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Background: There is a growing recognition of the inherent limitations of the use of the left ventricular ejection fraction (LVEF) to accurately phenotype patients with heart failure (HF).
Objectives: The authors sought to identify unique proteomic signatures for patients with HF with reduced ejection fraction (HFrEF), HF with a midrange LVEF (HFmrEF), and HF with preserved ejection fraction (HFpEF), as well as to identify molecular differences between patients with ischemic and nonischemic HF.
Methods: We used high-content aptamer-based proteomics technology (SOMAscan) to interrogate the blood proteome of age- and sex-matched patients with HF within different LVEF groups.
Results: Within the Washington University Heart Failure Registry, we identified age/sex-matched patients within 3 LVEF categories: HFrEF (LVEF <40%), HFmrEF (LVEF 40% to 50%), and HFpEF (LVEF >50%). We found that patients with HFrEF, HFmrEF, and HFpEF had unique variations in circulating proteins that reflected distinct biological pathophysiologies. Bioinformatics analysis revealed that there were biological themes that were unique to patients with HFrEF, HFpEF, or HFmrEF. Comparative analyses of patients with HFmrEF with improved LVEF and patients with HFmrEF with unchanged LVEF revealed marked differences between these 2 patient populations and indicated that patients with recovered LVEF are more similar to patients with HFpEF than to patients with HFrEF. Moreover, there were marked differences in the proteomic signatures of patients with ischemic and nonischemic HF.
Conclusions: Viewed together, these findings suggest that it may be possible to use high-content multiplexed proteomics assays in combination with the clinical assessment of LVEF to more accurately identify clinical phenotypes of patients with HF.
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http://dx.doi.org/10.1016/j.jacc.2020.08.061 | DOI Listing |
Ann Am Thorac Soc
September 2025
Brigham and Women's Hospital, Division of Sleep and Circadian Disorders, Boston, Massachusetts, United States.
Rationale: There are insufficient data to inform the management of central sleep apnea (CSA) in patients with heart failure (HF) with reduced ejection fraction (HFrEF). Nocturnal oxygen therapy (NOT) has been postulated to benefit CSA patients with HFrEF, but has not been rigorously studied. This article is open access and distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives License 4.
View Article and Find Full Text PDFJ Gerontol A Biol Sci Med Sci
September 2025
Department of Epidemiology and Biostatistics, College of Human Medicine, Michigan State University, East Lansing, MI.
Background: Poor olfaction may be associated with incident heart failure (HF) in older adults, but empirical evidence is scant.
Methods: We included 5,217 participants free of clinical HF and with a smell assessment in 2011-2013 from the Atherosclerosis Risk in Communities Study. Olfaction was measured by the 12-item Sniffin' Sticks odor identification test and defined as good (score 11-12), moderate (9-10), or poor (≤8).
JAMA Cardiol
September 2025
Seymour, Paul and Gloria Milstein Division of Cardiology, Department of Medicine, Columbia University Irving Medical Center and New York-Presbyterian Hospital, New York, New York.
Importance: Transthyretin cardiac amyloidosis (ATTR-CA) is an underdiagnosed but treatable cause of heart failure (HF) in older individuals that occurs in the context of normal wild-type (ATTRwt-CA) or an abnormal inherited (ATTRv-CA) TTR gene variant. While the most common inherited TTR variant, V142I, occurs in 3% to 4% of self-identified Black Americans and is associated with excess morbidity and mortality, the prevalence of ATTR-CA in this at-risk population is unknown.
Objective: To define the prevalence of ATTR-CA and proportions attributable to ATTRwt-CA or ATTRv-CA among older Black and Caribbean Hispanic individuals with HF.
JACC Case Rep
September 2025
Cardiovascular Division, Department of Medicine, Froedtert and Medical College of Wisconsin, Milwaukee, Wisconsin, USA. Electronic address:
Baroreflex activation therapy (BAT) improves functional status, quality of life, and exercise capacity in patients with heart failure with reduced ejection fraction; however, its direct effects on reversing adverse cardiac remodeling as assessed by improvements in cardiac structure, function, and coupling with the arterial system remain unclear. We present 2 cases of patients who initially presented with decompensated heart failure, and despite initial medical therapy and continued outpatient follow-up, were unable to tolerate full escalation of guideline-directed medical therapy. The patients remained symptomatic, with high biomarker levels, poor functional capacity, severe heart failure symptoms, and objectively had decreased stroke volume, low left ventricular ejection fraction, and high left ventricular mass.
View Article and Find Full Text PDFJ Comp Eff Res
September 2025
British Heart Foundation, University of Glasgow, Glasgow, UK.
The first paper of this two-part series critically examined the role of composite endpoints in health technology assessments (HTAs) and outlined strategies for determining whether to employ the composite estimate of treatment effect or disaggregate into the component endpoints of the composite and apply separate treatment effects within a modeling framework. In this second paper, we expand the discussion beyond a pivotal trial and consider the way in which additional evidence from the same indication for different drugs in the same class, or the same drug for different indications, could be employed within HTAs. We offer a continuation of the case study of dapagliflozin for the treatment of heart failure with preserved or mildly reduced ejection fraction, where the evidence base was expanded to consider empagliflozin for the same indication, as well as both dapagliflozin and empagliflozin for heart failure with reduced ejection fraction.
View Article and Find Full Text PDF