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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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Supplemental Digital Content is available in the text. 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. [ABSTRACT FROM AUTHOR]

Supplemental Digital Content is available in the text. 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 µm2; P <0.0001). Myocardial tissue analysis identified a dose-dependent upregulation of the ubiquitin ligase, MuRF1 (muscle ring finger-1; R2=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. [ABSTRACT FROM AUTHOR]

Background: Carotid intima-medial thickness (IMT) is an indicator of subclinical atherosclerosis and medial hypertrophy, and is easily quantified by ultrasonography. Although carotid IMT has been associated with systemic cardiovascular disease, its relation to silent brain infarctions (SBI) is not well established. The etiology of SBI is multifactorial; likely causes include atherosclerotic and thrombotic obstructions, microthrombi, and lipohyalinosis. Because arterial IMT reflects both atherogenesis and hypertensive remodeling, we hypothesized that elevated carotid IMT would be associated with SBI. Methods: The Atherosclerosis Risk in Communities (ARIC) study is an observational cohort of 15,792 black and white participants from 4 US communities. At visit 3 (1993-1995) a subset of stroke-free study participants (N=1,346) was screened by brain MRI and carotid ultrasound. IMT was averaged bilaterally, from 12 posterior wall measurements along a 1 cm segment of the distal common carotid artery up to the bifurcation. Consistent with European Society of Cardiology recommendations, IMT > 0.9 mm was considered elevated. Asymptomatic brain lesions ≥3 mm in diameter were considered SBI. Prevalence ratios (PRs) for number of SBI lesions associated with elevated IMT were analyzed using Poisson regression, adjusted for age, race-center, sex, current smoking, hypertension, diabetes, and hyperlipidemia. Model fit was ascertained by the deviance to degree of freedom ratio. Results: Of 1,346 individuals, 170 (13%) were classified with elevated IMT. Mean IMT was 1.0 ± 0.2 mm vs. 0.7 ± 0.1 mm for those with and without elevated IMT. Study participants with elevated IMT were more often male (49% vs. 38%; p=0.006), black (60% vs. 46%; p=0.0007), and older (64 vs. 62 years; p=0.0001); with a greater prevalence of both hypertension (65% vs. 42%; p<0.0001) and diabetes (27% vs. 13%; p<0.0001). SBI were detected in 157 individuals with a collective total of 247 lesions. A total of 30 (18%) participants with elevated IMT had at least one SBI lesion, compared to 127 (11%) with normal IMT (p=0.009). Elevated IMT was associated with 70% greater number of SBI lesions (PR=1.7; 95% CI: 1.3 - 2.3; p=0.0008). After adjustment for cardiovascular risk factors, elevated IMT remained associated with a 40% greater SBI count (PR= 1.4; 95% CI: 1.0 - 1.9; p=0.05). Conclusions: Although elevated IMT is often classified by a conservative 0.9 mm cut-point, it is a continuum, with advanced wall thickening (>1.5 mm) recognized as plaque. In this analysis from the ARIC Study, asymptomatic individuals classified with elevated IMT had mild wall thickening (mean IMT = 1.0 mm), which nonetheless was associated with greater number of SBI lesions. This association remains robust after adjustment for cardiovascular risk factors. [ABSTRACT FROM AUTHOR]

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.