Christopher L. Schlett

High-Sensitivity Troponin T Concentrations in Acute Chest Pain Patients Evaluated With Cardiac Computed Tomography

Background— For evaluation of patients with chest pain and suspected acute coronary syndrome (ACS), consensus guidelines recommend use of a cardiac troponin cut point that corresponds to the 99th percentile of a healthy population. Most conventional troponin methods lack sufficient precision at this low level. Methods and Results— In a cross-sectional study, 377 patients (mean age 53.7 years, 64.2% male) with chest pain and low to intermediate likelihood for ACS were enrolled in the emergency department. Blood was tested with a precommercial high-sensitivity troponin T assay (hsTnT) and compared with a conventional cardiac troponin T method. Patients underwent a 64-slice coronary computed tomography coronary angiogram at the time of phlebotomy, on average 4 hours from initial presentation. Among patients with acute chest pain, 37 (9.8%) had an ACS. Using the 99th percentile cut point for a healthy population (13 pg/mL), hsTnT had 62% sensitivity, 89% specificity, 38% positive predictive value, and 96% negative predictive value for ACS. Compared with the cardiac troponin T method, hsTnT detected 27% more ACS cases (P=.001), and an hsTnT above the 99th percentile strongly predicted ACS (odds ratio 9.0, 95% confidence interval 3.9 to 20.9, P<0.001). Independent of ACS diagnosis, computed tomography angiography demonstrated that concentrations of hsTnT were determined by numerous factors, including the presence and severity of coronary artery disease, left ventricular mass, left ventricular ejection fraction, and regional left ventricular dysfunction. Conclusions— Among low- to intermediate-risk patients with chest pain, hsTnT provides good sensitivity and specificity for ACS. Elevation of hsTnT identifies patients with myocardial injury and significant structural heart disease, irrespective of the diagnosis of ACS.

Peri-aortic fat, cardiovascular disease risk factors, and aortic calcification: the Framingham Heart Study.

OBJECTIVE Perivascular fat through the secretion of paracrine and pro-inflammatory mediators may play a role in obesity-mediated vascular disease. We sought to examine associations between adipose tissue depots immediately surrounding the thoracic aorta, metabolic risk factors, and vascular calcification. METHODS In participants free of cardiovascular disease (CVD) from the Framingham Heart Study Offspring cohort who underwent computed tomography (n=1067, mean age 59 years, 56.1% women), thoracic peri-aortic fat depots were quantified. Visceral abdominal tissue (VAT) and calcification of the thoracic and abdominal aorta were also measured. RESULTS Peri-aortic fat depots were correlated with body mass index, waist circumference (WC), VAT (all p<0.0001), hypertension (p=0.007), low HDL (p<0.0001), serum triglycerides (p<0.0001), impaired fasting glucose (p=0.005), and diabetes (p=0.02). These associations generally remained significant after adjustment for BMI and WC (all p-values<0.05), but not after VAT adjustment. Thoracic aortic fat was associated with thoracic calcification in models containing VAT (OR 1.31, 95% CI 1.01-1.71, p=0.04), but was not significant after adjustment for CVD risk factors (OR 1.16, 95% CI 0.88-1.51, p=0.30). Thoracic aortic fat, however, was associated with abdominal aortic calcification (OR 1.48, 95% CI 1.11-1.98, p=0.008) and coronary artery calcification (OR 1.47, 95% CI 1.09-1.98, p=0.001) even in models including CVD risk factors and VAT. CONCLUSIONS Thoracic peri-aortic fat is associated with measures of adiposity, metabolic risk factors, and coronary and abdominal aortic calcification.

Prognostic value of CT angiography for major adverse cardiac events in patients with acute chest pain from the emergency department: 2-year outcomes of the ROMICAT trial.

OBJECTIVES The aim of this study was to determine the 2-year prognostic value of cardiac computed tomography (CT) for predicting major adverse cardiac events (MACE) in patients presenting to the emergency department (ED) with acute chest pain. BACKGROUND CT has high potential for early triage of acute chest pain patients. However, there is a paucity of data regarding the prognostic value of CT in this ED cohort. METHODS We followed 368 patients from the ROMICAT (Rule Out Myocardial Infarction Using Computer Assisted Tomography) trial (age 53 ± 12 years; 61% male) who presented to the ED with acute chest pain, negative initial troponin, and a nonischemic electrocardiogram for 2 years. Contrast-enhanced 64-slice CT was obtained during index hospitalization, and caregivers and patients remained blinded to the results. CT was assessed for the presence of plaque, stenosis (>50% luminal narrowing), and left ventricular regional wall motion abnormalities (RWMA). The primary endpoint was MACE, defined as composite cardiac death, nonfatal myocardial infarction, or coronary revascularization. RESULTS Follow-up was completed in 333 patients (90.5%) with a median follow-up period of 23 months. At the end of the follow-up period, 25 patients (6.8%) experienced 35 MACE (no cardiac deaths, 12 myocardial infarctions, and 23 revascularizations). Cumulative probability of 2-year MACE increased across CT strata for coronary artery disease (CAD) (no CAD 0%; nonobstructive CAD 4.6%; obstructive CAD 30.3%; log-rank p < 0.0001) and across combined CT strata for CAD and RWMA (no stenosis or RWMA 0.9%; 1 feature-either RWMA [15.0%] or stenosis [10.1%], both stenosis and RWMA 62.4%; log-rank p < 0.0001). The c statistic for predicting MACE was 0.61 for clinical Thrombolysis In Myocardial Infarction risk score and improved to 0.84 by adding CT CAD data and improved further to 0.91 by adding RWMA (both p < 0.0001). CONCLUSIONS CT coronary and functional features predict MACE and have incremental prognostic value beyond clinical risk score in ED patients with acute chest pain. The absence of CAD on CT provides a 2-year MACE-free warranty period, whereas coronary stenosis with RWMA is associated with the highest risk of MACE.

Coronary artery plaques: Cardiac CT with model-based and adaptive-statistical iterative reconstruction technique

OBJECTIVES To compare image quality of coronary artery plaque visualization at CT angiography with images reconstructed with filtered back projection (FBP), adaptive statistical iterative reconstruction (ASIR), and model based iterative reconstruction (MBIR) techniques. METHODS The coronary arteries of three ex vivo human hearts were imaged by CT and reconstructed with FBP, ASIR and MBIR. Coronary cross-sectional images were co-registered between the different reconstruction techniques and assessed for qualitative and quantitative image quality parameters. Readers were blinded to the reconstruction algorithm. RESULTS A total of 375 triplets of coronary cross-sectional images were co-registered. Using MBIR, 26% of the images were rated as having excellent overall image quality, which was significantly better as compared to ASIR and FBP (4% and 13%, respectively, all p<0.001). Qualitative assessment of image noise demonstrated a noise reduction by using ASIR as compared to FBP (p<0.01) and further noise reduction by using MBIR (p<0.001). The contrast-to-noise-ratio (CNR) using MBIR was better as compared to ASIR and FBP (44±19, 29±15, 26±9, respectively; all p<0.001). CONCLUSIONS Using MBIR improved image quality, reduced image noise and increased CNR as compared to the other available reconstruction techniques. This may further improve the visualization of coronary artery plaque and allow radiation reduction.

Assessment of coronary plaque progression in coronary computed tomography angiography using a semiquantitative score.

OBJECTIVES We sought to describe the progression of coronary atherosclerotic plaque over time by computed tomography (CT) angiography stratified by plaque composition and its association with cardiovascular risk profiles. BACKGROUND Data on the progression of atherosclerosis stratified by plaque composition with the use of noninvasive assessment by CT are limited and hampered by high measurement variability. METHODS This analysis included patients who presented with acute chest pain to the emergency department but initially showed no evidence of acute coronary syndromes. All patients underwent contrast-enhanced 64-slice CT at baseline and after 2 years with the use of a similar protocol. CT datasets were coregistered and assessed for the presence of calcified and noncalcified plaque at 1 mm cross sections of the proximal 40 mm of each major coronary artery. Plaque progression over time and its association with risk factors were determined. Measurement reproducibility and correlation to plaque volume was performed in a subset of patients. RESULTS We included 69 patients (mean age 55 +/- 12 years, 59% male patients) and compared 8,311 coregistered cross sections at baseline and follow-up. At baseline, any plaque, calcified plaque, and noncalcified were detected in 12.5%, 10.1%, and 2.4% of cross sections per patient, respectively. There was significant progression in the mean number of cross sections containing any plaque (16.5 +/- 25.3 vs. 18.6 +/- 25.5, p = 0.01) and noncalcified plaque (3.1 +/- 5.8 vs. 4.4 +/- 7.0, p = 0.04) but not calcified plaque (13.3 +/- 23.1 vs. 14.2 +/- 22.0, p = 0.2). In longitudinal regression analysis, the presence of baseline plaque, number of cardiovascular risk factors, and smoking were independently associated with plaque progression after adjustment for age, sex, and follow-up time interval. The semiquantitative score based on cross sections correlated closely with plaque volume progression (r = 0.75, p < 0.0001) and demonstrated an excellent intraobserver and interobserver agreement (kappa = 0.95 and kappa = 0.93, respectively). CONCLUSIONS Coronary plaque burden of patients with acute chest pain significantly increases during the course of 2 years. Progression over time is dependent on plaque composition and cardiovascular risk profile. Larger studies are needed to confirm these results and to determine the effect of medical treatment on progression.

Development and validation of a score for prediction of postoperative respiratory complications.

Background:Postoperative respiratory failure is associated with increased morbidity and mortality, as well as high costs of hospital care. Methods:Using electronic anesthesia records, billing data, and chart review, the authors developed and validated a score predicting reintubation in the hospital after primary extubation in the operating room, leading to unplanned mechanical ventilation within the first 3 postoperative days. Using multivariable logistic regression analysis, independent predictors were determined and a score postulated and validated. Results:In the entire cohort (n = 33,769 surgical cases within 29,924 patients), reintubation occurred in 137 cases (0.41%). Of those, 16%, (n = 22) died subsequently, whereas the mortality in patients who were not reintubated was 0.26% (P < 0.0001). Independent predictors for reintubation were: American Society of Anesthesiologist Score 3 or more, emergency surgery, high-risk surgical service, history of congestive heart failure, and chronic pulmonary disease. A point value of 3, 3, 2, 2, and 1 were assigned to these predictors, respectively, based on their &bgr; coefficient in the predictive model. The score yielded a calculated area under the curve of 0.81, whereas each point increment was associated with a 1.7-fold (odds ratio: 1.72 [95% CI, 1.55–1.91]) increase in the odds for reintubation in the training dataset. Using the validation dataset (n = 16,884), the score had an area under the curve of 0.80 and similar estimated probabilities for reintubation. Conclusion:The authors developed and validated a score for the prediction of postoperative respiratory complications, a simple, 11-point score that can be used preoperatively by anesthesiologists to predict severe postoperative respiratory complications.

The napkin-ring sign indicates advanced atherosclerotic lesions in coronary CT angiography

OBJECTIVES This study sought to determine the accuracy of plaque pattern assessment by coronary computed tomography angiography (CCTA) to differentiate between early and advanced atherosclerotic lesions as defined by histology. BACKGROUND A ringlike attenuation pattern of coronary atherosclerotic plaques termed as napkin-ring sign (NRS) was described in CCTA of patients who had acute coronary syndrome. METHODS All procedures were performed in accordance with local and federal regulations and the Declaration of Helsinki. Approval of the local ethics committees was obtained. We investigated 21 coronary arteries of 7 donor hearts. Overall, 611 histological sections were obtained and coregistered with CCTA images. The CCTA cross sections were read in random order for conventional plaque categories (noncalcified [NCP], mixed [MP], calcified [CP]) and plaque patterns (homogenous, heterogeneous with no napkin-ring sign [non-NRS], and heterogeneous with NRS). RESULTS No plaque was detected in 134 (21.9%), NCP in 254 (41.6%), MP in 191 (31.3%), and CP in 32 (5.2%) CCTA cross sections. The NCP and MP were further classified into homogenous plaques (n = 207, 46.5%), non-NRS plaques (n = 200, 44.9%), and NRS plaques (n = 38, 8.6%). The specificities of NCP and MP to identify advanced lesions were moderate (57.9%, 95% confidence interval [CI]: 50.1% to 65.6%, and 72.1%, 95% CI: 64.7% to 79.4%, respectively), which were similar to the homogenous and heterogeneous plaques (62.6%, 95% CI: 54.8% to 70.3%, and 67.3%, 95% CI: 58.6% to 76.1%, respectively). In contrast, the specificity of the NRS to identify advanced lesions was excellent (98.9%, 95% CI: 97.6% to 100%). The diagnostic performance of the pattern-based scheme to identify advanced lesions was significantly better than that of the conventional plaque scheme (area under the curve: 0.761 vs. 0.678, respectively; p = 0.001). CONCLUSIONS The assessment of the plaque pattern improves diagnostic accuracy of CCTA to identify advanced atherosclerotic lesions. The CCTA finding of NRS has a high specificity and high positive predictive value for the presence of advanced lesions.

Novel measurements of periaortic adipose tissue in comparison to anthropometric measures of obesity, and abdominal adipose tissue

Background:Perivascular adipose tissue may be associated with the amount of local atherosclerosis. We developed a novel and reproducible method to standardize volumetric quantification of periaortic adipose tissue by computed tomography (CT) and determined the association with anthropometric measures of obesity, and abdominal adipose tissue.Methods:Measurements of adipose tissue were performed in a random subset of participants from the Framingham Heart Study (n=100) who underwent multidetector CT of the thorax (ECG triggering, 2.5 mm slice thickness) and the abdomen (helical CT acquisition, 2.5 mm slice thickness). Abdominal periaortic adipose tissue (AAT) was defined by a 5 mm cylindrical region of interest around the aortic wall; thoracic periaortic adipose tissue (TAT) was defined by anatomic landmarks. TAT and AAT were defined as any voxel between −195 and −45 HU and volumes were measured using dedicated semiautomatic software. Measurement reproducibility and association with anthropometric measures of obesity, and abdominal adipose tissue were determined.Results:The intra- and inter-observer reproducibility for both AAT and TAT was excellent (ICC: 0.97 and 0.97; 0.99 and 0.98, respectively). Similarly, the relative intra- and inter-observer difference was small for both AAT (−1.85±1.28% and 7.85±6.08%; respectively) and TAT (3.56±0.83% and −4.56±0.85%, respectively). Both AAT and TAT were highly correlated with visceral abdominal fat (r=0.65 and 0.77, P<0.0001 for both) and moderately correlated with subcutaneous abdominal fat (r=0.39 and 0.42, P<0.0001 and P=0.009), waist circumference (r=0.49 and 0.57, P<0.0001 for both) and body mass index (r=0.47 and 0.58, P<0.0001 for both).Conclusion:Standardized semiautomatic CT-based volumetric quantification of periaortic adipose tissue is feasible and highly reproducible. Further investigation is warranted regarding associations of periaortic adipose tissue with other body fat deposits, cardiovascular risk factors and clinical outcomes.

Significance of Cardiac Computed Tomography Incidental Findings in Acute Chest Pain

BACKGROUND Coronary computed tomography angiography might improve the management of patients presenting to the emergency department with acute chest pain; however, noncoronary incidental findings are frequently detected. The prevalence and clinical significance of these findings have not been well described. METHODS Consecutive patients presenting to the emergency department with acute chest pain and inconclusive initial evaluation between May 2005 and May 2007 underwent 64-slice coronary computed tomography angiography before hospital admission with noncoronary incidental findings immediately reported. An expert panel adjudicated which incidental findings changed in-hospital patient management, and projections for additional testing were based on standard medical practice. RESULTS Among 395 patients (37.0% were female, mean age 53 +/- 12 years), incidental findings were detected in 44.8% (n = 177): noncalcified pulmonary nodules (n = 94, 23.8%), simple liver cysts (n = 26, 6.6%), calcified pulmonary nodules (n = 16, 4.1%), and contrast-enhancing liver lesions (n = 9, 2.3%). In-hospital management was changed because of incidental finding reporting in 5 patients (1.3%), and a potential alternative diagnosis was offered in another 16 patients (4.1%). Subsequent diagnostic imaging tests were recommended in 81 patients (20.5%), including 74 chest computed tomography scans. After 6 months, biopsy was performed in 3 patients, revealing cancer in 2 (0.5%) who underwent successful tumor resection. CONCLUSION Clinically important findings are detected in up to 5% of patients with a lead symptom of acute chest pain and low to intermediate likelihood of acute coronary syndrome, but only few directly change patient management; 21% are recommended for further imaging tests, resulting in invasive procedures and detection of cancer in few patients.

Periaortic Fat Deposition Is Associated With Peripheral Arterial Disease The Framingham Heart Study

Background—Central obesity is associated with peripheral arterial disease, suggesting that ectopic fat depots may be associated with localized diseases of the aorta and lower-extremity arteries. We hypothesized that persons with greater amounts of periaortic fat are more likely to have clinical PAD and a low ankle-brachial index. Methods and Results—We quantified periaortic fat surrounding the thoracic aorta using a novel volumetric quantitative approach in 1205 participants from the Framingham Heart Study Offspring cohort (mean age, 65.9 years; women, 54%); visceral abdominal fat also was measured. Clinical peripheral arterial disease was defined as a history of intermittent claudication, and ankle-brachial index was dichotomized as low (⩽0.9) or lower-extremity revascularization versus normal (>0.9 to <1.4). Regression models were created to examine the association between periaortic fat and intermittent claudication or low ankle-brachial index (n=66). In multivariable logistic regression, per 1 SD increase in periaortic fat, the odds ratio for the combined end point was 1.52 (P=0.004); these results were strengthened with additional adjustment for body mass index (odds ratio, 1.69; P=0.002) or visceral abdominal fat (odds ratio, 1.67; P=0.009), whereas no association was observed for visceral abdominal fat (P=0.16). Similarly, per SD increase in body mass index or waist circumference, no association was observed after accounting for visceral abdominal fat (body mass index, P=0.35; waist circumference, P=0.49). Conclusions—Periaortic fat is associated with low ABI and intermittent claudication.