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Background: Red Blood Cell Distribution Width (RDW), a measure of variability in size of circulating red blood cells and is a marker of inflammation., Objectives: We sought to test the hypothesis that RDW reflects an inflammatory milieu permissive for cardiac fibrosis in those with Heart Failure and preserved ejection fraction (HFpEF)., Methods: We analyzed the association between RDW and fibrosis in two separate cohorts. Cohort 1 (n = 200) was a retrospective analysis of blood biomarkers measured in the RELAX trial (Clinicaltrials.gov NCT00763867) and Cohort 2 (n = 160) included a single center cohort of patients with preserved ventricular function referred for cardiac magnetic resonance imaging (cMRI). Linear regression was used to adjust for potential confounders, and a mediation analysis used to explore relationships with exercise intolerance (peak VO2 max)., Results: Within Cohort 1, anisocytosis (RDW > 14.5) was prevalent (49.5%) and was associated with greater baseline clinical comorbidities, a lower Peak VO2 and more frequent heart failure hospitalizations. The RDW was associated with biomarkers of inflammation and cardiac fibrosis. In Cohort 2, RDW was associated with cMRI myocardial fibrosis (extracellular volume; Spearman's rho=0.38, P<0.001) which was independent of age, sex, LV ejection fraction, and hematocrit (P = 0.026). Individuals with both anisocytosis and myocardial fibrosis identified a subgroup of at high risk for 2-year mortality (HR 16.28 [4.30-61.66], P<0.001)., Conclusions: In two independent cohorts of patients with HFpEF, elevated RDW is associated reduced exercise capacity and greater fibrosis as measured by serum biomarkers and cMRI. Additional studies are needed to validate this novel relationship., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Aims: Heart failure (HF) is one of the leading causes of cardiovascular morbidity and mortality in the ever-growing population of patients with chronic kidney disease (CKD). There is a need to enhance early prediction to initiate treatment in CKD. We sought to study the feasibility of a multi-variable biomarker approach to predict incident HF risk in CKD., Methods and Results: We examined 3182 adults enrolled in the Chronic Renal Insufficiency Cohort (CRIC) without prevalent HF who underwent serum/plasma assays for 11 blood biomarkers at baseline visit (B-type natriuretic peptide [BNP], CXC motif chemokine ligand 12, fibrinogen, fractalkine, high-sensitivity C-reactive protein, myeloperoxidase, high-sensitivity troponin T (hsTnT), fibroblast growth factor 23 [FGF23], neutrophil gelatinase-associated lipocalin, fetuin A, aldosterone). The population was randomly divided into derivation (n = 1629) and validation (n = 1553) cohorts. Biomarkers that were associated with HF after adjustment for established HF risk factors were combined into an overall biomarker score (number of biomarkers above the Youden's index cut-off value). Cox regression was used to explore the predictive role of a biomarker panel to predict incident HF. A total of 411 patients developed incident HF at a median follow-up of 7 years. In the derivation cohort, four biomarkers were associated with HF (BNP, FGF23, fibrinogen, hsTnT). In a model combining all four biomarkers, BNP (hazard ratio [HR] 2.96 [95% confidence interval 2.14-4.09]), FGF23 (HR 1.74 [1.30-2.32]), fibrinogen (HR 2.40 [1.74-3.30]), and hsTnT (HR 2.89 [2.06-4.04]) were associated with incident HF. The incidence of HF increased with the biomarker score, to a similar degree in both derivation and validation cohorts: from 2.0% in score of 0% to 46.6% in score of 4 in the derivation cohort to 2.4% in score of 0% to 43.5% in score of 4 in the validation cohort. A model incorporating biomarkers in addition to clinical factors reclassified risk in 601 (19%) participants (352 [11%] participants to higher risk and 249 [8%] to lower risk) compared with clinical risk model alone (net reclassification improvement of 0.16)., Conclusion: A basic panel of four blood biomarkers (BNP, FGF23, fibrinogen, and hsTnT) can be used as a standalone score to predict incident HF in patients with CKD allowing early identification of patients at high-risk for HF. Addition of biomarker score to clinical risk model modestly reclassifies HF risk and slightly improves discrimination., (© 2022 European Society of Cardiology.)

Advances in CT technology have resulted in improved imaging of the coronary anatomy in patients with stable coronary artery disease, using coronary CT angiography (CCTA). Recent data suggest that CCTA may play a role in higher risk patients, such as those evaluated in the emergency room with acute chest pain. Data thus far support the use of CCTA in low-risk patients with acute chest pain. Recent literature suggests that CCTA may play a role in the risk stratification of selected intermediate-risk patients. In this review, the authors discuss the emerging role of CCTA in higher risk patients, such as those with suspected or confirmed acute coronary syndrome (ACS). The excellent accuracy of CCTA in detecting obstructive coronary artery disease in patients with ACS is detailed, along with a highlighting of the safety of using CCTA in this setting. The authors also discuss the role for CCTA atheromatous plaque characterization, which is being increasingly recognized as an important predictor of clinical outcomes., Competing Interests: Disclosure: The authors have no conflicts of interest to declare., (Copyright © The Author(s), 2022. Published by Radcliffe Group Ltd.)

Patients with chronic kidney disease (CKD) are at increased risk for stroke. High-sensitivity troponin (hsTP), a marker of myocardial injury, has been associated with stroke risk in patients without CKD, but whether this applies to patients with CKD is not known. We assessed whether hsTP levels is associated with incident stroke in patients with mild-to-moderate CKD without a history of stroke enrolled in the Chronic Renal Insufficiency Cohort. Patients were followed for incident stroke, and the association with hsTP was assessed. A total of 3477 patients without prior stroke were included in this investigation. Over a median follow-up of 7.3 years, 101 (2.8%) patients had an incident stroke. Baseline hsTP was associated with a 9-year risk of stroke (quartile 1: 1.8%, quartile 2: 3.8%, quartile 3: 4.9%, quartile 4: 7.3%; P < .001). After adjusting for traditional stroke risk factors, patients in the fourth quartile (hazard ratio: 2.52, 95% CI: 1.10-5.76, P = .021) had higher risk of stroke when compared with the lowest quartile of hsTP. In conclusion, hsTP levels are associated with increased risk of incident stroke in patients with mild to moderate CKD, and this association remains significant despite the adjustment for traditional risk factors and CKD.

Chronic systemic inflammation is associated with an increased risk of heart failure (HF). We sought to determine the association between biomarkers of systemic inflammation interleukin (IL)-6, IL-2, tumor necrosis factor alpha (TNF-α), and C-reactive protein (CRP) with those of HF and its subtypes. We hypothesize that inflammatory biomarkers IL-6, IL-2, TNF-α, and CRP are associated with HF and its subtypes. We included participants from the Multi-Ethnic Study of Atherosclerosis (a prospective population-based cohort study [2000 to 2002]), without a history of HF, and with available baseline inflammatory biomarkers. We explored the association of IL-6, IL-2, TNF-α, and CRP with incident HF, HF with reduced ejection fraction (left ventricular ejection fraction [LVEF] <40%, HFrEF), HF with midrange EF (LVEF 40% to 50%, HFmrEF), and HF with preserved ejection fraction (LVEF >50%, HFpEF). Among 6,814 participants, 195 developed HF over 10.9 years (56 HFrEF, 30 HFmrEF, and 57 HFpEF). In the models adjusted for clinical risk factors of HF, IL-6 (hazard ratio [HR] 1.33 per doubling; 95% confidence interval [CI] 1.10 to 1.60), TNF-α (HR 2.49 per doubling; 95% CI 1.18 to 5.28), and CRP (HR 1.18 per doubling; 95% CI 1.06 to 1.30) were associated with all HF, and IL-6 (HR 1.51 per doubling; 95% CI 1.09 to 2.10) and CRP (HR 1.21 per doubling; 95% CI: 1.01 to 1.45) were associated with incident HFpEF, whereas none of the examined biomarkers were associated with HFmrEF or HFrEF. In conclusion, inflammatory biomarkers (IL-6, TNF-α, and CRP) are independently associated with incident HF. IL-6 and CRP are associated with incident HFpEF but not HFrEF or HFmrEF. These findings suggest that activation of the IL-6/CRP pathway (as cause, consequence, or epiphenomenon) may be unique to HFpEF., Competing Interests: Disclosures The authors have no conflicts of interest to declare. This manuscript was prepared using MESA Research Materials obtained from the National Heart, Lung, and Blood Institute Biologic Specimen and Data Repository Information Coordinating Center and does not necessarily reflect the opinions or views of MESA or the National Heart, Lung, and Blood Institute., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: Despite a rising prevalence of chronic inflammatory disease (CID), the recent trends in cardiovascular disease (CVD) mortality of patients with CID is scarce. In this study, we investigated patterns of CVD mortality in systemic lupus erythematosus (SLE), inflammatory bowel disease (IBD), and rheumatoid arthritis (RA) compared with the general population., Methods: We used the 1999 to 2019 multiple causes of death files from the national center for health statistics to analyze patterns and trends of proportionate CVD mortality in CID compared with the general population., Results: We analyzed a total of 11,154 CVD deaths in IBD, 58,337 CVD deaths in RA, 6227 CVD deaths in SLE, and 17,826,871 CVD deaths in the general population. Between 1999 and 2019, we found that proportionate CVD mortality decreased significantly in the IBD group (25% to 16%), RA group (34% to 25%), and the general population (41% to 31%), but did not change for the SLE group (15% to 15%). Patients with SLE who died of CVD were approximately 10 years younger compared with CVD decedents with RA, IBD, or general population. The White population had higher proportionate CVD mortality than African American (IBD [19% vs 16%-18%] and SLE [14%-16% vs 12-14%], respectively)., Conclusions: This study identifies current trends in CVD mortality in the CID population and elucidates current demographics in CVD mortality in CID. Although proportionate CVD mortality decreased in the general population, and in patients with RA and IBD, there was no change among patients with SLE. Further studies are needed to elucidate these differences., Competing Interests: The authors declare no conflict of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Introduction: Low-density lipoprotein cholesterol (LDL-C) is typically estimated from total cholesterol, high-density lipoprotein cholesterol, and triglycerides. The Friedewald, Martin-Hopkins, and National Institutes of Health equations are widely used but may estimate LDL-C inaccurately in certain patient populations, such as those with HIV. We sought to investigate the utility of machine learning for LDL-C estimation in a large cohort of women with and without HIV., Methods: We identified 7397 direct LDL-C measurements (5219 from HIV-infected individuals, 2127 from uninfected controls, and 51 from seroconvertors) from 2414 participants (age 39.4 ± 9.3 years) in the Women's Interagency HIV Study and estimated LDL-C using the Friedewald, Martin-Hopkins, and National Institutes of Health equations. We also optimized 5 machine learning methods [linear regression, random forest, gradient boosting, support vector machine (SVM), and neural network] using 80% of the data (training set). We compared the performance of each method using root mean square error, mean absolute error, and coefficient of determination (R2) in the holdout (20%) set., Results: SVM outperformed all 3 existing equations and other machine learning methods, achieving the lowest root mean square error and mean absolute error, and the highest R2 (11.79 and 7.98 mg/dL, 0.87, respectively, compared with those obtained using the Friedewald equation: 12.45 and 9.14 mg/dL, 0.87). SVM performance remained superior in subgroups with and without HIV, with nonfasting measurements, in LDL <70 mg/dL and triglycerides > 400 mg/dL., Conclusions: In this proof-of-concept study, SVM is a robust method that predicts directly measured LDL-C more accurately than clinically used methods in women with and without HIV. Further studies should explore the utility in broader populations., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Myocarditis can be refractory to medical therapy and require durable mechanical circulatory support (MCS). The characteristics and outcomes of these patients are not known. We identified all patients with clinically-diagnosed or pathology-proven myocarditis who underwent mechanical circulatory support in the International Society for Heart and Lung Transplantation Registry for Mechanically Assisted Circulatory Support registry (2013-2016). The characteristics and outcomes of these patients were compared to those of patients with nonischemic cardiomyopathy (NICM). Out of 14,062 patients in the registry, 180 (1.2%) had myocarditis and 6,602 (46.9%) had NICM. Among patients with myocarditis, duration of heart failure was <1 month in 22%, 1-12 months in 22.6%, and >1 year in 55.4%. Compared with NICM, patients with myocarditis were younger (45 vs. 52 years, P < 0.001) and were more often implanted with Interagency Registry for Mechanically Assisted Circulatory Support profile 1 (30% vs. 15%, P < 0.001). Biventricular mechanical support (biventricular ventricular assist device [BIVAD] or total artificial heart) was implanted more frequently in myocarditis (18% vs. 6.7%, P < 0.001). Overall postimplant survival was not different between myocarditis and NICM (left ventricular assist device: P = 0.27, BIVAD: P = 0.50). The proportion of myocarditis patients that have recovered by 12 months postimplant was significantly higher in myocarditis compared to that of NICM (5% vs. 1.7%, P = 0.0003). Adverse events (bleeding, infection, and neurologic dysfunction) were all lower in the myocarditis than NICM. In conclusion, although myocarditis patients who receive durable MCS are sicker preoperatively with higher needs for biventricular MCS, their overall MCS survival is noninferior to NICM. Patients who received MCS for myocarditis are more likely than NICM to have MCS explanted due to recovery, however, the absolute rates of recovery were low., Competing Interests: Disclosure: J.K.K. serves as the director of the data center for the STS INTERMACS database and received partial salary support from funds paid to the institution. J.C. has received honoraria from Medtronic and Abbot; serves as the vice chair of data studies for IMACS. S.S. has received honorarium from Medtronic as an advisor and proctor. D.G. has received personal fees from Abbot Inc as a Surgical Proctor, Educator, and Consultant. The other authors have no conflicts of interest to report., (Copyright © ASAIO 2021.)

The long-term prognostic significance of a coronary artery calcium (CAC) score of 0 is poorly defined in younger adults. We evaluated this among participants aged 45 to 55 years from the Multi-Ethnic Study of Atherosclerosis, and assessed whether additional biomarkers can identify subgroups at increased absolute risk. We included 1,407 participants (61% women) without diabetes or severe hypercholesterolemia, with estimated 10-year risk <20% and CAC = 0. We evaluated all and hard cardiovascular disease (CVD) events, overall and among subjects with each of the following: high-sensitivity C-reactive protein levels ≥2 mg/L, homocysteine ≥10 µmol/L, high-sensitivity cardiac troponin T ≥95th percentile, lipoprotein (a) >50 mg/dl, triglycerides ≥175 mg/dl, apolipoprotein B ≥130 mg/dl, albuminuria, thoracic aortic calcium, aortic valve calcium (AVC), mitral annular calcium, ankle-brachial index <0.9, any carotid plaque, and maximum internal carotid artery intima-media thickness (ICA-IMT) ≥1.5 mm. Median follow-up was 16 years, and overall CVD event rates were low (4% at 15 years). For most exposures evaluated, rates of all CVD events were <6 per 1,000 person-years, except for ICA-IMT ≥1.5 mm (6.43) and AVC (13.8). The number needed to screen to detect ICA-IMT ≥1.5 mm was 8, and 84 for AVC. Among participants with borderline/intermediate risk or premature family history, hard CVD event rates were <7 per 1,000 for most exposures, except for ICA-IMT ≥1.5 mm (8.25), albuminuria (8.30), and AVC (13.47). Nonsmokers and those with ICA-IMT <1.5 mm had very low rates. In conclusion, our results demonstrate a favorable long-term prognosis of CAC = 0 among adults aged ≤55 years, particularly among nonsmokers. ICA-IMT testing could be considered for further risk assessment in adults ≤55 years with CAC = 0 and uncertain management., Competing Interests: Disclosures The authors have no conflicts of interest to disclose., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: Substantial differences exist between United States counties with regards to premature (<65 years of age) cardiovascular disease (CVD) mortality. Whether underlying social vulnerabilities of counties influence premature CVD mortality is uncertain., Methods: In this cross-sectional study (2014-2018), we linked county-level CDC/ATSDR SVI (Centers for Disease Control and Prevention/Agency for Toxic Substances and Disease Registry Social Vulnerability Index) data with county-level CDC WONDER (Centers for Disease Control and Prevention Wide-Ranging Online Data for Epidemiological Research) mortality data. We calculated scores for overall SVI and its 4 subcomponents (ie, socioeconomic status; household composition and disability; minority status and language; and housing type and transportation) using 15 social attributes. Scores were presented as percentile rankings by county, further classified as quartiles on the basis of their distribution among all US counties (1st [least vulnerable] = 0 to 0.25; 4th [most vulnerable = 0.75 to 1.00]). We grouped age-adjusted mortality rates per 100 000 person-years for overall CVD and its subtypes (ischemic heart disease, stroke, hypertension, and heart failure) for nonelderly (<65 years of age) adults across SVI quartiles., Results: Overall, the age-adjusted CVD mortality rate per 100 000 person-years was 47.0 (ischemic heart disease, 28.3; stroke, 7.9; hypertension, 8.4; and heart failure, 2.4). The largest concentration of counties with more social vulnerabilities and CVD mortality were clustered across the southwestern and southeastern parts of the United States. The age-adjusted CVD mortality rates increased in a stepwise manner from 1st to 4th SVI quartiles. Counties in the 4th SVI quartile had significantly higher mortality for CVD (rate ratio, 1.84 [95% CI, 1.43-2.36]), ischemic heart disease (1.52 [1.09-2.13]), stroke (2.03 [1.12-3.70]), hypertension (2.71 [1.54-4.75]), and heart failure (3.38 [1.32-8.61]) than those in the 1st SVI quartile. The relative risks varied considerably by demographic characteristics. For example, among all ethnicities/races, non-Hispanic Black adults in the 4th SVI quartile versus the 1st SVI quartile exclusively had significantly higher relative risks of stroke (1.65 [1.07-2.54]) and heart failure (2.42 [1.29-4.55]) mortality. Rural counties with more social vulnerabilities had 2- to 5-fold higher mortality attributable to CVD and subtypes., Conclusions: In this analysis, US counties with more social vulnerabilities had higher premature CVD mortality, varied by demographic characteristics and rurality. Focused public health interventions should address the socioeconomic disparities faced by underserved communities to curb the growing burden of premature CVD.

Background Cardiac diffuse large B-cell lymphoma (cDLBCL) is an extremely rare disease. Introduction of rituximab has significantly improved survival in non-cardiac DLBCL, but there is limited data regarding the effects on outcomes in cDLBCL. We sought to evaluate the outcomes of cDLBCL in both pre- and rituximab eras. Methods We identified all cDLBCL cases in the Surveillance, Epidemiology and End Results (SEER) registry from 1975 to 2016. We compared survival (overall and lymphoma-specific) of patients diagnosed prior to versus after rituximab approval in 2006. Results A total of 106 patients were included in the final analysis. Median age was 69.5 years, 67% of the patients were white and 64% had local stage I/II disease. 67% of the patients were diagnosed after 2006 and thus belonged to the rituximab era group. Overall, 77% received chemotherapy, 24% had surgery and 15% had radiotherapy. Median overall survival (OS) for the entire cohort was 22 months. Median OS was 16 months (95% CI, 0.55-31) for the pre-rituximab group, versus 26 months (95% CI, 7.5-45) for the rituximab group (p = 0.34). Median lymphoma-specific survival (LSS) was 30 months (95% CI, 8.0-52) for the pre-rituximab group versus 36 months (95% CI, 16-158) for the rituximab group (p = 0.30). OS and LSS were also not significantly different between the two era groups when stratified by chemotherapy. In multivariable analysis, both OS and LSS were associated with lymphoma stage, insurance status and age but not with diagnosis era or chemotherapy. Conclusions Cardiac DLBCLs are rare and affecting mostly the elderly. Younger age, limited disease stage, and having health insurance but not lymphoma diagnosis era were associated with better outcomes., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Background Data are limited about young adults' characteristics and outcomes undergoing coronary artery bypass grafting (CABG). Methods and Results We used the National Inpatient Sample database to identify adults aged 18 to 45 years who underwent CABG between 2004 and 2018. The data were weighted to generate national estimates of the entire US hospitalized population. We identified 110 463 CABG cases, equivalent to 62.2 per 1 000 000 person-years; 27.1% were women, and 70.2% were White adults. Overall, annual CABG volume per 1 000 000 significantly decreased from 87.3 in 2004 to 45.7 in 2018. The prevalence of obesity, diabetes mellitus, hypertension, drug abuse, and chronic medical conditions increased over time. Overall, inpatient mortality was 1.76%; ST-segment-elevation myocardial infarction, non-ST-segment-elevation myocardial infarction, heart failure, peripheral vascular disease, renal failure, and valvular surgery were associated with higher inpatient mortality. Women had higher inpatient mortality than men (2.29% versus 1.57%), and Black patients had higher deaths than White patients (2.86% versus 1.58%). Inpatient mortality remained stable overall, according to sex, race, or clinical indication of CABG. However, the mean length of stay (8.4 days in 2004 to 9.5 days in 2018) and inflation-adjusted cost of care ($40 522.8 in 2004 to $52 434.2 in 2018) significantly increased during the study period. Conclusions Despite the increased burden of cardiometabolic risk factors, the inpatient mortality in young adults undergoing CABG remained stable during the last 15 years. However, CABG volumes have decreased, but length of stay and inflation-adjusted costs have increased over time.

Purpose of Review: During the past century, exposure to particulate matter (PM) air pollution < 2.5 μm in diameter (PM 2.5 ) has emerged as an all-pervading element of modern-day society. This increased exposure has come at the cost of heightened risk for cardiovascular (CV) morbidity and mortality. Not only can short-term PM 2.5 exposure trigger acute CV events in susceptible individuals, but longer-term exposure over years augments CV risk to a greater extent in comparison with short-term exposure. The purpose of this review is to examine the available evidence for how ambient air pollution exposure may precipitate events at various time frames., Recent Findings: Recent epidemiological studies have demonstrated an association between ambient PM 2.5 exposure and the presence and progression of atherosclerosis in humans. Multiple animal exposure experiments over two decades have provided strong corroborative evidence that chronic exposure in fact does enhance the progression and perhaps vulnerability characteristics of atherosclerotic lesions. Evidence from epidemiological studies including surrogates of atherosclerosis, human translational studies, and mechanistic investigations utilizing animal studies have improved our understanding of how ambient air pollution may potentiate atherosclerosis and precipitate cardiovascular events. Even so, future research is needed to fully understand the contribution of different constituents in ambient air pollution-mediated atherosclerosis as well as how other systems may modulate the impact of exposure including adaptive immunity and the gut microbiome. Nevertheless, due to the billions of people continually exposed to PM 2.5 , the long-term pro-atherosclerotic effects of this ubiquitous air pollutant are likely to be of enormous and growing global public health importance., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Left ventricular assist devices (LVADs) are surgically implanted mechanical devices indicated for patients with advanced heart failure and are known to come with several complications. Here we present a case series, and review 1 documented report, of LVAD vasculitis, a presumed new LVAD immune/humoral related phenomenon. ( Level of Difficulty: Advanced. )., Competing Interests: Dr Garcia is supported by the National Heart, Lung, and Blood Institute, Institutes of Health, under Aware Number 5T32HL110837. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (© 2021 Published by Elsevier on behalf of the American College of Cardiology Foundation.)

Background: Air pollution and socioeconomic status have both been strongly associated with cardiovascular (CV) outcomes. We sought to determine if socioeconomic status modifies the risk association between fine particulate matter air pollution (PM 2.5 ) and CV mortality., Methods: We linked county-level age-adjusted CV mortality data from Multiple Cause of Death files (2000-2016, ICD10: I00-I99) with 2015 Social Deprivation Index (SDI), a validated estimate of socioeconomic status, and modelled spatial and temporal mean annual PM 2.5 exposures (2012-2018). Higher SDI suggests greater deprivation and lower socioeconomic status. Associations between PM 2.5 and age adjusted CV mortality were estimated using linear models., Results: A total of 5,769,315 cardiovascular deaths from 2012-2018 across 3106 United States counties were analyzed. Both PM 2.5 (β (SE) 7.584 (0.938), P < .001) and SDI scores (β (SE) 0.591 (0.140), P < .001) were independently associated with age-adjusted CV mortality (R 2  = 0.341). The association between PM 2.5 and CV mortality were stronger among counties with highest SDI, P value for interaction = .012., Conclusion: Social deprivation and PM 2.5 exposures were independently associated with county level age-adjusted CV mortality. The associations between PM 2.5 and CV mortality were stronger in counties with high vs low social deprivation. SDI and PM 2.5 represent potential targets to reduce CV mortality disparities and interventions to reduce PM 2.5 exposure may be most impactful in communities of low socioeconomic status., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: Mechanisms of exercise intolerance in patients with heart failure with preserved ejection fraction (HFpEF) are not well understood. Pulmonary hypertension, a common accompaniment in patients with HFpEF, is associated with poor outcomes. While Endothelin -1 (ET-1) plays a mechanistic role in pulmonary hypertension, its role in exercise intolerance in HFpEF is not well established., Objective: To explore the association between plasma ET-1 levels and maximal oxygen consumption (pVO2), and their changes over 24 weeks in HFpEF., Methods: This is a post-hoc analysis of the Phosphodiesterase-5 Inhibition to Improve Clinical Status and Exercise Capacity in Heart Failure with Preserved Ejection Fraction (RELAX) trial. We performed linear regressions to assess the relationship between plasma ET-1 and pVO2. We also used linear regressions to determine whether ET-1 was associated with change in peak VO2 (ΔpVO 2 )., Results: A total of 210 patients were included. Baseline plasma ET-1 levels were associated with older age, higher NT-proBNP levels, higher serum creatinine levels, and higher prevalence of atrial fibrillation. Patients with higher ET1 levels also had higher plasma galectin-3 and CITP levels. After multiple adjustments, baseline ET1 levels were associated with lower pVO 2 (β -0.927, SE 0.196, p < 0.001). Over 24 weeks, the change in ET1 levels was associated with the change in pVO2 (multivariable adjusted β -0.415, SE 0.115, p = 0.018). Baseline ET1 levels did not modify the effect of sildenafil on change in peak VO 2 ., Conclusions: Plasma ET1 levels are significantly associated with lower exercise oxygen consumption both at baseline and longitudinally over 24 weeks. Future studies should explore Endothelin-1 antagonism to improve exercise tolerance in HFpEF., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: Low-density lipoprotein cholesterol (LDL-C) is estimated from total cholesterol, high-density lipoprotein cholesterol and triglycerides using predefined equations which assume fixed or varying relationships between these parameters and may underestimate or overestimate LDL-C. Data on the performance of these equations in persons with HIV are limited. We sought to investigate the utility of the 3 most widely used methods (Friedewald, Hopkins, and the recently proposed NIH equation) to predict LDL-C in persons with HIV., Methods: We identified 7397 direct LDL-C (5219 HIV, 2127 uninfected controls, 51 seroconvertors) measurements in the Women's Interagency HIV Study, and used the 3 equations (Friedewald, Hopkins, and NIH) to calculate LDL-C. We compared the performance of the 3 equations using root mean square error and coefficient of determination (R2)., Results: Overall, the Friedewald equation had the best performance characteristics, outperforming Hopkins and NIH methods with lower root mean square error and higher R2 at lower triglyceride levels. However, this association did not hold true at higher triglyceride levels (quartiles 3 and 4), whereas the Hopkins equation had better performance characteristics in quartile 3, none of the 3 equations were optimal in quartile 4. After adjusting for fasting status and triglycerides levels, HIV+ had larger mean difference compared with directly measured LDL using all 3 methods., Conclusions: All 3 methods have lower accuracy in HIV+ vs HIV- women, even after adjusting for triglyceride levels and fasting status. Further research should focus on identifying methods to estimate LDL-C in HIV., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Fine particulate matter <2.5 µm (PM 2.5 ) air pollution is implicated in global mortality, especially from cardiovascular causes. A large body of evidence suggests a link between PM 2.5 and elevation in blood pressure (BP), with the latter implicated as a potential mediator of cardiovascular events. We sought to determine if the outcomes of intensive BP lowering (systolic BP <120 mm Hg) on cardiovascular events are modified by PM 2.5 exposure in the SPRINT (Systolic BP Intervention Trial). We linked annual PM 2.5 exposure estimates derived from an integrated model to subjects participating in SPRINT. We evaluated the effect of intensive BP lowering by PM 2.5 exposure on the primary outcome in SPRINT using cox-proportional hazard models. A total of 9286 participants were linked to PM 2.5 levels (mean age 68±9 years). Intensive BP-lowering decreased risk of the primary outcome more among patients exposed to higher PM 2.5 ( P interaction =0.047). The estimate for lowering of primary outcome was numerically lower in the highest than in the lower quintiles. The benefits of intensive BP-lowering were larger among patients chronically exposed to PM 2.5 levels above US National Ambient Air Quality Standards of 12 µg/m 3 (hazard ratio, 0.47 [95% CI, 0.29-0.74]) compared with those living in cleaner locations (hazard ratio, 0.81 [95% CI, 0.68-0.97]), P interaction =0.037. This exploratory nonprespecified post hoc analysis of SPRINT suggests that the benefits of intensive BP lowering on the primary outcome was greater in patients exposed to higher PM 2.5 , suggesting that the magnitude of benefit may depend upon the magnitude of antecedent PM 2.5 exposure.

The purpose of this review is to provide a framework for the cardiovascular evaluation and management of patients undergoing hematopoietic cell transplantation (HCT). To accomplish this, we have performed an extensive literature review, critically analyzed the available evidence, and developed a set of recommendations to guide best practice. Herein, we discuss the cardiovascular risk profile of patients undergoing HCT along with putative mechanisms of HCT-induced cardiovascular injury. We then present an algorithm for cardiovascular testing and risk mitigation of potential recipients. Last, we address the management of the most prevalent cardiovascular conditions associated with HCT recipients.

Accurate identification of left ventricular masses (LVM) can be challenging, and if incorrect, may have devastating consequences. While transthoracic echocardiography is often the first test to identify intracardiac masses, cardiac MRI (CMRI) allows for better anatomical definition and tissue characterisation. We present a case of a 51-year-old man who presented with 4 weeks of shortness of breath, found on echocardiogram to have severely reduced LV function and a 2.5×4.0 cm LVM with a hypolucent/cystic core. Due to the unusual appearance, CMRI was required for confirmation of an LV thrombus. This case highlights the importance of multimodality imaging in the discovery and identification of LVM., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

Ambient air pollution due to particulate matter ≤2.5 μ is the leading environmental risk factor contributing to global mortality, with a preponderant majority of these deaths attributable to atherosclerotic cardiovascular disease (ASCVD) causes such as stroke and myocardial infarction. Epidemiological studies in humans have provided refined estimates of exposure risk, with evidence suggesting that risk association with particulate matter ≤2.5 levels and ASCVD continues at levels well below air quality guidelines in North America and Europe. Mechanistic studies in animals and humans have provided a framework of understanding of the duration and pathways by which air pollution exposure may predispose to atherosclerosis. Although acute exposure to particulate matter ≤2.5 is associated with oxidative stress and inflammation, system transmission of signals from the lungs to extrapulmonary sites may involve direct translocation of components, biologic intermediates, and autonomic nervous system activation. End-organ effector pathways such as endothelial barrier disruption/dysfunction, thrombosis, vasoconstriction/increased blood pressure, and plaque instability, may contribute to ASCVD. The strength of the association of air pollution with ASCVD offers an opportunity to mitigate its consequences. Although elimination of anthropogenic sources of air pollution with a switch to clean energy provides the ultimate solution, this may not be possible in the interim and may require personal protection efforts and an integrated approach to managing risk posed by air pollution for ASCVD.

We report a rare case of benign metastasizing leiomyoma in the heart of a 45-year-old woman 2 years after a uterine leiomyoma had been discovered during hysterectomy. Computed tomograms at presentation showed a large mixed cystic mass in the pelvis and bilateral lung nodules suggestive of metastatic disease. A large cardiac mass, attached to the chordae of the tricuspid valve and later shown to be histopathologically consistent with uterine leiomyoma, was successfully resected through a right atriotomy. This case suggests that benign metastasizing leiomyoma should be considered in the differential diagnosis of right-sided cardiac tumors.

Objective: Fibromuscular Dysplasia (FMD) is a rare non-atherosclerotic non-inflammatory vascular disease associated with arterial aneurysms and dissections. The epidemiology of FMD is not well understood. We sought to characterize the epidemiology of FMD utilizing a large aggregated electronic medical record database., Methods: We used a commercial database (Explorys, IBM Watson), which aggregates data from electronic health records from 26 major integrated healthcare systems in the United States. Fibromuscular dysplasia cases were identified using a unique systemized nomenclature of medical terminology (SNOMED CT) term. We calculated the overall and age-, race-, and sex-based prevalence of FMD, and evaluated sex and race-specific differences in manifestations., Results: A total of 40,566,670 individuals were active in the database from January 2015 to January 2020. Of these, 4860 had a diagnosis of FMD with an overall prevalence of 12.0 cases per 100,000 individuals. The majority of patients with FMD were female (n=4130, 85.0%), Caucasian (n=3960, 80.5%) and adults aged 18 to 65 years (n=2610, 53.7%). FMD was more common in women (prevalence 18.4 per 100,000) than men (4.0 per 100,000) and among Caucasians (15.8 per 100,000) than African Americans (11.2 per 100,000). Men and African Americans with FMD were more likely to have traditional atherosclerotic risk factors (hypertension, diabetes mellitus type 2, smoking, obesity, hyperlipidemia, chronic kidney disease), and vascular manifestations (stroke, renal infarction, claudication), compared with women and Caucasians. Men with FMD were more likely to have dissection of aorta and renal artery as well as aneurysm of vertebral artery, coronary artery, aorta and iliac artery. African-Americans were more likely to have ruptured aortic aneurysms than Caucasians., Conclusions: The overall prevalence of FMD in this large aggregated electronic medical record study is estimated at 12.0 per 100,000 persons. FMD is more common in women and Caucasians, with variable characteristics and manifestations., Competing Interests: Declaration of Competing Interest There are no potential conflicts (financial, professional, or personal) to disclose by the other authors (Mariam Nadeem Rana, MD, Sadeer Al-Kindi, MD)., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Red cell distribution width (RDW), a measure of anisocytosis, is observed in chronic inflammation and is a prognostic marker in critically ill patients without COVID-19, but data in COVID-19 are limited., Methods: Between March 12 and April 19, 2020, 282 individuals with confirmed COVID-19 and RDW available within 7 days prior to COVID-19 confirmation were evaluated. Individuals were grouped by quartiles of RDW. Association between quartiles of RDW and mortality was assessed using the Kaplan-Meier method and statistical significance was assessed using the log-rank test. The association between RDW and all-cause mortality was further assessed using a Cox proportional hazards model. Plasma cytokine levels in uninfected ambulatory adults without cardiovascular disease (n=38) were measured and bivariate Spearman correlations and principle components analysis were used to identify relationships between cytokine concentrations with RDW., Results: After adjusting for age, sex, race, cardiovascular disease, and hemoglobin, there was an association between RDW and mortality (Quartile 4 vs Quartile 1: HR 4.04 [1.08-15.07]), with each 1% increment in RDW associated with a 39% increased rate of mortality (HR 1.39 [1.21-1.59]). Remote RDW was also associated with mortality after COVID-19 infection. Among uninfected ambulatory adults without cardiovascular disease, RDW was associated with elevated pro-inflammatory cytokines (TNF-α, IL8, IL6, IL1b), but not regulatory cytokines (TGFb)., Conclusions: Anisocytosis predicts short-term mortality in COVID-19 patients, often predates viral exposure, and may be related to a pro-inflammatory phenotype. Additional study of whether the RDW can assist in the early identification of pending cytokine storm is warranted., Competing Interests: None of the authors have conflicts of interest relevant to the contents of this manuscript., (© Pathogens and Immunity 2020.)

Air pollution is well recognized as a major risk factor for chronic non-communicable diseases and has been estimated to contribute more to global morbidity and mortality than all other known environmental risk factors combined. Although air pollution contains a heterogeneous mixture of gases, the most robust evidence for detrimental effects on health is for fine particulate matter (particles ≤2.5 µm in diameter (PM 2.5 )) and ozone gas and, therefore, these species have been the main focus of environmental health research and regulatory standards. The evidence to date supports a strong link between the risk of cardiovascular events and all-cause mortality with PM 2.5 across a range of exposure levels, including to levels below current regulatory standards, with no 'safe' lower exposure levels at the population level. In this comprehensive Review, the empirical evidence supporting the effects of air pollution on cardiovascular health are examined, potential mechanisms that lead to increased cardiovascular risk are described, and measures to reduce this risk and identify key gaps in our knowledge that could help address the increasing cardiovascular morbidity and mortality associated with air pollution are discussed.

Peak exercise oxygen consumption (pVO 2 ) is an important predictor of prognosis in patients with heart failure (HF). The association between pretransplant pVO 2 and post-transplantation outcomes in HF patients has not been previously studied. We identified adult OHT recipients with available pVO 2 in the United Network for Organ Sharing registry (2000 to 2015). Patients were divided into 3 categories using Weber classification: class B (pVO 2 16 to 20 ml/kg/min), class C (pVO 2 10 to 16 ml/kg/min), and class D (pVO 2 <10 ml/kg/min). Postoperative outcomes (mortality, renal failure, rejection) were compared between the groups. A total of 9,623 patients were included in this analysis; the mean age was 54 ± 11 years, 74% were male, 75% were white and 59% had nonischemic etiology of HF. The mean pVO 2 was 11.7 ± 3.6 ml/kg/min: 1,202 (12.5%) in class B, 6,055 (62.9%) in class C, and 2,366 (24.6%) were in class D. At a median follow-up of 6.1 years, 2,730 (28.4%) died. Post-transplantation survival decreased with decreasing pVO 2 ; 1 and 5-year survival: B (92%, 80%), C (90%, 79%), and D (87%, 75%), p <0.001 by log-rank. After multiple adjustments, patients in class D had significantly higher post-transplantation mortality compared with class C (Hazard Ratio (HR) 1.21 [1.03 to 1.43], p = 0.02). When analyzed as a continuous variable, each 1 ml/kg/min increase in pVO 2 was associated with 2% decrease in mortality during follow-up (adjusted HR 0.98 [0.96 to 0.99], p <0.001). Patients in class D had significantly prolonged (>14 days) hospitalization (adjusted Odds Ratio (OR) 1.42 [1.20 to 1.68], p <0.001) and a trend toward increased need for dialysis (adjusted OR 1.36 [1.00 to 1.84], p = 0.05) compared with patients in class B. In this large cohort, lower pretransplant pVO 2 was associated with greater mortality and morbidity after OHT. These results suggest that earlier transplantation might improve post-transplantation outcomes in advanced HF patients., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: CD14 is a membrane glycoprotein primarily expressed by myeloid cells that plays a key role in inflammation. Soluble CD14 (sCD14) levels carry a poor prognosis in chronic heart failure (HF), but whether elevations in sCD14 precede HF is unknown. We tested the hypothesis that sCD14 is associated with HF incidence and its subtypes independent of major inflammatory biomarkers among older adults., Methods and Results: We included participants in the Cardiovascular Health Study without preexisting HF and available baseline sCD14. We evaluated the associations of sCD14, high-sensitivity C-reactive protein (hsCRP), interleukin (IL)-6, and white blood cell count (WBC) with incident HF and subtypes using Cox regression. Among 5217 participants, 1878 had incident HF over 13.6 years (609 classifiable as HF with preserved ejection fraction [HFpEF] and 419 as HF with reduced ejection fraction [HFrEF]). After adjusting for clinical and laboratory covariates, sCD14 was significantly associated with incident HF (hazard ratio [HR]: 1.56 per doubling, 95% confidence interval [CI]: 1.29-1.89), an association that was numerically stronger than for hsCRP (HR per doubling: 1.10, 95% CI: 1.06-1.15), IL-6 (HR: 1.18, 95% CI: 1.10-1.25), and WBC (HR: 1.24, 95% CI: 1.09-1.42), and that remained significant after adjustment for the other markers of inflammation. This association for sCD14 was observed with HFpEF (HR: 1.50, 95% CI: 1.07-2.10) but not HFrEF (HR: 0.99, 95% CI: 0.67-1.49)., Conclusions: Plasma sCD14 was associated with incident HF independently and numerically more strongly than other major inflammatory markers. This association was only observed with HFpEF in the subset with classifiable HF subtypes. Pending replication, these findings have potentially important therapeutic implications., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Cardiogenic shock is associated with significant mortality, morbidity, and healthcare cost. Utilization of extracorporeal membrane oxygenation in cardiogenic shock has increased in the United States. We sought to identify the rates and predictors of hospital readmissions in patients with cardiogenic shock after weaning from extracorporeal membrane oxygenation., Methods: Using the 2016 Nationwide Readmission Database, we identified all patients (⩾18 years) with cardiogenic shock (ICD-10 CM R57.0) that have been implanted with extracorporeal membrane oxygenation (ICD-10-PSC of 5A15223) and were discharged alive (January-November 2016). We explored the rates, causes, and predictors of all-cause readmissions within 30 days., Results: Out of 69,040 admissions with cardiogenic shock, 1641 (2.4%) underwent extracorporeal membrane oxygenation (581 were implanted during or after cardiac surgery). A total of 734 (44.7%) patients of all extracorporeal membrane oxygenations survived to discharge, and 661 were available for analysis. Out of those, 158 (23.9%) were readmitted within 30 days of discharge. More than 50% of these readmissions happened within the first 11 days. Out of 158 patients who were readmitted, 12 (7.4%) died during the readmission hospitalization. Leading causes of readmission were cardiovascular (31.6%) (heart failure: 24.1%, arrhythmia: 20.6%, neurovascular: 10.3%, hypertension: 10.3%, and endocarditis: 6.8%), followed by complications of medical/device care (17.7%), infection (11.3%), and gastrointestinal/liver (10.1%) complications. Factors associated with readmissions include the following: discharge to skilled nursing facility or with home healthcare (odds ratio: 2.10; 95% confidence interval: 1.18-3.74), durable ventricular assisted device implantation, asthma, and chronic liver disease., Conclusion: Patients with cardiogenic shock who underwent extracorporeal membrane oxygenation had a readmission rate. Identifying patients at high risk of readmissions might help improve outcomes.

Patients with chronic kidney disease (CKD) are at increased risk for peripheral arterial disease (PAD). A novel biomarker to accurately and reliably predict new onset PAD in high risk patients is needed. High sensitivity troponin (HsTP) is a new assay which allows detection of very low troponin levels with high precision. We sought to explore the association between HsTP and risk of PAD in CKD. The Chronic Renal Insufficiency Cohort (CRIC) is a prospective cohort of 3,939 individuals with mild to moderate CKD using age related criteria for glomerular filtration rate. High sensitivity troponin T was measured at study enrollment. Patients with previous history of PAD or coronary artery disease were excluded. Patients were followed for new-onset adjudicated PAD, and the association between HsTP and incident PAD was examined. A total of 2,909 participants free of PAD and coronary artery disease at enrollment were included in this analysis. Over a mean follow up 7.4 years [interquartile ranges 5.8 to 8.5] years, 79 (2.7%) patients developed PAD. The 3-, 6-, and 9-year incidence of PAD was 1.00%, 2.03%, and 2.72%, respectively. At 9 years, the cumulative rates of PAD increased with HsTP (Quartile 1: 0.3%, Quartile 2: 2.4%, Quartile 3: 3.7%, Quartile 4: 10.7%; p <0.001). After adjusting for clinical risk factors of PAD, patients in the third quartile (Hazards ratio 5.89, 95% confidence interval: 1.31 to 26.47, p = 0.021) and fourth quartile of HsTP (Hazards ratio 10.24, 95% confidence interval 2.23 to 47.08, p = 0.003) had higher risk of PAD compared with lowest quartile of HsTP. HsTP had good discrimination of PAD at 3 years (area under the curve [AUC] 0.76), 6 years (AUC 0.79) and 9 years (AUC 0.80). Addition of HsTP to Framingham risk score improved model discrimination of PAD. In conclusion, in patients with mild-moderate CKD, HsTP levels are associated with and predictive of risk of incident PAD. This association remains significant despite adjustment for traditional PAD risk factors and chronic kidney disease., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Objective: To assess the association between serum bicarbonate concentration and cause-specific mortality in the US general population., Methods: A total of 31,195 individuals enrolled in the National Health and Nutrition Examination Survey between 1999 and 2010 were followed for a median 6.7 (interquartile range, 3.7-9.8) years. Cause-specific mortality was defined as cardiovascular, malignancy, and noncardiovascular/nonmalignancy causes. Cox proportional hazards adjusted for demographics, comorbidities, medications, and renal function were used to test the association between baseline serum bicarbonate and the outcomes of interest., Results: Of the 2798 participants who died, 722 had a cardiovascular- and 620 had a malignancy-related death. Compared with participants with serum bicarbonate 22 to 26 mEq/L, those with a level below 22 mEq/L had an increased hazard of all-cause and malignancy-related mortality (hazard ratio [HR], 1.54; 95% CI, 1.30-1.83; and HR, 1.46; 95% CI 1.00-2.13, respectively). The hazard for cardiovascular mortality was increased by 8% with each 1 mEq/L increase in serum bicarbonate above 26 mEq/L (HR, 1.08; 95% CI, 1.01-1.15). The findings were consistent in participants with or without chronic kidney disease, with no significant interactions observed., Conclusion: In a large cohort of US adults, serum bicarbonate concentration level below 22 mEq/L was associated with malignancy-related mortality, whereas a concentration above 26 mEq/L was associated with cardiovascular mortality. Further studies to evaluate potential mechanisms for the differences in cause-specific mortality are warranted., (Copyright © 2019 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.)

Background: Heart transplant recipients are at high risk for mortality, with traditional risk scores performing modestly in predicting post-transplant survival, underscoring the importance of as yet unidentified factors in determining prognosis. In this analysis, the association between PM 2.5 exposure levels and survival after heart transplantation were investigated., Objectives: This study sought to study the association between PM 2.5 exposure and mortality following heart transplantation., Methods: On the basis of the zip code of residence, mortality data in patients who underwent heart transplantation (2004 to 2015) in the United Network for Organ Sharing (UNOS) database were linked with validated estimates of fine particulate matter concentrations (particles with diameter <2.5 μm [PM 2.5 ]; 1 × 1-km grids) for each calendar year during which a UNOS cardiac transplant recipient was at risk for death. Cox proportional hazard models were used to estimate the relationship between exposure and overall mortality adjusting for recipient, donor, and neighborhood variables., Results: A total of 21,800 patients with 86,713 patient-years of follow-up was included. Mean age at transplantation was 52.6 ± 12.6 years, 75% were male, 69% were white, and 39% had ischemic etiology of heart failure. Mean annual exposure to PM 2.5 was 10.6 ± 2.3 μg/m 3 . At a median follow-up of 4.8 (95% confidence interval: 2.0 to 7.8) years, 5,208 patients (23.9%) had died. The estimated mortality hazard ratio, per 10 μg/m 3 increment increase in annual PM 2.5 exposure was 1.43 (95% confidence interval: 1.21 to 1.49). After adjusting for 30 recipient, donor, and neighborhood variables, the estimated mortality hazard ratio per 10 μg/m 3 increment in annual exposure to PM 2.5 was 1.26 (95% confidence interval: 1.11 to 1.43) relative increase in hazard of mortality. This association was consistent across subgroups., Conclusions: This study provides evidence linking air pollution with mortality after heart transplantation. These results suggest an important influence of a key environmental factor in outcomes following heart transplantation, and supports the need for further studies in this population., (Copyright © 2019. Published by Elsevier Inc.)

Importance: Immune dysregulation can increase the risk of infection, malignant neoplasms, and cardiovascular disease, but improved methods are needed to identify and quantify immunologic hazard in the general population., Objective: To determine whether lymphopenia is associated with reduced survival in outpatients., Design, Setting, and Participants: This retrospective cohort study of the National Health and Nutrition Examination Survey (NHANES) included participants enrolled from January 1, 1999, to December 31, 2010, a large outpatient sample representative of the US adult population. Associations were evaluated between lymphopenia and other immunohematologic (IH) markers, clinical features, and survival during 12 years of follow-up, completed on December 31, 2011. Spearman correlations, Cox proportional hazards regression models, and Kaplan-Meier curves were used in univariable and multivariable models, allowing for nonlinear associations with bivariate cubic polynomials. Data were analyzed from September 1, 2018, through July 24, 2019., Exposures: Absolute lymphocyte counts (ALC), red blood cell distribution width (RDW), and C-reactive protein (CRP) level., Main Outcomes and Measures: All-cause survival., Results: Among the 31 178 participants, the median (interquartile range) age at baseline was 45 (30-63) years, 16 093 (51.6%) were women, 16 260 (52.2%) were nonwhite, and overall 12-year rate of survival was 82.8%. Relative lymphopenia (≤1500/μL) and severe lymphopenia (≤1000/μL) were observed in 20.1% and 3.0%, respectively, of this general population and were associated with increased risk of mortality (age- and sex-adjusted hazard ratios [HRs], 1.3 [95% CI, 1.2-1.4] and 1.8 [95% CI, 1.6-2.1], respectively) due to cardiovascular and noncardiovascular causes. Lymphopenia was also associated with worse survival in multivariable models, including traditional clinical risk factors, and this risk intensified when accompanied by bone marrow dysregulation (elevated RDW) and/or inflammation (elevated CRP level). Ten-year mortality ranged from 3.8% to 62.1% based on lymphopenia status, tertile of CRP level, and tertile of RDW. A high-risk IH profile was nearly twice as common as type 2 diabetes (19.3% and 10.0% of participants, respectively) and associated with a 3-fold risk of mortality (HR, 3.2; 95% CI, 2.6-4.0). Individuals aged 70 to 79 years with low IH risk had a better 10-year survival (74.1%) than those who were a decade younger with a high-risk IH profile (68.9%)., Conclusions and Relevance: These findings suggest that lymphopenia is associated with reduced survival independently of and additive to traditional risk factors, especially when accompanied by altered erythropoiesis and/or heightened inflammation. Immune risk may be analyzed as a multidimensional entity derived from routine tests, facilitating precision medicine and population health interventions.

Human Immunodeficiency Infection (HIV) is associated with increased risk for heart failure (HF). Outcomes of HF in patients living with HIV (PWH) are poorly understood. We sought to identify the risk of HF rehospitalizations (30 and 90 days) among PWH versus uninfected controls admitted with HF. Using the 2016 Nationwide Readmissions Database, we identified all patients (≥18 years) who were discharged alive with a primary diagnosis of HF (ICD10 I50.xx) with or without secondary diagnosis of HIV (ICD 10 Z21, B20, O98.7, or B97.35). Propensity score matching was used to match PWH with controls (1:1) based on 45 patient characteristics (demographics, hospitalization characteristics, and co-morbidities). Cox regression models were used to compare rates of HF rehospitalization (primary ICD10 I50.xx) within 30 and 90 days after discharge from the index HF hospitalization. A total of 312,264 patients with HF were identified, of whom 1,112 (0.4%) had HIV. After propensity score matching, 1,112 PWH were matched with 1,112 uninfected controls. The standard mean difference for each variable was <10% postmatching. Overall, HF rehospitalization rates were 11.2% and 19.2% at 30 and 90 days, respectively. The 2 groups (PWH and controls) were not different statistically with respect to all 45 covariates. Compared with controls, PWH had a higher risk of HF rehospitalization within 30 days (hazard ratio 1.45, 95% confidence interval 1.13 to 1.87, p = 0.004) and 90 days (hazard ratio 1.41, 95% CI 1.16 to 1.71, p <0.001). This risk was consistent across age groups, gender, types of HF, presence or absence of coronary artery disease, or chronic kidney disease. In conclusion, in this propensity-matched national cohort of patients admitted with HF, patients with HIV had increased risk of HF rehospitalizations compared with uninfected controls at 30 days and 90 days., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: Outcomes of patients with amyloid cardiomyopathy (ACM) undergoing heart transplantation have been reported, but there are scant data concerning the waitlist mortality (WLM) of these patients., Aim: The aim of this study was to investigate whether patients with ACM have higher waitlist mortality compared to those with other types of cardiomyopathies., Methods: We queried the United Network for Organ Sharing registry for all patients (age ≥ 18 years) listed for heart transplantation between 2008 and 2015. We compared patients with ACM to those with dilated cardiomyopathy (DCM) or idiopathic restrictive cardiomyopathy (RCM) for WLM and waitlist mortality or delisting for deterioration (WLM/D). We identified 306 patients with ACM, 183 with RCM and 8416 with DCM. Patients with ACM were older (ACM 61 vs RCM 49 vs DCM 51 years, P  <  .001), were more likely to be male (82% vs 60% vs 73%, P  <  .001) but less likely to be listed as status 1A (16% vs 18% vs 23%, P< .001). After adjusting for baseline characteristics, ACM was associated with increased risk of mortality and mortality/delisting compared with DCM (HR 2.03 [1.36-3.04], P = .001 for WLM; HR 2.07 [1.55-2.78], P < .001 for WLM/D) but not with other RCMs (HR 1.28 [0.54-3.02], P = .58 for WLM; HR 0.97 [0.56-1.69], P = .91 for WLM/D)., Results: Patients with ACM are listed with lower acuity and have higher waitlist mortality compared with those with dilated cardiomyopathies. Further studies are needed to identify whether special prioritization should be considered for patients with ACM listed for heart transplantation., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Diabetes mellitus (DM) is associated with increased mortality in advanced heart failure and in patients undergoing cardiac surgery. However, its impact on outcomes in patients supported with left ventricular assist devices (LVAD) is not well established. We queried the United Network for Organ Sharing (UNOS) for all adults listed for heart transplantation and bridged with continuous-flow LVAD in the United States from 2000 to 2015. We compared the pre- and post-transplant mortality of patients with and without DM. Unadjusted and adjusted time-event analyses were performed. A total of 4,978 patients were included in this analysis, of whom 33% had DM. Mean age was 53 ± 12 years, 79% were male, and 65% were Caucasian. Compared with those without, patients with DM were older (age 52 vs. 57 years; p < 0.001), more likely to be male (78% vs. 82%; p = 0.007), smokers (52% vs. 57%; p = 0.011), obese (mean body mass index [BMI] 28 vs. 30; p < 0.00), and have ischemic cardiomyopathy (37% vs. 53%; p < 0.001). Diabetes mellitus was not associated with increased wait-list mortality (adjusted hazard ratio [HR]: 1.16 [0.88-1.53]; p = 0.30), or wait-list mortality/delisting (HR: 1.17 [0.97-1.41]; p = 0.11). Among patients who underwent transplantation, DM was associated with increased adjusted overall mortality (HR: 1.23 [1.002-1.52]; p = 0.048). One-third of patients bridged-to-transplantation with LVAD in the United States have DM. While it does not increase wait-list mortality or delisting, DM is associated with decreased post-transplantation survival.