Influence of reconstruction kernels on the accuracy of CT-derived fractional flow reserve.

OBJECTIVES: We evaluated the influence of image reconstruction kernels on the diagnostic accuracy of CT-derived fractional flow reserve (FFRCT) compared to invasive FFR in patients with coronary artery disease. METHODS: Sixty-nine patients, in whom coronary CT angiography was performed and who were further referred for invasive coronary angiography with FFR measurement via pressure wire, were retrospectively included. CT data sets were acquired using a third-generation dual-source CT system and rendered with medium smooth (Bv40) and sharp (Bv49) reconstruction kernels. FFRCT was calculated on-site using prototype software. Coronary stenoses with invasive FFR ≤ 0.80 were classified as significant. Agreement between FFRCT and invasive FFR was determined for both reconstruction kernels. RESULTS: One hundred analyzed vessels in 69 patients were included. Twenty-five vessels were significantly stenosed according to invasive FFR. Using a sharp reconstruction kernel for FFRCT resulted in a significantly higher correlation with invasive FFR (r = 0.74, p < 0.01 vs. r = 0.58, p < 0.01; p = 0.04) and a higher AUC in ROC curve analysis to correctly identify/exclude significant stenosis (AUC = 0.92 vs. AUC = 0.82 for sharp vs. medium smooth kernel, respectively, p = 0.02). A FFRCT value of ≤ 0.8 using a sharp reconstruction kernel showed a sensitivity of 88% and a specificity of 92% for detecting ischemia-causing lesions, resulting in a diagnostic accuracy of 91%. The medium smooth reconstruction kernel performed worse (sensitivity 60%, specificity 89%, accuracy 82%). CONCLUSION: Compared to invasively measured FFR, FFRCT using a sharp image reconstruction kernel shows higher diagnostic accuracy for detecting lesions causing ischemia, potentially altering decision-making in a clinical setting. KEY POINTS: • Image reconstruction parameters influence the diagnostic accuracy of simulated fractional flow reserve derived from coronary computed tomography angiography. • Using a sharp kernel image reconstruction algorithm delivers higher diagnostic accuracy compared to medium smooth kernel image reconstruction (gold standard invasive fractional flow reserve).

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.

Perivascular Epicardial Fat Stranding at Coronary CT Angiography: A Marker of Acute Plaque Rupture and Spontaneous Coronary Artery Dissection.

Purpose To evaluate the frequency and implications of perivascular fat stranding on coronary computed tomography (CT) angiograms obtained for suspected acute coronary syndrome (ACS). Materials and Methods This retrospective registry study was approved by the institutional review board. The authors reviewed the medical records and images of 1403 consecutive patients (796 men, 607 women; mean age, 52.8 years) who underwent coronary CT angiography at the emergency department from February 2012 to March 2016. Fat attenuation, length and number of circumferential quadrants of the affected segment, and attenuation values in the unaffected epicardial and subcutaneous fat were measured. "Cases" were defined as patients with perivascular fat stranding. Patients with significant stenosis but without fat stranding were considered control subjects. Baseline imaging characteristics, ACS frequency, and results of subsequent downstream testing were compared between cases and control subjects by using two-sample t, Mann-Whitney U, and Fisher tests. Results Perivascular fat stranding was seen in 11 subjects, nine with atherosclerotic lesions and two with spontaneous coronary artery dissections, with a mean fat stranding length of 19.2 mm and circumferential extent averaging 2.9 quadrants. The mean attenuation of perivascular fat stranding, normal epicardial fat, and normal subcutaneous fat was 17, -93.2, and -109.3 HU, respectively (P < .001). Significant differences (P < .05) between cases and control subjects included lower Agatston score, presence of wall motion abnormality, and initial elevation of serum troponin level. ACS frequency was 45.4% in cases and 3.8% in control subjects (P = .001). Conclusion Recognition of perivascular fat stranding may be a helpful additional predictor of culprit lesion and marker of risk for ACS in patients with significant stenosis or spontaneous coronary artery dissection. © RSNA, 2018 Online supplemental material is available for this article.

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.

Contrast volume reduction using third generation dual source computed tomography for the evaluation of patients prior to transcatheter aortic valve implantation.

OBJECTIVES: Chronic renal failure is common in patients referred for transcatheter aortic valve implantation (TAVI). CT angiography is recommended and provides crucial information prior to TAVI. We evaluated the feasibility of a reduced contrast volume protocol for pre-procedural CT imaging. METHODS: Forty consecutive patients were examined with prospectively ECG-triggered high-pitch spiral acquisition using a novel third-generation dual-source CT system; 38 ml contrast agent was used. Image quality was graded on a visual scale (1-4). Contrast attenuation was measured at the level of the aortic root and at the iliac bifurcation. RESULTS: Mean patient age was 82 ± 6 years (23 males; 58 %). Mean attenuation/average image quality was 285 ± 60 HU/1.5 at the aortic annulus compared to 289 ± 74 HU/1.8 at the iliac bifurcation (p = 0.77/p = 0.29). Mean estimated effective radiation dose was 2.9 ± 0.3 mSv. A repeat acquisition was necessary in one patient due to image quality. Out of the 35 patients who underwent TAVI, 31 (89 %) patients had no or mild aortic regurgitation. Thirty-two (91 %) patients were discharged successfully. CONCLUSION: Pre-procedural CTA with a total of 38 ml contrast volume is feasible and clinically useful, using third-generation dual-source CT, allowing comprehensive imaging for procedural success. KEY POINTS: • Reduction of contrast agent volume is crucial in patients with chronic renal failure. • Novel third-generation computed tomography helps to reduce contrast agent volume. • Pre-procedural CT allows comprehensive imaging for procedural success before heart valve implantation. • A low-contrast CT protocol is feasible for pre-procedural TAVI planning.

Coronary CT Angiography as a Diagnostic and Prognostic Tool: Perspective from a Multicenter Randomized Controlled Trial: PROMISE.

The PROMISE (Prospective multicenter imaging study for evaluation of chest pain) trial compared the effectiveness of coronary CT angiography and functional testing as initial diagnostic test for patients with suspicion for stable coronary artery disease (CAD). With 10,003 patients randomized at 193 sites, the PROMISE trial provides a snapshot of real-world care for this very common presentation. Over a median follow-up of 25 months, PROMISE did not find significant differences in major clinical events (composite endpoint 164 vs. 151, HR 1.04 (0.83-1.29); p = 0.75) between the two strategies. Other major findings were the large discrepancy between estimates of pre-test likelihood and observed prevalence for obstructive CAD (≥50 %) and the proportion of noninvasive tests positive for ischemia or obstructive CAD (53 vs. 11 %; respectively) and the better efficiency of coronary computed tomography angiography (CTA) to select patients for invasive coronary angiography (ICA) who had obstructive CAD (72 vs. 48 % for coronary CTA and functional testing, respectively). Radiation exposure was higher in the CT arm compared to all functional testing but lower than for nuclear perfusion stress testing. Improvement of patient selection for diagnostic testing and risk stratification will be keys to increase efficacy and efficiency of management of patients with suspicion for stable CAD.

Lipoprotein subclasses are associated with Hepatic steatosis: insights from the prospective multicenter imaging study for the evaluation of chest pain (PROMISE) clinical trial.

Objectives: To determine the relationship between lipoprotein particle size/number with hepatic steatosis (HS), given its association with traditional lipoproteins and coronary atherosclerosis. Methods: Individuals with available CT data and blood samples enrolled in the PROMISE trial were studied. HS was defined based on CT attenuation. Lipoprotein particle size/number were measured by nuclear magnetic resonance spectroscopy. Principal components analysis (PCA) was used for dimensionality reduction. The association of PCA factors and individual lipoprotein particle size/number with HS were assessed in multivariable regression models. Associations were validated in an independent cohort of 59 individuals with histopathology defined HS. Results: Individuals with HS (n=410/1,509) vs those without (n=1,099/1,509), were younger (59±8 vs 61±8 years) and less often females (47.6 % vs 55.9 %). All PCA factors were associated with HS: factor 1 (OR:1.36, 95 %CI:1.21-1.53), factor 3 (OR:1.75, 95 %CI:1.53-2.02) and factor 4 (OR:1.49; 95 %CI:1.32-1.68) were weighted heavily with small low density lipoprotein (LDL) and triglyceride-rich (TRL) particles, while factor 2 (OR:0.86, 95 %CI:0.77-0.97) and factor 5 (OR:0.74, 95 %CI:0.65-0.84) were heavily loaded with high density lipoprotein (HDL) and larger LDL particles. These observations were confirmed with the analysis of individual lipoprotein particles in PROMISE. In the validation cohort, association between HS and large TRL (OR: 8.16, 95 %CI:1.82-61.98), and mean sizes of TRL- (OR: 2.82, 95 %CI:1.14-9.29) and HDL (OR:0.35, 95 %CI:0.13-0.72) were confirmed. Conclusions: Large TRL, mean sizes of TRL-, and HDL were associated with radiographic and histopathologic HS. The use of lipoprotein particle size/number could improve cardiovascular risk assessment in HS.

Computed Tomography-derived Characterization of Pericoronary, Epicardial, and Paracardial Adipose Tissue and Its Association With Myocardial Ischemia as Assessed by Computed Fractional Flow Reserve.

BACKGROUND: Increased pericoronary adipose tissue (PCAT) attenuation derived from coronary computed tomography (CT) angiography (CTA) relates to coronary inflammation and cardiac mortality. We aimed to investigate the association between CT-derived characterization of different cardiac fat compartments and myocardial ischemia as assessed by computed fractional flow reserve (FFRCT). METHODS: In all, 133 patients (median 64 y, 74% male) with coronary artery disease (CAD) underwent CTA including FFRCT measurement followed by invasive FFR assessment (FFRINVASIVE). CT attenuation and volume of PCAT were quantified around the proximal right coronary artery (RCA), left anterior descending artery (LAD), and left circumflex artery (LCX). Epicardial adipose tissue (EAT) and paracardial adipose tissue (PAT; all intrathoracic adipose tissue outside the pericardium) were quantified in noncontrast cardiac CT datasets. RESULTS: Median FFRCT was 0.86 [0.79, 0.91] and median FFRINVASIVE was 0.87 [0.81, 0.93]. Subjects with the presence of myocardial ischemia (n=26) defined by an FFRCT-threshold of ≤0.75 showed significantly higher RCA PCAT attenuation than individuals without myocardial ischemia (n=107) (-75.1±10.8 vs. -81.1±10.6 HU, P=0.011). In multivariable analysis adjusted for age, body mass index, sex and risk factors, increased RCA PCAT attenuation remained a significant predictor of myocardial ischemia. Between individuals with myocardial ischemia compared with individuals without myocardial ischemia, there was no significant difference in the volume and CT attenuation of EAT and PAT or in the PCAT volume of RCA, LAD, and LCX. CONCLUSIONS: Increased RCA PCAT attenuation is associated with the presence of myocardial ischemia as assessed by FFR, while PCAT volume, EAT, and PAT are not.

Differences of inflammatory cytokine profile in patients with vulnerable plaque: A coronary CTA study.

BACKGROUND AND AIMS: Various pro- and anti-inflammatory biomarkers are involved in the process of atherosclerosis. We analyzed the association of different biomarkers with coronary plaque volume and vulnerable plaque subcomponents. METHODS: In 301 patients undergoing coronary CT angiography (CTA), total coronary plaque volume (TPV) and subcomponents including non-calcified plaque volume (NCPV) and vulnerable plaque burden were quantified using semi-automated software. Serum was analyzed for various cytokines. RESULTS: Out of 301 patients, 207 (69%) were male. The mean age was 59 ± 10 years. Patients were divided using the median of TPV, NCPV and vulnerable plaque burden. In univariable analysis, patients with high TPV, high NCPV and high vulnerable plaque burden showed significant higher serum levels for IFNƔ, IL-1a, -2, -4, -10 and -17 and significant lower levels for IL-8 and MCP-1 (all p < 0.05). Multivariable analysis showed positive associations between high vulnerable plaque burden, IL-1a (OR 2.60, p = 0.001) and Eotaxin (OR 1.89, p = 0.020), and inverse association to MCP-1 (OR 0.33, p < 0.001), independent of age, gender and CVRF. In exploratory subanalyses, patients with presence of atherosclerosis (n = 247; 82%) showed significantly higher levels of IL-17 in all subgroups with high vulnerable plaque burden, irrespective of overall plaque volume (all p < 0.001). CONCLUSIONS: The cytokine profile significantly differs between patients with high and low coronary plaque volume. IL-1a and IL-17 seem to play a major proatherogenic role in vulnerable plaque formation, whereas MCP-1 paradoxically portends protective effects. Longitudinal studies with serial cytokine testing are needed to identify potential targets for therapeutic interventions.

Differences in Cardiovascular Risk, Coronary Artery Disease, and Cardiac Events Between Black and White Individuals Enrolled in the PROMISE Trial.

IMPORTANCE: Race and ethnicity have been studied as risk factors in cardiovascular disease. How risk factors, epicardial coronary artery disease, and cardiac events differ between Black and White individuals undergoing noninvasive testing for coronary artery disease is not known. OBJECTIVE: To assess differences in cardiovascular risk burden, coronary plaque, and major adverse cardiac events between Black and White individuals assigned to receive coronary computed tomography angiography (CCTA) or functional testing for stable chest pain. DESIGN, SETTING, AND PARTICIPANTS: A nested observational cohort study within the PROMISE trial was conducted at 193 outpatient sites in North America. A total of 1071 non-Hispanic Black (hereafter Black) and 7693 non-Hispanic White (hereafter White) participants with stable chest pain undergoing noninvasive cardiovascular testing were included. This analysis was conducted from February 13, 2015, to November 2, 2021. MAIN OUTCOMES AND MEASURES: The primary end point was the composite of death, myocardial infarction, or hospitalization for unstable angina over a median follow-up of 24.4 months. RESULTS: Among 1071 Black individuals (12.2%) (women, 646 [60.3%]; mean [SD] age, 59 [8] years) and 7693 White individuals (87.8%) (women, 4029 [52.4%]; mean [SD] age, 61.1 [8.4] years), Black participants had a higher cardiovascular risk burden (more hypertension and diabetes), yet there was a similarly low major adverse cardiovascular events rate over a median 2-year follow-up (32 [3.0%] vs 243 [3.2%]; P = .84). Sensitivity analyses restricted to the 79.8% (6993 of 8764) individuals with a normal or mildly abnormal noninvasive testing result and the 54.3% (4559 of 8396) not receiving statin therapy yielded similar findings. In comparison of Black and White individuals in the CCTA group (n = 3323), significant coronary stenosis (hazard ratio [HR], 7.21; 95% CI, 1.94-26.76 vs HR, 4.30; 95% CI, 2.62-7.04) and high-risk plaque (HR, 3.47; 95% CI, 1.00-12.06 vs HR, 2.21; 95% CI, 1.37-3.57) were associated with major adverse cardiovascular events in both Black and White patients. However, with respect to epicardial coronary artery disease burden, Black individuals had a less-prevalent coronary artery calcium score greater than 0 (45.1% vs 63.2%; P < .001), coronary stenosis greater than or equal to 50% (32 [8.7%] vs 430 [14.6%]; P = .001), and high-risk plaque (139 [37.6%] vs 1547 [52.4%]; P < .001). CONCLUSIONS AND RELEVANCE: The findings of this study suggest that, despite a greater cardiovascular risk burden in Black persons, rates of coronary artery calcium, stenosis, and high-risk plaque observed via CCTA were lower in Black persons than White persons. This result suggests differences in cardiovascular risk burden and coronary plaque in Black and White individuals with stable chest pain.

Coronary Atherosclerosis, Cardiac Troponin, and Interleukin-6 in Patients With Chest Pain: The PROMISE Trial Results.

BACKGROUND: Increased inflammation and myocardial injury can be observed in the absence of myocardial infarction or obstructive coronary artery disease (CAD). OBJECTIVES: The authors determined whether biomarkers of inflammation and myocardial injury-interleukin (IL)-6 and high-sensitivity cardiac troponin (hs-cTn)-were associated with the presence and extent of CAD and were independent predictors of major adverse cardiovascular events (MACEs) in stable chest pain. METHODS: Using participants from the PROMISE trial, the authors measured hs-cTn I and IL-6 concentrations and analyzed computed tomography angiography (CTA) images in the core laboratory for CAD characteristics: significant stenosis (≥70%), high-risk plaque (HRP), Coronary Artery Disease Reporting and Data System (CAD-RADS) categories, segment involvement score (SIS), and coronary artery calcium (CAC) score. The primary endpoint was a composite MACE (death, myocardial infarction, or unstable angina). RESULTS: The authors included 1,796 participants (age 60.2 ± 8.0 years; 47.5% men, median follow-up 25 months). In multivariable linear regression adjusted for atherosclerotic cardiovascular disease (ASCVD) risk, hs-cTn was associated with HRP, stenosis, CAD-RADS, and SIS. IL-6 was only associated with stenosis and CAD-RADS. hs-cTn above median (1.5 ng/L) was associated with MACEs in univariable analysis (HR: 2.1 [95% CI: 1.3-3.6]; P = 0.006), but not in multivariable analysis adjusted for ASCVD and CAD. IL-6 above median (1.8 ng/L) was associated with MACEs in multivariable analysis adjusted for ASCVD and HRP (HR: 1.9 [95% CI: 1.1-3.3]; P = 0.03), CAC (HR: 1.9 [95% CI: 1.0-3.4]; P = 0.04), and SIS (HR: 1.8 [95% CI: 1.0-3.2]; P = 0.04), but not for stenosis or CAD-RADS. In participants with nonobstructive CAD (stenosis 1%-69%), the presence of both hs-cTn and IL-6 above median was strongly associated with MACEs (HR: 2.5-2.7 after adjustment for CAD characteristics). CONCLUSIONS: Concentrations of hs-cTn and IL-6 were associated with CAD characteristics and MACEs, indicating that myocardial injury and inflammation may each contribute to pathways in CAD pathophysiology. This association was most pronounced among participants with nonobstructive CAD representing an opportunity to tailor treatment in this at-risk group. (PROspective Multicenter Imaging Study for Evaluation of Chest Pain [PROMISE]; NCT01174550).

Risk factors for cardiovascular disease among individuals with hepatic steatosis.

Cardiovascular disease (CVD) is the leading cause of mortality in adults with hepatic steatosis (HS). However, risk factors for CVD in HS are unknown. We aimed to identify factors associated with coronary artery disease (CAD) and incident major adverse cardiovascular events (MACE) in individuals with HS. We performed a nested cohort study of adults with HS detected on coronary computed tomography in the PROspective Multicenter Imaging Study for Evaluation of chest pain (PROMISE) trial. Obstructive CAD was defined as ≥50% coronary stenosis. MACE included hospitalization for unstable angina, nonfatal myocardial infarction, or all-cause death. Multivariate modeling, adjusted for age, sex, atherosclerotic CVD (ASCVD) risk score and body mass index, identified factors associated with obstructive CAD. Cox regression, adjusted for ASCVD risk score, determined the predictors of MACE. A total of 959 of 3,756 (mean age 59.4 years, 55.0% men) had HS. Obstructive CAD was present in 15.2% (145 of 959). Male sex (adjusted odds ratio [aOR] = 1.83, 95% confidence interval [CI] 1.18-1.2.84; p = 0.007), ASCVD risk score (aOR = 1.05, 95% CI 1.03-1.07; p < 0.001), and n-terminal pro-b-type natriuretic peptide (NT-proBNP; aOR = 1.90, 95% CI 1.38-2.62; p < 0.001) were independently associated with obstructive CAD. In the 25-months median follow-up, MACE occurred in 4.4% (42 of 959). Sedentary lifestyle (adjusted hazard ratio [aHR] = 2.53, 95% CI 1.27-5.03; p = 0.008) and NT-proBNP (aOR = 1.50, 95% CI 1.01-2.25; p = 0.046) independently predicted MACE. Furthermore, the risk of MACE increased by 3% for every 1% increase in ASCVD risk score (aHR = 1.03, 95% CI 1.01-1.05; p = 0.02). Conclusion: In individuals with HS, male sex, NT-pro-BNP, and ASCVD risk score are associated with obstructive CAD. Furthermore, ASCVD, NT-proBNP, and sedentary lifestyle are independent predictors of MACE. These factors, with further validation, may help risk-stratify adults with HS for incident CAD and MACE.

High levels of eicosapentaenoic acid are associated with lower pericoronary adipose tissue attenuation as measured by coronary CTA.

BACKGROUND AND AIMS: Higher pericoronary adipose tissue (PCAT) attenuation, a novel marker of inflammation in coronary CT angiography (CTA), has been shown to indicate increased cardiac mortality. Supplementation of eicosapentaenoic acid (EPA) has been shown to decrease cardiovascular death. Whether blood levels of n-3 fatty acids are associated with differences in PCAT attenuation is unknown. METHODS: This is a cross-sectional analysis including 64 symptomatic patients who underwent coronary CTA. PCAT attenuation was measured in Hounsfield Units (HU) around the proximal 40 mm of the right coronary artery using semi-automated software. Erythrocyte membrane fatty acid composition was analyzed using gas chromatography. Individual fatty acids were expressed as a percentage of total identified fatty acids. RESULTS: The patient cohort was divided into two groups using the median PCAT attenuation of -78.1 HU (each n = 32). No differences were seen in age, sex, BMI or traditional cardiovascular risk factors (CVRF) between groups (all p > 0.05). In univariable analysis, significantly higher values of EPA (1.00% [0.78; 1.26] vs. 0.78% [0.63; 0.99]; p = 0.02) were seen in patients with lower PCAT attenuation. All other fatty acids showed no differences (all p > 0.05). Moreover, a significant negative correlation was seen between PCAT attenuation and EPA (CC: 0.38; p = 0.002). In multivariable analysis, an inverse association of EPA with PCAT attenuation existed (ß = -0.31, p = 0.017), independent of age, gender, BMI and number of CVRF (all p > 0.1). CONCLUSIONS: High levels of EPA are associated with lower PCAT attenuation on coronary CTA. This may indicate a different composition of pericoronary adipose tissue, potentially caused by a lower degree of coronary inflammation.

Pericoronary adipose tissue CT attenuation and its association with serum levels of atherosclerosis-relevant inflammatory mediators, coronary calcification and major adverse cardiac events.

BACKGROUND: Increased attenuation of pericoronary adipose tissue (PCAT) around the right coronary artery (RCA) derived from coronary CTA might detect coronary inflammation. We investigated a potential association between RCA PCAT attenuation and serum levels of atherosclerosis-relevant cytokines and MACE (coronary revascularization, myocardial infarction and/or cardiac death). METHODS: Blood samples of 293 clinically stable individuals (59.0 â€‹± â€‹9.8 years, 69% males) were analyzed for atherosclerosis-relevant cytokines including interleukin (IL)-2, IL- 4, IL-6, IL-7, IL-8, IL-10, IL-13, IL-15, IL-17, TNF-a, IP-10, CRP, MCP-1, MIP-1a, Eotaxin and GM-CSF. Subjects also underwent coronary calcium scoring (CCS) followed by CTA. PCAT CT attenuation was measured around the RCA using semi-automated software. Increased RCA PCAT attenuation was defined as PCAT attenuation above the 75th percentile (>-73.5 HU). To assess MACE, 232 individuals were followed for a mean duration of 9.6 â€‹± â€‹2.1 years. RESULTS: In patients with increased RCA PCAT attenuation the serum levels of MCP-1 were increased (p â€‹< â€‹0.01), whereas levels of anti-inflammatory mediators IL-4 and -13 were significantly reduced (each p â€‹< â€‹0.05). Adipocytokine MCP-1 (r â€‹= â€‹0.23, p â€‹< â€‹0.01) and pro-inflammatory mediator IL-7 (r â€‹= â€‹0.12, p â€‹= â€‹0.04) showed a mild positive correlation with RCA PCAT attenuation, whereas anti-inflammatory mediators Il-4, -10 and -13 correlated inversely (each r < -0.12, each p â€‹< â€‹0.05). 40/232 patients experienced MACE during follow-up. In multivariable Cox regression analysis increased RCA PCAT attenuation was shown to be an independent predictor of MACE (HR 2.01, p â€‹= â€‹0.044). CONCLUSIONS: Increased RCA PCAT CT attenuation shows a weak association with serum levels of selected atherosclerosis-relevant inflammatory biomarkers. Increased RCA PCAT attenuation is an independent predictor of MACE and may potentially guide future prevention strategies in stable patients.

Risk Stratification With the Use of Coronary Computed Tomographic Angiography in Patients With Nonobstructive Coronary Artery Disease.

OBJECTIVES: The purpose of this study was to develop a risk prediction model for patients with nonobstructive CAD. BACKGROUND: Among stable chest pain patients, most cardiovascular (CV) events occur in those with nonobstructive coronary artery disease (CAD). Thus, developing tailored risk prediction approaches in this group of patients, including CV risk factors and CAD characteristics, is needed. METHODS: In PROMISE (Prospective Multicenter Imaging Study for Evaluation of Chest Pain) computed tomographic angiography patients, a core laboratory assessed prevalence of CAD (nonobstructive 1% to 49% left main or 1% to 69% stenosis any coronary artery), degree of stenosis (minimal: 1% to 29%; mild: 30% to 49%; or moderate: 50% to 69%), high-risk plaque (HRP) features (positive remodeling, low-attenuation plaque, and napkin-ring sign), segment involvement score (SIS), and coronary artery calcium (CAC). The primary end point was an adjudicated composite of unstable angina pectoris, nonfatal myocardial infarction, and death. Cox regression analysis determined independent predictors in nonobstructive CAD. RESULTS: Of 2,890 patients (age 61.7 years, 46% women) with any CAD, 90.4% (n = 2,614) had nonobstructive CAD (mean age 61.6 yrs, 46% women, atherosclerotic cardiovascular disease [ASCVD] risk 16.2%). Composite events were independently predicted by ASCVD risk (hazard ratio [HR]: 1.03; p = 0.001), degree of stenosis (30% to 69%; HR: 1.91; p = 0.011), and presence of ≥2 HRP features (HR: 2.40; p = 0.008). Addition of ≥2 HRP features to: 1) ASCVD and CAC; 2) ASCVD and SIS; or 3) ASCVD and degree of stenosis resulted in a statistically significant improvement in model fit (p = 0.0036; p = 0.0176; and p = 0.0318; respectively). Patients with ASCVD ≥7.5%, any HRP, and mild/moderate stenosis had significantly higher event rates than those who did not meet those criteria (3.0% vs. 6.2%; p = 0.007). CONCLUSIONS: Advanced coronary plaque features have incremental value over total plaque burden for the discrimination of clinical events in low-risk stable chest pain patients with nonobstructive CAD. This may be a first step to improve prevention in this cohort with the highest absolute risk for CV events.

Association of Metabolic Phenotypes With Coronary Artery Disease and Cardiovascular Events in Patients With Stable Chest Pain.

OBJECTIVE: Obesity and metabolic syndrome are associated with major adverse cardiovascular events (MACE). However, whether distinct metabolic phenotypes differ in risk for coronary artery disease (CAD) and MACE is unknown. We sought to determine the association of distinct metabolic phenotypes with CAD and MACE. RESEARCH DESIGN AND METHODS: We included patients from the Prospective Multicenter Imaging Study for Evaluation of Chest Pain (PROMISE) who underwent coronary computed tomography (CT) angiography. Obesity was defined as a BMI ≥30 kg/m2 and metabolically healthy as less than or equal to one metabolic syndrome component except diabetes, distinguishing four metabolic phenotypes: metabolically healthy/unhealthy and nonobese/obese (MHN, MHO, MUN, and MUO). Differences in severe calcification (coronary artery calcification [CAC] ≥400), severe CAD (≥70% stenosis), high-risk plaque (HRP), and MACE were assessed using adjusted logistic and Cox regression models. RESULTS: Of 4,381 patients (48.4% male, 60.5 ± 8.1 years of age), 49.4% were metabolically healthy (30.7% MHN and 18.7% MHO) and 50.6% unhealthy (22.3% MUN and 28.4% MUO). MHO had similar coronary CT findings as compared with MHN (severe CAC/CAD and HRP; P > 0.36 for all). Among metabolically unhealthy patients, those with obesity had similar CT findings as compared with nonobese (P > 0.10 for all). However, both MUN and MUO had unfavorable CAD characteristics as compared with MHN (P ≤ 0.017 for all). A total of 130 events occurred during follow-up (median 26 months). Compared with MHN, MUN (hazard ratio [HR] 1.61 [95% CI 1.02-2.53]) but not MHO (HR 1.06 [0.62-1.82]) or MUO (HR 1.06 [0.66-1.72]) had higher risk for MACE. CONCLUSIONS: In patients with stable chest pain, four metabolic phenotypes exhibit distinctly different CAD characteristics and risk for MACE. Individuals who are metabolically unhealthy despite not being obese were at highest risk in our cohort.

Prognostic Value of Coronary CTA in Stable Chest Pain: CAD-RADS, CAC, and Cardiovascular Events in PROMISE.

OBJECTIVES: The purpose of this study was to compare Coronary Artery Disease Reporting and Data System (CAD-RADS) to traditional stenosis categories and the coronary artery calcium score (CACS) for predicting cardiovascular events in patients with stable chest pain and suspected coronary artery disease (CAD). BACKGROUND: The 2016 CAD-RADS has been established to standardize the reporting of CAD on coronary CT angiography (CTA). METHODS: PROMISE (Prospective Multicenter Imaging Study for Evaluation of Chest Pain) trial participants' CTAs were assessed by a central CT core laboratory for CACS, traditional stenosis-based categories, and modified CAD-RADS grade including high-risk coronary plaque (HRP) features. Traditional stenosis categories and CAD-RADS grade were compared for the prediction of the composite endpoint of death, myocardial infarction, or hospitalization for unstable angina over a median follow-up of 25 months. Incremental prognostic value over traditional risk factors and CACS was assessed. RESULTS: In 3,840 eligible patients (mean age: 60.4 ± 8.2 years; 49% men), 3.0% (115) experienced events. CAD-RADS (concordance statistic [C-statistic] 0.747) had significantly higher discriminatory value than traditional stenosis-based assessments (C-statistic 0.698 to 0.717; all p for comparison ≤0.001). With no plaque (CAD-RADS 0) as the baseline, the hazard ratio (HR) for an event increased from 2.43 (95% confidence interval [CI]: 1.16 to 5.08) for CAD-RADS 1 to 21.84 (95% CI: 8.63 to 55.26) for CAD-RADS 4b and 5. In stepwise nested models, CAD-RADS added incremental prognostic value beyond ASCVD risk score and CACS (C-statistic 0.776 vs. 0.682; p < 0.001), and added incremental value persisted in all CACS strata. CONCLUSIONS: These data from a large representative contemporary cohort of patients undergoing coronary CTA for stable chest pain support the prognostic value of CAD-RADS as a standard reporting system for coronary CTA.

Subclinical Burden of Coronary Artery Calcium in Patients With Coarctation of the Aorta.

Coronary computed tomography (CT) angiography is often performed in adults with coarctation of the aorta (CoA) for anatomic assessment. As this population ages, assessment of atherosclerotic cardiovascular disease burden is important. Thus, quantitative and qualitative coronary artery calcium (CAC) scores were assessed for patients with CoA ≥16 years of age, who were seen at a referral center. CoA patients had either coronary CT angiography or chest CT with interpretable coronary information performed for clinical indications (follow-up, preoperative, or for symptoms) from 2004 to 2017. Qualitative CAC was determined based on low-dose CT and lung cancer screening protocols. Quantitative CAC scores were compared with an age- and gender-matched control cohort of patients chosen from an emergency department database of patients who received coronary CT angiography for chest pain evaluation. Atherosclerotic cardiovascular disease 10-year predicted risk scores were calculated for both cohorts. Out of 131 patients with CoA (mean age 46.1 ± 15.3 years), 22 patients (17%) had multivessel atherosclerotic disease on qualitative assessment. In the subgroup of patients ≥40 years, those with CoA were more likely to have a quantitative CAC score ≥400 compared with those without CoA (14% vs 4%, p = 0.02). Median atherosclerotic cardiovascular disease risk score was 8% (interquartile range 2% to 12%) for CoA patients ≥40 years, and 5% (interquartile range 2% to 9%) for patient without CoA ≥40 years. In conclusion, we determined that CoA patients have subclinical atherosclerosis identifiable on CT in high rates when compared with patients without CoA. Atherosclerotic cardiovascular disease should be assessed in these patients for prevention and treatment.