19%, p = 0.001) than controls. After adjustment for CCS, PFV and TFV remained the strongest predictors of ischemia (odds ratio [OR]: 2.91, 95% confidence interval [CI]: 1.53 to 5.52, p = 0.001 for each doubling of PFV; OR: 2.64, 95% CI: 1.48 to 4.72, p = 0.001 for TFV). Receiver operating characteristic analysis showed that prediction of ischemia, as indicated by receiver-operator characteristic area under the curve, improved significantly when PFV or TFV was added to CCS (0.75 vs. 0.68, p = 0.04 for both). CONCLUSIONS Pericardial fat was significantly associated with myocardial ischemia in patients without known CAD and may help improve risk assessment.

Computer-aided Non-contrast CT-based Quantification of Pericardial and Thoracic Fat and Their Associations with Coronary Calcium and Metabolic Syndrome

INTRODUCTION Pericardial fat is emerging as an important parameter for cardiovascular risk stratification. We extended previously developed quantitation of thoracic fat volume (TFV) from non-contrast coronary calcium (CC) CT scans to also quantify pericardial fat volume (PFV) and investigated the associations of PFV and TFV with CC and the Metabolic Syndrome (METS). METHODS TFV is quantified automatically from user-defined range of CT slices covering the heart. Pericardial fat contours are generated by spline interpolation between 5-7 control points, placed manually on the pericardium within this cardiac range. Contiguous fat voxels within the pericardium are identified as pericardial fat. PFV and TFV were measured from non-contrast CT for 201 patients. In 105 patients, abdominal visceral fat area (VFA) was measured from an additional single-slice CT. In 26 patients, images were quantified by two readers to establish inter-observer variability. TFV and PFV were examined in relation to Body Mass Index (BMI), waist circumference and VFA, standard coronary risk factors (RF), CC (Agatston score >0) and METS. RESULTS PFV and TFV showed excellent correlation with VFA (R=0.79, R=0.89, p<0.0001), and moderate correlation with BMI (R=0.49, R=0.48, p<0.0001). In 26 scans, the inter-observer variability was greater for PFV (8.0+/-5.3%) than for TFV (4.4+/-3.9%, p=0.001). PFV and TFV, but not RF, were associated with CC [PFV: p=0.04, Odds Ratio 3.1; TFV: p<0.001, OR 7.9]. PFV and TFV were also associated with METS [PFV: p<0.001, OR 6.1; TFV p<0.001, OR 5.7], unlike CC [OR=1.0 p=NS] or RF. PFV correlated with low-HDL and high-glucose; TFV correlated with low-HDL, low-adiponectin, and high glucose and triglyceride levels. CONCLUSIONS PFV and TFV can be obtained easily and reproducibly from routine CC scoring scans, and may be important for risk stratification and monitoring.

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.

Quantitative Upright–Supine High-Speed SPECT Myocardial Perfusion Imaging for Detection of Coronary Artery Disease: Correlation with Invasive Coronary Angiography

A recently developed camera system for high-speed SPECT (HS-SPECT) myocardial perfusion imaging shows excellent correlation with conventional SPECT. Our goal was to test the diagnostic accuracy of an automated quantification of combined upright and supine myocardial SPECT for detection of coronary artery disease (CAD) (≥70% luminal diameter stenosis or, in left main coronary artery, ≥50% luminal diameter stenosis) in comparison to invasive coronary angiography (ICA). Methods: We studied 142 patients undergoing upright and supine HS-SPECT, including 56 consecutive patients (63% men; mean age ± SD, 64 ± 13 y; 45% exercise stress) without known CAD who underwent diagnostic ICA within 6 mo of HS-SPECT and 86 consecutive patients with a low likelihood of CAD. Reference limits for upright and supine HS-SPECT were created from studies of patients with a low likelihood of CAD. Automated software adopted from supine–prone analysis was used to quantify the severity and extent of perfusion abnormality and was expressed as total perfusion deficit (TPD). TPD was obtained for upright (U-TPD), supine (S-TPD), and combined upright–supine acquisitions (C-TPD). Stress U-TPD ≥ 5%, S-TPD ≥ 5%, and C-TPD ≥ 3% myocardium were considered abnormal for per-patient analysis, and U-TPD, S-TPD, and C-TPD ≥ 2% in each coronary artery territory were considered abnormal for per-vessel analysis. Results: On a per-patient basis, the sensitivity was 91%, 88%, and 94% for U-TPD, S-TPD, and C-TPD, respectively, and specificity was 59%, 73%, and 86% for U-TPD, S-TPD, and C-TPD, respectively. C-TPD had a larger area under the receiver-operating-characteristic curve than U-TPD or S-TPD for identification of stenosis ≥ 70% (0.94 vs. 0.88 and 0.89, P < 0.05 and not significant, respectively). On a per-vessel basis, the sensitivity was 67%, 66%, and 69% for U-TPD, S-TPD, and C-TPD, respectively, and specificity was 91%, 94%, and 97% for U-TPD, S-TPD, and C-TPD, respectively (P = 0.02 for specificity U-TPD vs. C-TPD). Conclusion: In this first comparison of HS-SPECT with ICA, new automated quantification of combined upright and supine HS-SPECT shows high diagnostic accuracy for detecting clinically significant CAD, with findings comparable to those reported using conventional SPECT.

Coronary Arterial 18F-FDG Uptake by Fusion of PET and Coronary CT Angiography at Sites of Percutaneous Stenting for Acute Myocardial Infarction and Stable Coronary Artery Disease

Whether 18F-FDG PET can detect inflammation in the coronary arteries remains controversial. We examined 18F-FDG uptake at the culprit sites of acute myocardial infarction (AMI) after percutaneous coronary stenting (PCS) by coregistering PET and coronary CT angiography (CTA). Methods: Twenty nondiabetic patients with AMI (median age, 62 y; 16 men and 4 women) and 7 nondiabetic patients with stable coronary artery disease (CAD; median age, 67 y; 4 men and 3 women) underwent 18F-FDG PET and coronary CTA 1–6 d after PCS of culprit stenoses. After a low-carbohydrate dietary preparation and more than 12 h of fasting, 480 MBq of 18F-FDG were injected, and PET images were acquired 3 h later. Helical CTA was performed on a dual-source scanner. Stent position on attenuation-correction noncontrast CT and CTA was used to fuse PET and CTA. Two experienced readers masked to patient data independently quantified maximum target-to-background ratio (maxTBR) at each PCS site. A maxTBR greater than 2.0 was the criterion for significant uptake. Results: Compared with stable CAD patients, more AMI patients exhibited a PCS site maxTBR greater than 2.0 (12/20 vs. 1/7, P = 0.04). More AMI patients were active smokers (9/20 vs. 0/7 in stable CAD, P = 0.03). After adjusting for baseline demographic differences, stent–myocardium distance, and myocardial 18F-FDG uptake, presentation of AMI was positively associated with a PCS site maxTBR greater than 2.0 (odds ratio, 31.6; P = 0.044). Prevalence of excess myocardial 18F-FDG uptake was similar in both populations (8/20 AMI vs. 3/7 stable CAD, P = 0.89). Conclusion: Systematic fusion of 18F-FDG PET and coronary CTA demonstrated increased culprit site 18F-FDG uptake more commonly in patients with AMI than in patients with stable CAD. However, this approach failed to detect increased signal at the culprit site in nearly half of AMI patients, highlighting the challenging nature of in vivo coronary artery plaque metabolic imaging. Nonetheless, our findings suggest that imaging of coronary artery inflammation is feasible, and further work evaluating 18F-FDG uptake in high-risk coronary plaques prior to rupture would be of great interest.

Comparison of the Extent and Severity of Myocardial Perfusion Defects Measured by CT Coronary Angiography and SPECT Myocardial Perfusion Imaging

OBJECTIVES We compared electrocardiogram-gated computed tomography (CT) myocardial perfusion imaging (MPI) based on quantification of the extent and severity of perfusion abnormalities to that measured with single-photon emission computed tomography (SPECT) MPI. BACKGROUND Contrast-enhanced CT-MPI has been used for the identification of myocardial ischemia. METHODS We performed CT-MPI during intravenous adenosine infusion in 30 patients with perfusion abnormalities on rest/adenosine stress SPECT-MPI acquired within 60 days (18 stress-rest CT-MPI and 12 stress CT-MPI only). The extent and severity of perfusion defects on SPECT-MPI were assessed on a 5-point scale in a standard 17-segment model, and total perfusion deficit (TPD) was quantified by automated software. The extent and severity of perfusion defects on CT-MPI was visually assessed by 2 observers using the same grading scale and expressed as summed stress score and summed rest score; visually quantified TPD was given by summed stress score/(maximal score of 68) and summed rest score/68. The magnitude of perfusion abnormality on CT-MPI in regions of the myocardium was defined. RESULTS On a per-segment basis, there was good agreement between CT-MPI and SPECT-MPI with a kappa of 0.71 (p < 0.0001) for detection of stress perfusion abnormalities. Automated TPD on SPECT-MPI was similar to visual TPD from CT-MPI (p = 0.65 stress TPD, and p = 0.12 ischemic TPD stress-rest) with excellent agreement (bias = -0.3 for stress TPD, and bias = 1.2 for ischemic TPD) on Bland-Altman analysis. Software-based quantification of the magnitude of stress perfusion deficit and ischemia on CT-MPI were similar to that for automated TPD measured by SPECT (p = 0.88 stress, and p = 0.48 ischemia), with minimal bias (bias = 0.6, and bias = 1.2). CONCLUSIONS Stress and reversible myocardial perfusion deficit measured by CT-MPI using a visual semiquantitative approach and a visually guided software-based approach show strong similarity with SPECT-MPI, suggesting that CT-MPI-based assessment of myocardial perfusion defects may be of clinical and prognostic value.

Vulnerable Plaque Features on Coronary CT Angiography as Markers of Inducible Regional Myocardial Hypoperfusion from Severe Coronary Artery Stenoses

OBJECTIVE We explored whether the presence of 3 known features of plaque vulnerability on coronary CT angiography (CCTA)--low attenuation plaque content (LAP), positive remodeling (PR), and spotty calcification (SC)--identifies plaques associated with greater inducible myocardial hypoperfusion measured by myocardial perfusion imaging (MPI). METHODS We analyzed 49 patients free of cardiac disease who underwent CCTA and MPI within a 6-month period and were found on CCTA to have focal 70-99% stenosis from predominantly non-calcified plaque in the proximal or mid segment of 1 major coronary artery. Presence of LAP (≤ 30 Hounsfield Units), PR (outer wall diameter exceeds proximal reference by ≥ 5%), and SC (≤ 3 mm long and occupies ≤ 90° of cross-sectional artery circumference) was determined. On MPI, reversible hypoperfusion in the myocardial territory corresponding to the diseased artery was quantified both as percentage of total myocardium (RevTPD(ART)) by an automatic algorithm and as summed difference score (SDS(ART)) by two experienced readers. RevTPD(ART)≥ 3% and SDS(ART)≥ 3 defined significant inducible hypoperfusion in the territory of the diseased artery. RESULTS Plaques in patients with RevTPD(ART)≥ 3% more frequently exhibited LAP (70% vs. 14%, p < 0.001) and PR (70% vs. 24%, p = 0.001) but not SC (55% vs. 34%, p = 0.154). RevTPD(ART) increased from 1.3 ± 1.2% in arteries with LAP-/PR- plaques to 3.2 ± 4.3% with LAP+/PR- or LAP-/PR+ plaques to 8.3 ± 2.4% with LAP+/PR+ plaques (p < 0.001); SDS(ART) showed a similar increase: 0.3 ± 0.7 to 2.3 ± 2.8 to 6.0 ± 3.8 (p < 0.001). Using the same LAP/PR categorization, there was a marked increase in the frequency of significant hypoperfusion as determined by both RevTPD(ART)≥ 3% (1/19 to 10/21 to 9/9, p < 0.001) and SDS(ART)≥ 3 (1/19 to 8/21 to 8/9, p < 0.001). LAP and PR, but not SC, were strong predictors of RevTPD(ART) and SDS(ART) in regression models adjusting for potential confounders. CONCLUSIONS Presence of low attenuation plaque and positive remodeling in severely stenotic plaques on CCTA is strongly predictive of myocardial hypoperfusion and may be useful in assessing the hemodynamic significance of such lesions.

Relation of Diagonal Ear Lobe Crease to the Presence, Extent, and Severity of Coronary Artery Disease Determined by Coronary Computed Tomography Angiography

Controversy exists concerning the relation between diagonal ear lobe crease (DELC) and coronary artery disease (CAD). We examined whether DELC is associated with CAD using coronary computed tomography (CT) angiography. We studied 430 consecutive patients without a history of coronary artery intervention who underwent CT angiography on a dual-source scanner. Presence of DELC was agreed by 2 blinded observers. Two blinded readers evaluated CT angiography images for presence of CAD and for significant CAD (≥50% stenosis). Chi-square and t tests were used to assess demographic differences between subgroups with and without DELC and the relation of DELC to 4 measurements of CAD: any CAD, significant CAD, multivessel disease (cutoff ≥2), and number of segments with plaque (cutoff ≥3). Multivariable logistic regression was performed to adjust for CAD confounders: age, gender, symptoms, and CAD risk factors. Mean age was 61 ± 13 and 61% were men. DELC was found in 71%, any CAD in 71%, and significant CAD in 17% of patients. After adjusting for confounders, DELC remained a significant predictor of all 4 measurements of CAD (odds ratio 1.8 to 3.3, p = 0.002 to 0.017). Sensitivity, specificity, and positive and negative predictive values for DELC in detecting any CAD were 78%, 43%, 77%, and 45%. Test accuracy was calculated at 67%. Area under the receiver operator characteristic curve was 61% (p = 0.001). In conclusion, in this study of patients imaged with CT angiography, finding DELC was independently and significantly associated with increased prevalence, extent, and severity of CAD.