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Background and Aims: Peripheral artery disease (PAD) has not only been associated with recurrent hospitalization for acute decompensated heart failure (ADHF) but is also associated with chronic kidney disease (CKD), a known risk factor for worse heart failure outcomes. The interaction of CKD with PAD in post-discharge ADHF outcomes is not well known., Methods: Since 2005, hospitalizations for ADHF were sampled from 4 US regions by the Atherosclerosis Risk in Communities (ARIC) study and classified by physician review. We examined the adjusted association of PAD with 1-year ADHF readmissions, in patients with and without CKD (defined by glomerular filtration rate [GFR] ≤60 mL/min/1.73 m 2 [stage 3a or worse])., Results: From 2005 to 2018, there were 1049 index hospitalizations for patients with ADHF (mean age 77 years, 66 % white) with creatinine data, who were discharged alive. Of these, 155 (15 %) had PAD and 66 % had CKD. In comparison to those without PAD, patients with PAD had more comorbid conditions and higher 1-year ADHF readmission rates, irrespective of CKD status. After adjustment, PAD was associated with a greater risk of 1-year ADHF readmissions, both for patients with concomitant CKD (HR, 1.70; 95 % CI: 1.29-2.24) and those without CKD (HR, 1.97; 95 % CI: 1.14-3.40); p-interaction = 0.8., Conclusion: Among patients hospitalized with ADHF, those with concurrent PAD have more prevalent cardiovascular comorbidities and higher likelihood of 1-year ADHF readmission, irrespective of CKD status. Integrating a more holistic approach in management of patients with concomitant heart failure, PAD and CKD may be an important strategy to improve the prognosis in this vulnerable population., Competing Interests: Declaration of competing interest Dr. Bhatt discloses the following relationships - Advisory Board: Angiowave, Bayer, Boehringer Ingelheim, CellProthera, Cereno Scientific, Elsevier Practice Update Cardiology, High Enroll, Janssen, Level Ex, McKinsey, Medscape Cardiology, Merck, MyoKardia, NirvaMed, Novo Nordisk, PhaseBio, PLx Pharma, Stasys; Board of Directors: American Heart Association New York City, Angiowave (stock options), Bristol Myers Squibb (stock), DRS.LINQ (stock options), High Enroll (stock); Consultant: Broadview Ventures, Hims, SFJ, Youngene; Data Monitoring Committees: Acesion Pharma, Assistance Publique-Hôpitaux de Paris, Baim Institute for Clinical Research (formerly Harvard Clinical Research Institute, for the PORTICO trial, funded by St. Jude Medical, now Abbott), Boston Scientific (Chair, PEITHO trial), Cleveland Clinic, Contego Medical (Chair, PERFORMANCE 2), Duke Clinical Research Institute, Mayo Clinic, Mount Sinai School of Medicine (for the ENVISAGE trial, funded by Daiichi Sankyo; for the ABILITY-DM trial, funded by Concept Medical; for ALLAY-HF, funded by Alleviant Medical), Novartis, Population Health Research Institute; Rutgers University (for the NIH-funded MINT Trial); Honoraria: American College of Cardiology (Senior Associate Editor, Clinical Trials and News, ACC.org; Chair, ACC Accreditation Oversight Committee), Arnold and Porter law firm (work related to Sanofi/Bristol-Myers Squibb clopidogrel litigation), Baim Institute for Clinical Research (formerly Harvard Clinical Research Institute; RE-DUAL PCI clinical trial steering committee funded by Boehringer Ingelheim; AEGIS-II executive committee funded by CSL Behring), Belvoir Publications (Editor in Chief, Harvard Heart Letter), Canadian Medical and Surgical Knowledge Translation Research Group (clinical trial steering committees), CSL Behring (AHA lecture), Cowen and Company, Duke Clinical Research Institute (clinical trial steering committees, including for the PRONOUNCE trial, funded by Ferring Pharmaceuticals), HMP Global (Editor in Chief, Journal of Invasive Cardiology), Journal of the American College of Cardiology (Guest Editor; Associate Editor), K2P (Co-Chair, interdisciplinary curriculum), Level Ex, Medtelligence/ReachMD (CME steering committees), MJH Life Sciences, Oakstone CME (Course Director, Comprehensive Review of Interventional Cardiology), Piper Sandler, Population Health Research Institute (for the COMPASS operations committee, publications committee, steering committee, and USA national co-leader, funded by Bayer), WebMD (CME steering committees), Wiley (steering committee); Other: Clinical Cardiology (Deputy Editor); Patent: Sotagliflozin (named on a patent for sotagliflozin assigned to Brigham and Women's Hospital who assigned to Lexicon; neither I nor Brigham and Women's Hospital receive any income from this patent); Research Funding: Abbott, Acesion Pharma, Afimmune, Aker Biomarine, Alnylam, Amarin, Amgen, AstraZeneca, Bayer, Beren, Boehringer Ingelheim, Boston Scientific, Bristol-Myers Squibb, Cardax, CellProthera, Cereno Scientific, Chiesi, CinCor, Cleerly, CSL Behring, Eisai, Ethicon, Faraday Pharmaceuticals, Ferring Pharmaceuticals, Forest Laboratories, Fractyl, Garmin, HLS Therapeutics, Idorsia, Ironwood, Ischemix, Janssen, Javelin, Lexicon, Lilly, Medtronic, Merck, Moderna, MyoKardia, NirvaMed, Novartis, Novo Nordisk, Otsuka, Owkin, Pfizer, PhaseBio, PLx Pharma, Recardio, Regeneron, Reid Hoffman Foundation, Roche, Sanofi, Stasys, Synaptic, The Medicines Company, Youngene, 89Bio; Royalties: Elsevier (Editor, Braunwald’s Heart Disease); Site Co-Investigator: Abbott, Biotronik, Boston Scientific, CSI, Endotronix, St. Jude Medical (now Abbott), Philips, SpectraWAVE, Svelte, Vascular Solutions; Trustee: American College of Cardiology; Unfunded Research: FlowCo.Dr. Robert J. Mentz received research support and honoraria from Abbott, American Regent, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Boston Scientific, Cytokinetics, Fast BioMedical, Gilead, Innolife, Eli Lilly, Medtronic, Medable, Merck, Novartis, Novo Nordisk, Pfizer, Pharmacosmos, Relypsa, Respicardia, Roche, Rocket Pharmaceuticals, Sanofi, Verily, Vifor, Windtree Therapeutics, and Zoll. Dr. Grodin reports consulting fees from Pfizer, Eidos/BridgeBio, Alnylam, Alexion, Intellia, and Astra-Zeneca. Dr. Matsushita received research funding from NHLBI (R01HL146132) and Resolve to Save Lives and personal fee from Fukuda Denshi, Kowa Company, and RhythmX AI outside of the submitted work. Dr. Vaduganathan has received research grant support, served on advisory boards, or had speaker engagements with American Regent, Amgen, AstraZeneca, Bayer AG, Baxter Healthcare, BMS, Boehringer Ingelheim, Chiesi, Cytokinetics, Lexicon Pharmaceuticals, Merck, Novartis, Novo Nordisk, Pharmacosmos, Relypsa, Roche Diagnostics, Sanofi, and Tricog Health, and participates on clinical trial committees for studies sponsored by AstraZeneca, Galmed, Novartis, Bayer AG, Occlutech, and Impulse Dynamics. The other authors report no disclosures., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Intracranial vessel tortuosity is a key component of dolichoectasia and has been associated with atherosclerosis and adverse neurologic outcomes. However, the evaluation of tortuosity is mainly a descriptive assessment., Purpose: To compare the performance of three automated tortuosity metrics (angle metric [AM], distance metric [DM], and distance-to-axis metric [DTA]) for detection of dolichoectasia and presence of segment-specific plaques., Study Type: Observational, cross-sectional metric assessment., Population: 1899 adults from the general population; mean age = 76 years, female = 59%, and black = 29%., Field Strength/sequence: 3-T, three-dimensional (3D) time-of-flight MRA and 3D vessel wall MRI., Assessment: Tortuosity metrics and mean luminal area were quantified for designated segments of the internal carotid artery, middle cerebral artery, anterior cerebral artery, posterior cerebral artery, vertebral artery, and entire length of basilar artery (BA). Qualitative interpretations of BA dolichoectasia were assessed based on Smoker's visual criteria., Statistical Tests: Descriptive statistics (2-sample t-tests, Pearson chi-square tests) for group comparisons. Receiver operating characteristics area under the curve (AUC) for detection of BA dolichoectasia or segment-specific plaque. Model inputs included 1) tortuosity metrics, 2) mean luminal area, and 3) demographics (age, race, and sex)., Results: Qualitative dolichoectasia was identified in 336 (18%) participants, and atherosclerotic plaques were detected in 192 (10%) participants. AM-, DM-, and DTA-calculated tortuosity were good individual discriminators of basilar dolichoectasia (AUCs: 0.76, 0.74, and 0.75, respectively), with model performance improving with the mean lumen area: (AUCs: 0.88, 0.87, and 0.87, respectively). Combined characteristics (tortuosity and mean luminal area) identified plaques with better performance in the anterior (AUCs ranging from 0.66 to 0.78) than posterior (AUCs ranging from 0.54 to 0.65) circulation, with all models improving by the addition of demographics (AUCs ranging from 0.62 to 0.84)., Data Conclusion: Quantitative vessel tortuosity metrics yield good diagnostic accuracy for the detection of dolichoectasia., Level of Evidence: 1 TECHNICAL EFFICACY STAGE: 2., (© 2023 International Society for Magnetic Resonance in Medicine.)

Objective: The gram-negative bacterial cell wall component endotoxin (lipopolysaccharide, LPS) is a key component of particulate matter (PM). PM exposure is associated with cardiovascular morbidity and mortality. However, the contribution of individual components of PM to acute and chronic cardiovascular measures is not clear. This study examines whether systemic inflammation induced by LPS inhalation causes acute changes in cardiovascular physiology measures., Materials and Methods: In this double blinded, placebo-controlled crossover study, fifteen adult volunteers underwent inhalation exposure to 20,000 EU Clinical Center Reference Endotoxin (CCRE). Peripheral blood and induced sputum neutrophils were obtained at baseline and six hours post-exposure. Blood pressure, measures of left ventricular function (ejection fraction (LVEF) and global longitudinal strain (LVGLS)), and indices of endothelial function (flow mediated dilation (FMD) and velocity time integral during hyperemia (VTIhyp)) were measured before and after treatment. Wilcoxon sign-rank tests and linear mixed models were used for statistical analysis., Results: In comparison with normal saline, LPS inhalation resulted in significant increases in peripheral blood and sputum neutrophils but was not associated with significant alterations in blood pressure, LVGLS, LVEF, FMD, or VTIhyp., Discussion and Conclusions: In healthy adults, systemic inflammation after LPS inhalation was not associated with acute changes in cardiovascular physiology. Larger studies are needed to investigate the effects of other PM components on inflammation induced cardiovascular dysfunction.

Background Prevention strategies targeting standard modifiable cardiovascular risk factors (SMuRFs; diabetes, hypertension, smoking, hypercholesterolemia) are critical to improving cardiovascular disease outcomes. However, acute myocardial infarction (AMI) among individuals who lack 1 or more SMuRFs is not uncommon. Moreover, the clinical characteristics and prognosis of SMuRFless individuals are not well characterized. Methods and Results We analyzed AMI hospitalizations from 2000 to 2014 captured by the ARIC (Atherosclerosis Risk in Community) study community surveillance. AMI was classified by physician review using a validated algorithm. Clinical data, medications, and procedures were abstracted from the medical record. Main study outcomes included short- and long-term mortality within 28 days and 1 year of AMI hospitalization. Between 2000 and 2014, a total of 742 (3.6%) of 20 569 patients with AMI were identified with no documented SMuRFs. Patients without SMuRFs were less likely to receive aspirin, nonaspirin antiplatelet therapy, or beta blockers and less often underwent angiography and revascularization. Compared with those with one or more SMuRFs, patients without SMuRFs had significantly higher 28-day (odds ratio, 3.23 [95% CI, 1.78-5.88]) and 1-year (hazard ratio, 2.09 [95% CI, 1.29-3.37]) adjusted mortality. When examined across 5-year intervals from 2000 to 2014, the incidence of 28-day mortality significantly increased for patients without SMuRFs (7% to 15% to 27%), whereas it declined for those with 1 or more SMuRFs (7% to 5% to 5%). Conclusions Individuals without SMuRFs presenting with AMI have an increased risk of all-cause mortality with an overall lower prescription rate for guideline-directed medical therapy. These findings highlight the need for evidence-based pharmacotherapy during hospitalization and the need to discover new markers and mechanisms for early risk identification in this population.

A significant risk factor for ischemic stroke is carotid atherosclerotic plaque that is susceptible to rupture, with rupture potential conveyed by plaque morphology. Human carotid plaque composition and structure have been delineated noninvasively and in vivo by evaluating log(VoA), a parameter derived as the decadic log of the second time derivative of displacement induced by an acoustic radiation force impulse (ARFI). In prior work, ARFI-induced displacement was measured using conventional focused tracking; however, this requires a long data acquisition period, thereby reducing framerate. We herein evaluate if ARFI log(VoA) framerate can be increased without a reduction in plaque imaging performance using plane wave tracking instead. In silico, both focused- and plane wave-tracked log(VoA) decreased with increasing echobrightness, quantified as signal-to-noise ratio (SNR), but did not vary with material elasticity for SNRs below 40 dB. For SNRs of 40-60 dB, both focused- and plane wave-tracked log(VoA) varied with SNR and material elasticity. Above 60 dB SNR, both focused- and plane wave-tracked log(VoA) varied with material elasticity alone. This suggests that log(VoA) discriminates features according to a combination of their echobrightness and mechanical property. Further, while both focused- and plane-wave tracked log(VoA) values were artifactually inflated by mechanical reflections at inclusion boundaries, plane wave-tracked log(VoA) was more strongly impacted by off-axis scattering. Applied to three excised human cadaveric carotid plaques with spatially aligned histological validation, both log(VoA) methods detected regions of lipid, collagen, and calcium (CAL) deposits. These findings support that plane wave tracking performs comparably to focused tracking for log(VoA) imaging and that plane wave-tracked log(VoA) is a viable approach to discriminating clinically relevant atherosclerotic plaque features at a 30-fold higher framerate than by focused tracking.

Background Diabetes is associated with increased risk of acute myocardial infarction (AMI). The demographic trends, clinical presentation, management, and outcomes of patients with diabetes who are hospitalized with AMI have not been recently reported. Methods and Results The ARIC (Atherosclerosis Risk in Communities) study conducted hospital surveillance of AMI in 4 US communities. AMI was classified by physician review using a validated algorithm. Medications and procedures were abstracted from the medical record. From 2000 to 2014, 21 094 weighted hospitalizations for AMI were sampled. The prevalence of diabetes steadily increased, from 35% to 41% to 43% ( P -trend<0.0001) across 2000 to 2004, 2005 to 2009, and 2010 to 2014, respectively. Patients with diabetes were older (61 versus 59 years of age), more often Black (44% versus 31%), and more commonly women (42% versus 34%). The burden of cardiovascular comorbidities was higher with diabetes and increased temporally. Patients with diabetes less often presented with ST-segment elevation (9% versus 17%) or acute chest pain (72% versus 80%), and had higher mean GRACE (Global Registry of Acute Coronary Syndrome) score (123 versus 109), Thrombolysis in Myocardial Ischemia (TIMI) score (4.3 versus 4.0), and Killip class (1.9 versus 1.5). Patients with diabetes had a lower adjusted probability of receiving aspirin (relative probability, 0.95 [95% CI, 0.91-0.99]), nonaspirin antiplatelets (0.93 [95% CI, 0.86-0.99]), coronary angiography (0.85 [95% CI, 0.78-0.92]), and coronary revascularization (0.85 [95% CI, 0.76-0.92]). Diabetes was associated with a 52% higher hazard of all-cause 1-year mortality (hazard ratio, 1.52 [95% CI, 1.23-1.89]). Conclusions Diabetes is associated with higher risk of death in patients hospitalized with AMI, highlighting the need for adherence to evidence-based therapies in this high-risk population.

Background: Few studies characterize the epidemiology and outcomes of aortic stenosis (AS) in acute decompensated heart failure (ADHF). This study investigates the significance of AS in contemporary patients who have experienced an ADHF hospitalization., Methods: The ARIC study (Atherosclerosis Risk in Communities) surveilled ADHF hospitalizations for residents ≥55 years of age in 4 US communities. ADHF cases were stratified by left ventricular ejection fraction (LVEF). Demographic differences in AS burden and the association of varying AS severities with mortality were estimated using multivariable logistic regression., Results: From 2005 through 2014, there were 3597 (weighted n=16 692) ADHF hospitalizations of which 48.6% had an LVEF <50% and 51.4% an LVEF ≥50%. AS prevalence was 12.1% and 18.7% in those with an LVEF <50% and ≥50%, respectively. AS was less likely in Black than White patients regardless of LVEF: LVEF <50% (odds ratio [OR], 0.34 [95% CI, 0.28-0.42]); LVEF ≥50% (OR, 0.51 [95% CI, 0.44-0.59]). Higher AS severity was independently associated with 1-year mortality in both LVEF subgroups: LVEF <50% (OR, 1.16 [95% CI, 1.04-1.28]); LVEF ≥50% (OR, 1.40 [95% CI, 1.28-1.54]). Sensitivity analyses excluding severe AS patients detected that mild/moderate AS was independently associated with 1-year mortality in both LVEF subgroups: LVEF <50% (OR, 1.23 [95% CI, 1.02-1.47]); LVEF ≥50% (OR, 1.31 [95% CI, 1.14-1.51])., Conclusions: Among patients who have experienced an ADHF hospitalization, AS is prevalent and portends poor mortality outcomes. Notably, mild/moderate AS is independently associated with 1-year mortality in this high-risk population.

Background: Neighborhood socioeconomic status (SES) is associated with worse health outcomes, yet its relationship with in-hospital heart failure (HF) outcomes and quality metrics are underexplored. We examined the association between socioeconomic neighborhood disadvantage and in-hospital HF outcomes for patients from diverse neighborhoods in the Get With The Guidelines-Heart Failure registry., Methods: SES-disadvantage scores were derived from geocoded US census data using a validated algorithm, which incorporated household income, home value, rent, education, and employment. We examined the association between SES-disadvantage quintiles with all-cause in-hospital mortality, adjusting for demographics and comorbidities., Results: Of 593 053 patients hospitalized for HF between 2017 and 2020, 321 314 (54%) had residential ZIP Codes recorded. Patients from the most compared with least disadvantaged neighborhoods were younger (mean age 67 versus 76 years), more often Black (42% versus 9%) or Hispanic (14% versus 5%), and had higher comorbidity burden. Demographic-adjusted length of stay increased by ≈1.5 hours with each increment in worsening SES-disadvantage quintiles. Adjusted-mortality odds ratios increased with worsening SES-disadvantage quintiles ( P trend =0.003), and was 28% higher (adjusted OR=1.28 [1.12-1.48]) for the most compared with least disadvantaged neighborhood groups., Conclusions: Patients hospitalized for HF from disadvantaged neighborhoods were younger and more often Black or Hispanic. SES disadvantage was independently associated with higher in-hospital mortality. Further research is needed to characterize care delivery patterns in disadvantaged neighborhoods and to address social determinants of health among patients hospitalized for HF. REGISTRATION: URL: https://www., Clinicaltrials: gov; Unique identifier: NCT02693509.

Aims: We aimed to investigate the impact of obstructive coronary artery disease (CAD) in patients with acute decompensated heart failure (ADHF), and examine potential differences in prognostic utility for heart failure with reduced (HFrEF) versus preserved ejection fraction (HFpEF)., Methods and Results: The Atherosclerosis Risk in Communities study conducted hospital surveillance of ADHF from 2005 to 2014. Obstructive CAD was defined as ≥50% or ≥75% stenosis, respectively, for the left main and other major epicardial arteries. Adjusted associations between obstructive CAD and 30-, 60-, and 90-day mortality were analysed. A total of 934 (4146 weighted) patients admitted with ADHF (mean age 72 years, 46% women, 30% Black, 30% HFpEF) had available angiography (61% performed in hospital). Obstructive CAD was more prevalent with HFrEF than HFpEF, whether at the left main (15% vs. 11%), left anterior descending (LAD) (48% vs. 30%), left circumflex (37% vs. 32%), right coronary (42% vs. 32%), or multiple coronary arteries (45% vs. 33%). In-hospital revascularization was performed in 25% and 22% of patients with HFrEF and HFpEF, respectively. Obstructive CAD was associated with higher adjusted mortality, particularly with left main or LAD involvement, and had a more pronounced association with 90-day mortality in HFrEF (odds ratio [OR] 2.77; 95% confidence interval [CI] 1.53-5.02) than HFpEF (OR 0.94; 95% CI 0.36-2.41) (p-interaction = 0.05)., Conclusion: Patients hospitalized with ADHF and coexisting obstructive CAD have higher short-term mortality, warranting the need for effective interventions and secondary prevention., (© 2022 European Society of Cardiology.)

Background: Polyvascular disease is associated with increased mortality rates and decreased quality of life. Whether its prevalence or associated outcomes differ for patients hospitalized with heart failure with reduced vs preserved ejection fraction (HFrEF vs HFpEF, respectively) is uncertain., Methods: The Atherosclerosis Risk in Communities (ARIC) study conducted hospital surveillance of acute decompensated heart failure (ADHF) from 2005-2014. Polyvascular disease (coexisting disease in ≥ 2 arterial beds) was identified based on the finding of prevalent coronary artery disease, peripheral artery disease or cerebrovascular disease. Mortality risks associated with polyvascular disease were analyzed separately for HFpEF and HFrEF, with adjustment for potential confounders. All analyses were weighted by the inverse of the sampling probability., Results: Of 24,937 weighted (5460 unweighted) hospitalizations due to ADHF (52% female, 32% Black, mean age 75 years), polyvascular disease was prevalent in 22% with HFrEF and in 17% with HFpEF. One-year mortality risks increased sequentially with 0, 1 and ≥ 2 arterial bed involvement, both for patients with HFrEF (29%-32%-38%; P trend = 0.0006) and for those with HFpEF (26%-32%-37%; P trend < 0.0001). After adjustments, polyvascular disease was associated with a 26% higher mortality hazard for patients with HFrEF (HR = 1.26; 95% CI: 1.07-1.50) and a 29% higher hazard for patients with HFpEF (HR = 1.29; 95% CI: 1.03-1.62), with no interaction by HF type (P interaction = 0.9)., Conclusion: Patients hospitalized with ADHF and coexisting polyvascular disease have an increased risk of death, irrespective of HF type. Clinical attention should be directed toward polyvascular disease, with implementation of secondary prevention strategies to improve the prognosis of this high-risk population., Summary: Polyvascular disease is known to be associated with myocardial infarction, stroke or cardiovascular death and is a major risk factor for decreased quality of life. This study sought to evaluate the relationship between polyvascular disease and mortality in patients hospitalized with acute decompensated heart failure (ADHF), and to understand whether the associations differ based on ejection fraction. Patients hospitalized with ADHF and coexisting polyvascular disease had an increased risk of death, irrespective of heart failure type, implying the need for increased clinical attention directed toward polyvascular disease, along with implementation of secondary prevention strategies to improve prognosis., Tweet: Patients hospitalized with acute HF and coexisting polyvascular disease face an increased risk of death, irrespective of HF type., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Cardiac involvement has been noted in COVID-19 infection. However, the relationship between post-recovery COVID-19 and development of de novo heart failure has not been investigated in a large, nationally representative population. We examined post-recovery outcomes of 587,330 patients hospitalized in the United States (257,075 with COVID-19 and 330,255 without), using data from the National COVID Cohort Collaborative study. Patients hospitalized with COVID-19 were older (51 vs. 46 years), more often male (49% vs. 42%), and less often White (61% vs. 69%). Over a median follow up of 367 days, 10,979 incident heart failure events occurred. After adjustments, COVID-19 hospitalization was associated with a 45% higher hazard of incident heart failure (hazard ratio = 1.45; 95% confidence interval: 1.39-1.51), with more pronounced associations among patients who were younger (P-interaction = 0.003), White (P-interaction = 0.005), or who had established cardiovascular disease (P-interaction = 0.005). In conclusion, COVID-19 hospitalization is associated with increased risk of incident heart failure., (© 2022. The Author(s).)

Background: The fourth universal definition of myocardial infarction requires an increase or decrease in cardiac troponin for the classification of non-ST-segment elevation myocardial infarction. We sought to determine whether the characteristics, management, and outcomes of patients admitted with non-ST-segment elevation myocardial infarction differ by the initial biomarker pattern., Methods: We identified patients in the Atherosclerosis Risk in Communities Surveillance Study admitted with chest pain and an initially elevated cardiac troponin I, who presented within 12 hours of symptom onset and were classified with non-ST-segment elevation myocardial infarction. A change in cardiac troponin I required an absolute difference of at least 0.02 ng/mL on the first day of hospitalization, prior to invasive cardiac procedures., Results: A total of 1926 hospitalizations met the inclusion criteria, with increasing cardiac troponin I more commonly observed (78%). Patients with decreasing cardiac troponin I were more often black (45% vs. 35%) and women (54% vs. 40%), and were less likely to receive non-aspirin antiplatelets (44% vs. 63%), lipid-lowering agents (62% vs. 80%), and invasive angiography (38% vs. 64%). Inhospital mortality was 3%, irrespective of the cardiac troponin I pattern. However, patients with decreasing cardiac troponin I had twice the 28-day mortality (12% vs. 5%; P=0.01). Fatalities within 28 days were more often attributable to non-cardiovascular causes in those with decreasing versus increasing cardiac troponin I (75% vs. 38%; P=0.01)., Conclusion: Patients presenting with chest pain and an initially elevated cardiac troponin I which subsequently decreases are less often managed by evidence-based therapies and have greater mortality, primarily driven by non-cardiovascular causes. Whether associations are attributable to type 2 myocardial infarction or a subacute presentation merits further investigation., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2019. For permissions, please email: journals.permissions@oup.com.)

Background: Bedside evaluation of congestion is a mainstay of heart failure (HF) management. Whether detected physical examination signs have changed over time as obesity prevalence has increased in HF populations, or if the associated prognosis differs for HF with reduced or preserved ejection fraction (HFrEF or HFpEF) is uncertain., Methods: From 2005 to 2014, the ARIC study (Atherosclerosis Risk in Communities) conducted adjudicated hospital surveillance of acute decompensated HF. We analyzed trends in physical examination findings, imaging signs, and symptoms related to congestion, both over time and by obesity class, and associated 28-day mortality risks., Results: Of 24 937 weighted hospitalizations for acute decompensated HF (mean age 75 years, 53% women, 32% Black), 47% had HFpEF. The prevalence of obesity increased from 2005 to 2014 for both HF types. With increasing obesity category, detected edema increased, while jugular venous distension decreased, and rales remained stable. Detected edema also increased over time, for both HF types. Associations between 28-day mortality and individual signs and symptoms of congestion were similar for HFpEF and HFrEF; however, the adjusted mortality risk with all 3 (edema, rales, and jugular venous distension) versus <3 physical examination findings was higher for patients with HFpEF (odds ratio, 2.41 [95% CI, 1.53-3.79]) than HFrEF (odds ratio, 1.30 [95% CI, 0.87-1.93]); P for interaction by HF type =0.02., Conclusions: In patients hospitalized with acute decompensated HF, detected physical examination findings differ both temporally and by obesity. Combined findings from the physical examination are more prognostic of 28-day mortality for patients with HFpEF than HFrEF.

An expanding number of therapies are now indicated for comorbidity management in heart failure with preserved ejection fraction (HFpEF). Whether comorbidity burdens differ for patients with HFpEF who are hospitalized for acute decompensated heart failure (ADHF) versus those with chronic stable heart failure (CSHF) who are hospitalized for other causes is uncertain. Since 2005, the Atherosclerosis Risk in Communities (ARIC) study has conducted adjudicated community surveillance of hospitalized heart failure. Hospitalized ADHF and CSHF were sampled identically, using prespecified discharge codes and demographic strata, but were differentiated by signs or symptoms of acute or worsening heart failure upon physician review of the medical record. HFpEF was defined by an ejection fraction ≥50%. All events were weighted by the inverse of the sampling probability for statistical analyses. From 2005 to 2014, 13,706 weighted (2,936 unweighted) hospitalizations (mean age 77 years, 64% women, 29% Black) were sampled among patients with HFpEF and adjudicated ADHF (86%) or CSHF (14%). Comorbidity prevalence was high both for ADHF and CSHF hospitalizations, irrespective of gender. Women hospitalized with ADHF versus CSHF had greater prevalence of hypertension (89% vs 84%) diabetes mellitus (48% vs 39%) and renal disease (85% vs 74%). Echocardiographic features such as left ventricular hypertrophy and valvular abnormalities were more common with ADHF than CSHF, for both genders. However, the 28-day and 1-year mortality risk were comparable for ADHF and CSHF. In conclusion, hospitalized patients with HFpEF have a high comorbidity burden and risk of death, irrespective of the cause of hospitalization., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Aims: Shock index (SI), defined as the ratio of heart rate (HR) to systolic blood pressure (SBP), is easily obtained and predictive of mortality in patients with ST-segment elevation myocardial infarction. However, large-scale evaluations of SI in patients with non-ST-segment elevation myocardial infarction (NSTEMI) are lacking., Methods and Results: Hospitalizations for acute myocardial infarction were sampled from four US areas by the Atherosclerosis Risk in Communities (ARIC) study and classified by physician review. Shock index was derived from the HR and SBP at first presentation and considered high when ≥0.7. From 2000 to 2014, 18 301 weighted hospitalizations for NSTEMI were sampled and had vitals successfully obtained. Of these, 5753 (31%) had high SI (≥0.7). Patients with high SI were more often female (46% vs. 39%) and had more prevalent chronic kidney disease (40% vs. 32%). TIMI (Thrombolysis in Myocardial Infarction) risk scores were similar between the groups (4.3 vs. 4.2), but GRACE (Global Registry of Acute Coronary Syndrome) score was higher with high SI (140 vs. 118). Angiography, revascularization, and guideline-directed medications were less often administered to patients with high SI, and the 28-day mortality was higher (13% vs. 5%). Prediction of 28-day mortality by SI as a continuous measurement [area under the curve (AUC): 0.68] was intermediate to that of the GRACE score (AUC: 0.87) and the TIMI score (AUC: 0.54). After adjustments, patients with high SI had twice the odds of 28-day mortality (odds ratio = 2.02; 95% confidence interval: 1.46-2.80)., Conclusion: The SI is easily obtainable, performs moderately well as a predictor of short-term mortality in patients hospitalized with NSTEMI, and may be useful for risk stratification in emergency settings., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2021. For permissions, please email: journals.permissions@oup.com.)

Aims/hypothesis: Type 2 diabetes is a heterogeneous disease process with variable trajectories of CVD risk. We aimed to evaluate four phenomapping strategies and their ability to stratify CVD risk in individuals with type 2 diabetes and to identify subgroups who may benefit from specific therapies., Methods: Participants with type 2 diabetes and free of baseline CVD in the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial were included in this study (N = 6466). Clustering using Gaussian mixture models, latent class analysis, finite mixture models (FMMs) and principal component analysis was compared. Clustering variables included demographics, medical and social history, laboratory values and diabetes complications. The interaction between the phenogroup and intensive glycaemic, combination lipid and intensive BP therapy for the risk of the primary outcome (composite of fatal myocardial infarction, non-fatal myocardial infarction or unstable angina) was evaluated using adjusted Cox models. The phenomapping strategies were independently assessed in an external validation cohort (Look Action for Health in Diabetes [Look AHEAD] trial: n = 4211; and Bypass Angioplasty Revascularisation Investigation 2 Diabetes [BARI 2D] trial: n = 1495)., Results: Over 9.1 years of follow-up, 789 (12.2%) participants had a primary outcome event. FMM phenomapping with three phenogroups was the best-performing clustering strategy in both the derivation and validation cohorts as determined by Bayesian information criterion, Dunn index and improvement in model discrimination. Phenogroup 1 (n = 663, 10.3%) had the highest burden of comorbidities and diabetes complications, phenogroup 2 (n = 2388, 36.9%) had an intermediate comorbidity burden and lowest diabetes complications, and phenogroup 3 (n = 3415, 52.8%) had the fewest comorbidities and intermediate burden of diabetes complications. Significant interactions were observed between phenogroups and treatment interventions including intensive glycaemic control (p-interaction = 0.042) and combination lipid therapy (p-interaction < 0.001) in the ACCORD, intensive lifestyle intervention (p-interaction = 0.002) in the Look AHEAD and early coronary revascularisation (p-interaction = 0.003) in the BARI 2D trial cohorts for the risk of the primary composite outcome. Favourable reduction in the risk of the primary composite outcome with these interventions was noted in low-risk participants of phenogroup 3 but not in other phenogroups. Compared with phenogroup 3, phenogroup 1 participants were more likely to have severe/symptomatic hypoglycaemic events and medication non-adherence on follow-up in the ACCORD and Look AHEAD trial cohorts., Conclusions/interpretation: Clustering using FMMs was the optimal phenomapping strategy to identify replicable subgroups of patients with type 2 diabetes with distinct clinical characteristics, CVD risk and response to therapies.

[Figure: see text].

Background/objectives: Obesity increases with age, is disproportionately prevalent in black populations, and is associated with heart failure with preserved ejection fraction (HFpEF). An "obesity paradox," or improved survival with obesity, has been reported in patients with HFpEF. The aim of this study was to examine whether racial differences exist in the temporal trends and outcomes associated with obesity among older patients with HFpEF., Design: Community surveillance of acute decompensated heart failure (ADHF) hospitalizations, sampled by stratified design from 2005 to 2014., Setting: Atherosclerosis Risk in Communities Study (NC, MS, MD, MN)., Participants: A total of 10,147 weighted hospitalizations for ADHF (64% female, 74% white, mean age 77 years), with ejection fraction ≥50%., Measurements: ADHF classified by physician review, HFpEF defined by ejection fraction ≥50%. Body mass index (BMI) calculated from weight at hospital discharge. Obesity defined by BMI ≥30 kg/m 2 , class III obesity by BMI ≥40 kg/m 2 ., Results: When aggregated across 2005-2014, the mean BMI was higher for black compared to white patients (34 vs 30 kg/m 2 ; P < .0001), as was prevalence of obesity (56% vs 43%; P < .0001) and class III obesity (24% vs 13%; P < .0001). Over time, the annual mean BMI and prevalence of class III obesity remained stable for black patients, but steadily increased for white patients, with annual rates statistically differing by race (P-interaction = .04 and P = .03, respectively). For both races, a U-shaped adjusted mortality risk was observed across BMI categories, with the highest risk among patients with a BMI ≥40 kg/m 2 ., Conclusion: Black patients were disproportionately burdened by obesity in this decade-long community surveillance of older hospitalized patients with HFpEF. However, temporal increases in mean BMI and class III obesity prevalence among white patients narrowed the racial difference in recent years. For both races, the worst survival was observed with class III obesity. Effective strategies are needed to manage obesity in patients with HFpEF., (© 2021 The American Geriatrics Society.)

Objectives: This study evaluated the application of a biomarker-based risk score to identify individuals with dysglycemia who are at high risk for incident heart failure (HF) and to inform allocation of effective preventive interventions., Background: Risk stratification tools to identify patients with diabetes and pre-diabetes at highest risk for HF are needed to inform cost-effective allocation of preventive therapies. Whether a biomarker score can meaningfully stratify HF risk is unknown., Methods: Participants free of cardiovascular disease from 3 cohort studies (ARIC [Atherosclerosis Risk In Communities], DHS [Dallas Heart Study], and MESA [Multi-Ethnic Study of Atherosclerosis]) were included. An integer-based biomarker score included high-sensitivity cardiac troponin T ≥6 ng/l, N-terminal pro-B-type natriuretic peptide ≥125 pg/ml, high-sensitivity C-reactive protein ≥3 mg/l, and left ventricular hypertrophy by electrocardiography, with 1 point for each abnormal parameter. The 5-year risk of HF was estimated among participants with diabetes and pre-diabetes across biomarker score groups (0 to 4)., Results: The primary analysis included 6,799 participants with dysglycemia (diabetes: 33.2%; pre-diabetes: 66.8%). The biomarker score demonstrated good discrimination and calibration for predicting 5- and 10-year HF risk among pre-diabetes and diabetes cohorts. The 5-year risk of HF among subjects with a biomarker score of ≤1 was low and comparable to participants with euglycemia (0.78%). The 5-year risk for HF increased in a graded fashion with an increasing biomarker score, with the highest risk noted among those with scores of ≥3 (diabetes: 12.0%; pre-diabetes: 7.8%). The estimated number of HF events that could be prevented using a sodium-glucose cotransporter-2 inhibitor per 1,000 treated subjects over 5 years was 11 for all subjects with diabetes and ranged from 4 in the biomarker score zero group to 44 in the biomarker score ≥3 group., Conclusions: Among adults with diabetes and pre-diabetes, a biomarker score can stratify HF risk and inform allocation of HF prevention therapies., Competing Interests: Funding Support and Author Disclosures Dr. Pandey was supported by the Texas Health Resources Clinical Scholarship, Gilead Sciences Research Scholar Program, and the National Institute of Aging GEMSSTAR Grant (1R03AG067960-01). The ARIC study is conducted as a collaborative study supported by National Heart, Lung, and Blood Institute contracts (HHSN268201100005C, HHSN2 68201100006C, HHSN268201100007C, HHSN268201100008C, HHSN26820 1100009C, HHSN268201100010C, HHSN268201100011C, and HHSN268201 100012C). The Dallas Heart Study was funded by a grant from the Donald W. Reynolds Foundation. Research reported in this publication was supported by the National Center for Advancing Translational Sciences of the National Institutes of Health (award number UL1TR001105) to the University of Texas Southwestern Medical Center. The Multi-Ethnic Study of Atherosclerosis was supported by the National Heart, Lung, and Blood Institute (R01 HL071739 and contracts N01-HC-95159, N01-HC-95160, N01-HC-95161, N01-HC-95162, N01-HC-95163, N01-HC-95164, N01-HC-95165, and N01-C-95169). Dr. Vaduganathan has been supported by the KL2/Catalyst Medical Research Investigator Training award from Harvard Catalyst (NIH/NCATS Award UL 1TR002541); and has served on advisory boards for Amgen, AstraZeneca, Baxter Healthcare, Bayer AG, Boehringer Ingelheim, Cytokinetics, and Relypsa. Dr. Pandey has served on the advisory board of Roche Diagnostics. Dr. Patel was supported by the National Heart, Lung, and Blood Institute T32 postdoctoral training grant (5T32HL125247-03). Dr. Kosiborod has received research grant support from AstraZeneca and Boehringer Ingelheim; has served as a consultant or on advisory boards for Amgen, Applied Therapeutics, Astra Zeneca, Bayer, Boehringer Ingelheim, Eli Lilly, Janssen, Merck (Diabetes), Novo Nordisk, Sanofi, and Vifor Pharma; has received other research support from AstraZeneca and honorarium from AstraZeneca, Boehringer Ingelheim, and Novo Nordisk. Dr. de Lemos has received grant support from Roche Diagnostics and Abbott Diagnostics; and has received consulting fees from Roche Diagnostics, Abbott Diagnostics, Ortho Clinical Diagnostics, Siemen’s Health Care Diagnostics, Quidel Cardiovascular, Inc, Novo Nordisk, Amgen, Regeneron, Eli Lilly, and Esperion. Drs. DeFilippi and de Lemos hold a patent pending (U.S. Patent Number: 15/309,754) entitled: “Methods for Assessing Differential Risk for Developing Heart Failure.” Dr. McGuire has received personal fees for trial leadership from GlaxoSmithKline, Janssen, Lexicon, AstraZeneca, CSL Behring, Sanofi, Boehringer Ingelheim, Merck & Co, Pfizer, Novo Nordisk, Eisai Inc., Esperion, and Lilly USA; and has received personal consultancy fees from AstraZeneca, Lilly USA, Boehringer Ingelheim, Merck & Co, Novo Nordisk, Metavant, Applied Therapeutics, Sanofi, and Afimmune. Dr. Everett has received personal consultancy fees from Amarin, Amgen, Gilead, FDA, Merck & Co., National Institute of Diabetes and Digestive and Kidney Diseases, and Roche Diagnostics outside the present work; and has received significant investigator-initiated grant funding from the National Institute of Heart, Lung, and Blood Institute outside the present work. A full list of participating MESA investigators and institutions can be found at http://www.mesa-nhlbi.org., (Copyright © 2021 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Objectives: This study investigates the prevalence and prognostic significance of mitral regurgitation (MR) in acute decompensated heart failure (ADHF) patients., Background: Few studies characterize the burden of MR in heart failure., Methods: The ARIC (Atherosclerosis Risk In Communities) study surveilled ADHF hospitalizations for residents ≥55 years of age in 4 U.S. communities. ADHF cases were stratified by left ventricular ejection fraction (LVEF): <50% and ≥50%. Odds of moderate or severe MR in patients with varying sex and race, and odds of 1-year mortality in those with higher MR severity were estimated using multivariable logistic regression., Results: From 2005 to 2014, there were 17,931 weighted ADHF hospitalizations of which 49.2% had an LVEF <50% and 50.8% an LVEF ≥50%. Moderate or severe MR prevalence was 44.5% in those with an LVEF <50% and 27.5% in those with an LVEF ≥50%. Moderate or severe MR was more likely in females than males regardless of LVEF; LVEF <50% (odds ratio [OR]: 1.21 [95% confidence interval (CI): 1.11 to 1.33]), LVEF ≥50% (OR: 1.52 [95% CI: 1.36 to 1.69]). Among hospitalizations with an LVEF ≥50%, moderate or severe MR was less likely in blacks than whites (OR: 0.72 [95% CI: 0.64 to 0.82]). Higher MR severity was independently associated with increased 1-year mortality in those with an LVEF <50% (OR: 1.30 [95% CI: 1.16 to 1.45])., Conclusions: Patients with ADHF have a significant MR burden that varies with sex and race. In ADHF patients with an LVEF <50%, higher MR severity is associated with excess 1-year mortality., Competing Interests: Funding Support and Author Disclosures The ARIC study has been funded in whole or in part with Federal funds from the National Heart, Lung, and Blood Institute, National Institutes of Health (NIH), Department of Health and Human Services, under contract nos. HHSN268201700001I, HHSN268201700002I, HHSN268201700003I, HHSN268201700005I, and HHSN268201700004I. Dr. Qamar is supported by Daiichi Sankyo, the NIH T32 Program, and the American Heart Association Strategically Focused Research Networks in Vascular Disease grant. Dr. Vaduganathan is supported by the KL2/Catalyst Medical Research Investigator Training award from Harvard Catalyst NIH/NCATS Award UL 1TR002541. Dr. Vavalle is supported by a research grant from CSI Inc. Dr. Qamar has been an AD hoc consultant/speaker for the American College of Cardiology, Society for Cardiovascular Angiography and Interventions, Pfizer, Medscape, and the Clinical Exercise Physiology Association. Dr. Vaduganathan has served on advisory boards for Amgen, AstraZeneca, Baxter Healthcare, Bayer AG, Boehringer Ingelheim, Cytokinetics, and Relypsa; and has participated on clinical endpoint committees for studies sponsored by Novartis and the NIH. Dr. Pandey has served as an advisory board member for Roche Diagnostics; and has also received research funding from the Texas Health Resources Clinical Scholarship, Gilead Sciences Research Scholar Program, and the National Institute of Aging GEMSSTAR Grant (1R03AG067960-01). Dr. Cavender has received non-salary research support from Amgen, AstraZeneca, Chiesi, CSL Behring, GlaxoSmithKline, and Novartis; salary research support from Novo-Nordisk; and consulting fees from Amgen, AstraZeneca, Boehringer Ingelheim, Boston Scientific, Edwards Lifesciences, and Merck. Dr. Vavalle has been a principal investigator for Abbott Medical Device Company, Boston Scientific, and Cardiac Dimensions, Inc.; has received consulting fees from Edwards Lifesciences; and has an honorarium from ZOLL Medical Corporation. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2021 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background Acute myocardial infarction (AMI) with in-hospital onset (AMI-IHO) has poor prognosis but is clinically underappreciated. Whether its occurrence has changed over time is uncertain. Methods and Results Since 1987, the ARIC (Atherosclerosis Risk in Communities) study has conducted adjudicated surveillance of AMI hospitalizations in 4 US communities. Our analysis was limited to patients aged 35 to 74 years with symptomatic AMI. Patients with symptoms initiating after hospital arrival were considered AMI-IHO. A total of 26 678 weighted hospitalizations (14 276 unweighted hospitalizations) for symptomatic AMI were identified from 1995 to 2014, with 1137 (4%) classified as in-hospital onset. The population incidence rate of AMI-IHO increased in the 4 ARIC communities from 1995 through 2004 to 2005 through 2014 (12.7-16.9 events per 100 000 people; P for 20-year trend <0.0001), as did the proportion of AMI hospitalizations with in-hospital onset (3.7%-6.1%; P for 20-year trend =0.03). The 10-year proportions were stable for patients aged 35 to 64 years (3.0%-3.4%; P for 20-year trend =0.3) but increased for patients aged ≥65 years (4.6%-7.8%; P for 20-year trend =0.008; P for interaction by age group =0.04). AMI-IHO had a more severe clinical course with lower use of AMI therapies or invasive strategies and higher in-hospital (7% versus 3%), 28-day (19% versus 5%), and 1-year (29% versus 12%) mortality ( P< 0.0001 for all). Conclusions In this population-based community surveillance, AMI-IHO increased from 2005 to 2014, particularly among older patients. Quality initiatives to improve recognition and management of AMI-IHO should be especially focused on hospitalized patients aged >65.

This study evaluates the performance of an acoustic radiation force impulse (ARFI)-based outcome parameter, the decadic logarithm of the variance of acceleration, or log(VoA), for measuring carotid fibrous cap thickness. Carotid plaque fibrous cap thickness measurement by log(VoA) was compared to that by ARFI peak displacement (PD) in patients undergoing clinically indicated carotid endarterectomy using a spatially-matched histological validation standard. Fibrous caps in parametric log(VoA) and PD images were automatically segmented using a custom clustering algorithm, and a pathologist with expertise in atherosclerosis hand-delineated fibrous caps in histology. Over 10 fibrous caps, log(VoA)-derived thickness was more strongly correlated to histological thickness than PD-derived thickness, with Pearson correlation values of 0.98 for log(VoA) compared to 0.89 for PD. The log(VoA)-derived cap thickness also had better agreement with histology-measured thickness, as assessed by the concordance correlation coefficient (0.95 versus 0.62), and, by Bland-Altman analysis, was more consistent than PD-derived fibrous cap thickness. These results suggest that ARFI log(VoA) enables improved discrimination of fibrous cap thickness relative to ARFI PD and further contributes to the growing body of evidence demonstrating ARFI's overall relevance to delineating the structure and composition of carotid atherosclerotic plaque for stroke risk prediction.

Background Peripheral artery disease (PAD) is both a common comorbidity and a contributing factor to heart failure. Whether PAD is associated with hospitalization for recurrent decompensation among patients with established heart failure is uncertain. Methods and Results Since 2005, the ARIC (Atherosclerosis Risk in Communities) study has conducted active surveillance of hospitalized acute decompensated heart failure (ADHF), with events verified by physician review. From 2005 to 2016, 1481 patients were hospitalized with ADHF and discharged alive (mean age, 78 years; 69% White). Of these, 207 (14%) had diagnosis of PAD. Those with PAD were more often men (55% versus 44%) and smokers (17% versus 8%), with a greater prevalence of coronary artery disease (72% versus 52%). Patients with PAD had an increased risk of at least 1 ADHF readmission, both within 30 days (11% versus 7%) and 1 year (39% versus 28%) of discharge from the index hospitalization. After adjustments, PAD was associated with twice the hazard of ADHF readmission within 30 days (HR, 2.02; 95% CI, 1.14-3.60) and a 60% higher hazard of ADHF readmission within 1 year (HR, 1.60; 95% CI, 1.25-2.05). The 1-year hazard of ADHF readmission associated with PAD was stronger with heart failure with reduced ejection fraction (HR, 2.01; 95% CI, 1.29-3.13) than preserved ejection fraction (HR, 1.04; 95% CI, 0.69-1.56); P for interaction=0.05. Conclusions Patients with ADHF and concomitant PAD have a higher likelihood of ADHF readmission. Strategies to prevent ADHF readmissions in this high-risk group are warranted.

Background: Pulmonary hypertension (PH) is frequently reported in patients with advanced chronic kidney disease and is associated with early allograft failure and death. However, the causes of PH are heterogeneous, and patient prognosis may vary by etiologic subtype., Methods: Data from the University of North Carolina Cardiorenal Registry were examined to determine associations between PH, with or without elevated left atrial pressure (eLAP), and mortality in candidates for kidney transplantation. PH and eLAP were determined by Doppler echocardiography and by tissue Doppler imaging, respectively., Results: From 2006 to 2013, 778 registry patients were screened preoperatively by echocardiography. Most patients were black (64%) and men (56%); the mean age was 56 years. PH was identified in 97 (12%) patients; of these, eLAP was prevalent in half. During a median follow-up of 4.4 years, 179 (23%) received a kidney transplant, and 195 (25%) died. After adjustments for demographics, comorbidities, dialysis vintage, and kidney transplantation, PH was associated with twice the 5-year mortality (hazard ratio [HR] = 2.11; 95% confidence interval [CI]: 1.48-3.03), with stronger associations in the absence of eLAP (HR = 2.87; 95% CI: 1.83-4.49) than with eLAP (HR = 1.11; 95% CI: 0.57-2.17), P for interaction = 0.01., Conclusions: The mortality risk associated with PH among patients with advanced chronic kidney disease appears to differ by etiology. Patients with PH in the absence of eLAP are at high risk of death and in need of focused attention. Future research efforts should investigate potential strategies to improve outcomes for these patients.

Objective: To evaluate the associations between long-term change and variability in glycemia with risk of heart failure (HF) among patients with type 2 diabetes mellitus (T2DM)., Research Design and Methods: Among participants with T2DM enrolled in the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial, variability in HbA 1c was assessed from stabilization of HbA 1c following enrollment (8 months) to 3 years of follow-up as follows: average successive variability (ASV) (average absolute difference between successive values), coefficient of variation (SD/mean), and SD. Participants with HF at baseline or within 3 years of enrollment were excluded. Adjusted Cox models were used to evaluate the association of percent change (from baseline to 3 years of follow-up) and variability in HbA 1c over the first 3 years of enrollment and subsequent risk of HF., Results: The study included 8,576 patients. Over a median follow-up of 6.4 years from the end of variability measurements at year 3, 388 patients had an incident HF hospitalization. Substantial changes in HbA 1c were significantly associated with higher risk of HF (hazard ratio [HR] for ≥10% decrease 1.32 [95% CI 1.08-1.75] and for ≥10% increase 1.55 [1.19-2.04]; reference <10% change in HbA 1c ). Greater long-term variability in HbA 1c was significantly associated with higher risk of HF (HR per 1 SD of ASV 1.34 [95% CI 1.17-1.54]) independent of baseline risk factors and interval changes in cardiometabolic parameters. Consistent patterns of association were observed with use of alternative measures of glycemic variability., Conclusions: Substantial long-term changes and variability in HbA 1c were independently associated with risk of HF among patients with T2DM., (© 2020 by the American Diabetes Association.)

Background: Patients with heart failure (HF) have multiple coexisting comorbidities. The temporal trends in the burden of comorbidities and associated risk of mortality among patients with HF with preserved ejection fraction (HFpEF) and HF with reduced ejection fraction (HFrEF) are not well established., Methods: HF-related hospitalizations were sampled by stratified design from 4 US areas in 2005 to 2014 by the community surveillance component of the ARIC study (Atherosclerosis Risk in Communities). Acute decompensated HF was classified by standardized physician review and a previously validated algorithm. An ejection fraction <50% was considered HFrEF. A total of 15 comorbidities were abstracted from the medical record. Mortality outcomes were ascertained for up to 1-year postadmission by linking hospital records with death files., Results: A total of 5460 hospitalizations (24 937 weighted hospitalizations) classified as acute decompensated HF had available ejection fraction data (53% female, 68% white, 53% HFrEF, 47% HFpEF). The average number of comorbidities was higher for patients with HFpEF versus HFrEF, both for women (5.53 versus 4.94; P <0.0001) and men (5.20 versus 4.82; P <0.0001). There was a significant temporal increase in the overall burden of comorbidities, both for patients with HFpEF (women: 5.17 in 2005-2009 to 5.87 in 2010-2013; men: 4.94 in 2005-2009 and 5.45 in 2010-2013) and HFrEF (women: 4.78 in 2005-2009 to 5.14 in 2010-2013; men: 4.62 in 2005-2009 and 5.06 in 2010-2013; P -trend<0.0001 for all). Higher comorbidity burden was significantly associated with higher adjusted risk of 1-year mortality, with a stronger association noted for HFpEF (hazard ratio [HR] per 1 higher comorbidity, 1.19 [95% CI, 1.14-1.25] versus HFrEF (HR, 1.10 [95% CI, 1.05-1.14]; P for interaction by HF type=0.02). The associated mortality risk per 1 higher comorbidity also increased significantly over time for patients with HFpEF and HFrEF, as well ( P for interaction with time=0.002 and 0.02, respectively) Conclusions: The burden of comorbidities among hospitalized patients with acute decompensated HFpEF and HFrEF has increased over time, as has its associated mortality risk. Higher burden of comorbidities is associated with higher risk of mortality, with a stronger association noted among patients with HFpEF versus HFrEF.

Background: The arterial effects of hormone therapy remain controversial. This study tested the effects of transdermal estradiol plus intermittent micronized progesterone (TE + IMP) in healthy perimenopausal and early postmenopausal women on several mechanisms involved in the pathophysiology of arterial disease., Methods: Healthy perimenopausal and early postmenopausal women, ages 45 to 60 years, were enrolled in this randomized, double-blind, placebo-controlled trial. Women were randomized to receive TE (0.1 mg/day) + IMP (200 mg/day for 12 days) or identical placebo patches and pills for 12 months. Outcomes included: change in stress reactivity composite z-score (combining inflammatory, cortisol, and hemodynamic responses to a standardized psychological laboratory stressor); flow-mediated dilation (FMD) of the brachial artery (an index of vascular endothelial function); baroreflex sensitivity; and metabolic risk (presence of the metabolic syndrome or insulin resistance), all assessed at baseline and at months 6 and 12., Results: Of 172 women enrolled, those assigned to TE + IMP tended to have higher resting baroreflex sensitivity than those assigned to placebo across the 6- and 12-month visits. Although treatment groups did not differ in terms of the other prespecified outcomes, a significant treatment-by-age interaction was found for FMD and stress reactivity such that an age-related decrease in FMD and increase in stress reactivity were seen among women assigned to placebo but not those assigned to TE + IMP. Women on TE + IMP also had lower resting diastolic blood pressure, lower levels of low-density lipoprotein cholesterol, and higher baroreflex sensitivity during stress testing., Conclusions: TE + IMP tended to improve cardiac autonomic control and prevented age-related changes in stress reactivity and endothelial function among healthy perimenopausal and early postmenopausal women., (© Endocrine Society 2019. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Aims: To study the correlation between intra-procedural left ventricular end-diastolic pressure (LVEDP) and the development of contrast-induced acute kidney injury (CI-AKI) in patients undergoing percutaneous coronary intervention (PCI)., Methods and Results: A single center retrospective observational study compared clinical and hemodynamic characteristics of patients who developed post-PCI CI-AKI with those did not. CI-AKI was defined as an absolute increase in serum creatinine ≥0.5 mg/dl or an increase ≥25% from baseline 48-72 h after the administration of contrast medium. Among 1301 consecutive patients who underwent PCI, 125 patients (9.6%) developed CI-AKI. The CI-AKI group had a higher average LVEDP (18.4 ± 8.7 vs 14.4 ± 6.6 mm Hg; p < .0001) and higher prevalence of elevated LVEDP (≥20 mm Hg) than those without CI-AKI (47.2% vs 23.3%, p < .0001). After adjustments, elevated LVEDP remained independently associated with CI-AKI (OR 2.21; 95% CI 1.40-3.50). LVEDP predicted the development of CI-AKI with a receiver operating characteristic area under curve (AUC) of 0.64. The association between elevated LVEDP and the risk of CI-AKI was stronger in patients with reduced ejection fraction (EF ≤ 40%) (OR = 4.08; 95% CI: 1.68-9.91) than those with preserved EF (OR = 1.69; 95% CI: 0.94-3.04) (p value for interaction = .0003). Patients who had LVEDP ≥ 20 mm Hg and LVEF ≤ 40% had a post-PCI incidence rate of developing CI-AKI of 36.5%., Conclusions: Elevated intra-procedural LVEDP (≥20 mm Hg) is independently associated with increased risk of CI-AKI for patients undergoing cardiac catheterization and PCI, especially in the setting of reduced LVEF (≤40%)., (Copyright © 2020. Published by Elsevier B.V.)

Sickle cell trait (SCT) has been associated with hypercoagulability, chronic kidney disease (CKD), and ischemic stroke. Whether concomitant CKD modifies long-term ischemic stroke risk in individuals with SCT is uncertain. We analyzed data from 3602 genotyped black adults (female = 62%, mean baseline age = 54 years) who were followed for a median 26 years by the Atherosclerosis Risk in Communities Study. Ischemic stroke was verified by physician review. Associations between SCT and ischemic stroke were analyzed using repeat-events Cox regression, adjusted for potential confounders. SCT was identified in 236 (7%) participants, who more often had CKD at baseline than noncarriers (18% vs 13%, P = .02). Among those with CKD, elevated factor VII activity was more prevalent with SCT genotype (36% vs 22%; P = .05). From 1987-2017, 555 ischemic strokes occurred in 436 individuals. The overall hazard ratio of ischemic stroke associated with SCT was 1.31 (95% CI: 0.95-1.80) and was stronger in participants with concomitant CKD (HR = 2.18; 95% CI: 1.16-4.12) than those without CKD (HR = 1.09; 95% CI: 0.74-1.61); P for interaction = .04. The hazard ratio of composite ischemic stroke and/or death associated with SCT was 1.20 (95% CI: 1.01-1.42) overall, 1.44 (95% CI: 1.002-2.07) among those with CKD, and 1.15 (95% CI: 0.94-1.39) among those without CKD; P for interaction = .18. The long-term risk of ischemic stroke associated with SCT relative to noncarrier genotype appears to be modified by concomitant CKD., (© 2019 Wiley Periodicals, Inc.)

Background Hospital staffing is usually reduced on weekends, potentially impacting inpatient care and postdischarge coordination of care for patients with acute decompensated heart failure (ADHF). However, investigations of in-hospital mortality on the weekend versus weekday, and post-hospital outcomes of weekend versus weekday discharge are scarce. Methods and Results Hospitalizations for ADHF were sampled by stratified design from 4 US areas by the Community Surveillance component of the ARIC (Atherosclerosis Risk in Communities) study. ADHF was classified by a standardized computer algorithm and physician review of the medical records. Discharges or deaths on Saturday, Sunday, or national holidays were considered to occur on the "weekend." In-hospital mortality was compared between hospitalizations ending on a weekend versus weekday. Post-hospital (28-day) mortality was compared among patients discharged alive on a weekend versus weekday. From 2005 to 2014, 39 699 weighted ADHF hospitalizations were identified (19% terminating on a weekend). Demographics, comorbidities, length of stay, and guideline-directed therapies were similar for patients with hospitalizations ending on a weekend versus weekday. In-hospital death doubled on the weekend compared with weekday (12% versus 6%) and was not attenuated by adjustment for potential confounders (odds ratio, 2.37; 95% CI, 1.93-2.91). There was no association between weekend discharge and 28-day mortality among patients discharged alive. Conclusions The risk of in-hospital death among patients admitted with ADHF appears to be doubled on the weekends when hospital staffing is usually reduced. However, among patients discharged alive, hospital discharge on a weekend is not adversely associated with mortality.

The kidney is an anisotropic organ, with higher elasticity along versus across nephrons. The degree of mechanical anisotropy in the kidney may be diagnostically relevant if properly exploited; however, if improperly controlled, anisotropy may confound stiffness measurements. The purpose of this study is to demonstrate the clinical feasibility of acoustic radiation force (ARF)-induced peak displacement (PD) measures for both exploiting and obviating mechanical anisotropy in the cortex of human kidney allografts, in vivo. Validation of the imaging methods is provided by preclinical studies in pig kidneys, in which ARF-induced PD values were significantly higher ( , Wilcoxon) when the transducer executing asymmetric ARF was oriented across versus along the nephrons. The ratio of these PD values obtained with the transducer oriented across versus along the nephrons strongly linearly correlated ( R 2 = 0.95 ) to the ratio of shear moduli measured by shear wave elasticity imaging. On the contrary, when a symmetric ARF was implemented, no significant difference in PD was observed ( p > 0.01 ). Similar results were demonstrated in vivo in the kidney allografts of 14 patients. The symmetric ARF produced PD measures with no significant difference ( p > 0.01 ) between along versus across alignments, but the asymmetric ARF yielded PD ratios that remained constant over a six-month observation period post-transplantation, consistent with stable serum creatinine level and urine protein-to-creatinine ratio in the same patient population ( p > 0.01 ). The results of this pilot in vivo clinical study suggest the feasibility of 1) implementing symmetrical ARF to obviate mechanical anisotropy in the kidney cortex when anisotropy is a confounding factor and 2) implementing asymmetric ARF to exploit mechanical anisotropy when mechanical anisotropy is a potentially relevant biomarker.

Background Anthracycline chemotherapeutics, such as doxorubicin, are used widely in the treatment of numerous malignancies. The primary dose-limiting adverse effect of anthracyclines is cardiotoxicity that often presents as heart failure due to dilated cardiomyopathy years after anthracycline exposure. Recent data from animal studies indicate that anthracyclines cause cardiac atrophy. The timing of onset and underlying mechanisms are not well defined, and the relevance of these findings to human disease is unclear. Methods and Results Wild-type mice were sacrificed 1 week after intraperitoneal administration of doxorubicin (1-25 mg/kg), revealing a dose-dependent decrease in cardiac mass ( R 2 =0.64; P<0.0001) and a significant decrease in cardiomyocyte cross-sectional area (336±29 versus 188±14 µm 2 ; P<0.0001). Myocardial tissue analysis identified a dose-dependent upregulation of the ubiquitin ligase, MuRF1 (muscle ring finger-1; R 2 =0.91; P=0.003) and a molecular profile of muscle atrophy. To investigate the determinants of doxorubicin-induced cardiac atrophy, we administered doxorubicin 20 mg/kg to mice lacking MuRF1 (MuRF1 -/- ) and wild-type littermates. MuRF1 -/- mice were protected from cardiac atrophy and exhibited no reduction in contractile function. To explore the clinical relevance of these findings, we analyzed cardiac magnetic resonance imaging data from 70 patients in the DETECT-1 cohort and found that anthracycline exposure was associated with decreased cardiac mass evident within 1 month and persisting to 6 months after initiation. Conclusions Doxorubicin causes a subacute decrease in cardiac mass in both mice and humans. In mice, doxorubicin-induced cardiac atrophy is dependent on MuRF1. These findings suggest that therapies directed at preventing or reversing cardiac atrophy might preserve the cardiac function of cancer patients receiving anthracyclines.

While in vivo acoustic radiation force impulse (ARFI)-induced peak displacement (PD) has been demonstrated to have high sensitivity and specificity for differentiating soft from stiff plaque components in patients with carotid plaque, the parameter exhibits poorer performance for distinguishing between plaque features with similar stiffness. To improve discrimination of carotid plaque features relative to PD, we hypothesize that signal correlation and signal-to-noise ratio (SNR) can be combined, outright or via displacement variance. Plaque feature detection by displacement variance, evaluated as the decadic logarithm of the variance of acceleration and termed "log(VoA)," was compared to that achieved by exploiting SNR, cross correlation coefficient, and ARFI-induced PD outcome metrics. Parametric images were rendered for 25 patients undergoing carotid endarterectomy, with spatially matched histology confirming plaque composition and structure. On average, across all plaques, log(VoA) was the only outcome metric with values that statistically differed between regions of lipid-rich necrotic core (LRNC), intraplaque hemorrhage (IPH), collagen (COL), and calcium (CAL). Further, log(VoA) achieved the highest contrast-to-noise ratio (CNR) for discriminating between LRNC and IPH, COL and CAL, and grouped soft (LRNC and IPH) and stiff (COL and CAL) plaque components. More specifically, relative to the previously demonstrated ARFI PD parameter, log(VoA) achieved 73% higher CNR between LRNC and IPH and 59% higher CNR between COL and CAL. These results suggest that log(VoA) enhances the differentiation of LRNC, IPH, COL, and CAL in human carotid plaques, in vivo, which is clinically relevant to improving stroke risk prediction and medical management.

Background: Sex differences are known to exist in the management of older patients presenting with acute myocardial infarction (AMI). Few studies have examined the incidence and risk factors of AMI among young patients, or whether clinical management differs by sex., Methods: The Atherosclerosis Risk in Communities (ARIC) Surveillance study conducts hospital surveillance of AMI in 4 US communities (MD, MN, MS, and NC). AMI was classified by physician review, using a validated algorithm. Medications and procedures were abstracted from the medical record. Our study population was limited to young patients aged 35 to 54 years., Results: From 1995 to 2014, 28 732 weighted hospitalizations for AMI were sampled among patients aged 35 to 74 years. Of these, 8737 (30%) were young. The annual incidence of AMI hospitalizations increased for young women but decreased for young men. The overall proportion of AMI admissions attributable to young patients steadily increased, from 27% in 1995 to 1999 to 32% in 2010 to 2014 ( P for trend=0.002), with the largest increase observed in young women. History of hypertension (59% to 73%, P for trend<0.0001) and diabetes mellitus (25% to 35%, P for trend<0.0001) also increased among young AMI patients. Compared to young men, young women presenting with AMI were more often black and had a greater comorbidity burden. In adjusted analyses, young women had a lower probability of receiving lipid-lowering therapies (relative risk [RR]=0.87; 95% confidence interval [CI], 0.80-0.94), nonaspirin antiplatelets (RR=0.83; 95% CI, 0.75-0.91), beta blockers (RR=0.96; 95% CI, 0.91-0.99), coronary angiography (RR=0.93; 95% CI, 0.86-0.99) and coronary revascularization (RR = 0.79; 95% CI, 0.71-0.87). However, 1-year all-cause mortality was comparable for women versus men (HR=1.10; 95% CI, 0.83-1.45)., Conclusions: The proportion of AMI hospitalizations attributable to young patients increased from 1995 to 2014 and was especially pronounced among women. History of hypertension and diabetes among young patients admitted with AMI increased over time as well. Compared with young men, young women presenting with AMI had a lower likelihood of receiving guideline-based AMI therapies. A better understanding of factors underlying these changes is needed to improve care of young patients with AMI.

Our group has previously found that in silico, mechanical anisotropy may be interrogated by exciting transversely isotropic materials with geometrically asymmetric acoustic radiation force excitations and then monitoring the associated induced displacements in the region of excitation. We now translate acoustic radiation force-based anisotropy assessment to human muscle in vivo and investigate its clinical relevance to monitoring muscle degeneration in Duchenne muscular dystrophy (DMD). Clinical anisotropy assessments were performed using Viscoelastic Response ultrasound, with a degree of anisotropy reflected by the ratios of Viscoelastic Response relative elasticity (RE) or relative viscosity (RV) measured with the asymmetric radiation force oriented parallel versus perpendicular to muscle fiber alignment. In vivo results from rectus femoris and gastrocnemius muscles of boys aged ∼7.9-10.4 y indicate that RE and RV anisotropy ratios in rectus femoris muscles of boys with DMD were significantly higher than those of healthy control boys (RE: DMD = 1.51 ± 0.87, control = 0.99 ± 0.69, p = 0.04, Wilcoxon rank sum test; RV: DMD = 1.04 ± 0.71, control = 0.74 ± 0.22, p = 0.02). In the gastrocnemius muscle, only the RV anisotropy ratio was significantly higher in dystrophic than control patients (DMD = 1.23 ± 0.35, control = 0.88 ± 0.31, p = 0.04). In the dystrophic rectus femoris muscle, the RE anisotropy ratio was inversely correlated (slope = -0.03/lbf, r = -0.43, p = 0.07, Pearson correlation) with quantitative muscle testing functional output measures but was not correlated with quantitative muscle testing in the dystrophic gastrocnemius. These results suggest that Viscoelastic Response RE and RV measures reflect differences in mechanical anisotropy associated with functional impairment with dystrophic degeneration that are relevant to monitoring DMD clinically., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Objectives: To identify invasive hemodynamic parameters that correlate with infarction size in patients with ST-elevation myocardial infarction (STEMI)., Background: Invasive hemodynamics obtained during primary percutaneous coronary intervention (PPCI) are predictive of mortality in STEMI, but which parameters correlate best with the size of the infarction are unknown., Methods: This is a single-center study of 405 adult patients with STEMI who had left ventricular end-diastolic pressure (LVEDP) measured during PPCI. Size of infarction was estimated by peak troponin I level and ejection fraction (LVEF) determined by echocardiography., Results: The average (±SD) age was 61 ± 14 years, TIMI STEMI risk score was 3.5 ± 2.7 and Grace score was 157 ± 42. Hemodynamic parameters that correlated best with EF were LVEDP (r = -0.40), PP (r = 0.24), and SBP/LVEDP ratio (r = 0.22) and with peak troponin were SBP/LVEDP ratio (r = -0.41), LVEDP (r = 0.31), and PP (r = -0.29). SBP/LVEDP (AUC = 0.76) and SBP (AUC = 0.77) had a stronger association with in-hospital mortality than did LVEDP (AUC = 0.66) or PP (AUC = 0.64). Door-to-balloon time did not affect the correlations between hemodynamic parameters and infarct size., Conclusions: In this sample of 405 patients undergoing PPCI, SBP/LVEDP ratio had the strongest correlation with peak troponin levels and LVEDP with EF, whereas SBP/LVEDP and SBP had a strong association with in-hospital mortality. These results suggest that measurement of LVEDP as well as SBP may help risk stratify patients during PPCI., (© 2018 Wiley Periodicals, Inc.)

Background Standardization of evidence-based medical therapies has improved outcomes for patients with non- ST -segment-elevation myocardial infarction ( NSTEMI ). Although racial differences in NSTEMI management have previously been reported, it is uncertain whether these differences have been ameliorated over time. Methods and Results The ARIC (Atherosclerosis Risk in Communities) Community Surveillance study conducts hospital surveillance of acute myocardial infarction in 4 US communities. NSTEMI was classified by physician review, using a validated algorithm. From 2000 to 2014, 17 755 weighted hospitalizations for NSTEMI (patient race: 36% black, 64% white) were sampled by ARIC . Black patients were younger (aged 60 versus 66 years), more often female (45% versus 38%), and less likely to have medical insurance (88% versus 93%) but had more comorbidities. Black patients were less often administered aspirin (85% versus 92%), other antiplatelet therapy (45% versus 60%), β-blockers (85% versus 88%), and lipid-lowering medications (68% versus 76%). After adjustments, black patients had a 24% lower probability of receiving nonaspirin antiplatelets (relative risk: 0.76; 95% confidence interval, 0.71-0.81), a 29% lower probability of angiography (relative risk: 0.71; 95% confidence interval, 0.67-0.76), and a 45% lower probability of revascularization (relative risk: 0.55; 95% confidence interval, 0.50-0.60). No suggestion of a changing trend over time was observed for any NSTEMI therapy ( P values for interaction, all >0.20). Conclusions This longitudinal community surveillance of hospitalized NSTEMI patients suggests black patients have more comorbidities and less likelihood of receiving guideline-based NSTEMI therapies, and these findings persisted across the 15-year period. Focused efforts to reduce comorbidity burden and to more consistently implement guideline-directed treatments in this high-risk population are warranted.

Chronic kidney disease is most desirably and cost-effectively treated by renal transplantation, but graft survival is a major challenge. Although irreversible graft damage can be averted by timely treatment, intervention is delayed when early graft dysfunction goes undetected by standard clinical metrics. A more sensitive and specific parameter for delineating graft health could be the viscoelastic properties of the renal parenchyma, which are interrogated non-invasively by Viscoelastic Response (VisR) ultrasound, a new acoustic radiation force (ARF)-based imaging method. Assessing the performance of VisR imaging in delineating histologically confirmed renal transplant pathologies in vivo is the purpose of the study described here. VisR imaging was performed in patients with (n = 19) and without (n = 25) clinical indication for renal allograft biopsy. The median values of VisR outcome metrics (τ, relative elasticity [RE] and relative viscosity [RV]) were calculated in five regions of interest that were manually delineated in the parenchyma (outer, center and inner) and in the pelvis (outer and inner). The ratios of a given VisR metric for all possible region-of-interest combinations were calculated, and the corresponding ratios were statistically compared between biopsied patients subdivided by diagnostic categories versus non-biopsied, control allografts using the two-sample Wilcoxon test (p <0.05). Although τ ratios non-specifically differentiated allografts with vascular disease, tubular/interstitial scarring, chronic allograft nephropathy and glomerulonephritis from non-biopsied control allografts, RE distinguished only allografts with vascular disease and tubular/interstitial scarring, and RV distinguished only vascular disease. These results suggest that allografts with scarring and vascular disease can be identified using non-invasive VisR RE and RV metrics., (Copyright © 2018 World Federation for Ultrasound in Medicine and Biology. Published by Elsevier Inc. All rights reserved.)

Background: Both hypertensive and atherosclerotic processes contribute to common carotid artery intima-media thickness (CCA-IMT). Elevated CCA-IMT may be indicative of subclinical cerebrovascular disease; however, its role in the absence of concomitant carotid artery plaque is uncertain, and few studies have examined associations in Black populations., Materials and Methods: At cohort visit 3 (1993-1995) a subset of stroke-free participants (641 Blacks and 702 Whites, mean age 63) from the Atherosclerosis Risk in Communities (ARIC) study was imaged by brain MRI and carotid ultrasound. A CCA-IMT >0.9 mm was considered elevated. Asymptomatic brain lesions ≥3 mm were considered silent brain infarctions (SBI). Subcortical SBI measuring 3 to <20 mm were considered lacunes. Associations between elevated CCA-IMT and SBI were analyzed with Poisson regression., Results: Elevated CCA-IMT was identified in 168 participants (16% of Blacks, 10% of Whites), and SBI were observed in 156 (15% of Blacks, 8% of Whites). Elevated CCA-IMT was strongly related to anterior circulation SBI, posterior circulation SBI, and lacunes. After adjustments, elevated CCA-IMT remained associated with greater number of lacunes in Blacks ([prevalence ratio, PR] = 1.60; 95% confidence interval [CI]: 1.02-2.51), but not Whites (PR = 0.85; 95% CI: 0.35-2.04); P value for interaction = 0.12. Among Black participants without concomitant carotid plaque, elevated CCA-IMT was associated with twice the number of lacunes (PR = 2.00; 95% CI: 1.05-3.82)., Conclusions: In older Black adults, elevated CCA-IMT is independently associated with lipohyalinosis of the cerebral small vessels, irrespective of concomitant carotid plaque and vascular risk factors.

Hospitals are required to report all-cause 30-day readmissions for patients discharged with heart failure. Same-cause readmissions have received less attention but may differ for heart failure with reduced ejection fraction (HFrEF) versus heart failure with preserved ejection fraction (HFpEF). The ARIC study began abstracting medical records for cohort members hospitalized with acute decompensated heart failure (ADHF) in 2005. ADHF was validated by physician review, with HFrEF defined by ejection fraction <50%. Recurrent admissions for ADHF were analyzed within 30 days, 90 days, 6 months, and 1 year of the index hospitalization using repeat-measures Cox regression models. All recurrent ADHF admissions per patient were counted rather than the more typical analysis of only the first occurring readmission. From 2005 to 2014, 1,133 cohort members survived at least 1 hospitalization for ADHF and had ejection fraction recorded. Half were classified as HFpEF. Patients with HFpEF were more often women and had more co-morbidities. The overall ADHF readmission rate was greatest within 30 days of discharge but was higher for patients with HFrEF (115 vs 88 readmissions per 100 person-years). After adjustments for demographics, year of admission, and co-morbidities, there was a trend for higher ADHF readmissions with HFrEF, relative to HFpEF, at 30 days (hazard ratio [HR] 1.41, 95% confidence interval [CI] 0.92 to 2.18), 90 days (HR 1.39, 95% CI 1.05 to 1.85), 6 months (HR 1.47, 95% CI, 1.18 to 1.84), and 1 year (HR 1.42, 95% CI 1.18 to 1.70) of follow-up. In conclusion, patients with HFrEF have a greater burden of short- and long-term readmissions for recurrent ADHF., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: The optimal anticoagulation strategy for percutaneous coronary interventions (PCIs) remains debated. We report outcomes after switching from a bivalirudin-first to an unfractionated heparin (UFH)-first strategy for PCIs in a large academic center., Methods: Patients undergoing PCI from June 1 st 2013-May 31 st , 2015 were identified through the National Cardiovascular Data Registry (NCDR), and divided into the "bivalirudin era" (June 2013-July 2014) and the "UFH era" (October 2014-May 2015). Bleeding outcomes were compared using multivariable logistic regression adjusted for potential confounders., Results: A total of 1,145 patients were identified (bivalirudin era =752, UFH era =393). Radial access for PCI increased over time, and was lower in the bivalirudin era (26% vs. 34%, P<0.05). There were 32 major bleeds (4.3%) in the bivalirudin era and 29 major bleeds (7.4%) in the UFH era (P=0.03), with the majority being hemoglobin drops (≥3 g/dL) without overt clinical bleeding (85.7% of bleeds in the bivalirudin era and 86.2% of bleeds in the UFH era). After adjustments for other common major causes of bleeding, bivalirudin was associated with 78% lower odds of bleeding (OR =0.22; 95% CI: 0.05-0.91)., Conclusions: An increase in major bleeding events occurred after switching to an UFH-first strategy, primarily associated with hemoglobin drop (≥3 g/dL) without overt clinical bleeding. Major overt bleeding was rare (0.3%) and similar in both groups. These results suggest a UFH-first strategy for PCI may have a role in patients with low bleeding risk., Competing Interests: Conflicts of Interest: The authors have no conflicts of interest to declare.

Background: Current guidelines recommend early invasive intervention (<24 hr) for high risk patients with non-ST-segment elevation myocardial infarction (NSTEMI). A delayed invasive strategy (24-72 hr) is considered reasonable for low risk patients. The real-world effectiveness of this strategy is unknown., Methods: The ARIC Study has conducted hospital surveillance of acute myocardial infarction (MI) since 1987. NSTEMI was classified using a validated algorithm. We limited our study to patients undergoing early (<24 hr of the event onset), or late (≥24 hr) percutaneous coronary intervention (PCI). Patients were stratified into low (TIMI score 2-4), and high risk (TIMI score 5-7, or presence of cardiogenic shock, ventricular fibrillation, or cardiac arrest). Associations between early versus late PCI and mortality were analyzed using multivariable logistic regression adjusted for demographics, hospitalization year, TIMI score, and comorbidities., Results: From 1987 to 2012, 6,746 patients were hospitalized with NSTEMI and underwent PCI. Most were white (79%), male (68%), with mean age 61 years. The 28-day and 1-year mortality were 2% and 5%, respectively. Most revascularizations (65%) were late. After accounting for potential confounders, early PCI was associated with a 58% reduced 28-day mortality (OR = 0.42; 95% CI: 0.21-0.84) for the entire population, and 57% reduced mortality (OR = 0.43; 95% CI: 0.21-0.88) for high risk patients. By 1-year of follow up, there was no significant difference in mortality with respect to early vs. late PCI., Conclusion: In hospitalized NSTEMI patients with high risk of clinical events, early PCI is associated with improved 28-day survival., (© 2017 Wiley Periodicals, Inc.)