Case Series of Coronary Artery Anomalies in Athletes: Challenges in Clinical Management and Sports Eligibility.

Coronary artery anomalies include a spectrum of pathologic changes associated with sudden cardiac death in athletes. We highlight the inherent challenges in risk stratification and management of athletes with coronary artery anomalies by presenting 3 cases, each with distinct pathologic coronary anatomy and clinical management decisions. (Level of Difficulty: Intermediate.).

Metabolic syndrome, fatty liver, and artificial intelligence-based epicardial adipose tissue measures predict long-term risk of cardiac events: a prospective study.

BACKGROUND: We sought to evaluate the association of metabolic syndrome (MetS) and computed tomography (CT)-derived cardiometabolic biomarkers (non-alcoholic fatty liver disease [NAFLD] and epicardial adipose tissue [EAT] measures) with long-term risk of major adverse cardiovascular events (MACE) in asymptomatic individuals. METHODS: This was a post-hoc analysis of the prospective EISNER (Early-Identification of Subclinical Atherosclerosis by Noninvasive Imaging Research) study of participants who underwent baseline coronary artery calcium (CAC) scoring CT and 14-year follow-up for MACE (myocardial infarction, late revascularization, or cardiac death). EAT volume (cm3) and attenuation (Hounsfield units [HU]) were quantified from CT using fully automated deep learning software (< 30 s per case). NAFLD was defined as liver-to-spleen attenuation ratio < 1.0 and/or average liver attenuation < 40 HU. RESULTS: In the final population of 2068 participants (59% males, 56 ± 9 years), those with MetS (n = 280;13.5%) had a greater prevalence of NAFLD (26.0% vs. 9.9%), higher EAT volume (114.1 cm3 vs. 73.7 cm3), and lower EAT attenuation (-76.9 HU vs. -73.4 HU; all p < 0.001) compared to those without MetS. At 14 ± 3 years, MACE occurred in 223 (10.8%) participants. In multivariable Cox regression, MetS was associated with increased risk of MACE (HR 1.58 [95% CI 1.10-2.27], p = 0.01) independently of CAC score; however, not after adjustment for EAT measures (p = 0.27). In a separate Cox analysis, NAFLD predicted MACE (HR 1.78 [95% CI 1.21-2.61], p = 0.003) independently of MetS, CAC score, and EAT measures. Addition of EAT volume to current risk assessment tools resulted in significant net reclassification improvement for MACE (22% over ASCVD risk score; 17% over ASCVD risk score plus CAC score). CONCLUSIONS: MetS, NAFLD, and artificial intelligence-based EAT measures predict long-term MACE risk in asymptomatic individuals. Imaging biomarkers of cardiometabolic disease have the potential for integration into routine reporting of CAC scoring CT to enhance cardiovascular risk stratification. Trial registration NCT00927693.

Machine learning integration of circulating and imaging biomarkers for explainable patient-specific prediction of cardiac events: A prospective study.

BACKGROUND AND AIMS: We sought to assess the performance of a comprehensive machine learning (ML) risk score integrating circulating biomarkers and computed tomography (CT) measures for the long-term prediction of hard cardiac events in asymptomatic subjects. METHODS: We studied 1069 subjects (age 58.2 ± 8.2 years, 54.0% males) from the prospective EISNER trial who underwent coronary artery calcium (CAC) scoring CT, serum biomarker assessment, and long-term follow-up. Epicardial adipose tissue (EAT) was quantified from CT using fully automated deep learning software. Forty-eight serum biomarkers, both established and novel, were assayed. An ML algorithm (XGBoost) was trained using clinical risk factors, CT measures (CAC score, number of coronary lesions, aortic valve calcium score, EAT volume and attenuation), and circulating biomarkers, and validated using repeated 10-fold cross validation. RESULTS: At 14.5 ± 2.0 years, there were 50 hard cardiac events (myocardial infarction or cardiac death). The ML risk score (area under the receiver operator characteristic curve [AUC] 0.81) outperformed the CAC score (0.75) and ASCVD risk score (0.74; both p = 0.02) for the prediction of hard cardiac events. Serum biomarkers provided incremental prognostic value beyond clinical data and CT measures in the ML model (net reclassification index 0.53 [95% CI: 0.23-0.81], p < 0.0001). Among novel biomarkers, MMP-9, pentraxin 3, PIGR, and GDF-15 had highest variable importance for ML and reflect the pathways of inflammation, extracellular matrix remodeling, and fibrosis. CONCLUSIONS: In this prospective study, ML integration of novel circulating biomarkers and noninvasive imaging measures provided superior long-term risk prediction for cardiac events compared to current risk assessment tools.

Deep Learning-Based Quantification of Epicardial Adipose Tissue Volume and Attenuation Predicts Major Adverse Cardiovascular Events in Asymptomatic Subjects.

BACKGROUND: Epicardial adipose tissue (EAT) volume (cm3) and attenuation (Hounsfield units) may predict major adverse cardiovascular events (MACE). We aimed to evaluate the prognostic value of fully automated deep learning-based EAT volume and attenuation measurements quantified from noncontrast cardiac computed tomography. METHODS: Our study included 2068 asymptomatic subjects (56±9 years, 59% male) from the EISNER trial (Early Identification of Subclinical Atherosclerosis by Noninvasive Imaging Research) with long-term follow-up after coronary artery calcium measurement. EAT volume and mean attenuation were quantified using automated deep learning software from noncontrast cardiac computed tomography. MACE was defined as myocardial infarction, late (>180 days) revascularization, and cardiac death. EAT measures were compared to coronary artery calcium score and atherosclerotic cardiovascular disease risk score for MACE prediction. RESULTS: At 14±3 years, 223 subjects suffered MACE. Increased EAT volume and decreased EAT attenuation were both independently associated with MACE. Atherosclerotic cardiovascular disease risk score, coronary artery calcium, and EAT volume were associated with increased risk of MACE (hazard ratio [95%CI]: 1.03 [1.01-1.04]; 1.25 [1.19-1.30]; and 1.35 [1.07-1.68], P<0.01 for all) and EAT attenuation was inversely associated with MACE (hazard ratio, 0.83 [95% CI, 0.72-0.96]; P=0.01), with corresponding Harrell C statistic of 0.76. MACE risk progressively increased with EAT volume ≥113 cm3 and coronary artery calcium ≥100 AU and was highest in subjects with both (P<0.02 for all). In 1317 subjects, EAT volume was correlated with inflammatory biomarkers C-reactive protein, myeloperoxidase, and adiponectin reduction; EAT attenuation was inversely related to these biomarkers. CONCLUSIONS: Fully automated EAT volume and attenuation quantification by deep learning from noncontrast cardiac computed tomography can provide prognostic value for the asymptomatic patient, without additional imaging or physician interaction.

Machine learning to predict the long-term risk of myocardial infarction and cardiac death based on clinical risk, coronary calcium, and epicardial adipose tissue: a prospective study.

AIMS: Our aim was to evaluate the performance of machine learning (ML), integrating clinical parameters with coronary artery calcium (CAC), and automated epicardial adipose tissue (EAT) quantification, for the prediction of long-term risk of myocardial infarction (MI) and cardiac death in asymptomatic subjects. METHODS AND RESULTS: Our study included 1912 asymptomatic subjects [1117 (58.4%) male, age: 55.8 ± 9.1 years] from the prospective EISNER trial with long-term follow-up after CAC scoring. EAT volume and density were quantified using a fully automated deep learning method. ML extreme gradient boosting was trained using clinical co-variates, plasma lipid panel measurements, risk factors, CAC, aortic calcium, and automated EAT measures, and validated using repeated 10-fold cross validation. During mean follow-up of 14.5 ± 2 years, 76 events of MI and/or cardiac death occurred. ML obtained a significantly higher AUC than atherosclerotic cardiovascular disease (ASCVD) risk and CAC score for predicting events (ML: 0.82; ASCVD: 0.77; CAC: 0.77, P < 0.05 for all). Subjects with a higher ML score (by Youden's index) had high hazard of suffering events (HR: 10.38, P < 0.001); the relationships persisted in multivariable analysis including ASCVD-risk and CAC measures (HR: 2.94, P = 0.005). Age, ASCVD-risk, and CAC were prognostically important for both genders. Systolic blood pressure was more important than cholesterol in women, and the opposite in men. CONCLUSIONS: In this prospective study, machine learning used to integrate clinical and quantitative imaging-based variables significantly improves prediction of MI and cardiac death compared with standard clinical risk assessment. Following further validation, such a personalized paradigm could potentially be used to improve cardiovascular risk assessment.

Simultaneous Tc-99m PYP/Tl-201 dual-isotope SPECT myocardial imaging in patients with suspected cardiac amyloidosis.

INTRODUCTION: Assessment of myocardial uptake of Tc-99m-pyrophosphate (Tc-99m PYP) is pivotal in distinguishing transthyretin-associated cardiac amyloidosis (ATTR) from light chain amyloid (AL). It is often difficult to differentiate myocardial uptake from blood pool radioactivity with planar imaging or SPECT. We studied whether simultaneous dual-isotope Tc-99m PYP/Tl-201 SPECT improves assessment of Tc-99m PYP uptake compared to single-isotope SPECT. METHODS: Simultaneous Tc-99m PYP/Tl-201 dual-isotope SPECT was acquired in 112 patients studied for possible cardiac amyloidosis. Visual interpretation was performed by two observers on single-isotope followed by dual-isotope SPECT. Heart-to-contralateral lung ratio (H/CL) of myocardial counts quantified by single-isotope and dual-isotope SPECT was compared between ATTR, AL, and no amyloidosis groups. RESULTS: In 112 patients (39 ATTR and 26 AL patients, and 47 no amyloidosis), a lower proportion of no amyloidosis and AL patients were classified visually as equivocal with dual-isotope SPECT compared to single-isotope SPECT (2% vs 19%, P = 0.02 and 8% vs 35%, P = 0.04, respectively). H/CL measurements with single-isotope and dual-isotope were lower in AL and no amyloidosis patients vs ATTR patients (P < 0.05). Interobserver agreement of visual assessment was improved with dual-isotope SPECT (P = 0.03). AUCs for detection of ATTR by visual assessment and H/CL quantification were higher with dual-isotope (0.94 and 0.95, respectively) compared to single-isotope SPECT (0.84, P = 0.001 and 0.92, P = 0.02). CONCLUSION: Tc-99m PYP/Tl-201 SPECT improves visual differentiation of ATTR and AL amyloidosis compared to single-isotope SPECT. Visual assessment and H/CL quantitation with dual-isotope SPECT provide similar discrimination between patients with ATTR and AL amyloidosis.

Revascularization in Patients With Spontaneous Coronary Artery Dissection and ST-Segment Elevation Myocardial Infarction.

BACKGROUND: Spontaneous coronary artery dissection (SCAD) is an increasingly recognized cause of myocardial infarction (MI) in younger women, often treated conservatively due to revascularization risks. Revascularization outcomes are largely unknown in SCAD presenting with ST-segment elevation myocardial infarction (STEMI). OBJECTIVES: The purpose of this study was to compare revascularization strategies and outcomes of STEMI-SCAD with STEMI atherosclerosis (STEMI-ATH). METHODS: Consecutive STEMI patients were retrospectively analyzed (2003 to 2017) at 2 regional STEMI programs (Minneapolis Heart Institute and Cedars-Sinai Smidt Heart Institute) with 3-year outcomes. RESULTS: Among 5,208 STEMI patients, SCAD was present in 53 (1%; 93% female). SCAD prevalence was 19% in female STEMI patients age ≤50 years. Compared with STEMI-ATH, STEMI-SCAD patients were younger (age 49 ± 10 years vs. 63 ± 13 years), were more often female (93% vs. 27%), and had more frequent cardiogenic shock (19% vs. 9%); all p ≤ 0.03. In STEMI-SCAD, the culprit artery was more commonly left main (13% vs. 1%) or left anterior descending (47% vs. 38%); both p = 0.003. Acute revascularization was lower in STEMI-SCAD (70% vs. 97%); p < 0.001. In STEMI-SCAD, acute revascularization included percutaneous coronary intervention (PCI), n = 33 (62%), or bypass grafting, n = 4 (8%); PCI success was 91%. Those with revascularization were more likely to have shock, left main culprit, proximal dissection, and initial TIMI (Thrombolysis In Myocardial Infarction) flow grade 0 to 1. The 3-year survival was 98% for STEMI-SCAD versus 84% for STEMI-ATH; p < 0.001. CONCLUSIONS: STEMI-SCAD represents an important STEMI subset, particularly among younger women, characterized by significantly greater frequency of left main or left anterior descending culprit and cardiogenic shock than STEMI-ATH. Primary PCI is successful in most STEMI-SCAD patients, with low 3-year mortality.

Fertile and selectively flirty: women's behavior toward men changes across the ovulatory cycle.

Past research shows that men respond to women differently depending on where women are in their ovulatory cycle. But what leads men to treat ovulating women differently? We propose that the ovulatory cycle alters women's flirting behavior. We tested this hypothesis in an experiment in which women interacted with different types of men at different points in their cycle. Results revealed that women in the ovulatory phase reported more interest in men who had purported markers of genetic fitness as short-term mates, but not as long-term mates. Furthermore, behavioral ratings of the interactions indicated that women displayed more flirting behaviors when they were at high than at low fertility. Importantly, fertile women flirted more only when interacting with men who had genetic-fitness markers, not with other men. In summary, fertility not only alters women's behavior but does so in a context-dependent way that follows adaptive logic.

Pretreatment 25-hydroxyvitamin D levels and durability of anti-tumor necrosis factor-α therapy in inflammatory bowel diseases.

INTRODUCTION: Emerging evidence supports an immunologic role for 25-hydroxyvitamin D (25(OH)D) in inflammatory bowel disease (IBD). Here we examined if pretreatment vitamin D status influences durability of anti-tumor necrosis factor (TNF)-α therapy in patients with Crohn's disease (CD) or ulcerative colitis (UC). METHODS: All IBD patients who had plasma 25(OH)D level checked <3 months prior to initiating anti-TNF-α therapy were included in this retrospective single-center cohort study. Our main predictor variable was insufficient plasma 25(OH)D (<30 ng/mL). Cox proportional hazards model adjusting for potential confounders was used to identify the independent effect of pretreatment vitamin D on biologic treatment cessation. RESULTS: Our study included 101 IBD patients (74 CD; median disease duration 9 years). The median index 25(OH)D level was 27 ng/mL (interquartile range, 20-33 ng/mL). One-third of the patients had prior exposure to anti-TNF-α therapy. On multivariate analysis, patients with insufficient vitamin D demonstrated earlier cessation of anti-TNF-α therapy (hazard ratio [HR], 2.13; 95% confidence interval [CI], 1.03-4.39; P = .04). This effect was significant in patients who stopped treatment for loss of response (HR, 3.49; 95% CI, 1.34-9.09) and stronger for CD (HR, 2.38; 95% CI, 0.95-5.99) than UC (P = NS). CONCLUSIONS: Our findings suggest that vitamin D levels may influence durability of anti-TNF-α induction and maintenance therapy. Larger cohort studies and clinical trials of supplemental vitamin D use with disease activity as an end point may be warranted.

When the economy falters, do people spend or save? Responses to resource scarcity depend on childhood environments.

Just as modern economies undergo periods of boom and bust, human ancestors experienced cycles of abundance and famine. Is the adaptive response when resources become scarce to save for the future or to spend money on immediate gains? Drawing on life-history theory, we propose that people's responses to resource scarcity depend on the harshness of their early-life environment, as reflected by childhood socioeconomic status (SES). In the three experiments reported here, we tested how people from different childhood environments responded to resource scarcity. We found that people who grew up in lower-SES environments were more impulsive, took more risks, and approached temptations more quickly. Conversely, people who grew up in higher-SES environments were less impulsive, took fewer risks, and approached temptations more slowly. Responses similarly diverged according to people's oxidative-stress levels-a urinary biomarker of cumulative stress exposure. Overall, whereas tendencies associated with early-life environments were dormant in benign conditions, they emerged under conditions of economic uncertainty.

Ovulation leads women to perceive sexy cads as good dads.

Why do some women pursue relationships with men who are attractive, dominant, and charming but who do not want to be in relationships--the prototypical sexy cad? Previous research shows that women have an increased desire for such men when they are ovulating, but it is unclear why ovulating women would think it is wise to pursue men who may be unfaithful and could desert them. Using both college-age and community-based samples, in 3 studies we show that ovulating women perceive charismatic and physically attractive men, but not reliable and nice men, as more committed partners and more devoted future fathers. Ovulating women perceive that sexy cads would be good fathers to their own children but not to the children of other women. This ovulatory-induced perceptual shift is driven by women who experienced early onset of puberty. Taken together, the current research identifies a novel proximate reason why ovulating women pursue relationships with sexy cads, complementing existing research that identifies the ultimate, evolutionary reasons for this behavior.

Sex ratio and women's career choice: does a scarcity of men lead women to choose briefcase over baby?

Although the ratio of males to females in a population is known to influence behavior in nonhuman animals, little is known about how sex ratio influences human behavior. We propose that sex ratio affects women's family planning and career choices. Using both historical data and experiments, we examined how sex ratio influences women's career aspirations. Findings showed that a scarcity of men led women to seek high-paying careers and to delay starting a family. This effect was driven by how sex ratio altered the mating market, not just the job market. Sex ratios involving a scarcity of men led women to seek lucrative careers because of the difficulty women have in finding an investing, long-term mate under such circumstances. Accordingly, this low-male sex ratio produced the strongest desire for lucrative careers in women who are least able to secure a mate. These findings demonstrate that sex ratio has far-reaching effects in humans, including whether women choose briefcase over baby.