Do obesity and visceral adiposity promote heart failure with reduced ejection fraction?

Obesity or excess visceral adiposity plays a fundamental role in the pathogenesis of heart failure with preserved ejection fraction (HFpEF), but it is not clear that an expanded adipose tissue mass contributes importantly to the evolution and progression of heart failure with reduced ejection fraction (HFrEF). Whereas central adiposity characterizes most patients with HFpEF, obesity was not a remarkable feature of HFrEF in the large-scale trials carried out in the 1980s and 1990s, and studies typically characterized obesity as a protective factor against adverse outcomes. In the general community without apparent heart disease, the finding of obesity or central adiposity precedes and predicts the subsequent occurrence of HFpEF, but not HFrEF.

The Adipokine Hypothesis of Heart Failure With a Preserved Ejection Fraction: A Novel Framework to Explain Pathogenesis and Guide Treatment.

Hypothesis: The paper proposes a novel unifying hypothesis-that heart failure with preserved ejection fraction (HFpEF) arises primarily from the expansion and dysfunctional transformation of visceral adipose tissue, leading to the secretion of altered suite of signaling molecules (adipokines), which causes systemic inflammation, plasma volume expansion, and cardiac hypertrophy and fibrosis.

Elements Of The Framework: The framework groups adipokines into 3 domains. Domain I adipokines are cardioprotective molecules but are suppressed in patients with excess adiposity.

Sacubitril/valsartan and Quality of Life Assessed Using the EuroQol 5-Dimension 3-Level Questionnaire Level Sum Score (EQ-5D-3L-LSS) in Patients with HFrEF and HFmrEF/HFpEF.

Objectives: To investigate the EQ-5D-3L Level Sum Score (LSS) in patients with heart failure (HF) and reduced (HFrEF) and mildly reduced or preserved ejection fraction (HFmrEF/HFpEF) and the effect of sacubitril/valsartan on this score using patient-level data from the PARADIGM-HF and PARAGON-HF trials.

Methods: The LSS was calculated by summating the 3 levels (1-3) for each of the 5 domains (minimum sum score=5; maximum sum score=15). Patient characteristics and outcomes were compared across LSS tertiles (T1-T3) at baseline.

The HEALERS: a patient, community, and stakeholder advisory board focus group series to refine a novel virtual world-based cardiac rehabilitation intervention and clinical trial.

Background: Cardiac rehabilitation (CR) is a widely underutilized secondary cardiovascular disease prevention strategy, due to a variety of barriers to participation that disproportionately impact women, minoritized racial and ethnic groups, and patients with low socioeconomic status. , a virtual world-based CR (VWCR) program designed by our team in collaboration with patients and community members to mitigate the barriers to CR participation, has demonstrated feasibility and acceptability. In anticipation of a randomized controlled trial (RCT) to further validate the intervention, this qualitative descriptive analysis provides insights garnered from a patient/community/stakeholder-advisory board (PCS-AB, HEALERS) focus group series, convened to inform iterative refinements to a RCT protocol.

Race and Ethnicity in Heart Failure Trials: Time to Update Recommended Categories for Global Relevance.

Background: The collection of race and ethnicity data in clinical trials using standardized categories is recommended by the US Food and Drug Administration, although this is primarily for domestic reasons. The applicability and understanding of the categories in multinational trials are uncertain.

Methods: We analyzed patient-level data from 13 major heart failure trials, examining race and ethnicity data recorded by country, as recommended by the Food and Drug Administration: "American Indian or Alaska Native," "Asian," "Black or African American," "Native Hawaiian or Other Pacific Islander," and "White" for race and "Hispanic or Latino" as a minimum for ethnicity (with an expanded list of ethnicities available).

Cardiovascular Health in Cardiac Rehabilitation: Applying the American Heart Association Life's Simple 7 Framework in a Center-Based Cohort.

Background: Cardiac rehabilitation (CR) is a comprehensive secondary cardiovascular disease program with structured lifestyle interventions to reduce morbidity and mortality. The American Heart Association cardiovascular health (CVH) framework measures health-promoting behaviors and clinical factors, but it has not been rigorously evaluated in the CR setting.

Methods: This retrospective cohort study analyzed patients attending CR from January 2018 to September 2020.

Effect of Empagliflozin on the Mechanisms Driving Erythropoiesis and Iron Mobilization in Patients With Heart Failure: The EMPEROR Program.

Background: Sodium-glucose cotransporter 2 (SGLT2) inhibitors stimulate erythropoiesis, but the mechanisms and clinical relevance of the effect of SGLT2 inhibitors on systemic iron metabolism in patients with heart failure is not well understood.

Objectives: The authors sought to characterize a comprehensive suite of iron metabolism biomarkers-particularly the erythroblast signaling molecule, erythroferrone-in patients with heart failure before and after short- and long-term treatment with empagliflozin in patients with heart failure and a reduced or preserved ejection fraction.

Methods: We measured serum iron metabolism biomarkers at baseline, 12 weeks, and 52 weeks in 1,139 patients who were treated with placebo or empagliflozin in the EMPEROR (EMPagliflozin outcomE tRial in Patients With chrOnic heaRt Failure) program, and we characterized the inter-relationships of these biomarkers with clinical status and with the effect of empagliflozin on erythropoiesis and heart failure outcomes.

Prognostic Significance of Nutritional Scores in Patients With Heart Failure: Insights From the PARAGON-HF Trial.

Background: The Controlling Nutritional Status (CONUT) and Geriatric Nutritional Risk Index (GNRI) are indices that identify individuals at risk of malnutrition. Our study sought to examine the incidence and prognostic implications of abnormal CONUT and/or GNRI in patients with heart failure with preserved ejection fraction.

Methods And Results: The CONUT score and GNRI were serially analyzed in this post hoc analysis of the PARAGON-HF (Prospective Comparison of Angiotensin Receptor-Neprilysin Inhibitor With Angiotensin-Receptor Blockers Global Outcomes in Heart Failure With Preserved Ejection Fraction) trial.

Comprehensive Analysis of the Effects of Sacubitril/Valsartan According to Sex Among Patients With Heart Failure and Reduced Ejection Fraction in PARADIGM-HF.

Background: Women with heart failure (HF) ejection fraction appeared to respond more favorably to sacubitril/valsartan, compared with valsartan, than men in PARAGON-HF (Prospective Comparison of ARNI With ARB Global Outcomes in Heart Failure With Preserved Ejection Fraction), driven by a greater reduction in total (first and recurrent) HF hospitalizations. Sex-specific efficacy and safety of sacubitril/valsartan in PARADIGM-HF (Prospective Comparison of ARNI With ACEI to Determine Impact on Global Mortality and Morbidity in Heart Failure) remain unreported.

Methods And Results: This post hoc analysis of PARADIGM-HF examined sex-based outcomes in patients with HF and reduced ejection fraction randomized to sacubitril/valsartan or enalapril.

Effects of Sacubitril/Valsartan According to Natriuretic Peptide Levels in Patients Enrolled in PARADIGM-HF and PARAGON-HF.

Background: Recent trials of new heart failure (HF) treatments suggest the effect of therapy may vary by N-terminal pro-B type natriuretic peptide (NT-proBNP) level.

Objectives: The authors examined the efficacy of sacubitril/valsartan according to NT-proBNP levels in patients with reduced, mildly reduced, and preserved left ventricular ejection fraction (LVEF) enrolled in PARADIGM-HF (Prospective Comparison of Angiotensin Receptor-Neprilysin Inhibitor with Angiotensin-Converting-Enzyme Inhibitor to Determine Impact on Global Mortality and Morbidity in Heart Failure Trial) and PARAGON-HF (Prospective Comparison of Angiotensin Receptor-Neprilysin Inhibitor with Angiotensin-Receptor Blockers Global Outcomes in HF with Preserved Ejection Fraction).

Methods: Individual patient data from PARADIGM-HF and PARAGON-HF were pooled and participants were divided into categories defined by quintiles of NT-proBNP level.

Impact of Multimorbidity on Mortality in Heart Failure With Mildly Reduced and Preserved Ejection Fraction.

Background: How different combinations of comorbidities influence risk at the patient level and population level in patients with heart failure with mildly reduced ejection fraction/heart failure with preserved ejection fraction is unknown. We aimed to investigate the prevalence of different combinations of cardiovascular and noncardiovascular comorbidities (ie, multimorbidity) and associated risk of death at the patient level and population level.

Methods: Using patient-level data from the TOPCAT trial (Treatment of Preserved Cardiac Function Heart Failure With an Aldosterone Antagonist) and PARAGON-HF trial (Prospective Comparison of ARNI With ARB Global Outcomes in HF With Preserved Ejection Fraction), we investigated the 5 most common cardiovascular and noncardiovascular comorbidities and the resultant 45 comorbidity pairs.

Incident heart failure and recurrent coronary events following acute myocardial infarction.

Background And Aims: Recurrent myocardial infarction (MI) and incident heart failure (HF) are major post-MI complications. Herein, contemporary post-MI risks for recurrent MI and HF are described.

Methods: A total of 6804 patients with a primary discharge diagnosis of MI at 28 Baylor Scott & White Health hospitals (January 2015 to December 2021) were studied.

Did Finerenone Improve Health Status in the FINEARTS Trial?: A Critical Reevaluation of the Analysis of Patient-Reported Outcomes in Heart Failure.

Patient-reported health status is an important assessment of patients with heart failure, but current approaches have substantial methodological and analytical limitations. Changes in the Kansas City Cardiomyopathy Questionnaire (KCCQ) are commonly presented as a measure of the effect of drugs and devices, most often as the between-group difference in population means or as the odds of showing threshold changes of 5, 10, 15, and 20 points. However, the presentation of mean differences is based on statistical assumptions that are routinely violated in most trials.

Clinical Characteristics and Outcomes of Patients With Heart Failure With Preserved Ejection Fraction and With Reduced Ejection Fraction According to the Prognostic Nutritional Index: Findings From PARADIGM-HF and PARAGON-HF.

Background: The importance of nutritional status is underappreciated in patients with heart failure (HF). This study aimed to describe the range of the prognostic nutrition index (PNI), and the clinical characteristics and outcomes according to PNI, in patients with HF with preserved ejection fraction (HFpEF) and reduced ejection fraction (HFrEF). The primary outcome was the composite of HF hospitalization or cardiovascular death.