Daily Cardiology Research Analysis

BACKGROUND: Despite the high morbidity and mortality of heart failure with preserved ejection fraction (HFpEF), treatment options remain limited. The HFpEF syndrome is associated with a high comorbidity burden, including high prevalence of obesity and hypertension. Although inflammation is implicated to play a key role in HFpEF pathophysiology, underlying causal mechanisms remain unclear. METHODS: Comparing patient samples and animal models, we defined the innate immune response during HFpEF in situ and through flow cytometry and single-cell RNA sequencing. After identifying transcriptional and cell signatures, we implemented a high-fat diet and hypertensive model of HFpEF and tested roles for myeloid and hematopoietic stem cells during HFpEF. Contributions of macrophage metabolism were also evaluated, including through mass spectrometry and carbon labeling. Primary macrophages were studied ex vivo to gain insight into complementary cell-intrinsic mechanisms. RESULTS: Here we report evidence that patients with cardiometabolic HFpEF exhibit elevated peripheral blood hematopoietic stem cells. This phenotype was conserved across species in a murine mode of high-fat diet and hypertension. Hematopoietic stem cell proliferation was coupled to striking remodeling of the peripheral hematopoietic stem cell niche and expression of the macrophage adhesion molecule CONCLUSIONS: These findings identify a significant new stem cell signature of cardiometabolic HFpEF and support a role for myeloid maladaptive fatty acid metabolism in the promotion of systemic inflammation and cardiac diastolic dysfunction.

Atrial fibrillation (AF) is one of the most common cardiac diseases and a complicating comorbidity for multiple associated diseases. Many clinical decisions regarding AF are currently based on the binary recognition of AF being present or absent with the categorical appraisal of AF as continued or intermittent. Assessment of AF in clinical trials is largely limited to the time to (first) detection of an AF episode. Substantial evidence shows, however, that the quantitative characteristic of intermittent AF has a relevant impact on symptoms, onset, and progression of AF and AF-related outcomes, including mortality. Atrial fibrillation burden is increasingly recognized as a suitable quantitative measure of intermittent AF that provides an estimate of risk attributable to AF, the efficacy of antiarrhythmic treatment, and the need for oral anticoagulation. However, the diversity of assessment methods and the lack of a consistent definition of AF burden prevent a wider clinical applicability and validation of actionable thresholds of AF burden. To facilitate progress in this field, the AF burden Consensus Group, an international and multidisciplinary collaboration, proposes a unified definition of AF burden. Based on current evidence and using a modified Delphi technique, consensus statements were attained on the four main areas describing AF burden: Defining the characteristics of AF burden, the recording principles, the clinical relevance in major clinical conditions, and implementation as an outcome in the clinic and in clinical trials. According to this consensus, AF burden is defined as the proportion of time spent in AF expressed as a percentage of the recording time, undertaken during a specified monitoring duration. A pivotal requirement for validity and comparability of AF burden assessment is a continuous or near-continuous duration of monitoring that needs to be reported together with the AF burden assessment. This proposed unified definition of AF burden applies independent of comorbidities and outcomes. However, the disease-specific actionable thresholds of AF burden need to be defined according to the targeted clinical outcomes in specific populations. The duration of the longest episode of uninterrupted AF expressed as a time duration should also be reported when appropriate. A unified definition of AF burden will allow for comparability of clinical study data to expand evidence and to establish actionable thresholds of AF burden in various clinical conditions. This proposed definition of AF burden will support risk evaluation and clinical treatment decisions in AF-related disease. It will further promote the development of clinical trials studying the clinical relevance of intermittent AF. A unified approach on AF burden will finally inform the technology development of heart rhythm monitoring towards validated technology to meet clinical needs.

IMPORTANCE: Food insecurity is associated with prevalent cardiovascular disease (CVD), but studies have been limited to cross-sectional data. OBJECTIVES: To study whether food insecurity is associated with incident CVD and to determine whether this association varies by sex, education, or race. DESIGN, SETTING, AND PARTICIPANTS: This prospective cohort study was conducted among US adults without preexisting CVD participating in the CARDIA (Coronary Artery Risk Development in Young Adults) study from 2000 to August 31, 2020. Data analysis was conducted from December 2022 to April 2024. EXPOSURE: Food insecurity, defined as endorsing limitations in household food variety and/or food quantity, assessed in the period 2000-2001. MAIN OUTCOMES AND MEASURES: The primary outcome was CVD events, consisting of fatal and nonfatal coronary heart disease, heart failure, stroke, transient ischemic attack, or peripheral arterial disease, identified annually through August 31, 2020. RESULTS: Of 3616 total participating adults, mean (SD) age was 40.1 (3.6) years, and 2027 participants (56%) were female. Of 3616 participants, 1696 (47%) self-reported Black race and 529 participants (15%) had food insecurity at baseline. Individuals with food insecurity were more likely to self-identify as Black and report lower educational attainment. The mean (SD) follow-up period was 18.8 (3.4) years, during which 255 CVD events occurred: 57 events (11%) in food-insecure participants and 198 events (6%) in food-secure participants over the study period. After adjusting for age, sex, and field center, food insecurity was associated with incident CVD (adjusted hazard ratio [aHR], 1.90; 95% CI, 1.41-2.56). The association persisted (aHR, 1.47; 95% CI, 1.08-2.01) after further adjustment for the socioeconomic factors of education, marital status, and usual source of medical care. CONCLUSIONS AND RELEVANCE: In this prospective cohort study among participants in the CARDIA study, food insecurity was associated with incident CVD even after adjustment for socioeconomic factors, suggesting that food insecurity may be an important social deprivation measure in clinical assessment of CVD risk. Whether interventions to reduce food insecurity programs can potentially alleviate CVD should be further studied.