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Aims Heart failure with preserved ejection fraction (HFpEF) is characterized by diastolic dysfunction, microvascular dysfunction, and myocardial fibrosis with recent evidence implicating the immune system in orchestrating cardiac remodelling. Methods and results Here, we show the mouse model of deoxycorticosterone acetate (DOCA)-salt hypertension induces key elements of HFpEF, including diastolic dysfunction, exercise intolerance, and pulmonary congestion in the setting of preserved ejection fraction. A modified single-cell sequencing approach, cellular indexing of transcriptomes and epitopes by sequencing, of cardiac immune cells reveals an altered abundance and transcriptional signature in multiple cell types, most notably cardiac macrophages. The DOCA-salt model results in differential expression of several known and novel genes in cardiac macrophages, including up-regulation of Trem2, which has been recently implicated in obesity and atherosclerosis. The role of Trem2 in hypertensive heart failure, however, is unknown. We found that mice with genetic deletion of Trem2 exhibit increased cardiac hypertrophy, diastolic dysfunction, renal injury, and decreased cardiac capillary density after DOCA-salt treatment compared to wild-type controls. Moreover, Trem2-deficient macrophages have impaired expression of pro-angiogenic gene programmes and increased expression of pro-inflammatory cytokines. Furthermore, we found that plasma levels of soluble TREM2 are elevated in DOCA-salt treated mice and humans with heart failure. Conclusions Together, our data provide an atlas of immunological alterations that can lead to improved diagnostic and therapeutic strategies for HFpEF. We provide our dataset in an easy to explore and freely accessible web application making it a useful resource for the community. Finally, our results suggest a novel cardioprotective role for Trem2 in hypertensive heart failure. [ABSTRACT FROM AUTHOR]

Capturing these social drivers of health would help elucidate and contextualize health inequities; however, few CVD studies collect and report social and structural determinants of health. CVD mortality remains 30% higher for Black men and women[1] and Native Americans are 50% more likely to be diagnosed with CVD compared with their White counterparts. Keywords: cardiovascular diseases; clinical trials as topic; health equity; research EN cardiovascular diseases clinical trials as topic health equity research 204 206 3 07/20/23 20230718 NES 230718 Despite substantial investments in cardiovascular disease (CVD) research and groundbreaking advances in treatment, longstanding inequities in CVD outcomes persist among marginalized racial and ethnic groups. [Extracted from the article]

Background: Greater left ventricular (LV) wall stress is associated with adverse outcomes among patients with prevalent heart failure (HF). Less is known about the association between LV wall stress and incident HF., Objectives: The purpose of the study was to identify clinical factors associated with wall stress and test the association between wall stress and incident HF., Methods: We studied 4,601 ARIC (Atherosclerosis Risk In Communities) study participants without prevalent HF who underwent echocardiography between 2011 and 2013. LV end systolic and diastolic wall stress (LVESWS, LVEDWS) were calculated from chamber and wall thickness, systemic blood pressure, and transmitral Doppler E/e' as a surrogate for LV end diastolic pressure. Incident HF was ascertained by International Classification of Diseases (ICD)-9/10 claims for hospitalized HF through December 31, 2016. We used Cox regression to test the association between wall stress and incident HF, adjusted for demographics, traditional cardiovascular risk factors, prevalent coronary artery disease and atrial fibrillation, creatinine, N-terminal pro-B-type natriuretic peptide, troponin, triglycerides, C-reactive protein, LV ejection fraction, and LV mass., Results: The cohort had a median age of 75 years and 58% women, with 18% identifying as Black. Median LVESWS and LVEDWS were 48.8 (25th-75th percentile: 39.3-60.1) and 18.9 (25th-75th percentile: 15.8-22.5) kdynes/cm 2 , respectively. LVESWS and LVEDWS were modestly related (rho = 0.30, P  < 0.001). Over 4.6 years of median follow-up (156 HF events), each 1 kdyne/cm 2 greater LVEDWS was significantly associated with higher risk of incident HF (HR: 1.03; 95% CI: 1.01-1.06), while LVESWS was not (HR: 1.00; 95% CI: 0.99-1.01)., Conclusions: Among community-dwelling elderly individuals, greater LVEDWS is associated with a higher risk for incident HF., Competing Interests: This study was funded by the 10.13039/100000002National Institutes of Health (Drs White, Brittain, Lindman, Mosley, Shah, Wells, Kuipers, Gupta [R01HL153607, R01HL148661, R01HL154153, R38HL167237]); 10.13039/100005485American College of Cardiology/Association of Black Cardiologists Bristol Myers Squibb (Dr Dixon), Department of Veteran’s Affairs (VA), 10.13039/100000968American Heart Association (Drs Perry and Shah), 10.13039/100006520Edwards Lifesciences (Dr Lindman), and Cytokinetics (Dr Shah). Dr Shah is a co-inventor on a patent for ex-RNAs’ signatures of cardiac remodeling and in the past 12 months has served as a consultant for Cytokinetics. Dr Lindman has in the past 12 months served as a consultant for Edwards Lifesciences. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (© 2024 The Authors.)