Multi-Ethnic Study of Atherosclerosis: Relationship between Left Ventricular Shape at Cardiac MRI and 10-year Outcomes.

Background Left ventricular (LV) subclinical remodeling is associated with adverse outcomes and indicates mechanisms of disease development. Standard metrics such as LV mass and volumes may not capture the full range of remodeling. Purpose To quantify the relationship between LV three-dimensional shape at MRI and incident cardiovascular events over 10 years. Materials and Methods In this retrospective study, 5098 participants from the Multi-Ethnic Study of Atherosclerosis who were free of clinical cardiovascular disease underwent cardiac MRI from 2000 to 2002. LV shape models were automatically generated using a machine learning workflow. Event-specific remodeling signatures were computed using partial least squares regression, and random survival forests were used to determine which features were most associated with incident heart failure (HF), coronary heart disease (CHD), and cardiovascular disease (CVD) events over a 10-year follow-up period. The discrimination improvement of adding LV shape to traditional cardiovascular risk factors, coronary artery calcium scores, and N-terminal pro-brain natriuretic peptide levels was assessed using the index of prediction accuracy and time-dependent area under the receiver operating characteristic curve (AUC). Kaplan-Meier survival curves were used to illustrate the ability of remodeling signatures to predict the end points. Results Overall, 4618 participants had sufficient three-dimensional MRI information to generate patient-specific LV models (mean age, 60.6 years ± 9.9 [SD]; 2540 women). Among these participants, 147 had HF, 317 had CHD, and 455 had CVD events. The addition of LV remodeling signatures to traditional cardiovascular risk factors improved the mean AUC for 10-year survival prediction and achieved better performance than LV mass and volumes; HF (AUC, 0.83 ± 0.01 and 0.81 ± 0.01, respectively; P < .05), CHD (AUC, 0.77 ± 0.01 and 0.75 ± 0.01, respectively; P < .05), and CVD (AUC, 0.78 ± 0.0 and 0.76 ± 0.0, respectively; P < .05). Kaplan-Meier analysis demonstrated that participants with high-risk HF remodeling signatures had a 10-year survival rate of 56% compared with 95% for those with low-risk scores. Conclusion Left ventricular event-specific remodeling signatures were more predictive of heart failure, coronary heart disease, and cardiovascular disease events over 10 years than standard mass and volume measures and enable an automatic personalized medicine approach to tracking remodeling. © RSNA, 2022 Online supplemental material is available for this article.

Thoracic Aortic Volume as a Predictor of Cardiovascular Events: The Multi-Ethnic Study of Atherosclerosis.

BACKGROUND: It is unclear whether thoracic aortic volume (TAV) is useful for cardiovascular (CV) disease prognosis and risk assessment. PURPOSE: This study evaluated cross-sectional associations of TAV with CV risk factors, and longitudinal association with incident CV events in the multiethnic study of atherosclerosis. STUDY TYPE: Retrospective cohort analysis of prospective data. POPULATION: 1182 participants (69 ± 9 years, 54% female, 37% Caucasian, 18% Chinese, 31% African American, 14% Hispanic, 60% hypertensive, and 20% diabetic) without prior CV disease. FIELD STRENGTH AND SEQUENCES: Axial black-blood turbo spin echo or bright blood steady-state free precession images on 1.5T scanners. ASSESSMENT: TAV was calculated using Simpson's method from axial images, and included the ascending arch and descending segments. Traditional CV risk factors were assessed at the time of MRI. CV outcomes over a 9-year follow-up period were recorded and represented a composite of stroke, stroke death, coronary heart disease (CHD), CHD death, atherosclerotic death, and CVD death. STATISTICAL TESTS: Multivariable linear regression models adjusted for height and weight were used to determine the relationship (ß coefficient) between TAV and CV risk factors. Cox regression models assessed the association of TAV and incident CV events. A P-value of <0.05 was deemed statistically significant. RESULTS: Mean TAV was = 139 ± 41 mL. In multivariable regression, TAV was directly associated with age (ß = 1.6), male gender (ß = 23.9), systolic blood pressure (ß = 0.1), and hypertension medication use (ß = 7.9); and inversely associated with lipid medication use (ß = -5.3) and treated diabetes (ß = -8.9). Compared to Caucasians, Chinese Americans had higher TAV (ß = 11.4), while African Americans had lower TAV (ß = -7.0). Higher TAV was independently associated with incident CV events (HR: 1.057 per 10 mL). CONCLUSION: Greater TAV is associated with incident CV events, increased age, and hypertension in a large multiethnic population while treated diabetes and lipid medication use were associated with lower TAV. LEVEL OF EVIDENCE: 2 TECHNICAL EFFICACY: Stage 2.

CT-derived pectoralis composition and incident pneumonia hospitalization using fully automated deep-learning algorithm: multi-ethnic study of atherosclerosis.

BACKGROUND: Pneumonia-related hospitalization may be associated with advanced skeletal muscle loss due to aging (i.e., sarcopenia) or chronic illnesses (i.e., cachexia). Early detection of muscle loss may now be feasible using deep-learning algorithms applied on conventional chest CT. OBJECTIVES: To implement a fully automated deep-learning algorithm for pectoralis muscle measures from conventional chest CT and investigate longitudinal associations between these measures and incident pneumonia hospitalization according to Chronic Obstructive Pulmonary Disease (COPD) status. MATERIALS AND METHODS: This analysis from the Multi-Ethnic Study of Atherosclerosis included participants with available chest CT examinations between 2010 and 2012. We implemented pectoralis muscle composition measures from a fully automated deep-learning algorithm (Mask R-CNN, built on the Faster Region Proposal Network (R-) Convolutional Neural Network (CNN) with an extension for mask identification) for two-dimensional segmentation. Associations between CT-derived measures and incident pneumonia hospitalizations were evaluated using Cox proportional hazards models adjusted for multiple confounders which include but are not limited to age, sex, race, smoking, BMI, physical activity, and forced-expiratory-volume-at-1 s-to-functional-vital-capacity ratio. Stratification analyses were conducted based on baseline COPD status. RESULTS: This study included 2595 participants (51% female; median age: 68 (IQR: 61, 76)) CT examinations for whom we implemented deep learning-derived measures for longitudinal analyses. Eighty-six incident pneumonia hospitalizations occurred during a median 6.67-year follow-up. Overall, pectoralis muscle composition measures did not predict incident pneumonia. However, in fully-adjusted models, only among participants with COPD (N = 507), CT measures like extramyocellular fat index (hazard ratio: 1.98, 95% CI: 1.22, 3.21, p value: 0.02), were independently associated with incident pneumonia. CONCLUSION: Reliable deep learning-derived pectoralis muscle measures could predict incident pneumonia hospitalization only among participants with known COPD. CLINICAL RELEVANCE STATEMENT: Pectoralis muscle measures obtainable at zero additional cost or radiation exposure from any chest CT may have independent predictive value for clinical outcomes in chronic obstructive pulmonary disease patients. KEY POINTS: •Identification of independent and modifiable risk factors of pneumonia can have important clinical impact on patients with chronic obstructive pulmonary disease. •Opportunistic CT measures of adipose tissue within pectoralis muscles using deep-learning algorithms can be quickly obtainable at zero additional cost or radiation exposure. •Deep learning-derived pectoralis muscle measurements of intermuscular fat and its subcomponents are independently associated with subsequent incident pneumonia hospitalization.

Cardiovascular magnetic resonance for evaluation of cardiac involvement in COVID-19: recommendations by the Society for Cardiovascular Magnetic Resonance.

Coronavirus disease 2019 (COVID-19) is an ongoing global pandemic that has affected nearly 600 million people to date across the world. While COVID-19 is primarily a respiratory illness, cardiac injury is also known to occur. Cardiovascular magnetic resonance (CMR) imaging is uniquely capable of characterizing myocardial tissue properties in-vivo, enabling insights into the pattern and degree of cardiac injury. The reported prevalence of myocardial involvement identified by CMR in the context of COVID-19 infection among previously hospitalized patients ranges from 26 to 60%. Variations in the reported prevalence of myocardial involvement may result from differing patient populations (e.g. differences in severity of illness) and the varying intervals between acute infection and CMR evaluation. Standardized methodologies in image acquisition, analysis, interpretation, and reporting of CMR abnormalities across would likely improve concordance between studies. This consensus document by the Society for Cardiovascular Magnetic Resonance (SCMR) provides recommendations on CMR imaging and reporting metrics towards the goal of improved standardization and uniform data acquisition and analytic approaches when performing CMR in patients with COVID-19 infection.

MRA as the Preferred Test for Pulmonary Embolism During the Iodinated Contrast Media Shortage of 2022: A Single-Center Experience.

BACKGROUND. Closure of a GE Healthcare facility in Shanghai, China, in 2022 disrupted the iodinated contrast media supply. Technologic advances have addressed limitations associated with the use of pulmonary MRA for diagnosis of pulmonary embolism (PE). OBJECTIVE. The purpose of this study was to describe a single institution's experience in the use of pulmonary MRA as an alternative to CTA for the diagnosis of PE in the general population during the iodinated contrast media shortage in 2022. METHODS. This retrospective single-center study included all CTA and MRA examinations performed to exclude PE from April 1 through July 31 (18 weekly periods) in 2019 (before the COVID-19 pandemic and contrast media shortage), 2021 (during the pandemic but before the shortage), and 2022 (during both the pandemic and the shortage). From early May through mid-July of 2022, MRA served as the preferred test for PE diagnosis, to preserve iodinated contrast media. CTA and MRA reports were reviewed. The total savings in iodinated contrast media volume resulting from preferred use of MRA was estimated. RESULTS. The study included 4491 examinations of 4006 patients (mean age, 57 ± 18 [SD] years; 1715 men, 2291 women): 1245 examinations (1111 CTA, 134 MRA) in 2019, 1547 examinations (1403 CTA, 144 MRA) in 2021, and 1699 examinations (1282 CTA, 417 MRA) in 2022. In 2022, the number of MRA examinations was four (nine when normalized to a 7-day period) in week 1, and this number increased to a maximum of 63 in week 10 and then decreased to 10 in week 18. During weeks 8-11, more MRA examinations (range, 45-63 examinations) than CTA examinations (range, 27-46 examinations) were performed. In 2022, seven patients with negative MRA underwent subsequent CTA within 2 weeks; CTA was negative in all cases. In 2022, 13.9% of CTA examinations (vs 10.3% of MRA examinations) were reported as having limited image quality. The estimated 4-month savings resulting from preferred use of MRA in 2022, under the assumption of uniform simple linear growth in CTA utilization annually and a CTA dose of 1 mL/kg, was 27 L of iohexol (350 mg I/mL). CONCLUSION. Preferred use of pulmonary MRA for PE diagnosis in the general population helped to conserve iodinated contrast media during the 2022 shortage. CLINICAL IMPACT. This single-center experience shows pulmonary MRA to be a practical substitute for pulmonary CTA in emergency settings.

Long COVID: post-acute sequelae of COVID-19 with a cardiovascular focus.

Emerging as a new epidemic, long COVID or post-acute sequelae of coronavirus disease 2019 (COVID-19), a condition characterized by the persistence of COVID-19 symptoms beyond 3 months, is anticipated to substantially alter the lives of millions of people globally. Cardiopulmonary symptoms including chest pain, shortness of breath, fatigue, and autonomic manifestations such as postural orthostatic tachycardia are common and associated with significant disability, heightened anxiety, and public awareness. A range of cardiovascular (CV) abnormalities has been reported among patients beyond the acute phase and include myocardial inflammation, myocardial infarction, right ventricular dysfunction, and arrhythmias. Pathophysiological mechanisms for delayed complications are still poorly understood, with a dissociation seen between ongoing symptoms and objective measures of cardiopulmonary health. COVID-19 is anticipated to alter the long-term trajectory of many chronic cardiac diseases which are abundant in those at risk of severe disease. In this review, we discuss the definition of long COVID and its epidemiology, with an emphasis on cardiopulmonary symptoms. We further review the pathophysiological mechanisms underlying acute and chronic CV injury, the range of post-acute CV sequelae, and impact of COVID-19 on multiorgan health. We propose a possible model for referral of post-COVID-19 patients to cardiac services and discuss future directions including research priorities and clinical trials that are currently underway to evaluate the efficacy of treatment strategies for long COVID and associated CV sequelae.

Change in Left Atrioventricular Coupling Index to Predict Incident Atrial Fibrillation: The Multi-Ethnic Study of Atherosclerosis (MESA).

Background Left atrial (LA) and left ventricular (LV) structural and functional parameters have independent prognostic values as predictors of atrial fibrillation (AF). Purpose To investigate the prognostic value of a left atrioventricular coupling index (LACI) and average annualized change in LACI (hereafter, ΔLACI) measured by cardiac MRI to predict incident AF in a population-based sample from the Multi-Ethnic Study of Atherosclerosis (MESA). Materials and Methods In a secondary analysis of the prospective MESA, 1911 study participants without clinically recognized AF and cardiovascular disease at baseline had LACI assessed with cardiac MRI at baseline (examination 1, 2000-2002) and 10 years later (examination 5, 2010-2012). LACI was defined as the ratio of LA to LV end-diastolic volumes. Univariable and multivariable Cox proportional hazard models were used to evaluate the associations of LACI and average ΔLACI with incident AF. Results Among the 1911 participants (mean age, 59 years ± 9 [standard deviation]; 907 men), 87 incident AF events occurred over 3.9 years ± 0.9 after the second imaging (examination 5). After adjustment for traditional risk factors, greater LACI and ΔLACI were independently associated with AF (hazard ratio, 1.69 [95% CI: 1.46, 1.96] and 1.71 [95% CI: 1.50, 1.94], respectively; both P < .001). Adjusted models for LACI and ΔLACI showed improvement in model discrimination compared with currently used AF risk score (Cohort for Heart and Aging Research in Genomic Epidemiology-Atrial Fibrillation, or CHARGE-AF, score) model (area under receiver operating characteristic curve [AUC], 0.78 vs 0.74; and AUC, 0.80 vs 0.74, respectively; both P < .001); and to the final model including individual LA or LV parameters for predicting AF incidence (AUC, 0.78 vs 0.76; and AUC, 0.80 vs 0.78, respectively; both P < .001). Conclusion Atrioventricular coupling (left atrioventricular coupling index [LACI]) and coupling change (annual change in LACI) were strong predictors for atrial fibrillation (AF) in a multiethnic population. Both had incremental prognostic value for predicting AF over traditional risk factors, and superior discrimination compared with the Cohort for Heart and Aging Research in Genomic Epidemiology-Atrial Fibrillation, or CHARGE-AF, score and to individual left atrial or left ventricular parameters. © RSNA, 2022 Online supplemental material is available for this article. See also the editorial by Leiner in this issue.

Temporal assessment of lesion morphology on radiological images beyond lesion volumes-a proof-of-principle study.

OBJECTIVES: To develop a general framework to assess temporal changes in lesion morphology on radiological images beyond volumetric changes and to test whether cocaine abstinence changes coronary plaque structure on serial coronary CT angiography (CTA). METHODS: Chronic cocaine users with human immunodeficiency virus (HIV) infection were prospectively enrolled to undergo cash-based contingency management to achieve cocaine abstinence. Participants underwent coronary CTA at baseline and 6 and 12 months following recruitment. We segmented all coronary plaques and extracted 1103 radiomic features. We implemented weighted correlation network analysis to derive consensus eigen radiomic features (named as different colors) and used linear mixed models and mediation analysis to assess whether cocaine abstinence affects plaque morphology correcting for clinical variables and plaque volumes and whether serum biomarkers causally mediate these changes. Furthermore, we used Bayesian hidden Markov network changepoint analysis to assess the potential rewiring of the radiomic network. RESULTS: Sixty-nine PLWH (median age 55 IQR: 52-59 years, 19% female) completed the study, of whom 26 achieved total abstinence. Twenty consensus eigen radiomic features were derived. Cocaine abstinence significantly affected the pink and cyan eigen features (-0.04 CI: [-0.06; -0.02], p = 0.0009; 0.03 CI: [0.001; 0.04], p = 0.0017, respectively). These effects were mediated through changes in endothelin-1 levels. In abstinent individuals, we observed significant rewiring of the latent radiomic signature network. CONCLUSIONS: Using our proposed framework, we found 1 year of cocaine abstinence to significantly change specific latent coronary plaque morphological features and rewire the latent morphologic network above and beyond changes in plaque volumes and clinical characteristics. KEY POINTS: • We propose a general methodology to decompose the latent morphology of lesions on radiological images using a radiomics-based systems biology approach. • As a proof-of-principle, we show that 1 year of cocaine abstinence results in significant changes in specific latent coronary plaque morphologic features and rewiring of the latent morphologic network above and beyond changes in plaque volumes and clinical characteristics. • We found endothelin-1 levels to mediate these structural changes providing potential pathological pathways warranting further investigation.

Deep Learning-based Automated Aortic Area and Distensibility Assessment: the Multi-Ethnic Study of Atherosclerosis (MESA).

This study details application of deep learning for automatic segmentation of the ascending and descending aorta from 2D phase-contrast cine magnetic resonance imaging for automatic aortic analysis on the large MESA cohort with assessment on an external cohort of thoracic aortic aneurysm (TAA) patients. This study includes images and corresponding analysis of the ascending and descending aorta at the pulmonary artery bifurcation from the MESA study. Train, validation, and internal test sets consisted of 1123 studies (24,282 images), 374 studies (8067 images), and 375 studies (8069 images), respectively. The external test set of TAAs consisted of 37 studies (3224 images). CNN performance was evaluated utilizing a dice coefficient and concordance correlation coefficients (CCC) of geometric parameters. Dice coefficients were as high as 97.55% (CI: 97.47-97.62%) and 93.56% (CI: 84.63-96.68%) on the internal and external test of TAAs, respectively. CCC for maximum and minimum and ascending aortic area were 0.969 and 0.950, respectively, on the internal test set and 0.997 and 0.995, respectively, for the external test. The absolute differences between manual and deep learning segmentations for ascending and descending aortic distensibility were 0.0194 × 10-4 ± 9.67 × 10-4 and 0.002 ± 0.001 mmHg-1, respectively, on the internal test set and 0.44 × 10-4 ± 20.4 × 10-4 and 0.002 ± 0.001 mmHg-1, respectively, on the external test set. We successfully developed a U-Net-based aortic segmentation and analysis algorithm in both MESA and in external cases of TAA.

Adipose tissue biomarkers and type 2 diabetes incidence in normoglycemic participants in the MESArthritis Ancillary Study: A cohort study.

BACKGROUND: Given the central role of skeletal muscles in glucose homeostasis, deposition of adipose depots beneath the fascia of muscles (versus subcutaneous adipose tissue [SAT]) may precede insulin resistance and type 2 diabetes (T2D) incidence. This study was aimed to investigate the associations between computed tomography (CT)-derived biomarkers for adipose tissue and T2D incidence in normoglycemic adults. METHODS AND FINDINGS: This study was a population-based multiethnic retrospective cohort of 1,744 participants in the Multi-Ethnic Study of Atherosclerosis (MESA) with normoglycemia (baseline fasting plasma glucose [FPG] less than 100 mg/dL) from 6 United States of America communities. Participants were followed from April 2010 and January 2012 to December 2017, for a median of 7 years. The intermuscular adipose tissue (IMAT) and SAT areas were measured in baseline chest CT exams and were corrected by height squared (SAT and IMAT indices) using a predefined measurement protocol. T2D incidence, as the main outcome, was based on follow-up FPG, review of hospital records, or self-reported physician diagnoses. Participants' mean age was 69 ± 9 years at baseline, and 977 (56.0%) were women. Over a median of 7 years, 103 (5.9%) participants were diagnosed with T2D, and 147 (8.4%) participants died. The IMAT index (hazard ratio [HR]: 1.27 [95% confidence interval [CI]: 1.15-1.41] per 1-standard deviation [SD] increment) and the SAT index (HR: 1.43 [95% CI: 1.16-1.77] per 1-SD increment) at baseline were associated with T2D incidence over the follow-up. The associations of the IMAT and SAT indices with T2D incidence were attenuated after adjustment for body mass index (BMI) and waist circumference, with HRs of 1.23 (95% CI: 1.09-1.38) and 1.29 (95% CI: 0.96-1.74) per 1-SD increment, respectively. The limitations of this study include unmeasured residual confounders and one-time measurement of adipose tissue biomarkers. CONCLUSIONS: In this study, we observed an association between IMAT at baseline and T2D incidence over the follow-up. This study suggests the potential role of intermuscular adipose depots in the pathophysiology of T2D. TRIAL REGISTRATION: ClinicalTrials.gov NCT00005487.

Next-Generation Hardware Advances in CT: Cardiac Applications.

Impending major hardware advances in cardiac CT include three areas: ultra-high-resolution (UHR) CT, photon-counting CT, and phase-contrast CT. Cardiac CT is a particularly demanding CT application that requires a high degree of temporal resolution, spatial resolution, and soft-tissue contrast in a moving structure. In this review, cardiac CT is used to highlight the strengths of these technical advances. UHR CT improves visualization of calcified and stented vessels but may result in increased noise and radiation exposure. Photon-counting CT uses multiple photon energies to reduce artifacts, improve contrast resolution, and perform material decomposition. Finally, phase-contrast CT uses x-ray refraction properties to improve spatial and soft-tissue contrast. This review describes these hardware advances in CT and their relevance to cardiovascular imaging.

Quantitative Analysis of Adipose Depots by Using Chest CT and Associations with All-Cause Mortality in Chronic Obstructive Pulmonary Disease: Longitudinal Analysis from MESArthritis Ancillary Study.

Background Obesity and sarcopenia are associated with mortality in chronic obstructive pulmonary disease (COPD). Routine chest CT examinations may allow assessment of obesity and sarcopenia by soft-tissue markers for predicting risks of mortality. Purpose To investigate associations between soft-tissue markers subcutaneous adipose tissue (SAT), intermuscular adipose tissue (IMAT), and pectoralis muscle (PM) index from chest CT with mortality in participants with COPD. Materials and Methods In this secondary analysis of a prospectively enrolled cohort from the Multi-Ethnic Study of Atherosclerosis, participants with available chest CT in 2010-2012 were included. CT examinations were analyzed to determine SAT, IMAT (within PM), and PM areas. The spirometry evaluations were used to establish COPD diagnosis. Mortality data were extracted from the National Death Index (April 2010 to December 2017). The correlations of the soft-tissue markers with fat mass index were studied. The associations of these markers and risks of mortality in participants with COPD were assessed by using Cox proportional-hazard models adjusted for confounders. Results Among 2994 participants who were included (mean age, 69 years ± 9 [standard deviation]; 1551 women), 265 had COPD (9%; mean age, 72 years ± 9; 162 men) and 49 participants with COPD (18%) died during follow-up. The SAT, IMAT, and PM areas had moderate-to-excellent reliabilities (intraclass correlation coefficient, 0.88-0.99). In the 2994 participants, the SAT (ρ = 0.80; 95% CI: 0.78, 0.81; P < .001) and IMAT indexes (ρ = 0.37; 95% CI: 0.34, 0.41; P < .001) were correlated with fat mass index. Those with COPD and higher SAT index had lower risks of mortality (hazard ratio, 0.2; 95% CI: 0.1, 0.4; P < .001, per doubling), whereas a higher IMAT index was associated with a higher risk of mortality (hazard ratio, 1.4; 95% CI: 1.0, 1.9; P = .04, per doubling). Conclusion Soft-tissue markers were reliably obtained by using chest CT performed for lung assessment. In participants with chronic obstructive pulmonary disease, a high intermuscular adipose tissue index was associated with a higher risk of mortality than was a high subcutaneous adipose tissue index. © RSNA, 2021 Online supplemental material is available for this article. See also the editorial by Sverzellati and Cademartiri in this issue.

Contribution of Risk Factors to the Development of Coronary Atherosclerosis as Confirmed via Coronary CT Angiography: A Longitudinal Radiomics-based Study.

Background Various cardiovascular risk factors are thought to modify atherosclerosis in a similar fashion (ie, by increasing the magnitude of coronary artery disease [CAD]). However, coronary CT angiography allows precision phenotyping of plaque characteristics through use of radiomics. Purpose To assess whether different cardiovascular risk factors have distinctive contributions to the changes in plaque morphologic features over time. Materials and Methods Individuals with or without HIV infection and cocaine use and without cardiovascular symptoms underwent coronary CT angiography between May 2004 and August 2015. In the current HIPAA-compliant study, the effects of cocaine use, HIV infection, and atherosclerotic cardiovascular disease (ASCVD) risk on the temporal changes (mean ± standard deviation, 4.0 years ± 2.3 between CT angiographic examinations) in CAD structure were analyzed by using radiomic analysis. The changes in radiomic features were analyzed by using linear mixed models, with correction for factors that may change plaque structure: high-sensitivity C-reactive protein level, statin use, positive family history of CAD, and total plaque volume to account for any potential intrinsic correlation between volume and morphologic features. Clusters among significant radiomic features were identified by using hierarchical clustering. Bonferroni-corrected P values less than .00004 (.05 divided by 1276) were considered to indicate significant differences. Results Of 1429 participants, 300 with CAD confirmed at coronary CT angiography were randomly selected (mean age, 48 years ± 7; 210 men, 226 people infected with HIV, 174 people who use cocaine) and 1276 radiomic features were quantified for each plaque. Cocaine use was significantly associated with 23.7% (303 of 1276) of the radiomic features, HIV infection was significantly associated with 1.3% (17 of 1276), and elevated ASCVD risk was significantly associated with 8.2% (104 of 1276) (P < .00004 for all). Parameters associated with elevated ASCVD risk or cocaine use and HIV infection did not overlap. There were 13 clusters among the 409 parameters, eight of which were affected only by cocaine use and three of which were affected only by ASCVD risk. Conclusion Radiomics-based precision phenotyping indicated that conventional risk factors, cocaine use, and HIV infection each had different effects on CT angiographic morphologic changes in coronary atherosclerosis over 4 years. © RSNA, 2021 Online supplemental material is available for this article. See also the editorial by Schoepf and Emrich in this issue.

Associations of Angiopoietins With Heart Failure Incidence and Severity.

BACKGROUND: Angiopoietin-1 and 2 (Ang1, Ang2) are important mediators of angiogenesis. Angiopoietin levels are perturbed in cardiovascular disease, but it is unclear whether angiopoietin signaling is causative, an adaptive response, or merely epiphenomenon of disease activity. METHODS AND RESULTS: In a cohort free of cardiovascular disease at baseline (Multi-Ethnic Study of Atherosclerosis [MESA]), relationships between angiopoietins, cardiac morphology, and subsequent incidence of heart failure or cardiovascular death were evaluated. In cohorts with pulmonary arterial hypertension or left heart disease, associations between angiopoietins, invasive hemodynamics, and adverse clinical outcomes were evaluated. In MESA, Ang2 was associated with a higher incidence of heart failure or cardiovascular death (hazard ratio 1.21 per standard deviation, P < .001). Ang2 was associated with increased right atrial pressure (pulmonary arterial hypertension cohort) and increased wedge pressure and right atrial pressure (left heart disease cohort). Elevated Ang2 was associated with mortality in the pulmonary arterial hypertension cohort. CONCLUSIONS: Ang2 was associated with incident heart failure or death among adults without cardiovascular disease at baseline and with disease severity in individuals with existing heart failure. Our finding that Ang2 is increased before disease onset and that elevations reflect disease severity, suggests Ang2 may contribute to heart failure pathogenesis.

Cardiovascular risk factors and illicit drug use may have a more profound effect on coronary atherosclerosis progression in people living with HIV.

OBJECTIVES: To assess whether HIV infection directly or indirectly promotes coronary artery disease (CAD) volume progression in a longitudinal study of African Americans. METHODS: We randomly selected 300 individuals with subclinical CAD (210 male; age: 48.0 ± 7.2 years; 226 HIV infected, 174 cocaine users) from 1429 cardiovascularly asymptomatic participants of a prospective epidemiological study between May 2004 and August 2015. Individuals underwent coronary CT angiography at two time points (mean follow-up: 4.0 ± 2.3 years). We quantified noncalcified (NCP: -100-350HU), low-attenuation noncalcified (LA-NCP: -100-30HU), and calcified (CP: ≥ 351 HU) plaque volumes. Linear mixed models were used to assess the effects of HIV infection, atherosclerotic cardiovascular disease (ASCVD) risk, and years of cocaine use on plaque volumes. RESULTS: There was no significant difference in annual progression rates between HIV-infected and HIV-uninfected regarding NCP (8.7 [IQR: 3.0-19.4] mm3/year vs. 4.9 [IQR: 1.5-18.3] mm3/year, p = 0.14), LA-NCP (0.2 [IQR: 0.0-1.6] mm3/year vs. 0.2 [IQR: 0.0-0.9] mm3/year, p = 0.07) or CP volumes (0.3 [IQR: 0.0-3.4] mm3/year vs. 0.1 [IQR: 0.0-3.2] mm3/year, p = 0.30). Multivariately, HIV infection was not associated with NCP (-6.9mm3, CI: [-32.8-19.0], p = 0.60), LA-NCP (-0.1mm3, CI: [-2.6-2.4], p = 0.92), or CP volumes (-0.3mm3, CI: [-9.3-8.6], p = 0.96). However, each percentage of ASCVD and each year of cocaine use significantly increased total, NCP, and CP volumes among HIV-infected individuals, but not among HIV-uninfected. Importantly, none of the HIV-associated medications had any effect on plaque volumes (p > 0.05 for all). CONCLUSIONS: The more profound adverse effect of risk factors in HIV-infected individuals may explain the accelerated progression of CAD in these people, as HIV infection was not independently associated with any coronary plaque volume. KEY POINTS: • Human immunodeficiency virus-infected individuals may have similar subclinical coronary artery disease, as the infection is not independently associated with coronary plaque volumes. • However, cardiovascular risk factors and illicit drug use may have a more profound effect on atherosclerosis progression in those with human immunodeficiency virus infection, which may explain the accelerated progression of CAD in these people. • Nevertheless, through rigorous prevention and abstinence from illicit drugs, these individuals may experience similar cardiovascular outcomes as -uninfected individuals.

Left ventricular fibro-fatty replacement in arrhythmogenic right ventricular dysplasia/cardiomyopathy: prevalence, patterns, and association with arrhythmias.

BACKGROUND: Left ventricular (LV) fibrofatty infiltration in arrhythmogenic right ventricular (RV) dysplasia/cardiomyopathy (ARVD/C) has been reported, however, detailed cardiovascular magnetic resonance (CMR) characteristics and association with outcomes are uncertain. We aim to describe LV findings on CMR in ARVD/C patients and their relationship with arrhythmic outcomes. METHODS: CMR of 73 subjects with ARVD/C according to the 2010 Task Force Criteria (TFC) were analyzed for LV involvement, defined as ≥ 1 of the following features: LV wall motion abnormality, LV late gadolinium enhancement (LGE), LV fat infiltration, or LV ejection fraction (LVEF) < 50%. Ventricular volumes and function, regional wall motion abnormalities, and the presence of ventricular fat or fibrosis were recorded. Findings on CMR were correlated with arrhythmic outcomes. RESULTS: Of the 73 subjects, 50.7% had CMR evidence for LV involvement. Proband status and advanced RV dysfunction were independently associated with LV abnormalities. The most common pattern of LV involvement was focal fatty infiltration in the sub-epicardium of the apicolateral LV with a "bite-like" pattern. LGE in the LV was found in the same distribution and most often had a linear appearance. LV involvement was more common with non-PKP2 genetic mutation variants, regardless of proband status. Only RV structural disease on CMR (HR 3.47, 95% CI 1.13-10.70) and prior arrhythmia (HR 2.85, 95% CI 1.33-6.10) were independently associated with arrhythmic events. CONCLUSION: Among patients with 2010 TFC for ARVD/C, CMR evidence for LV abnormalities are seen in half of patients and typically manifest as fibrofatty infiltration in the subepicardium of the apicolateral wall and are not associated with arrhythmic outcomes.

Metabolic syndrome and its factors are associated with noncalcified coronary burden in psoriasis: An observational cohort study.

BACKGROUND: Psoriasis is associated with a heightened risk of cardiovascular disease and higher prevalence of metabolic syndrome. OBJECTIVE: Investigate the effect of metabolic syndrome and its factors on early coronary artery disease assessed as noncalcified coronary burden by coronary computed tomography angiography in psoriasis. METHODS: This cross-sectional study consisted of 260 participants with psoriasis and coronary computed tomography angiography characterization. Metabolic syndrome was defined according to the harmonized International Diabetes Federation criteria. RESULTS: Of the 260 participants, 80 had metabolic syndrome (31%). The metabolic syndrome group had a higher burden of cardiometabolic disease, systemic inflammation, noncalcified coronary burden, and high-risk coronary plaque. After adjusting for Framingham risk score, lipid-lowering therapy, and biologic use, metabolic syndrome (ß = .31; P < .001) and its individual factors of waist circumference (ß = .33; P < .001), triglyceride levels (ß = .17; P = .005), blood pressure (ß = .18; P = .005), and fasting glucose (ß = .17; P = .009) were significantly associated with noncalcified coronary burden. After adjusting for all other metabolic syndrome factors, blood pressure and waist circumference remained significantly associated with noncalcified coronary burden. LIMITATIONS: Observational nature with limited ability to control for confounders. CONCLUSIONS: In psoriasis, individuals with metabolic syndrome had more cardiovascular disease risk factors, systemic inflammation, and noncalcified coronary burden. Efforts to increase metabolic syndrome awareness in psoriasis should be undertaken to reduce the heightened cardiovascular disease risk.

Genome-Wide Analysis of Left Ventricular Image-Derived Phenotypes Identifies Fourteen Loci Associated With Cardiac Morphogenesis and Heart Failure Development.

BACKGROUND: The genetic basis of left ventricular (LV) image-derived phenotypes, which play a vital role in the diagnosis, management, and risk stratification of cardiovascular diseases, is unclear at present. METHODS: The LV parameters were measured from the cardiovascular magnetic resonance studies of the UK Biobank. Genotyping was done using Affymetrix arrays, augmented by imputation. We performed genome-wide association studies of 6 LV traits-LV end-diastolic volume, LV end-systolic volume, LV stroke volume, LV ejection fraction, LV mass, and LV mass to end-diastolic volume ratio. The replication analysis was performed in the MESA study (Multi-Ethnic Study of Atherosclerosis). We identified the candidate genes at genome-wide significant loci based on the evidence from extensive bioinformatic analyses. Polygenic risk scores were constructed from the summary statistics of LV genome-wide association studies to predict the heart failure events. RESULTS: The study comprised 16 923 European UK Biobank participants (mean age 62.5 years; 45.8% men) without prevalent myocardial infarction or heart failure. We discovered 14 genome-wide significant loci (3 loci each for LV end-diastolic volume, LV end-systolic volume, and LV mass to end-diastolic volume ratio; 4 loci for LV ejection fraction, and 1 locus for LV mass) at a stringent P<1×10-8. Three loci were replicated at Bonferroni significance and 7 loci at nominal significance (P<0.05 with concordant direction of effect) in the MESA study (n=4383). Follow-up bioinformatic analyses identified 28 candidate genes that were enriched in the cardiac developmental pathways and regulation of the LV contractile mechanism. Eight genes (TTN, BAG3, GRK5, HSPB7, MTSS1, ALPK3, NMB, and MMP11) supported by at least 2 independent lines of in silico evidence were implicated in the cardiac morphogenesis and heart failure development. The polygenic risk scores of LV phenotypes were predictive of heart failure in a holdout UK Biobank sample of 3106 cases and 224 134 controls (odds ratio 1.41, 95% CI 1.26 - 1.58, for the top quintile versus the bottom quintile of the LV end-systolic volume risk score). CONCLUSIONS: We report 14 genetic loci and indicate several candidate genes that not only enhance our understanding of the genetic architecture of prognostically important LV phenotypes but also shed light on potential novel therapeutic targets for LV remodeling.

Imaging Publications in the COVID-19 Pandemic: Applying New Research Results to Clinical Practice.

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Prospective Clinical Trials: 10-year Trends in Radiology.

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