Application of Quantitative Assessment of Coronary Atherosclerosis by Coronary Computed Tomographic Angiography.

Coronary computed tomography angiography (CCTA) has emerged as a pivotal tool for diagnosing and risk-stratifying patients with suspected coronary artery disease (CAD). Recent advancements in image analysis and artificial intelligence (AI) techniques have enabled the comprehensive quantitative analysis of coronary atherosclerosis. Fully quantitative assessments of coronary stenosis and lumen attenuation have improved the accuracy of assessing stenosis severity and predicting hemodynamically significant lesions. In addition to stenosis evaluation, quantitative plaque analysis plays a crucial role in predicting and monitoring CAD progression. Studies have demonstrated that the quantitative assessment of plaque subtypes based on CT attenuation provides a nuanced understanding of plaque characteristics and their association with cardiovascular events. Quantitative analysis of serial CCTA scans offers a unique perspective on the impact of medical therapies on plaque modification. However, challenges such as time-intensive analyses and variability in software platforms still need to be addressed for broader clinical implementation. The paradigm of CCTA has shifted towards comprehensive quantitative plaque analysis facilitated by technological advancements. As these methods continue to evolve, their integration into routine clinical practice has the potential to enhance risk assessment and guide individualized patient management. This article reviews the evolving landscape of quantitative plaque analysis in CCTA and explores its applications and limitations.

Time and event-specific deep learning for personalized risk assessment after cardiac perfusion imaging.

Standard clinical interpretation of myocardial perfusion imaging (MPI) has proven prognostic value for predicting major adverse cardiovascular events (MACE). However, personalizing predictions to a specific event type and time interval is more challenging. We demonstrate an explainable deep learning model that predicts the time-specific risk separately for all-cause death, acute coronary syndrome (ACS), and revascularization directly from MPI and 15 clinical features. We train and test the model internally using 10-fold hold-out cross-validation (n = 20,418) and externally validate it in three separate sites (n = 13,988) with MACE follow-ups for a median of 3.1 years (interquartile range [IQR]: 1.6, 3.6). We evaluate the model using the cumulative dynamic area under receiver operating curve (cAUC). The best model performance in the external cohort is observed for short-term prediction - in the first six months after the scan, mean cAUC for ACS and all-cause death reaches 0.76 (95% confidence interval [CI]: 0.75, 0.77) and 0.78 (95% CI: 0.78, 0.79), respectively. The model outperforms conventional perfusion abnormality measures at all time points for the prediction of death in both internal and external validations, with improvement increasing gradually over time. Individualized patient explanations are visualized using waterfall plots, which highlight the contribution degree and direction for each feature. This approach allows the derivation of individual event probability as a function of time as well as patient- and event-specific risk explanations that may help draw attention to modifiable risk factors. Such a method could help present post-scan risk assessments to the patient and foster shared decision-making.

Assessment of lifestyle-related risk factors enhances the effectiveness of cardiac stress testing.

Cardiac stress tests have been widely utilized since the 1960s for the diagnostic and prognostic assessment of patients with suspected coronary artery disease (CAD). Clinical risk is primarily based on assessing the presence and magnitude of inducible myocardial ischemia. However, the primary factors driving mortality risk have changed over recent decades. Factors such as typical angina and inducible ischemia have decreased, whereas the percentage of patients with diabetes, obesity and hypertension have increased. There has also been a marked temporal increase in the percentage of patients who require pharmacologic testing due to inability to perform treadmill exercise at the time of cardiac stress testing and this need has emerged as the most potent predictor of mortality risk in contemporary stress test populations. However, the long-term clinical risk posed by the inability to perform exercise and concomitant CAD risk factors are rarely reflected in the assessment of patients' prognostic risk in cardiac stress test reports. In this review, we suggest that the clinical utility of present-day cardiac stress testing can be improved by developing a more comprehensive assessment that integrates and reports all factors which modulate patients' long-term clinical risk following stress and testing. This should include assessment of patients' CAD risk factors, physical activity habits and mobility risks, and identification of the reasons why patients could not exercise at the time of cardiac stress testing. In addition, the assessment of four core non-aerobic functional parameters should be considered among patients who cannot exercise: assessment of gait speed, handgrip strength, lower extremity strength, and standing balance.

Assessment of lifestyle "vital signs" in healthcare settings.

Unhealthy lifestyles, such as maintenance of poor diets and physical inactivity, are a powerful driver of disease-producing risk factors and chronic illnesses. This has led to an increasing call to assess adverse lifestyle factors in healthcare settings. This approach could be aided by designating health-related lifestyle factors as "vital signs" that can be recorded during patient visits. Just such an approach has been used for assessing patients' smoking habits since the 1990s. In this review, we assess the rationale for addressing six other health-related lifestyle factors, beyond smoking, in patient care settings: physical activity (PA), sedentary behavior (SB), participation in muscle strengthening exercises, mobility limitations, diet, and sleep quality. For each domain, we evaluate the evidence that supports currently proposed ultra-short screening tools. Our analysis indicates strong medical evidence to support the use of one to two-item screening questions for assessing patients' PA, SB, muscle strengthening activities, and presence of "pre-clinical" mobility limitations. We also present a theoretical basis for measuring patients' diet quality through use of an ultrashort dietary screen, based on evaluation of healthy food intake (fruits/vegetables) and unhealthy food intake (high consumption of highly processed meats and/or consumption of sugary foods and beverages) and a proposed evaluation of sleep quality using a single-item screener. The result is a 10-item lifestyle questionnaire that is based on patient self-report. As such, this questionnaire has the potential to be employed as a practical tool for assessing health behaviors in clinical care settings without impairing the normal workflow of healthcare providers.

Direct Risk Assessment From Myocardial Perfusion Imaging Using Explainable Deep Learning.

BACKGROUND: Myocardial perfusion imaging (MPI) is frequently used to provide risk stratification, but methods to improve the accuracy of these predictions are needed. OBJECTIVES: The authors developed an explainable deep learning (DL) model (HARD MACE [major adverse cardiac events]-DL) for the prediction of death or nonfatal myocardial infarction (MI) and validated its performance in large internal and external testing groups. METHODS: Patients undergoing single-photon emission computed tomography MPI were included, with 20,401 patients in the training and internal testing group (5 sites) and 9,019 in the external testing group (2 different sites). HARD MACE-DL uses myocardial perfusion, motion, thickening, and phase polar maps combined with age, sex, and cardiac volumes. The primary outcome was all-cause mortality or nonfatal MI. Prognostic accuracy was evaluated using area under the receiver-operating characteristic curve (AUC). RESULTS: During internal testing, patients with normal perfusion and elevated HARD MACE-DL risk were at higher risk than patients with abnormal perfusion and low HARD MACE-DL risk (annualized event rate, 2.9% vs 1.2%; P < 0.001). Patients in the highest quartile of HARD MACE-DL score had an annual rate of death or MI (4.8%) 10-fold higher than patients in the lowest quartile (0.48% per year). In external testing, the AUC for HARD MACE-DL (0.73; 95% CI: 0.71-0.75) was higher than a logistic regression model (AUC: 0.70), stress total perfusion deficit (TPD) (AUC: 0.65), and ischemic TPD (AUC: 0.63; all P < 0.01). Calibration, a measure of how well predicted risk matches actual risk, was excellent in both groups (Brier score, 0.079 for internal and 0.070 for external). CONCLUSIONS: The DL model predicts death or MI directly from MPI, by estimating patient-level risk with good calibration and improved accuracy compared with traditional quantitative approaches. The model incorporates mechanisms to explain to the physician which image regions contribute to the adverse event prediction.

Longitudinal Quantitative Assessment of Coronary Atherosclerotic Plaque Burden Related to Serum Hemoglobin Levels.

Background: Despite a potential role of hemoglobin in atherosclerosis, data on coronary plaque volume changes (PVC) related to serum hemoglobin levels are limited. Objectives: The authors sought to evaluate coronary atherosclerotic plaque burden changes related to serum hemoglobin levels using serial coronary computed tomographic angiography (CCTA). Methods: A total of 830 subjects (age 61 ± 10 years, 51.9% male) who underwent serial CCTA were analyzed. The median interscan period was 3.2 (IQR: 2.5-4.4) years. Quantitative assessment of coronary plaques was performed at both scans. All participants were stratified into 4 groups based on the quartile of baseline hemoglobin levels. Annualized total PVC (mm3/year) was defined as total PVC divided by the interscan period. Results: Baseline total plaque volume (mm3) was not different among all groups (group I [lowest]: 34.1 [IQR: 0.0-127.4] vs group II: 28.8 [IQR: 0.0-123.0] vs group III: 49.9 [IQR: 5.6-135.0] vs group IV [highest]: 34.3 [IQR: 0.0-130.7]; P = 0.235). During follow-up, serum hemoglobin level changes (Δ hemoglobin; per 1 g/dL) was related to annualized total PVC (ß = -0.114) in overall participants (P < 0.05). After adjusting for age, sex, traditional risk factors, baseline hemoglobin and creatinine levels, baseline total plaque volume, and the use of aspirin, beta-blocker, angiotensin-converting enzyme inhibitor or angiotensin receptor blocker, and statin, Δ hemoglobin significantly affected annualized total PVC in only the composite of groups I and II (ß = -2.401; P = 0.004). Conclusions: Serial CCTA findings suggest that Δ hemoglobin has an independent effect on coronary atherosclerosis. This effect might be influenced by baseline hemoglobin levels. (Progression of Atherosclerotic Plaque Determined by Computed Tomographic Angiography Imaging [PARADIGM]; NCT02803411).

Longitudinal quantitative assessment of coronary atherosclerosis related to normal systolic blood pressure maintenance in the absence of established cardiovascular disease.

BACKGROUND: Atherosclerosis-related adverse events are commonly observed even in conditions with low cardiovascular (CV) risk. Longitudinal data regarding the association of normal systolic blood pressure maintenance (SBPmaintain ) with coronary plaque volume changes (PVC) has been limited in adults without traditional CV disease. HYPOTHESIS: Normal SBPmaintain is important to attenuate coronary atherosclerosis progression in adults without baseline CV disease. METHODS: We analyzed 95 adults (56.7 ± 8.5 years; 40.0% men) without baseline CV disease who underwent serial coronary computed tomographic angiography with mean 3.5 years of follow-up. All participants were divided into two groups of normal SBPmaintain (follow-up SBP < 120 mm Hg) and ≥elevated SBPmaintain (follow-up SBP ≥ 120 mm Hg). Annualized PVC was defined as PVC divided by the interscan period. RESULTS: Compared to participants with normal SBPmaintain , those with ≥elevated SBPmaintain had higher annualized total PVC (mm3 /year) (0.0 [0.0-2.2] vs. 4.1 [0.0-13.0]; p < .001). Baseline total plaque volume (ß = .10) and the levels of SBPmaintain (ß = .23) and follow-up high-density lipoprotein cholesterol (ß = -0.28) were associated with annualized total PVC (all p < .05). The optimal cutoff of SBPmaintain for predicting plaque progression was 118.5 mm Hg (sensitivity: 78.2%, specificity: 62.5%; area under curve: 0.700; 95% confidence interval [CI]: 0.59-0.81; p < .05). SBPmaintain ≥ 118.5 mm Hg (odds ratio [OR]: 4.03; 95% CI: 1.51-10.75) and baseline total plaque volume (OR: 1.03; 95% CI: 1.01-1.06) independently influenced coronary plaque progression (all p < .05). CONCLUSION: Normal SBPmaintain is substantial to attenuate coronary atherosclerosis progression in conditions without established CV disease.

Evaluation of California Non-Comprehensive Death File Against National Death Index.

The National Death Index (NDI) by the Centers for Disease Control and Prevention and Death Master File (DMF) by Social Security Administration are the two most broadly utilized data files for mortality outcomes in clinical research. NDI's high costs and the elimination of protected death records from California in DMF calls for alternative death files. The recently emerged California Non-Comprehensive Death File (CNDF) serves as an alternative source for vital statistics. This study aims to evaluate the sensitivity and specificity of CNDF compared to NDI. Of 40,724 consented subjects in the Cedars-Sinai Cardiac Imaging Research Registry, 25,836 eligible subjects were queried through the NDI and the CDNF. After exclusion of death records to establish the same temporal and geographic availability of data, NDI identified 5,707 exact matches, while CNDF identified 6,051 death records. CNDF had a sensitivity of 94.3% and specificity of 96.4% compared to NDI exact matches. NDI also produced 581 close matches: all were verified as deaths by CNDF through matching death date and patient identifiers. Combining all NDI death records, CNDF had a sensitivity of 94.8% and specificity of 99.5%. CNDF is a reliable source for obtaining mortality outcomes and providing additional mortality validation. The use of CNDF can aid and replace the use of NDI in the state of California.

Quantitative Assessment of Cardiac Hypermetabolism and Perfusion for Diagnosis of Cardiac Sarcoidosis.

BACKGROUND: Quantitative assessment of cardiac hypermetabolism from 18Flourodeoxy glucose (FDG) positron emission tomography (PET) may improve diagnosis of cardiac sarcoidosis (CS). We assessed different approaches for quantification of cardiac hypermetabolism and perfusion in patients with suspected CS. METHODS AND RESULTS: Consecutive patients undergoing 18FDG PET assessment for possible CS between January 2014 and March 2019 were included. Cardiac hypermetabolism was quantified using maximal standardized uptake value (SUVMAX), cardiometabolic activity (CMA) and volume of inflammation, using relative thresholds (1.3× and 1.5× left ventricular blood pool [LVBP] activity), and absolute thresholds (SUVMAX > 2.7 and 4.1). Diagnosis of CS was established using the Japanese Ministry of Health and Wellness criteria. In total, 69 patients were studied, with definite or possible CS in 29(42.0%) patients. CMA above 1.5× LVBP SUVMAX had the highest area under the receiver operating characteristic curve (AUC 0.92). Quantitative parameters using relative thresholds had higher AUC compared to absolute thresholds (p < 0.01). Interobserver variability was low for CMA, with excellent agreement regarding absence of activity (Kappa 0.970). CONCLUSIONS: Quantitation with scan-specific thresholds has superior diagnostic accuracy compared to absolute thresholds. Based on the potential clinical benefit, programs should consider quantification of cardiac hypermetabolism when interpreting 18F-FDG PET studies for CS.

Value of semiquantitative assessment of high-risk plaque features on coronary CT angiography over stenosis in selection of studies for FFRct.

INTRODUCTION: The degree of stenosis on coronary CT angiography (CCTA) guides referral for CT-derived flow reserve (FFRct). We sought to assess whether semiquantitative assessment of high-risk plaque (HRP) features on CCTA improves selection of studies for FFRct over stenosis assessment alone. METHODS: Per-vessel FFRct was computed in 1,395 vessels of 836 patients undergoing CCTA with 25-99% maximal stenosis. By consensus analysis, stenosis severity was graded as 25-49%, 50-69%, 70-89%, and 90-99%. HRPs including low attenuation plaque (LAP), positive remodeling (PR), and spotty calcification (SC) were assessed in lesions with maximal stenosis. Lesion FFRct was measured distal to the lesion with maximal stenosis, and FFRct<0.80 was defined as abnormal. Association of HRP and abnormal lesion FFRct was evaluated by univariable and multivariable logistic regression models. RESULTS: The frequency of abnormal lesion FFRct increased with increase of stenosis severity across each stenosis category (25-49%:6%; 50-69%:30%; 70-89%:54%; 90-99%:91%, p â€‹< â€‹0.001). Univariable analysis demonstrated that stenosis severity, LAP, and PR were predictive of abnormal lesion FFRct, while SC was not. In multivariable analyses considering stenosis severity, presence of PR, LAP, and PR and/or LAP were independently associated with abnormal FFRct: Odds ratio 1.58, 1.68, and 1.53, respectively (p â€‹< â€‹0.02 for all). The presence of PR and/or LAP increased the frequency of abnormal FFRct with mild stenosis (p â€‹< â€‹0.05) with a similar trend with 70-89% stenosis. The combination of 2 HRP (LAP and PR) identified more lesions with FFR < 0.80 than only 1 HRP. CONCLUSIONS: Semiquantitative visual assessment of high-risk plaque features may improve the selection of studies for FFRct.

Global access to existing and future antimicrobials and diagnostics: antimicrobial subscription and pooled procurement.

The COVID-19 pandemic has underlined the importance of an efficient and equitable supply of and access to essential health products. These factors are equally pertinent to the antimicrobial resistance pandemic, in which access to a portfolio of existing and pipeline antimicrobials plus complementary diagnostics is crucial. This Viewpoint focuses on market shaping in low-income and middle-income countries (LMICs), where the need for effective antimicrobials and complementary diagnostics is most acute. We propose the creation of a subscription and pooled procurement model that consolidates the growing demand for a portfolio of antimicrobials and diagnostics in LMICs. Anchored by regional market leaders, these pooling mechanisms would guarantee consistent private-sector and public-sector access in participating countries, while creating conditions for long-term best practice in stewardship. Supported by data from South Africa and India, this proposal sets out an innovative approach to tackle the antimicrobial resistance crisis in LMICs.

Synergistic Assessment of Mortality Risk According to Body Mass Index and Exercise Ability and Capacity in Patients Referred for Radionuclide Stress Testing.

OBJECTIVE: To determine the interrelationship between body mass index (BMI), mode of stress testing (exercise or pharmacological), exercise capacity, and all-cause mortality in patients referred for stress-rest single photon emission computed tomography myocardial perfusion imaging. PATIENTS AND METHODS: We evaluated all-cause mortality in 21,638 patients undergoing stress-rest single photon emission computed tomography myocardial perfusion imaging between January 2, 1991, and December 31, 2012. Patients were divided into exercise and pharmacologically tested groups and 9 BMI categories. The median follow-up was 12.8 years (range, 5.0-26.8 years). RESULTS: In exercise patients, mortality was increased with both low and high BMI vs patients with a normal referent BMI of 22.5 to 24.9 kg/m2. In pharmacologically tested patients, only low BMI, but not high BMI, was associated with increased mortality vs normal BMI. When exercise and pharmacologically tested groups were compared directly, pharmacologically tested patients manifested a marked increase in mortality risk vs exercise patients within each BMI category, ranging from an approximately 4-fold increase in mortality in those with normal or high BMI to a 12.3-fold increase in those with low BMI values. Similar findings were observed in a cohort of 4804 exercise and 4804 pharmacologically tested patients matched to have similar age and coronary artery disease risk factor profiles. In exercise patients, further risk stratification was achieved when considering both BMI and metabolic equivalent tasks of achieved exercise. CONCLUSION: The combined assessment of BMI and exercise ability and capacity provides synergistic and marked risk stratification of future mortality risk in patients referred for radionuclide stress testing, providing considerable insights into the "obesity paradox" that is observed in populations referred for stress testing.

Contrast-enhanced computed tomography assessment of aortic stenosis.

OBJECTIVES: Non-contrast CT aortic valve calcium scoring ignores the contribution of valvular fibrosis in aortic stenosis. We assessed aortic valve calcific and non-calcific disease using contrast-enhanced CT. METHODS: This was a post hoc analysis of 164 patients (median age 71 (IQR 66-77) years, 78% male) with aortic stenosis (41 mild, 89 moderate, 34 severe; 7% bicuspid) who underwent echocardiography and contrast-enhanced CT as part of imaging studies. Calcific and non-calcific (fibrosis) valve tissue volumes were quantified and indexed to annulus area, using Hounsfield unit thresholds calibrated against blood pool radiodensity. The fibrocalcific ratio assessed the relative contributions of valve fibrosis and calcification. The fibrocalcific volume (sum of indexed non-calcific and calcific volumes) was compared with aortic valve peak velocity and, in a subgroup, histology and valve weight. RESULTS: Contrast-enhanced CT calcium volumes correlated with CT calcium score (r=0.80, p<0.001) and peak aortic jet velocity (r=0.55, p<0.001). The fibrocalcific ratio decreased with increasing aortic stenosis severity (mild: 1.29 (0.98-2.38), moderate: 0.87 (1.48-1.72), severe: 0.47 (0.33-0.78), p<0.001) while the fibrocalcific volume increased (mild: 109 (75-150), moderate: 191 (117-253), severe: 274 (213-344) mm3/cm2). Fibrocalcific volume correlated with ex vivo valve weight (r=0.72, p<0.001). Compared with the Agatston score, fibrocalcific volume demonstrated a better correlation with peak aortic jet velocity (r=0.59 and r=0.67, respectively), particularly in females (r=0.38 and r=0.72, respectively). CONCLUSIONS: Contrast-enhanced CT assessment of aortic valve calcific and non-calcific volumes correlates with aortic stenosis severity and may be preferable to non-contrast CT when fibrosis is a significant contributor to valve obstruction.

Comparative differences in the atherosclerotic disease burden between the epicardial coronary arteries: quantitative plaque analysis on coronary computed tomography angiography.

AIMS: Anatomic series commonly report the extent and severity of coronary artery disease (CAD), regardless of location. The aim of this study was to evaluate differences in atherosclerotic plaque burden and composition across the major epicardial coronary arteries. METHODS AND RESULTS: A total of 1271 patients (age 60 ± 9 years; 57% men) with suspected CAD prospectively underwent coronary computed tomography angiography (CCTA). Atherosclerotic plaque volume was quantified with categorization by composition (necrotic core, fibrofatty, fibrous, and calcified) based on Hounsfield Unit density. Per-vessel measures were compared using generalized estimating equation models. On CCTA, total plaque volume was lowest in the LCx (10.0 ± 29.4 mm3), followed by the RCA (32.8 ± 82.7 mm3; P < 0.001), and LAD (58.6 ± 83.3 mm3; P < 0.001), even when correcting for vessel length or volume. The prevalence of ≥2 high-risk plaque features, such as positive remodelling or spotty calcification, occurred less in the LCx (3.8%) when compared with the LAD (21.4%) or RCA (10.9%, P < 0.001). In the LCx, the most stenotic lesion was categorized as largely calcified more often than in the RCA and LAD (55.3% vs. 39.4% vs. 32.7%; P < 0.001). Median diameter stenosis was also lowest in the LCx (16.2%) and highest in the LAD (21.3%; P < 0.001) and located more distal along the LCx when compared with the RCA and LAD (P < 0.001). CONCLUSION: Atherosclerotic plaque, irrespective of vessel volume, varied across the epicardial coronary arteries; with a significantly lower burden and different compositions in the LCx when compared with the LAD and RCA. These volumetric and compositional findings support a diverse milieu for atherosclerotic plaque development and may contribute to a varied acute coronary risk between the major epicardial coronary arteries.

Association of Body Mass Index With Coronary Artery Calcium and Subsequent Cardiovascular Mortality: The Coronary Artery Calcium Consortium.

BACKGROUND: Obesity is associated with higher risk for coronary artery calcium (CAC), but the relationship between body mass index (BMI) and mortality is complex and frequently paradoxical. METHODS: We analyzed BMI, CAC, and subsequent mortality using data from the CAC Consortium, a multi-centered cohort of individuals free of established cardiovascular disease (CVD) who underwent CAC testing. Mortality was assessed through linkage to the Social Security Death Index and cause of death from the National Death Index. Multivariable logistic regression was used to determine odds ratios for the association of clinically relevant BMI categories and prevalent CAC. Cox proportional hazards regression modeling was used to determine hazard ratios for coronary heart disease, CVD, and all-cause mortality according to categories of BMI and CAC. RESULTS: Our sample included 36 509 individuals, mean age 54.1 (10.3) years, 34.4% female, median BMI 26.6 (interquartile range, 24.1-30.1), 46.6% had zero CAC, and 10.5% had CAC ≥400. Compared with individuals with normal BMI, the multivariable adjusted odds of CAC >0 were increased in those overweight (odds ratio, 1.13 [95% CI, 1.1-1.2]) and obese (odds ratio, 1.5 [95% CI, 1.4-1.6]). Over a median follow-up of 11.4 years, there were 1550 deaths (4.3%). Compared with normal BMI, obese individuals had a higher risk of coronary heart disease, CVD, and all-cause mortality while overweight individuals, despite a higher odds of CAC, showed no significant increase in mortality. In a sex-stratified analysis, the increase in coronary heart disease, CVD, and all-cause mortality in obese individuals appeared largely limited to men, and there was a lower risk of all-cause mortality in overweight women (hazard ratio, 0.79 [95% CI, 0.63-0.98]). CONCLUSIONS: In a large sample undergoing CAC scoring, obesity was associated with a higher risk of CAC and subsequent coronary heart disease, CVD, and all-cause mortality. However, overweight individuals did not have a higher risk of mortality despite a higher risk for CAC.

Quantitative assessment of coronary plaque volume change related to triglyceride glucose index: The Progression of AtheRosclerotic PlAque DetermIned by Computed TomoGraphic Angiography IMaging (PARADIGM) registry.

BACKGROUND: The association between triglyceride glucose (TyG) index and coronary atherosclerotic change remains unclear. We aimed to evaluate the association between TyG index and coronary plaque progression (PP) using serial coronary computed tomography angiography (CCTA). METHODS: A total of 1143 subjects (aged 60.7 ± 9.3 years, 54.6% male) who underwent serial CCTA with available data on TyG index and diabetic status were analyzed from The Progression of AtheRosclerotic PlAque DetermIned by Computed TomoGraphic Angiography IMaging (PARADIGM) registry. PP was defined as plaque volume (PV) (mm3) at follow-up minus PV at index > 0. Annual change of PV (mm3/year) was defined as PV change divided by inter-scan period. Rapid PP was defined as the progression of percent atheroma volume (PV divided by vessel volume multiplied by 100) ≥ 1.0%/year. RESULTS: The median inter-scan period was 3.2 (range 2.6-4.4) years. All participants were stratified into three groups based on TyG index tertiles. The overall incidence of PP was 77.3%. Baseline total PV (group I [lowest]: 30.8 (0.0-117.7), group II: 47.2 (6.2-160.4), and group III [highest]: 57.5 (8.4-154.3); P < 0.001) and the annual change of total PV (group I: 5.7 (0.0-20.2), group II: 7.6 (0.5-23.5), and group III: 9.4 (1.4-27.7); P = 0.010) were different among all groups. The risk of PP (odds ratio [OR] 1.648; 95% confidence interval [CI] 1.167-2.327; P = 0.005) and rapid PP (OR 1.777; 95% CI 1.288-2.451; P < 0.001) was increased in group III compared to that in group I. TyG index had a positive and significant association with an increased risk of PP and rapid PP after adjusting for confounding factors. CONCLUSION: TyG index is an independent predictive marker for the progression of coronary atherosclerosis. Clinical registration ClinicalTrials.gov NCT02803411.

Whole-vessel coronary 18F-sodium fluoride PET for assessment of the global coronary microcalcification burden.

PURPOSE: 18F-sodium fluoride (18F-NaF) has shown promise in assessing disease activity in coronary arteries, but currently used measures of activity - such as maximum target to background ratio (TBRmax) - are defined by single pixel count values. We aimed to develop a novel coronary-specific measure of 18F-NaF PET reflecting activity throughout the entire coronary vasculature (coronary microcalcification activity [CMA]). METHODS: Patients with recent myocardial infarction and multi-vessel coronary artery disease underwent 18F-NaF PET and coronary CT angiography. We assessed the association between coronary 18F-NaF uptake (both TBRmax and CMA) and coronary artery calcium scores (CACS) as well as low attenuation plaque (LAP, attenuation < 30 Hounsfield units) volume. RESULTS: In 50 patients (64% males, 63 ± 7 years), CMA and TBRmax were higher in vessels with LAP compared to those without LAP (1.09 [0.02, 2.34] versus 0.0 [0.0, 0.0], p < 0.001 and 1.23 [1.16, 1.37] versus 1.04 [0.93, 1.11], p < 0.001). Compared to a TBRmax threshold of 1.25, CMA > 0 had a higher diagnostic accuracy for detection of LAP: sensitivity of 93.1 (83.3-98.1)% versus 58.6 (44.9-71.4)% and a specificity of 95.7 (88.0-99.1)% versus 80.0 (68.7-88.6)% (both p < 0.001). 18F-NaF uptake assessed by CMA correlated more closely with LAP (r = 0.86, p < 0.001) than the CT calcium score (r = 0.39, p < 0.001), with these associations outperforming those observed for TBRmax values (LAP r = 0.63, p < 0.001; CT calcium score r = 0.30, p < 0.001). CONCLUSIONS: Automated assessment of disease activity across the entire coronary vasculature is feasible using 18F-NaF CMA, providing a single measurement that has closer agreement with CT markers of plaque vulnerability than more traditional measures of plaque activity.

Optimizing the Assessment of Patient Clinical Risk at the Time of Cardiac Stress Testing.

Due to a marked temporal decline in inducible myocardial ischemia over recent decades, most diagnostic patients now referred for cardiac stress testing have nonischemic studies. Among nonischemic patients, however, long-term risk is heterogeneous and highly influenced by a variety of clinical parameters. Herein, we review 8 factors that can govern long-term clinical risk: coronary risk factor burden; patient symptoms; exercise capacity and exercise test responses; the need for pharmacologic stress testing; autonomic function; musculoskeletal status; subclinical atherosclerosis; and psychosocial risk. To capture the clinical benefit provided by both assessing myocardial ischemia and these additional parameters, the authors propose that a cardiac stress tests report have an additional component beyond statements as to the likelihood of obstructive coronary artery disease and/or magnitude of ischemia. This added component could be a comment section designed to make referring physicians aware of aspects of long-term risk that may influence clinical management and potentially lead to changes in the intensity of risk factor management, frequency of follow-up, need for further testing, or other management decisions. In this manner, the increasingly frequent normal stress test result might more commonly influence treatment recommendations and even patient behavior, thus leading to improvement in patient outcomes even in the setting of normal stress test results.

Gender Disparity between Donor Sites of the Trochlea Used for Autologous Osteoarticular Transfer: An MRI Analysis.

The purpose of this study was to assess potential gender differences in size of the lateral and medial trochlea of the male and female knee as well as the variation within gender of potential osteochondral autograft transfer (OAT) donor site area. Two hundred and twelve skeletally mature patients, 106 males and 106 females, who underwent a 3T magnetic resonance imaging of the knee for a variety of indications were utilized for analysis. Exclusion criteria included degenerative arthritis, trochlear dysplasia, and poor image quality. Medial and lateral femoral trochlear cartilage width was obtained using a linear radiologic measurement tool. Widths were measured from a reproducible anatomic location representing the maximal trochlear dimension in a region where donor plugs are commonly harvested. Trochlear width was also plotted as a function of patient height. Statistical analysis was performed using a two-sample t-test. The mean and standard deviation of the lateral trochlear cartilage width (mm) for males and females were 23.38 +/- 2.14 and 20.44 +/- 2.16, respectively (p < 0.00001). The mean and standard deviation of the medial trochlear cartilage width (mm) for males and females were 14.16 +/- 2.17 and 11.78 +/- 2.03, respectively (p < 0.00001). The overall range in trochlear width for both the lateral and medial sides was 22.22 and 19.73 mm for males and females, respectively. A graft measuring 10 mm could represent as little as 34% of the lateral trochlea in males versus as much as 65% in females. Our results indicate that donor OAT plug diameter relative to available trochlear cartilage width will vary significantly both between genders and individual patients. Trochlear width variability and its potential implications on donor site morbidity may be an important consideration when contemplating osteochondral plug harvest for OAT or other indications. The level of evidence is IV.