Search Results (372)

Heart failure (HF) is a major cardiovascular complication in people with type 2 diabetes (T2D), where heart failure with preserved ejection fraction (HFpEF) is the most common presentation. Despite its high prevalence, HF in T2D often remains undiagnosed during its early stages due to nonspecific symptoms and the limitations of conventional diagnostic tools. Epicardial adipose tissue (EAT), a visceral fat depot surrounding the myocardium, has emerged as a mechanistic and clinically relevant contributor to myocardial dysfunction. In T2D, EAT expansion fosters a pro-inflammatory, fibrotic, and metabolically adverse milieu that may directly promote the onset and progression of HF. This perspective synthesizes current translational evidence on the role of EAT in the pathogenesis of HF among individuals with T2D. We highlight diagnostic challenges related to imaging-based quantification and the limited sensitivity of natriuretic peptide-based screening, while emphasizing the potential relevance of emerging biomarkers such as GDF-15, Galectin-3, sST2, LDL particle size, GGT, and soluble low-density lipoprotein receptor-related protein 1 (sLRP1) to enhance early detection and risk stratification. Additionally, therapeutic approaches—including lifestyle modification, SGLT2 inhibitors, and GLP-1 receptor agonists—are considered for their potential to modulate EAT volume and reduce cardiovascular risk. Advancing knowledge on EAT biology and its circulating biomarkers holds promise to refine HF risk stratification and support translational efforts toward precision cardiometabolic care. Full article

Background: Heart failure with preserved ejection fraction (HFpEF) is a complex and heterogeneous clinical syndrome that represents an increasing global health challenge due to its high rates of morbidity, hospitalization, and mortality. In this context, cardiopulmonary exercise testing (CPET) has emerged as a valuable diagnostic modality, particularly in patients presenting with unexplained exertional dyspnea and inconclusive resting imaging results. Objectives and Clinical Implications: This narrative review examines current evidence on the clinical relevance and prognostic value of CPET parameters in HFpEF. Peak VO₂, a marker of aerobic capacity and cardiovascular fitness, has established prognostic value in heart failure with reduced ejection fraction (HFrEF). However, its prognostic significance in HFpEF remains less well defined. Oxygen pulse has emerged as another important measure for evaluating functional capacity and predicting response to exercise-based interventions, offering potential prognostic insight into adverse outcomes in HFpEF. Finally, the VE/VCO₂ slope, an index of ventilatory efficiency during exercise, also holds clinical relevance in HFpEF, particularly with concomitant pulmonary hypertension, though evidence remains heterogeneous. Conclusions: CPET-derived variables are valuable parameters for HFpEF assessment. Their systematic integration into clinical evaluation of HFpEF patients could guide individualized management strategies and inform clinicians for improving outcomes in this challenging condition. Full article

Background: Heart failure with preserved ejection fraction (HFpEF) is a major cause of hospitalization and mortality in older adults. Sudden cardiac arrest (SCA) is a leading cause of death in this population, yet national trends in incidence, outcomes, and disparities remain poorly defined. Methods: We performed a retrospective cohort study using the National Inpatient Sample from 2016 to 2020. Hospitalizations for patients aged ≥65 years with HFpEF and in-hospital cardiac arrest (CA) were identified using ICD-10-CM codes. Demographics, comorbidities, hospital outcomes, and temporal trends were examined. The primary outcome was in-hospital mortality. Secondary outcomes included length of stay, hospital charges, and discharge disposition. Results: Among 7,738,108 HFpEF admissions, 93,440 (1.2%) involved CA. Incidence rose from 1.1% in 2016 to 1.5% in 2020 (36% relative increase). The median age was 81 years; 54% were female, 70% White, 19% Black, and 8% Hispanic. CA incidence increased across all groups, with the largest relative rises among Native American (1.0% to 1.9%), Black (1.7% to 2.3%), and Hispanic patients (1.4% to 2.0%). In-hospital mortality was high, increasing from 58.2% to 61.7% over the study period (p < 0.001). Mortality rose most steeply among Black and low-income patients. Comorbidity patterns shifted toward greater metabolic complexity, including higher rates of complicated diabetes, hypertension, hyperlipidemia, and obesity. Conclusions: Elderly patients hospitalized with HFpEF are experiencing rising rates of in-hospital CA and persistently high mortality, with marked racial and socioeconomic disparities. These findings highlight the need for better risk stratification, targeted metabolic and inflammatory therapies, and more equitable care delivery. Full article

Background: Atrial fibrillation (AF) is a common comorbidity in heart failure with preserved ejection fraction (HFpEF), yet the optimal rhythm control strategies and the emerging role of sodium–glucose cotransporter-2 inhibitors (SGLT2i) in maintaining sinus rhythm remain unclear. Methods: We conducted a single-centre, retrospective study of 120 consecutive HFpEF patients with paroxysmal or persistent AF, treated by electrical cardioversion, radiofrequency ablation (RFA), or cryoablation. The primary outcome was AF recurrence, with secondary outcomes including time to recurrence and the impact of SGLT2i on AF recurrence. Results: Both cryoablation (HR = 0.226, 95% CI: 0.089–0.573, p = 0.002) and RFA (HR = 0.293, 95% CI: 0.131–0.654, p = 0.003) were associated with lower AF recurrence rates and longer arrhythmia-free survival compared to electrical cardioversion. SGLT2i therapy was independently associated with fewer recurrences (HR = 0.421, 95% CI: 0.266–0.786, p = 0.007) and a 12-week extension of AF-free time. Conclusions: In HFpEF with AF, prioritising catheter ablation over cardioversion and combining rhythm control with SGLT2i improves rhythm durability. Full article

Background: Heart failure (HF) remains a major global health challenge with substantial morbidity, mortality, and healthcare burden. Finerenone, a novel non-steroidal mineralocorticoid receptor antagonist (MRA), has demonstrated cardiovascular and renal benefits in patients with diabetes mellitus (DM) and chronic kidney disease (CKD), as well as reduced HF events, in patients with HF with preserved or mildly reduced ejection fraction (HFpEF/HFmrEF). However, its efficacy and safety in patients with HF with reduced EF (HFrEF) or HFmrEF, DM, and CKD, remain unclear. Notably, finerenone is currently reimbursed only for DM and CKD but not for HF itself. Methods: We conducted a retrospective, single-center study of patients with HFrEF/HFmrEF who received finerenone between August 2022 and June 2025. Clinical data were obtained 6 months before, at baseline, and 6 months after the initiation of finerenone. The primary outcome was the change in serum NT pro-B-type natriuretic peptide (BNP). Results: Among 37 patients screened, 22 who initiated finerenone on a de novo basis were included. Median age was 75 years, 73% were male, and all had DM and CKD, which are current indications of finerenone. NT pro-BNP decreased significantly during the on-treatment period compared with the pre-treatment period (p < 0.001). Left ventricular end-diastolic diameter and left ventricular ejection fraction remained unchanged during the pre-treatment period but improved significantly during the on-treatment period (p < 0.001 for both). Renal function and serum potassium remained stable during the whole study period (p > 0.05 for both). Conclusions: In this real-world study of patients with HFrEF/HFmrEF complicated by DM and CKD, finerenone was associated with significant improvements in NT pro-BNP and cardiac remodeling indices without worsening renal function or hyperkalemia. Full article

Background and Objectives: Left ventricular diastolic dysfunction (LVDD) is a known precursor of heart failure with preserved ejection fraction (HFpEF), particularly in patients with metabolic comorbidities. Acute coronary syndrome (ACS) and percutaneous coronary interventions (PCI) may exacerbate LVDD via systemic inflammation. This study aimed to explore the association between post-procedural systemic inflammation and the severity of diastolic dysfunction in patients with ACS and metabolic comorbidities. Materials and Methods: A retrospective observational study was conducted in 181 patients with ACS who underwent PCI. Inflammatory markers (leukocytes, neutrophils, and C-reactive protein [CRP]) measured at 24–48 h post-intervention were analyzed in relation to diastolic dysfunction, assessed by echocardiography. Multivariable ordinal logistic regression and correlation analyses were performed. Results: CRP showed a non-significant trend toward association with more advanced diastolic dysfunction (p = 0.081). Hypertension had a positive but nonsignificant coefficient. Other metabolic comorbidities (diabetes, dyslipidemia, and obesity) were not significantly associated. The correlation between N-terminal pro-B-type natriuretic peptide (NT-proBNP) and troponin was exploratory. NT-proBNP was the only marker significantly correlated with high-sensitivity troponin (TrHS) at 48 h, indicating a link between myocardial injury and wall stress. Conclusions: CRP may be weakly associated with the severity of diastolic dysfunction post-PCI. However, classical metabolic comorbidities were not independently predictive. Post-PCI inflammation showed only modest, non-significant trends toward diastolic impairment, warranting confirmation in larger prospective studies. Full article

Glucagon-like peptide-1 receptor agonists (GLP1-RAs) have demonstrated significant cardiometabolic benefits, particularly in patients with type 2 diabetes and obesity. Their role in heart failure (HF) is gaining increasing attention, with growing evidence supporting their efficacy in HF with preserved ejection fraction (HFpEF). Recent trials have shown that semaglutide improves symptoms, functional capacity, and weight loss in patients with HFpEF. However, these trials did not demonstrate a reduction in HF hospitalizations or mortality. In contrast, tirzepatide has revealed a significant reduction in cardiovascular death and worsening HF events in patients with obesity-related HFpEF, suggesting broader cardioprotective effects. Concordantly, the benefit of GLP1-RAs in the setting of HF with reduced ejection fraction (HFrEF) remains uncertain. Although their mechanisms suggest potential advantages, particularly for patients with a cardiometabolic phenotype, clinical evidence supporting improvements in major clinical outcomes is lacking. Additionally, concerns regarding risk of increased HF hospitalizations, fluid retention and arrhythmic risk have led to a cautious approach in this population. As HF management continues to evolve, GLP1-RAs emerge as a promising yet complex therapeutic option. This review synthesizes the current evidence, highlights key knowledge gaps, and explores how these medications might be integrated into guideline-directed medical therapy (GDMT) to determine their optimal role across the LVEF spectrum in HF. Full article

Heart failure with preserved ejection fraction (HFpEF) currently accounts for half of the heart failure (HF) cases world-wide, affecting nearly 32 million people. HFpEF has a skewed prevalence toward females and those older than 65 years old. The pathophysiology of HFpEF is suggestive of a conglomerate of inflammatory, hypertensive, as well as metabolic dysfunction, giving rise to the syndrome. Disruptions in ceramide metabolism do occur in heart failure as well as within the HFpEF-associated risk factors, both modifiable inflammation, obesity, hypertension, diabetes, and non-modifiable-aging, and female sex. The focus of this review is to draw attention to the links between changes in female biophysiology, such as pregnancy, menopause and aging, in which ceramide is dysregulated and consequently gives rise to the same pathologies that are labeled as risk factors for HFpEF. Our objective is to highlight ceramides as potential biomarkers for prevention and initial diagnostic tools for HFpEF, especially for women later in life. Full article

Cardiopulmonary bypass (CPB) can lead to cardiac damage due to oxidative stress (OS) and inflammation in heart failure (HF). We tested the hypothesis that preoperative HF patients with reduced ejection fraction (HFrEF) subjected to CBP have higher levels of OS and NLRP3 (NOD-, LRR- and pyrin domain-containing protein 3) in heart and plasma and in those that develop postoperative AF (pAF) as a clinical outcome. HF was categorized for preoperative left ventricular EF: preserved (HFpEF > 50%, n = 27) and reduced EF (HFrEF ≤ 40%, n = 25). Samples of atrial tissue, pericardial fluid, and plasma were collected at surgery to assess NLRP3 expression; 3-nitrotyrosine (3-NT), thiobarbituric acid reaction (TBARS), and nuclear factor erythroid 2-related factor 2 (Nrf2) in atrial tissue; NLRP3, IL-1β, and IL-18 expression in pericardial fluid; and antioxidant capacity, 8-isoprostanes, and malondialdehyde (MDA) in plasma. Reactive oxygen species, 3-NT, and NLRP3 in atrial tissue were determined by immunohistochemistry in a subset of pAF patients. Plasma and atrial tissue 3-NT and MDA were higher in HFrEF compared with HFpEF. Lipid peroxidation products were higher in both plasma and atrial tissue in pAF (n = 29), compared to sinus rhythm (SR) (n = 23). In HFrEF patients, the values of tissue ROS, 3-NT, and NLRP3 were higher than in HFpEF patients. In addition, the expression levels of NLRP3, IL-1β, and IL-18 were higher in atrial tissue and pericardial fluid in HFrEF. Patients with preoperative HFrEF showed higher OS in plasma and the expression of NLRP3, ROS, and 3-NT in atrial tissue biopsies and pericardial fluid. This finding suggests a potential pharmacologic therapy for pAF and clinical complications due to CPB. Full article

Heart failure with preserved ejection fraction (HFpEF) remains a major clinical challenge due to its heterogeneous presentation and limited therapeutic options. Accurate patient phenotyping is essential to improve diagnosis, prognostication, and treatment personalization. Machine learning (ML) has emerged as a powerful tool to identify clinically meaningful HFpEF subgroups by integrating diverse data sources, including clinical, imaging, biomarker, and physiological parameters. ML-based models can uncover subtle patterns not captured by traditional methods, offering improved risk stratification, earlier intervention, and guidance toward individualized therapy. Future progress will rely on standardized data collection, validation across populations, and incorporation into clinical decision support systems. Advancements in explainable artificial intelligence, federated learning, and multi-omics integration are expected to further refine phenotyping strategies and translate into improved patient outcomes. Continued interdisciplinary collaboration is essential to unlock the full potential of ML in transforming HFpEF management. Full article

Background: Wild-type transthyretin cardiac amyloidosis (ATTRwt-CM) is a frequent but underdiagnosed cause of heart failure with preserved ejection fraction (HFpEF) and left ventricular hypertrophy (LVH). Early identification is essential given the availability of disease-modifying therapies. The T-Amylo and Davies scores are non-invasive tools for estimating ATTR CM probability, but their comparative performance in the same real-world population is not well defined. Objectives: To compare the diagnostic accuracy of T-Amylo and Davies scores in consecutive patients referred for suspected cardiac amyloidosis. Methods: We retrospectively analyzed 81 patients (mean age 76.8 ± 8.3 years, 74% male) who underwent a standardized work-up: ECG, echocardiography with strain, NT-proBNP and troponin, bone scintigraphy, and immunofixation. ATTR CM was diagnosed according to established non-biopsy criteria. Both scores were calculated retrospectively, and sensitivity, specificity, predictive values, accuracy, and agreement were assessed. Results: ATTR CM was confirmed in 28 patients (34.5%). T-Amylo showed higher sensitivity (91.2% vs. 73.5%) and NPV (89.7% vs. 79.1%), while Davies had greater specificity (85.0% vs. 65.0%) and PPV (80.5% vs. 70.8%). Overall accuracy was comparable (T-Amylo 77.0% vs. Davies 79.7%). Agreement between scores was moderate (κ = 0.59). Conclusions: T-Amylo is best suited as a screening tool for suspected ATTR CM, while Davies offers confirmatory value in high-probability cases. Combining these tools in a sequential strategy may optimize diagnostic efficiency, reduce unnecessary testing, and expedite initiation of disease-modifying therapy. Full article

Heart failure with preserved ejection fraction (HFpEF) is a complex syndrome characterized by left ventricular diastolic dysfunction, exercise intolerance, low-grade chronic inflammation, and comorbidities such as hypertension, obesity, and glucose intolerance. Myocardial infiltration by activated macrophages has been proposed as a mechanism linking low-grade inflammation to increased diastolic LV stiffness in HFpEF. Changes in the relative abundance of cardiac macrophage populations may precede and promote the development of HFpEF in the aged heart. This study aimed to characterize the cardiac macrophage subsets that predominate during progression from experimental preclinical to established HFpEF. To generate the model, wild-type male C57BL/6N mice were randomized to control chow or a combination of high-fat diet plus L-NAME in drinking water for 5 weeks (asymptomatic pre-HFpEF) or 15 weeks (established HFpEF). At the end of each period, we measured body weight, running distance, metabolic biomarkers, systolic and diastolic blood pressure, myocardial function and morphology, cardiac remodeling by hypertrophic markers, morphometric analyses, fibrosis, cytokines TNF-α and IL-10, cardiac macrophage phenotype profiles (CCR2⁺ and CCR2⁻), and AMP-Activated Protein Kinase (AMPK)activity.Significant changes in myocardial macrophage populations were observed at 5 weeks (pre-HFpEF), specifically a decrease in resident reparative CCR2⁻MHCII⁻ and increase in proinflammatory CCR2⁺MHCII⁺ macrophages. These early changes were associated with higher circulating TNF-α, decreased myocardial AMPK activation, and more severe myocardial fibrosis. At 15 weeks (established HFpEF), proinflammatory CCR2⁺MHCII⁺ macrophage levels remained elevated in the myocardium; whereas the initial number of resident reparative CCR2⁻MHCII^- levels was reduced, it subsequently returned to baseline. In this model of HFpEF induced by a high-fat diet and L-NAME, which produced obesity, glucose intolerance, and hypertension, myocardial resident reparative CCR2⁻MHCII⁻ macrophages decreased and proinflammatory CCR2⁺MHCII⁺ macrophages increased during preclinical stages. These early changes in cardiac macrophage profile were associated with low-grade inflammation and myocardial remodeling and preceded the onset of HFpEF. Full article

Background/Objectives: Real-world data about clinical characteristics and edoxaban performance in patients with heart failure (HF) and atrial fibrillation (AF) are lacking. The EMAYIC study aimed to assess and compare the profile and cardiovascular outcomes in those patients according to HF subtypes based on left ventricular ejection fraction (LVEF). Methods: Multicentre, prospective (follow-up: 12 months), observational study. Consecutive adult patients were included at cardiology and internal medicine clinics across Spain with HF (NT-proBNP > 600 pg/mL) and AF, receiving edoxaban as per routine clinical practice. Incidence of major or clinically relevant non-major (CRNM) bleeding and composite of incidence of stroke or systemic embolism (SE) were assessed according to HF subtypes: reduced (HFrEF, LVEF < 40%), mildly reduced (HFmrEF, LVEF40–49%), and preserved (HFpEF, LVEF ≥ 50%) left ventricular ejection fraction. Results: Between March 2021 and January 2022, 497 patients were enrolled (HFrEF: 30.4%, HFmrEF: 17.3%, HFpEF: 52.3%). The median age was 76.3 years, 57.9% were male, and the mean CHA2DS2-VASc score was 4. A 60 mg edoxaban dose was prescribed in 70% of patients. The observed rate of bleeding was 6.6% (95% CI: 4.5–9.3%), without differences across HF subtypes (HFrEF: 7.5%, HFmrEF: 3.6%, HFpEF: 7.1%; p = 0.474). Intracranial bleeding occurred in one patient (HFrEF). Stroke occurred in seven patients (1.5%) (HFrEF: 3, HFmrEF: 1, HFpEF: 3), two cases of which were fatal (HFrEF: 1, HFpEF: 1). No SE events were reported. Cardiovascular death occurred in 19 patients (4.1%) (HFrEF: 4.8%, HFmrEF: 3.6%, HFpEF: 3.8%; p = 0.871). Conclusions: This study evidences a low incidence of major or CRNM bleeding in patients with HF and AF treated with edoxaban, regardless of HF subtype. Low rates of stroke (1.5%) and SE events (0%) were assessed. Full article

Heart failure (HF) remains a leading cause of morbidity and mortality globally, with increasing prevalence driven by aging populations and comorbidities such as diabetes mellitus. Recent advances have highlighted sodium-glucose cotransporter-2 (SGLT2) inhibitors, particularly empagliflozin and dapagliflozin, as effective agents in HF management across a broad spectrum of ejection fractions. Initially developed for glycemic control in type 2 diabetes, both drugs have demonstrated significant cardiovascular benefits, including reductions in HF hospitalizations and improvements in symptoms and quality of life. Their mechanisms extend beyond glucose lowering, involving natriuresis, osmotic diuresis, improved myocardial energetics, reduced sympathetic activation, and anti-inflammatory effects. While empagliflozin and dapagliflozin share a core renal mechanism via selective SGLT2 inhibition, subtle differences in pharmacokinetics, potency, and tissue selectivity may influence their clinical profiles. Emerging evidence suggests empagliflozin may confer stronger benefits in heart failure with reduced ejection fraction (HFrEF), while dapagliflozin could offer enhanced efficacy in heart failure with preserved ejection franction (HFpEF), although head-to-head comparisons are lacking. This review synthesizes current evidence comparing the mechanisms of action and clinical performance of empagliflozin and dapagliflozin in HF, providing insight into agent selection and future directions in therapy personalization. Full article

Heart failure (HF) is a growing public health concern, driven by the increasing prevalence of obesity, diabetes, and aging. Despite therapeutic advances, HF continues to be associated with high morbidity and mortality. Glucagon-like peptide-1 receptor agonists (GLP-1 RAs), originally developed for glycemic control in type 2 diabetes, have demonstrated cardiovascular benefits in clinical trials. Recent studies, including STEP-HFpEF and SUMMIT, have shown improvement in symptoms and weight loss in patients with HF with preserved ejection fraction (HFpEF). GLP-1 RAs are involved in multiple biological pathways relevant to heart failure pathophysiology. These include pathways related to sympathetic nervous system activity, inflammatory cytokine signaling, oxidative stress, calcium handling, natriuretic peptide signaling, and cardiac metabolism. GLP-1 receptor agonists modulate vascular pathways involving nitric oxide signaling, endothelial function, and renal sodium handling, contributing to improved hemodynamics and neurohormonal balance. Together, these actions intersect with key neurohormonal and cellular processes contributing to chronic heart failure progression. This review explores the mechanistic overlap between GLP-1 receptor signaling and heart failure pathophysiology. This mechanistic overlap suggests a plausible role for these agents as adjunctive treatments in heart failure, especially in metabolically driven phenotypes. While direct cardiac effects remain incompletely defined, systemic metabolic and anti-inflammatory actions provide a mechanistic basis for observed clinical benefits. Full article