Layered plaque is associated with high levels of vascular inflammation and vulnerability in patients with stable angina pectoris.

Layered plaque, a signature of previous plaque destabilization and healing, is a known predictor for rapid plaque progression; however, the mechanism of which is unknown. The aim of the current study was to compare the level of vascular inflammation and plaque vulnerability in layered plaques to investigate possible mechanisms of rapid plaque progression. This is a retrospective, observational, single-center cohort study. Patients who underwent both coronary computed tomography angiography (CTA) and optical coherence tomography (OCT) for stable angina pectoris (SAP) were selected. Plaques were defined as any tissue (noncalcified, calcified, or mixed) within or adjacent to the lumen. Perivascular inflammation was measured by pericoronary adipose tissue (PCAT) attenuation at the plaque levels on CTA. Features of plaque vulnerability were assessed by OCT. Layered plaques were defined as plaques presenting one or more layers of different optical densities and a clear demarcation from underlying components on OCT. A total of 475 plaques from 195 patients who presented with SAP were included. Layered plaques (n = 241), compared with non-layered plaques (n = 234), had a higher level of vascular inflammation (-71.47 ± 10.74 HU vs. -73.69 ± 10.91 HU, P = 0.026) as well as a higher prevalence of the OCT features of plaque vulnerability, including lipid-rich plaque (83.8% vs. 66.7%, P < 0.001), thin-cap fibroatheroma (26.1% vs. 17.5%, P = 0.026), microvessels (61.8% vs. 34.6%, P < 0.001), and cholesterol crystals (38.6% vs. 25.6%, P = 0.003). Layered plaque was associated with a higher level of vascular inflammation and a higher prevalence of plaque vulnerability, which might play an important role in rapid plaque progression.Clinical trial registration: https://classic.clinicaltrials.gov/ct2/show/NCT04523194 .

Prognostic value of CT-derived coronary artery disease characteristics varies by ASCVD risk: insights from the PROMISE trial.

OBJECTIVES: To compare the prognostic value of individual CT-derived coronary artery disease (CAD) characteristics across categories of clinical cardiovascular risk. METHODS: The central core laboratory assessed coronary artery calcium (CAC), obstructive CAD (stenosis ≥ 50%), and high-risk plaque (HRP) in stable outpatients with suspected CAD enrolled in the PROMISE trial. Multivariable Cox regression models (endpoint: unstable angina, nonfatal myocardial infarction, or all-cause mortality; median follow-up: 2 years) were used to compare hazard ratios (HR) of the CT measures between low-borderline (< 7.5%) and moderate-high (≥ 7.5%) atherosclerotic cardiovascular disease (ASCVD) risk based on the pooled cohort equation. RESULTS: Among 4356 included patients (aged 61 ± 8 years, 52% women), 67% had ASCVD risk ≥ 7.5%. Stratified by ASCVD risk, CAD ≥ 50% had nearly threefold greater HR in individuals with ASCVD < 7.5% (aHR, 6.85; 95% CI, 2.33-20.15; p < 0.001) vs. ASCVD ≥ 7.5% (aHR: 2.66, 95% CI: 1.67-4.25, p < 0.001; interaction p = 0.041). CAC predicted events solely in ASCVD ≥ 7.5% patients (aHR: 1.92, 95% CI: 1.01-3.63, p = 0.045; interaction p = 0.571), while HRP predicted events only in ASCVD < 7.5% (aHR: 3.11, 95% CI: 1.09-8.85, p = 0.034; interaction p = 0.034). CONCLUSIONS: Prognostic values of CT-derived CAD characteristics differ by ASCVD risk categories. While CAD ≥ 50% has the highest prognostic value regardless of ASCVD risk, CAC is prognostic in high and HRP in low ASCVD risk. These findings suggest that CAD ≥ 50% and HRP detection rather than CAC scoring may better risk-stratify symptomatic low-risk patients and thus potentially improve downstream care. KEY POINTS: • Prognostic value of individual CT-derived CAD characteristics differs by categories of cardiovascular risk. • Presence of obstructive coronary artery stenosis ≥ 50% has the highest prognostic value regardless of cardiovascular risk. • Coronary artery calcium is independently prognostic in high and high-risk plaque features in low cardiovascular risk.

Associations of a polygenic risk score with coronary artery disease phenotypes in the Prospective Multicenter Imaging Study for Evaluation of Chest Pain (PROMISE) trial.

A polygenic risk score (PGS) is associated with obstructive coronary artery disease (CAD) independent of traditional risk factors. Coronary computed tomography angiography (CTA) can characterize coronary plaques, including features of highrisk CAD. However, it is unknown if a PGS is associated with obstructive CAD and high-risk CAD phenotypes in patients with symptoms suggestive of CAD.

Does Hospital Admission/Observation for Chest Pain Improve Patient Outcomes after Emergency Department Evaluation for Suspected Acute Coronary Syndrome?

BACKGROUND: Chest pain is the top reason for hospitalization/observation in the USA, but it is unclear if this strategy improves patient outcomes. OBJECTIVE: The objective of this study was to compare 30-day outcomes for patients admitted versus discharged after a negative emergency department (ED) evaluation for suspected acute coronary syndrome. DESIGN: A retrospective, multi-site, cohort study of adult encounters with chest pain presenting to one of 13 Kaiser Permanente Southern California EDs between January 1, 2015, and December 1, 2017. Instrumental variable analysis was used to mitigate potential confounding by unobserved factors. PATIENTS: All adult patients presenting to an ED with chest pain, in whom an acute myocardial infarction was not diagnosed in the ED, were included. MAIN MEASURES: The primary outcome was 30-day acute myocardial infarction or all-cause mortality, and secondary outcomes included 30-day revascularization and major adverse cardiac events. KEY RESULTS: In total, 77,652 patient encounters were included in the study (n=11,026 admitted, 14.2%). Three hundred twenty-two (0.4%) had an acute myocardial infarction (n=193, 0.2%) or death (n=137, 0.2%) within 30 days of ED visit (1.5% hospitalized versus 0.2% discharged). Very few (0.3%) patients underwent coronary revascularization within 30 days (0.7% hospitalized versus 0.2% discharged). Instrumental variable analysis found no adjusted differences in 30-day patient outcomes between the hospitalized cohort and those discharged (risk reduction 0.002, 95% CI -0.002 to 0.007). Similarly, there were no differences in coronary revascularization (risk reduction 0.003, 95% CI -0.002 to 0.007). CONCLUSION: Among ED patients with chest pain not diagnosed with an acute myocardial infarction, risk of major adverse cardiac events is quite low, and there does not appear to be any benefit in 30-day outcomes for those admitted or observed in the hospital compared to those discharged with outpatient follow-up.

Automated abstraction of myocardial perfusion imaging reports using natural language processing.

BACKGROUND: Findings and interpretations of myocardial perfusion imaging (MPI) studies are documented in free-text MPI reports. MPI results are essential for research, but manual review is prohibitively time consuming. This study aimed to develop and validate an automated method to abstract MPI reports. METHODS: We developed a natural language processing (NLP) algorithm to abstract MPI reports. Randomly selected reports were double-blindly reviewed by two cardiologists to validate the NLP algorithm. Secondary analyses were performed to describe patient outcomes based on abstracted-MPI results on 16,957 MPI tests from adult patients evaluated for suspected ACS. RESULTS: The NLP algorithm achieved high sensitivity (96.7%) and specificity (98.9%) on the MPI categorical results and had a similar degree of agreement compared to the physician reviewers. Patients with abnormal MPI results had higher rates of 30-day acute myocardial infarction or death compared to patients with normal results. We identified issues related to the quality of the reports that not only affect communication with referring physicians but also challenges for automated abstraction. CONCLUSION: NLP is an accurate and efficient strategy to abstract results from the free-text MPI reports. Our findings will facilitate future research to understand the benefits of MPI studies but requires validation in other settings.

Statin Use for the Primary Prevention of Cardiovascular Disease in Adults: Updated Evidence Report and Systematic Review for the US Preventive Services Task Force.

Importance: A 2016 review for the US Preventive Services Task Force (USPSTF) found use of statins for primary prevention of cardiovascular disease (CVD) was associated with reduced mortality and cardiovascular outcomes. Objective: To update the 2016 review on statins for primary prevention of CVD to inform the USPSTF. Data Sources: Ovid MEDLINE, Cochrane Central Register of Controlled Trials, and Cochrane Database of Systematic Reviews (to November 2021); surveillance through May 20, 2022. Study Selection: Randomized clinical trials on statins vs placebo or no statin and statin intensity in adults without prior cardiovascular events; large cohort studies on harms. Data Extraction and Synthesis: One investigator abstracted data; a second checked accuracy. Two investigators independently rated study quality. Main Outcomes and Measures: All-cause and cardiovascular mortality, myocardial infarction, stroke, composite cardiovascular outcomes, and adverse events. Results: Twenty-six studies were included: 22 trials (N = 90 624) with 6 months to 6 years of follow-up compared statins vs placebo or no statin, 1 trial (n = 5144) compared statin intensities, and 3 observational studies (n = 417 523) reported harms. Statins were significantly associated with decreased risk of all-cause mortality (risk ratio [RR], 0.92 [95% CI, 0.87 to 0.98]; absolute risk difference [ARD], -0.35% [95% CI, -0.57% to -0.14%]), stroke (RR, 0.78 [95% CI, 0.68 to 0.90]; ARD, -0.39% [95% CI, -0.54% to -0.25%]), myocardial infarction (RR, 0.67 [95% CI, 0.60 to 0.75]; ARD, -0.85% [95% CI, -1.22% to -0.47%]), and composite cardiovascular outcomes (RR, 0.72 [95% CI, 0.64 to 0.81]; ARD, -1.28% [95% CI, -1.61% to -0.95%]); the association with cardiovascular mortality was not statistically significant (RR, 0.91 [95% CI, 0.81 to 1.02]; ARD, -0.13%). Relative benefits were consistent in groups defined by demographic and clinical characteristics, although data for persons older than 75 years were sparse. Statin therapy was not significantly associated with increased risk of serious adverse events (RR, 0.97 [95% CI, 0.93 to 1.01]), myalgias (RR, 0.98 [95% CI, 0.86 to 1.11]), or elevated alanine aminotransferase level (RR, 0.94 [95% CI, 0.78 to 1.13]). Statin therapy was not significantly associated with increased diabetes risk overall (RR, 1.04 [95% CI, 0.92 to 1.19]), although 1 trial found high-intensity statin therapy was significantly associated with increased risk (RR, 1.25 [95% CI, 1.05 to 1.49]). Otherwise, there were no clear differences in outcomes based on statin intensity. Conclusions and Relevance: In adults at increased CVD risk but without prior CVD events, statin therapy for primary prevention of CVD was associated with reduced risk of all-cause mortality and CVD events. Benefits of statin therapy appear to be present across diverse demographic and clinical populations, with consistent relative benefits in groups defined by demographic and clinical characteristics.

Association of Hepatic Steatosis With Major Adverse Cardiovascular Events, Independent of Coronary Artery Disease.

BACKGROUND & AIMS: Hepatic steatosis has been associated with increased risk of major adverse cardiovascular events (MACE) but it is not clear whether steatosis is independently associated with risk of MACE. We investigated whether steatosis is associated with risk of MACE independently of the presence and extent of baseline coronary artery disease, assessed by comprehensive contrast-enhanced computed tomography angiography (CTA). METHODS: We conducted a nested cohort study of 3756 subjects (mean age, 60.6 years; 48.4% men) who underwent coronary CTA at 193 sites in North America, from July 2010 through September 2013, as part of the PROMISE study, which included noninvasive cardiovascular analyses of symptomatic outpatients without coronary artery disease. Independent core laboratory readers measured hepatic and splenic attenuation, using non-contrast computed tomography images to identify steatosis, and evaluated coronary plaques and stenosis in coronary CTA images. We collected data on participants' cardiovascular risk factors, presence of metabolic syndrome, and body mass index. The primary endpoint was an adjudicated composite of MACE (death, myocardial infarction, or unstable angina) during a median follow-up time of 25 months. RESULTS: Among the 959 subjects who had steatosis (25.5% of the cohort), 42 had MACE (4.4%), whereas among the 2797 subjects without steatosis, 73 had MACE (2.6%) (hazard ratio [HR] for MACE in subjects with steatosis, 1.69; 95% CI, 1.16-2.48; P = .006 for MACE in subjects with vs without steatosis). This association remained after adjustment for atherosclerotic cardiovascular disease risk scores, significant stenosis, and metabolic syndrome (adjusted HR, 1.72; 95% CI, 1.16-2.54; P = .007) or obesity (adjusted HR, 1.75; 95% CI, 1.19-2.59; P = .005). Steatosis remained independently associated with MACE after adjustment for all CTA measures of plaques and stenosis. CONCLUSIONS: Hepatic steatosis is associated with MACE independently of other cardiovascular risk factors or extent of coronary artery disease. Strategies to reduce steatosis might reduce risk of MACE. ClinicalTrials.gov no: NCT01174550.

Small whole heart volume predicts cardiovascular events in patients with stable chest pain: insights from the PROMISE trial.

OBJECTIVES: The size of the heart may predict major cardiovascular events (MACE) in patients with stable chest pain. We aimed to evaluate the prognostic value of 3D whole heart volume (WHV) derived from non-contrast cardiac computed tomography (CT). METHODS: Among participants randomized to the CT arm of the Prospective Multicenter Imaging Study for Evaluation of Chest Pain (PROMISE), we used deep learning to extract WHV, defined as the volume of the pericardial sac. We compared the WHV across categories of cardiovascular risk factors and coronary artery disease (CAD) characteristics and determined the association of WHV with MACE (all-cause death, myocardial infarction, unstable angina; median follow-up: 26 months). RESULTS: In the 3798 included patients (60.5 ± 8.2 years; 51.5% women), the WHV was 351.9 ± 57.6 cm3/m2. We found smaller WHV in no- or non-obstructive CAD, women, people with diabetes, sedentary lifestyle, and metabolic syndrome. Larger WHV was found in obstructive CAD, men, and increased atherosclerosis cardiovascular disease (ASCVD) risk score (p < 0.05). In a time-to-event analysis, small WHV was associated with over 4.4-fold risk of MACE (HR (per one standard deviation) = 0.221; 95% CI: 0.068-0.721; p = 0.012) independent of ASCVD risk score and CT-derived CAD characteristics. In patients with non-obstructive CAD, but not in those with no- or obstructive CAD, WHV increased the discriminatory capacity of ASCVD and CT-derived CAD characteristics significantly. CONCLUSIONS: Small WHV may represent a novel imaging marker of MACE in stable chest pain. In particular, WHV may improve risk stratification in patients with non-obstructive CAD, a cohort with an unmet need for better risk stratification. KEY POINTS: • Heart volume is easily assessable from non-contrast cardiac computed tomography. • Small heart volume may be an imaging marker of major adverse cardiac events independent and incremental to traditional cardiovascular risk factors and established CT measures of CAD. • Heart volume may improve cardiovascular risk stratification in patients with non-obstructive CAD.

Evaluating Sex Disparities in the Emergency Department Management of Patients With Suspected Acute Coronary Syndrome.

STUDY OBJECTIVE: We compare clinical management and outcomes of emergency department (ED) encounters by sex after implementation of a clinical care pathway in 15 community EDs that standardized recommendations based on patient risk, using the History, ECG, Age, Risk Factors, and Troponin (HEART) score. METHODS: This was a retrospective analysis of adult ED encounters evaluated for suspected acute coronary syndrome with a documented HEART score from May 20, 2016, to December 1, 2017. The primary outcomes were hospitalization or 30-day stress testing. Secondary outcomes included 30-day acute myocardial infarction or all-cause death (major adverse cardiac event). A generalized estimating equation regression model was used to compare the odds of hospitalization or stress testing by sex; we report HEART scores (0 to 10) stratified by sex and describing major adverse cardiac events. RESULTS: A total of 34,715 adult ED encounters met the inclusion criteria (56.0% women). A higher proportion of women were classified as low risk (60.5% versus 52.4%; odds ratio [OR] 1.39; 95% confidence interval [CI] 1.33 to 1.45). Women were hospitalized or received stress testing less frequently than men for low HEART scores (18.8% versus 22.8%; OR 0.79; 95% CI 0.73 to 0.84) and intermediate ones (46.7% versus 49.7%; OR 0.88; 95% CI 0.83 to 0.95), but similarly for high-risk ones (74.1% versus 74.4%; OR 0.99; 95% CI 0.77 to 1.28). Women had 18% lower odds of hospitalization or noninvasive cardiac testing (OR 0.82; 95% CI 0.78 to 0.86), even after adjusting for HEART score and comorbidities. Men had higher risks of major adverse cardiac events than women for all HEART score categories but the risk for men was significantly higher among low-risk HEART scores (0.4% versus 0.1%). CONCLUSION: Women with low-risk HEART scores are hospitalized or stress tested less than men, which is likely appropriate, and women have better outcomes than men. Use of the HEART score has the potential to reduce sex disparities in acute coronary syndrome care.

Density and morphology of coronary artery calcium for the prediction of cardiovascular events: insights from the Framingham Heart Study.

OBJECTIVES: To investigate the association between directly measured density and morphology of coronary artery calcium (CAC) with cardiovascular disease (CVD) events, using computed tomography (CT). METHODS: Framingham Heart Study (FHS) participants with CAC in noncontrast cardiac CT (2002-2005) were included and followed until 2016. Participants with known CVD or uninterpretable CT scans were excluded. We assessed and correlated (Spearman) CAC density, CAC volume, and the number of calcified segments. Moreover, we counted morphology features including shape (cylindrical, spherical, semi-tubular, and spotty), location (bifurcation, facing pericardium, or facing myocardium), and boundary regularity. In multivariate Cox regression analyses, we associated all CAC characteristics with CVD events (CVD-death, myocardial infarction, stroke). RESULTS: Among 1330 included participants (57.8 ± 11.7 years; 63% male), 73 (5.5%) experienced CVD events in a median follow-up of 9.1 (7.8-10.1) years. CAC density correlated strongly with CAC volume (Spearman's ρ = 0.75; p < 0.001) and lower number of calcified segments (ρ = - 0.86; p < 0.001; controlled for CAC volume). In the survival analysis, CAC density was associated with CVD events independent of Framingham risk score (HR (per SD) = 2.09; 95%CI, 1.30-3.34; p = 0.002) but not after adjustment for CAC volume (p = 0.648). The extent of spherically shaped and pericardially sided calcifications was associated with fewer CVD events accounting for the number of calcified segments (HR (per count) = 0.55; 95%CI, 0.31-0.98; p = 0.042 and HR = 0.66; 95%CI, 0.45-0.98; p = 0.039, respectively). CONCLUSIONS: Directly measured CAC density does not predict CVD events due to the strong correlation with CAC volume. The spherical shape and pericardial-sided location of CAC are associated with fewer CVD events and may represent morphological features related to stable coronary plaques. KEY POINTS: • Coronary calcium density may not be independently associated with cardiovascular events. • Coronary calcium density correlates strongly with calcium volume. • Spherical shape and pericardial-sided location of CAC are associated with fewer CVD events.

Evaluation of Outpatient Cardiac Stress Testing After Emergency Department Encounters for Suspected Acute Coronary Syndrome.

STUDY OBJECTIVE: Professional guidelines recommend 72-hour cardiac stress testing after an emergency department (ED) evaluation for possible acute coronary syndrome. There are limited data on actual compliance rates and effect on patient outcomes. Our aim is to describe rates of completion of noninvasive cardiac stress testing and associated 30-day major adverse cardiac events. METHODS: We conducted a retrospective analysis of ED encounters from June 2015 to June 2017 across 13 community EDs within an integrated health system in Southern California. The study population included all adults with a chest pain diagnosis, troponin value, and discharge with an order for an outpatient cardiac stress test. The primary outcome was the proportion of patients who completed an outpatient stress test within the recommended 3 days, 4 to 30 days, or not at all. Secondary analysis described the 30-day incidence of major adverse cardiac events. RESULTS: During the study period, 24,459 patients presented with a chest pain evaluation requiring troponin analysis and stress test ordering from the ED. Of these, we studied the 7,988 patients who were discharged home to complete diagnostic testing, having been deemed appropriate by the treating clinicians for an outpatient stress test. The stress test completion rate was 31.3% within 3 days and 58.7% between 4 and 30 days, and 10.0% of patients did not complete the ordered test. The 30-day rates of major adverse cardiac events were low (death 0.0%, acute myocardial infarction 0.7%, and revascularization 0.3%). Rapid receipt of stress testing was not associated with improved 30-day major adverse cardiac events (odds ratio 0.92; 95% confidence interval 0.55 to 1.54). CONCLUSION: Less than one third of patients completed outpatient stress testing within the guideline-recommended 3 days after initial evaluation. More important, the low adverse event rates suggest that selective outpatient stress testing is safe. In this cohort of patients selected for outpatient cardiac stress testing in a well-integrated health system, there does not appear to be any associated benefit of stress testing within 3 days, nor within 30 days, compared with those who never received testing at all. The lack of benefit of obtaining timely testing, in combination with low rates of objective adverse events, may warrant reassessment of the current guidelines.

Effect of a HEART Care Pathway on Chest Pain Management Within an Integrated Health System.

STUDY OBJECTIVE: We describe the association of implementing a History, ECG, Age, Risk Factors, and Troponin (HEART) care pathway on use of hospital care and noninvasive stress testing, as well as 30-day patient outcomes in community emergency departments (EDs). METHODS: We performed a prospective interrupted-time-series study of adult encounters for patients evaluated for suspected acute coronary syndrome. The primary outcome was hospitalization or observation, noninvasive stress testing, or both within 30 days. The secondary outcome was 30-day all-cause mortality or acute myocardial infarction. A generalized estimating equation segmented logistic regression model was used to compare the odds of the primary outcome before and after HEART implementation. All models were adjusted for patient and facility characteristics and fit with physicians as a clustering variable. RESULTS: A total of 65,393 ED encounters (before, 30,522; after, 34,871) were included in the study. Overall, 33.5% (before, 35.5%; after, 31.8%) of ED chest pain encounters resulted in hospitalization or observation, noninvasive stress testing, or both. Primary adjusted results found a significant decrease in the primary outcome postimplementation (odds ratio 0.984; 95% confidence interval [CI] 0.974 to 0.995). This resulted in an absolute adjusted month-to-month decrease of 4.39% (95% CI 3.72% to 5.07%) after 12 months' follow-up, with a continued trend downward. There was no difference in 30-day mortality or myocardial infarction (0.6% [before] versus 0.6% [after]; odds ratio 1.02; 95% CI 0.97 to 1.08). CONCLUSION: Implementation of a HEART pathway in the ED evaluation of patients with chest pain resulted in less inpatient care and noninvasive cardiac testing and was safe. Using HEART to risk stratify chest pain patients can improve the efficiency and quality of care.

Applications of Cardiac Computed Tomography in the Cardio-Oncology Population.

OPINION STATEMENT: The increased risk for cardiovascular events in aging cancer survivors and those undergoing certain chemotherapeutic treatments has raised concern for more rigorous screening and surveillance methods above that of the general population. At this time, there are limited guidelines for how to best manage this vulnerable cohort. Questions regarding timing of screening, choice of imaging modality and risk reduction strategies-especially in those patients with known atherosclerotic disease-remain to be elucidated. Over a decade of case series, retrospective studies and clinical trials have shed light on the evolving role of cardiac computed tomography (CT) in this population, of which there is a relative paucity of data regarding its potential utility in the specific cardio-oncology population. Focusing on ability of cardiac CT to evaluate multiple cardiac and vascular structures, provide diagnostic and prognostic information, as well as assist interventional and surgical colleagues in surgical/percutaneous valve replacement and revascularization strategies is the premise for this review.

Prognostic Value of Coronary Artery Calcium in the PROMISE Study (Prospective Multicenter Imaging Study for Evaluation of Chest Pain).

BACKGROUND: Coronary artery calcium (CAC) is an established predictor of future major adverse atherosclerotic cardiovascular events in asymptomatic individuals. However, limited data exist as to how CAC compares with functional testing (FT) in estimating prognosis in symptomatic patients. METHODS: In the PROMISE trial (Prospective Multicenter Imaging Study for Evaluation of Chest Pain), patients with stable chest pain (or dyspnea) and intermediate pretest probability for obstructive coronary artery disease were randomized to FT (exercise electrocardiography, nuclear stress, or stress echocardiography) or anatomic testing. We evaluated those who underwent CAC testing as part of the anatomic evaluation (n=4209) and compared that with results of FT (n=4602). We stratified CAC and FT results as normal or mildly, moderately, or severely abnormal (for CAC: 0, 1-99 Agatston score [AS], 100-400 AS, and >400 AS, respectively; for FT: normal, mild=late positive treadmill, moderate=early positive treadmill or single-vessel ischemia, and severe=large ischemic region abnormality). The primary end point was all-cause death, myocardial infarction, or unstable angina hospitalization over a median follow-up of 26.1 months. Cox regression models were used to calculate hazard ratios (HRs) and C statistics to determine predictive and discriminatory values. RESULTS: Overall, the distribution of normal or mildly, moderately, or severely abnormal test results was significantly different between FT and CAC (FT: normal, n=3588 [78.0%]; mild, n=432 [9.4%]; moderate, n=217 [4.7%]; severe, n=365 [7.9%]; CAC: normal, n=1457 [34.6%]; mild, n=1340 [31.8%]; moderate, n=772 [18.3%]; severe, n=640 [15.2%]; P<0.0001). Moderate and severe abnormalities in both arms robustly predicted events (moderate: CAC: HR, 3.14; 95% confidence interval, 1.81-5.44; and FT: HR, 2.65; 95% confidence interval, 1.46-4.83; severe: CAC: HR, 3.56; 95% confidence interval, 1.99-6.36; and FT: HR, 3.88; 95% confidence interval, 2.58-5.85). In the CAC arm, the majority of events (n=112 of 133, 84%) occurred in patients with any positive CAC test (score >0), whereas fewer than half of events occurred in patients with mildly, moderately, or severely abnormal FT (n=57 of 132, 43%; P<0.001). In contrast, any abnormality on FT was significantly more specific for predicting events (78.6% for FT versus 35.2% for CAC; P<0.001). Overall discriminatory ability in predicting the primary end point of mortality, nonfatal myocardial infarction, and unstable angina hospitalization was similar and fair for both CAC and FT (C statistic, 0.67 versus 0.64). Coronary computed tomographic angiography provided significantly better prognostic information compared with FT and CAC testing (C index, 0.72). CONCLUSIONS: Among stable outpatients presenting with suspected coronary artery disease, most patients experiencing clinical events have measurable CAC at baseline, and fewer than half have any abnormalities on FT. However, an abnormal FT was more specific for cardiovascular events, leading to overall similarly modest discriminatory abilities of both tests. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01174550.

Prognostic Value of Noninvasive Cardiovascular Testing in Patients With Stable Chest Pain: Insights From the PROMISE Trial (Prospective Multicenter Imaging Study for Evaluation of Chest Pain).

BACKGROUND: Optimal management of patients with stable chest pain relies on the prognostic information provided by noninvasive cardiovascular testing, but there are limited data from randomized trials comparing anatomic with functional testing. METHODS: In the PROMISE trial (Prospective Multicenter Imaging Study for Evaluation of Chest Pain), patients with stable chest pain and intermediate pretest probability for obstructive coronary artery disease (CAD) were randomly assigned to functional testing (exercise electrocardiography, nuclear stress, or stress echocardiography) or coronary computed tomography angiography (CTA). Site-based diagnostic test reports were classified as normal or mildly, moderately, or severely abnormal. The primary end point was death, myocardial infarction, or unstable angina hospitalizations over a median follow-up of 26.1 months. RESULTS: Both the prevalence of normal test results and incidence rate of events in these patients were significantly lower among 4500 patients randomly assigned to CTA in comparison with 4602 patients randomly assigned to functional testing (33.4% versus 78.0%, and 0.9% versus 2.1%, respectively; both P<0.001). In CTA, 54.0% of events (n=74/137) occurred in patients with nonobstructive CAD (1%-69% stenosis). Prevalence of obstructive CAD and myocardial ischemia was low (11.9% versus 12.7%, respectively), with both findings having similar prognostic value (hazard ratio, 3.74; 95% confidence interval [CI], 2.60-5.39; and 3.47; 95% CI, 2.42-4.99). When test findings were stratified as mildly, moderately, or severely abnormal, hazard ratios for events in comparison with normal tests increased proportionally for CTA (2.94, 7.67, 10.13; all P<0.001) but not for corresponding functional testing categories (0.94 [P=0.87], 2.65 [P=0.001], 3.88 [P<0.001]). The discriminatory ability of CTA in predicting events was significantly better than functional testing (c-index, 0.72; 95% CI, 0.68-0.76 versus 0.64; 95% CI, 0.59-0.69; P=0.04). If 2714 patients with at least an intermediate Framingham Risk Score (>10%) who had a normal functional test were reclassified as being mildly abnormal, the discriminatory capacity improved to 0.69 (95% CI, 0.64-0.74). CONCLUSIONS: Coronary CTA, by identifying patients at risk because of nonobstructive CAD, provides better prognostic information than functional testing in contemporary patients who have stable chest pain with a low burden of obstructive CAD, myocardial ischemia, and events. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01174550.

Central Core Laboratory versus Site Interpretation of Coronary CT Angiography: Agreement and Association with Cardiovascular Events in the PROMISE Trial.

Purpose To assess concordance and relative prognostic utility between central core laboratory and local site interpretation for significant coronary artery disease (CAD) and cardiovascular events. Materials and Methods In the Prospective Multicenter Imaging Study for Evaluation of Chest Pain (PROMISE) trial, readers at 193 North American sites interpreted coronary computed tomographic (CT) angiography as part of the clinical evaluation of stable chest pain. Readers at a central core laboratory also interpreted CT angiography blinded to clinical data, site interpretation, and outcomes. Significant CAD was defined as stenosis greater than or equal to 50%; cardiovascular events were defined as a composite of cardiovascular death or myocardial infarction. Results In 4347 patients (51.8% women; mean age ± standard deviation, 60.4 years ± 8.2), core laboratory and site interpretations were discordant in 16% (683 of 4347), most commonly because of a finding of significant CAD by site but not by core laboratory interpretation (80%, 544 of 683). Overall, core laboratory interpretation resulted in 41% fewer patients being reported as having significant CAD (14%, 595 of 4347 vs 23%, 1000 of 4347; P < .001). Over a median follow-up period of 25 months, 1.3% (57 of 4347) sustained myocardial infarction or cardiovascular death. The C statistic for future myocardial infarction or cardiovascular death was 0.61 (95% confidence interval [CI]: 0.54, 0.68) for the core laboratory and 0.63 (95% CI: 0.56, 0.70) for the sites. Conclusion Compared with interpretation by readers at 193 North American sites, standardized core laboratory interpretation classified 41% fewer patients as having significant CAD. © RSNA, 2017 Online supplemental material is available for this article. Clinical trial registration no. NCT01174550.

Age- and sex-based resource utilisation and costs in patients with acute chest pain undergoing cardiac CT angiography: pooled evidence from ROMICAT II and ACRIN-PA trials.

OBJECTIVES: To determine resource utilisation according to age and gender-specific subgroups in two large randomized diagnostic trials. METHODS: We pooled patient-specific data from ACRIN-PA 4005 and ROMICAT II that enrolled subjects with acute chest pain at 14 US sites. Subjects were randomized between a standard work-up and a pathway utilizing cardiac computed tomography angiography (CCTA) and followed for the occurrence of acute coronary syndrome (ACS) and resource utilisation during index hospitalisation and 1-month follow-up. Study endpoints included diagnostic accuracy of CCTA for the detection of ACS as well as resource utilisation. RESULTS: Among 1240 patients who underwent CCTA, negative predictive value of CCTA to rule out ACS remained very high (≥99.4%). The proportion of patients undergoing additional diagnostic testing and cost increased with age for both sexes (p < 0.001), and was higher in men as compared to women older than 60 years (43.1% vs. 23.4% and $4559 ± 3382 vs. $3179 ± 2562, p < 0.01; respectively). Cost to rule out ACS was higher in men (p < 0.001) and significantly higher for patients older than 60 years ($2860-5935 in men, p < 0.001). CONCLUSIONS: CCTA strategy in patients with acute chest pain results in varying resource utilisation according to age and gender-specific subgroups, mandating improved selection for advanced imaging. KEY POINTS: • In this analysis, CAD and ACS increased with age and male gender. • CCTA in patients with acute chest pain results in varying resource utilisation. • Significant increase of diagnostic testing and cost with age for both sexes. • Cost to rule out ACS is higher in men and patients >60 years. • Improved selection of subjects for cardiac CTA result in more resource-driven implementation.

Torso geometry reconstruction and body surface electrode localization using three-dimensional photography.

We conducted a prospective clinical study (n=14; 29% female) to assess the accuracy of a three-dimensional (3D) photography-based method of torso geometry reconstruction and body surface electrodes localization. The position of 74 body surface electrocardiographic (ECG) electrodes (diameter 5mm) was defined by two methods: 3D photography, and CT (marker diameter 2mm) or MRI (marker size 10×20mm) imaging. Bland-Altman analysis showed good agreement in X (bias -2.5 [95% limits of agreement (LoA) -19.5 to 14.3] mm), Y (bias -0.1 [95% LoA -14.1 to 13.9] mm), and Z coordinates (bias -0.8 [95% LoA -15.6 to 14.2] mm), as defined by the CT/MRI imaging, and 3D photography. The average Hausdorff distance between the two torso geometry reconstructions was 11.17±3.05mm. Thus, accurate torso geometry reconstruction using 3D photography is feasible. Body surface ECG electrodes coordinates as defined by the CT/MRI imaging, and 3D photography, are in good agreement.

Coronary Artery Manifestation of Ormond Disease: The "Mistletoe Sign".

A 69-year-old woman presented with symptoms of presumed cardiac involvement of idiopathic retroperitoneal fibrosis, otherwise known as Ormond disease. Distinct pericoronary tissue proliferations were depicted at cardiac magnetic resonance (MR) imaging and coronary computed tomographic (CT) angiography. On images, the coronary manifestation was termed the "mistletoe sign." The presence of the mistletoe sign on cardiac MR and coronary CT angiographic images is probably rare, but it might be a characteristic manifestation of retroperitoneal fibrosis. With the increasing number of noninvasive cardiac imaging tests performed worldwide, the recognition of the mistletoe sign could be helpful in diagnosing retroperitoneal fibrosis. © RSNA, 2016 Online supplemental material is available for this article.

High-Sensitivity Cardiac Troponin I as a Gatekeeper for Coronary Computed Tomography Angiography and Stress Testing in Patients with Acute Chest Pain.

BACKGROUND: Most patients presenting to the emergency department (ED) with suspected acute coronary syndrome (ACS) undergo noninvasive cardiac testing with a low diagnostic yield. We determined whether a combination of high-sensitivity cardiac troponin I (hs-cTnI) and cardiovascular risk factors might improve selection of patients for cardiac testing. METHODS: We included patients from the Rule Out Myocardial Infarction/Ischemia Using Computer Assisted Tomography (ROMICAT) I and II trials who presented to the ED with acute chest pain and were referred for cardiac testing. Based on serial hs-cTnI measurements and cardiovascular risk factors, we derived and validated the criterion for no need of cardiac testing. We predicted the effect of this criterion on the effectiveness of patient management. RESULTS: A combination of baseline hs-cTnI (<4 ng/L) and cardiovascular risk factors (<2) ruled out ACS with a negative predictive value of 100% in ROMICAT I. We validated this criterion in ROMICAT II, identifying 29% patients as not needing cardiac testing. An additional 5% of patients were identified by adding no change or a decrease between baseline and 2 h hs-cTnI as a criterion. Assuming those patients would be discharged from the ED without cardiac testing, implementation of hs-cTnI would increase ED discharge rate (24.3% to 50.2%, P < 0.001) and decrease the length of hospital stay (21.4 to 8.2 h, P < 0.001), radiation dose (10.2 to 7.7 mSv, P < 0.001), and costs of care (4066 to 3342 US$, P < 0.001). CONCLUSIONS: We derived and validated a criterion for combined hs-cTnI and cardiovascular risk factors that identified acute chest pain patients with no need for cardiac testing and could improve effectiveness of patient management. ClinicalTrials.gov Identifiers: NCT00990262 and NCT01084239.