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Objective: Adiposity is associated with oxidative stress, inflammation, and glucose intolerance. Previous data suggest that platelet gene expression is associated with key cardiometabolic phenotypes, including body mass index but stable in healthy individuals over time. However, modulation of gene expression in platelets in response to metabolic shifts (eg, weight reduction) is unknown and may be important to defining mechanism. Approach and Results: Platelet RNA sequencing and aggregation were performed from 21 individuals with massive weight loss (>45 kg) following bariatric surgery. Based on RNA sequencing data, we measured the expression of 67 genes from isolated platelet RNA using high-throughput quantitative reverse transcription quantitative PCR in 1864 FHS (Framingham Heart Study) participants. Many transcripts not previously studied in platelets were differentially expressed with bariatric surgical weight loss, appeared specific to platelets (eg, not differentially expressed in leukocytes), and were enriched for a nonalcoholic fatty liver disease pathway. Platelet aggregation studies did not detect alteration in platelet function after significant weight loss. Linear regression models demonstrated several platelet genes modestly associated with cross-sectional cardiometabolic phenotypes, including body mass index. There were no associations between studied transcripts and incident diabetes or cardiovascular end points. Conclusions: In summary, while there is no change in platelet aggregation function after significant weight loss, the human platelet experiences a dramatic transcriptional shift that implicates pathways potentially relevant to improved cardiometabolic risk postweight loss (eg, nonalcoholic fatty liver disease). Further studies are needed to determine the mechanistic importance of these observations.

This study aims to evaluate the efficacy of the Pooled Cohort Equation (PCE), U.S. Preventative Services Task Force (USPSTF), and Framingham Risk Score (FRS) models in predicting ASCVD events among patients receiving radiation therapy (RT) for head and neck cancer (HNCA). From a large cohort of HNCA patients treated with RT, ASCVD events were adjudicated. Observed vs. predicted ASCVD events were compared. We compared rates by statin eligibility status. Regression models and survival analysis were used to identify the relationship between predicted risk and post-RT outcomes. Among the 723 identified patients, 274 (38%) were statin-eligible based on USPSTF criteria, 359 (49%) based on PCE, and 234 (32%) based on FRS. During follow-up, 17% developed an ASCVD, with an event rate of 27 per 1000 person-years, 68% higher than predicted (RR 1.68 (95% CI: 1.02, 2.12), p < 0.001). In multivariable regression, there was no difference in event rates by statin eligibility status (p > 0.05). Post-RT, the observed event rate was higher than the predicted ASCVD risk across all grades of predicted risk (p < 0.05) and the observed risk of an ASCVD event was high even among patients predicted to have a low risk of ASCVD. In conclusion, current ASCVD risk calculators significantly underestimate the risk for ASCVD among patients receiving RT for HNCA.

Importance Clinical and economic consequences of statin treatment guidelines supplemented by targeted coronary artery calcium (CAC) assessment have not been evaluated in African American individuals, who are at increased risk for atherosclerotic cardiovascular disease and less likely than non–African American individuals to receive statin therapy. Objective To evaluate the cost-effectiveness of the 2013 American College of Cardiology/American Heart Association (ACC/AHA) guideline without a recommendation for CAC assessment vs the 2018 ACC/AHA guideline recommendation for use of a non-0 CAC score measured on one occasion to target generic-formulation, moderate-intensity statin treatment in African American individuals at risk for atherosclerotic cardiovascular disease. Design, Setting, and Participants A microsimulation model was designed to estimate life expectancy, quality of life, costs, and health outcomes over a lifetime horizon. African American–specific data from 472 participants in the Jackson Heart Study (JHS) at intermediate risk for atherosclerotic cardiovascular disease and other US population-specific data on individuals from published sources were used. Data analysis was conducted from November 11, 2018, to November 1, 2019. Main Outcomes and Measures Lifetime costs and quality-adjusted life-years (QALYs), discounted at 3% annually. Results In a model-based economic evaluation informed in part by follow-up data, the analysis was focused on 472 individuals in the JHS at intermediate risk for atherosclerotic cardiovascular disease; mean (SD) age was 63 (6.7) years. The sample included 243 women (51.5%) and 229 men (48.5%). Of these, 178 of 304 participants (58.6%) who underwent CAC assessment had a non-0 CAC score. In the base-case scenario, implementation of 2013 ACC/AHA guidelines without CAC assessment provided a greater quality-adjusted life expectancy (0.0027 QALY) at a higher cost ($428.97) compared with the 2018 ACC/AHA guideline strategy with CAC assessment, yielding an incremental cost-effectiveness ratio of $158 325/QALY, which is considered to represent low-value care by the ACC/AHA definition. The 2018 ACC/AHA guideline strategy with CAC assessment provided greater quality-adjusted life expectancy at a lower cost compared with the 2013 ACC/AHA guidelines without CAC assessment when there was a strong patient preference to avoid use of daily medication therapy. In probability sensitivity analyses, the 2018 ACC/AHA guideline strategy with CAC assessment was cost-effective compared with the 2013 ACC/AHA guidelines without CAC assessment in 76% of simulations at a willingness-to-pay value of $100 000/QALY when there was a preference to lose 2 weeks of perfect health to avoid 1 decade of daily therapy. Conclusions and Relevance A CAC assessment-guided strategy for statin therapy appears to be cost-effective compared with initiating statin therapy in all African American individuals at intermediate risk for atherosclerotic cardiovascular disease and may provide greater quality-adjusted life expectancy at a lower cost than a non-CAC assessment-guided strategy when there is a strong patient preference to avoid the need for daily medication. Coronary artery calcium testing may play a role in shared decision-making regarding statin use.

Supplemental appendix. Table S1. Primary TTE Indication for each year and for all years. Table S2. Reasons for left ventricular function assessment. Table S3. Univariate mixed effects logistic regression model for factors that are associated with major discordance. Table S4. Multivariate mixed effects logistic regression model for factors that are associated with major discordance. Table S5. Total number of fellow TTEs interpreted by each individual NBE certified echo attending and the attending discordance rate. (DOCX 30 kb)

Purpose The early post-heart transplantation (HT) period entails frequent biopsies, which poses a unique challenge to administration of therapeutic anticoagulation when indicated. Heightened sensitivity to enoxaparin has been described primarily in lung transplant recipients but has not been assessed in relation to anti-Xa levels specifically in HT recipients. Herein we report our institutional experience with a range of doses of enoxaparin relative to anti-Xa levels. Methods We examined HT recipients who received therapeutic anticoagulation with enoxaparin and included patients with steady state anti-Xa levels at appropriate post-dosing time intervals (i.e. 4 hours) and GFR > 30. Based on suspected heightened sensitivity to enoxaparin, we initiated doses below 1mg/kg every 12 hours (Q12). Spearman's rank correlation was used to relate non-parametric data. Results A total of 14 patients (2016-2019) were included. Average age at the time of enoxaparin exposure was 62 years, 71% were male. Four patients (29%) had a GFR 30-60 while 10 patients (71%) had a GFR > 60. Of 39 anti-Xa levels collected, levels correlated with dose of enoxaparin in mg/kg (rho=0.48, p=0.002, Figure) but not GFR (rho=0.04, p=0.80). Dosing of 1 mg/kg Q12 resulted in average anti-Xa levels above the therapeutic range (mean ± SEM: 1.13±0.23 IU/mL), whereas doses of 0.6mg/kg Q12 resulted in average levels of 0.75±0.07 IU/mL, the midpoint of the desired therapeutic anticoagulation range. Lower doses of enoxaparin (between 0.2-0.5 mg/kg Q12, including those used for prophylaxis) often resulted in anti-Xa levels approaching the therapeutic range (Figure). Conclusion In our small population of HT recipients requiring therapeutic anticoagulation, use of enoxaparin 0.6 mg/kg BID results in average anti-Xa levels at the midpoint of the therapeutic range (0.75 IU/mL) and represents a preferable dosing strategy to FDA-label dosing of 1mg/kg Q12.

Purpose Donor availability has continued to be a major issue limiting the number of cardiac transplantations in the United States. Given this shortage, it is necessary to consider strategies aimed at increasing the donor pool. We sought to evaluate the expanded use of hepatitis C virus (HCV) donor hearts, and characterize early allograft function in HCV-negative patients receiving pre-emptive anti-viral therapy following receipt of an HCV-infected donor heart. Methods Patients who underwent heart transplantation with HCV-positive donors at our institution between November 2017 and October 2018 were studied. Invasive hemodynamic and echocardiographic data were collected from routine scheduled post-transplant procedures. Intensive care unit (ICU) time, time on inotropes and time until discharge were evaluated from the index hospitalization for heart transplantation and compared to data from our center in patients receiving non-HCV hearts between January 2016 and June 2018. Results In total, there have been 23 recipients of donor HCV-positive heart transplants. Cardiac allograft and patient survival has been 100% at a median of 114 (IQR 81-190) days post-transplant. The average time on inotropes was 4.7±3.3 days in recipients of donor HCV-positive heart transplants, average time spent in the ICU was 7.2±4 days in the study group compared with 7.8±7.8 days in patients receiving non-HCV hearts and the average time to discharge was 19 ± 9 days in the study group compared with 21±22 days in patients receiving non-HCV hearts (both p>0.05). Among 80 echocardiograms done on or after post-operative day 2 in recipients of HCV-positive donor hearts, the ejection fraction (EF) was 65±9% with a single value falling below 50% (45%) that normalized 6 days later. One and 8-week hemodynamic values, respectively, were as follows: right atrial pressure of 7±5 and 5±3 mmHg, mean pulmonary arterial pressure of 20±7 and 20±6 mmHg, mean pulmonary capillary wedge pressure of 14±6 and 11±5 mmHg, and cardiac index of 2.8±0.8 and 2.9±0.4 L/min/m2. Conclusion In this single-center prospective study, patients who received preemptive direct-acting antiviral therapy following receipt of an HCV-positive donor heart demonstrated preserved early allograft function post-transplant.

Atrial fibrillation is the most common sustained arrhythmia worldwide [(1)][1], and catheter-based pulmonary vein isolation (PVI) is becoming a dominant approach to its management. Stroke and transient ischemic attack are known risks of PVI [(2)][2]. To improve PVI safety, atrial thrombus needs to

Modern prevention guidelines substantially increase the number of individuals who are eligible for treatment with statins. Efforts to refine statin eligibility via coronary calcification have been studied in white populations but not, to our knowledge, in large African American populations.To compare the relative accuracy of US Preventive Services Task Force (USPSTF) and American College of Cardiology/American Heart Association (ACC/AHA) recommendations in identifying African American individuals with subclinical and clinical atherosclerotic cardiovascular disease (ASCVD).In this prospective, community-based study, 2812 African American individuals aged 40 to 75 years without prevalent ASCVD underwent assessment of ASCVD risk. Of these, 1743 participants completed computed tomography.Nonzero coronary artery calcium (CAC) score, abdominal aortic calcium score, and incident ASCVD (ie, myocardial infarction, ischemic stroke, or fatal coronary heart disease).Of the 2812 included participants, the mean (SD) age at baseline was 55.4 (9.4) years, and 1837 (65.3%) were female. The USPSTF guidelines captured 404 of 732 African American individuals (55.2%) with a CAC score greater than 0; the ACC/AHA guidelines identified 507 individuals (69.3%) (risk difference, 14.1%; 95% CI, 11.2-17.0; P .001). Statin recommendation under both guidelines was associated with a CAC score greater than 0 (odds ratio, 5.1; 95% CI, 4.1-6.3; P .001). While individuals indicated for statins under both guidelines experienced 9.6 cardiovascular events per 1000 patient-years, those indicated under only ACC/AHA guidelines were at low to intermediate risk (4.1 events per 1000 patient-years). Among individuals who were statin eligible by ACC/AHA guidelines, the 10-year ASCVD incidence per 1000 person-years was 8.1 (95% CI, 5.9-11.1) in the presence of CAC and 3.1 (95% CI, 1.6-5.9) without CAC (P = .02). While statin-eligible individuals by USPSTF guidelines did not have a significantly higher 10-year ASCVD event rate in the presence of CAC, African American individuals not eligible for statins by USPSTF guidelines had a higher ASCVD event rate in the presence of CAC (2.8 per 1000 person-years; 95% CI, 1.5-5.4) relative to without CAC (0.8 per 1000 person-years; 95%, CI 0.3-1.7) (P = .03).The USPSTF guidelines focus treatment recommendations on 38% of high-risk African American individuals at the expense of not recommending treatment in nearly 25% of African American individuals eligible for statins by ACC/AHA guidelines with vascular calcification and at low to intermediate ASCVD risk.

Background— The lifetime risk of heart failure (HF) is higher in the black population than in other racial groups in the United States. Methods and Results— We measured the Life’s Simple 7 ideal cardiovascular health metrics in 4195 blacks in the JHS (Jackson Heart Study; 2000–2004). We evaluated the association of Simple 7 metrics with incident HF and left ventricular structure and function by cardiac magnetic resonance (n=1188). Mean age at baseline was 54.4 years (65% women). Relative to 0 to 2 Simple 7 factors, blacks with 3 factors had 47% lower incident HF risk (hazard ratio [HR], 0.53; 95% confidence interval [CI], 0.39–0.73; P P =0.0002). Higher blood pressure (HR, 2.32; 95% CI, 1.28–4.20; P =0.005), physical inactivity (HR, 1.65; 95% CI, 1.07–2.55; P =0.02), smoking (HR, 2.04; 95% CI, 1.43–2.91; P P Conclusions— Cardiovascular risk factors in midlife (specifically elevated blood pressure, physical inactivity, smoking, and poor glucose control) are associated with incident HF in blacks and represent targets for intensified HF prevention.