Search Results (156)

Background and Objectives: Heart failure (HF) and chronic kidney disease (CKD) frequently coexist and are closely interrelated, significantly affecting clinical outcomes. Among CKD-related markers, albuminuria and estimated glomerular filtration rate (eGFR) have emerged as key prognostic indicators in HF. However, their specific predictive value across different HF phenotypes—namely HF with preserved ejection fraction (HFpEF) and HF with reduced ejection fraction (HFrEF)—remains incompletely understood. This systematic review aims to evaluate the prognostic significance of albuminuria and eGFR in patients with HF and to compare their predictive roles in HFpEF versus HFrEF populations. Materials and Methods: We conducted a systematic search of major databases to identify clinical studies evaluating the association between albuminuria, eGFR, and adverse outcomes in HF patients. Inclusion criteria encompassed studies reporting on cardiovascular events, all-cause mortality, or HF-related hospitalizations, with subgroup analyses based on ejection fraction. Data extraction and quality assessment were performed independently by two reviewers. Results: Twenty-one studies met the inclusion criteria, including diverse HF populations and various biomarker assessment methods. Both albuminuria and reduced eGFR were consistently associated with increased risk of mortality and hospitalization. In HFrEF populations, reduced eGFR demonstrated stronger prognostic associations, whereas albuminuria was predictive across both HF phenotypes. Heterogeneity in study design and outcome definitions limited comparability. Conclusions: Albuminuria and eGFR are valuable prognostic biomarkers in HF and may enhance risk stratification and clinical decision-making, particularly when integrated into clinical assessment models. Differential prognostic implications in HFpEF versus HFrEF highlight the need for phenotype-specific approaches. Further research is warranted to validate these findings and clarify their role in guiding personalized therapeutic strategies in HF populations. Limitations: The current evidence base consists primarily of observational studies with variable methodological quality and inconsistent reporting of effect estimates. Full article

Background/Objectives: Sodium-glucose cotransporter-2 inhibitors (SGLT2i) have revolutionized heart failure (HF) therapies and are an essential component of guideline-directed medical therapy (GDMT); however, their significance in arrhythmia prevention is still uncertain. This meta-analysis evaluates the benefits of SGLT2i on arrhythmias in HF. Methods: A comprehensive examination was performed with PubMed, ScienceDirect, PLOS One, Cochrane, Google Scholar, and ClinicalTrials.gov from January 2014 to March 2025, complying with PRISMA guidelines. Randomized controlled trials (RCTs) comparing SGLT2i with placebo were incorporated. Primary results included ventricular arrhythmias (VA), sudden cardiac death (SCD), atrial arrhythmias, and conduction disorders. Subgroup analyses investigated the effects on arrhythmias in HF with reduced ejection fraction (HFrEF) and preserved ejection fraction (HFpEF). Results: A total of 11 RCTs involving 23,701 patients, 11,848 on SGLT2i (mean age: 68.26 ± 10 yrs, 53.5% males) and 11,853 on placebo (mean age: 67.91 ± 10 yrs, 53% males), were analyzed with a mean follow-up of 2.71 yrs. No significant differences were reported between SGLT2i and placebo for VA [relative risk (RR): 1.02, 95% confidence interval (CI): 0.83–1.25], I² =0%), atrial arrhythmias (RR: 0.92 [CI: 0.67–1.27], I² = 65.3%), or conduction disorders (RR:1.22 [CI: 0.86–1.73], I² = 10.4%). Notably, significant reductions in risk of SCD (RR: 0.68 [CI: 0.49–0.93], I² = 0%) and in the risk of atrial arrhythmias in HFrEF (RR: 0.66 [CI: 0.49–0.89], I² = 10.3%) were witnessed, although no such reduction was seen in HFpEF (RR: 1.14 [CI: 0.94–1.40], I² = 33.8%). Conclusions: SGLT2i do not reduce overall arrhythmia or conduction disorder risk in HF but significantly reduce the risk of SCD and atrial arrhythmias in HFrEF patients. These results highlight potential arrhythmia prevention benefits in HFrEF, warranting further targeted studies. Full article

Heart failure (HF), a prevalent global health issue characterized by the heart’s impaired ability to pump or fill blood, affects millions worldwide and continues to pose significant challenges despite advancements in treatment. This review delves into the critical and increasingly recognized role of inflammation in the development and progression of this complex syndrome. While the incidence of HF has seen a decline in some regions due to improved cardiac care, its overall prevalence is rising, particularly among younger adults and those with heart failure with a preserved ejection fraction (HFpEF). Given the persistently high rates of hospitalization and mortality associated with HF, understanding the underlying mechanisms, including the contribution of inflammation, is crucial for identifying novel therapeutic strategies. Inflammation in heart failure is a multifaceted process involving the activation of the immune system, both innate and adaptive, and encompasses various mechanisms such as the release of pro-inflammatory mediators, endothelial dysfunction, and neurohormonal activation. Myocardial damage triggers the innate immune response, while humoral immunity and chronic systemic inflammation, often linked to cardiovascular risk factors and autoimmune diseases, also play significant roles. Notably, heart failure and inflammation have a reciprocal relationship, with HF itself contributing to inflammatory processes within the cardiac tissue and systemically. Understanding these intricate pathways, including the involvement of specific immune cells and molecular mediators, is essential for comprehending the pathogenesis of heart failure and exploring potential therapeutic interventions. The review further examines various inflammatory biomarkers that have been implicated in heart failure, such as cytokines (including TNF-α and IL-1) and C-reactive protein (CRP). While these markers often correlate with the severity and prognosis of HF, clinical trials targeting specific inflammatory mediators have largely yielded disappointing results, highlighting the complexity of the inflammatory response in this context. The exploration of these biomarkers and the challenges encountered in translating anti-inflammatory strategies into effective treatments underscore the need for continued research to unravel the precise role of inflammation across different HF subtypes and to develop more targeted and effective anti-inflammatory therapies. Full article

Heart failure (HF) is a well-known leading cause of mortality, associated with a high symptom burden in advanced stages, frequent hospitalizations, and increasing economic costs. HF is typically classified into three main subgroups, based on left ventricular ejection fraction (LVEF): HF with reduced ejection fraction (HFrEF), HF with mildly reduced ejection fraction (HFmrEF), and HF with preserved ejection fraction (HFpEF). Recently, two additional subgroups have been proposed: HF with improved ejection fraction (HFimpEF) and HF with supernormal ejection fraction (HFsnEF). These five phenotypes exhibit distinct risk factors, clinical presentations, therapeutic responses, and prognosis. However, the LVEF thresholds used to define these subgroups remain a subject of considerable debate, with significant differences in opinions among leading experts. A major criticism concerns the reliability of LVEF in accurately classifying HF subgroups. Due to substantial intra and interobserver variability, determining the appropriate therapy and prognosis can be challenging, particularly in patients with HFmrEF. Additionally, patients classified under HFpEF are often too heterogeneous to be effectively managed as a single group. This narrative review explores these issues, and suggests a possible need for a new approach to HF classification, one that involves revising the LVEF reference values for HF phenotypes and highlighting LVEF trajectories rather than relying on a single measurement. Moreover, in light of the relatively limited therapeutic options for patients with LVEF > 40%, a new, simplified classification may be proposed: HF with reduced EF (LVEF ≤ 40%), HF with below-normal EF (41% ≤ LVEF ≤ 55%), and HF with normal EF (LVEF > 55%). This mindset would better equip clinical cardiologists to manage the diverse spectrum of HF syndromes, always with the patient at the center. Full article

Background/aim: We aimed to analyze eight-year mortality in patients with ST-elevation myocardial infarction (STEMI) complicated by the development of in-hospital heart failure with preserved ejection fraction (HFpEF). Method: We analyzed 3260 STEMI patients treated with primary PCI (pPCI). Reduced EF was defined as value <50% and preserved EF as value ≥50%. Patients were divided in three groups: without HF, with HFpEF, and with HF with reduced EF (HFrEF). Patients with cardiogenic shock at admission were excluded. Results: In-hospital HF was registered in 759 (23.2%) patients. Among the patients with in-hospital HF, 80 (10.5%) patients had HFpEF. Patients with HFpEF had significantly higher 8-year mortality compared with patients without HF (11.2% vs. 3.5%, respectively, p < 0.001), but significantly lower mortality compared with patients with HFrEF: 11.2% vs. 25.1%, respectively, p < 0.001. In the Cox regression model, HFpEF and HFrEF were independent predictors for 8-year mortality-HFpEF: HR1.85 (95%CI 1.26–4.25); HFrEF: 4.89 (95%CI 3.19–6.42). Conclusion: Development of in-hospital HFpEF in STEMI patients was an independent predictor for long-term mortality. The negative prognostic impact of HFpEF was weaker when compared to the impact of in-hospital HFrEF. Full article

Heart failure (HF) has become an epidemic, with a prevalence of ~7 million cases in the USA. Despite accounting for nearly 50% of all HF cases, heart failure with a preserved ejection fraction (HFpEF) remains challenging to treat. Common pathophysiological mechanisms in HFpEF include oxidative stress, microvascular dysfunction, and chronic unresolved inflammation. Our lab focuses on oxidative stress-mediated cellular dysfunction, particularly the toxic effects of lipid peroxidation products like 4-hydroxy-2-nonenal (4HNE). Aldehyde dehydrogenase 2 (ALDH2), a mitochondrial enzyme, plays a vital role in detoxifying 4HNE and thereby protecting the heart against pathological stress. ALDH2 activity is reduced in various metabolic stress-mediated cardiac pathologies. The dysfunction of coronary vascular endothelial cells (CVECs) is critical in initiating HFpEF development. Thus, we hypothesized that ectopic overexpression of ALDH2 in CVECs could mitigate metabolic stress-induced HFpEF pathogenesis. In this study, we tested the efficacy of intracardiac injections of the ALDH2 gene into CVECs in db/db mice—a model of obesity-induced type 2 diabetes mellitus (T2DM)—and their controls, db/m mice, by injection with ALDH2 constructs (AAV9-VE-cadherin-hALDH2-HA tag-P2A) or control constructs (AAV9-VE-cadherin-HA tag-P2A-eGFP). We found that intracardiac ALDH2 gene transfer increased ALDH2 levels specifically in CVECs compared to other myocardial cells. Additionally, we observed increased ALDH2 levels and activity, along with decreased 4HNE adducts, in the hearts of mice receiving ALDH2 gene transfer compared to control GFP transfer. Furthermore, ALDH2 gene transfer to CVECs improved diastolic function compared to GFP control alone. In conclusion, ectopic ALDH2 expression in CVECs can contribute, at least partially, to the amelioration of HFpEF. Full article

Background/Objectives: Evidence of patient experiences with heart failure with preserved ejection fraction (HFpEF) and disease impact on quality of life (QoL) is scarce. This study explored perceived impacts on QoL and healthcare experiences of HFpEF patients and their caregivers. Methods: This was a mixed-methods study with HFpEF patients, ≥40 years, New York Heart Association functional classes I-IV in Spain. Qualitative data were collected through semi-structured interviews with patients (n = 19) and caregivers (n = 17). The EuroQoL 5D-5L, Patient Global Impression of Severity, and Kansas City Cardiomyopathy Questionnaire were used to collect QoL measures. Results: The themes were as follows. (1) Impact of HFpEF on QoL; (2) new roles of informal caregiving; and (3) the increasing value of multidisciplinary care. Qualitative data were supported by a trend of worsening QoL on quantitative measures as HF progressed, despite quantitative measures not fully capturing the burden. Qualitative data further captured discrepancies of QoL perceptions. Conclusions: The impact of HFpEF on patients and their caregivers was similar to the HFrEF population’s. Insights from discrepancies between PROMs data and interviews could help with tailoring QoL questionnaires to capture the broader impact of HFpEF, identify unmet needs, and customize care. Full article

Background/Objectives: The prevalence of heart failure with preserved ejection fraction (HFpEF) is expected to surpass that of heart failure with reduced ejection fraction (HFrEF), yet it remains under-researched. Compared to HFrEF, patients with HFpEF have similarly poor survival rates, physical impairments, and quality of life (QOL) and similar improvements following exercise training. However, Medicare currently excludes coverage for cardiopulmonary rehabilitation (CR) for HFpEF. The purpose of this study was to evaluate the impact of HF at baseline and the effects of CR in both subtypes. Methods: Ninety-nine patients (forty-three with HFrEF and fifty-six with HFpEF) who completed CR were included. Demographic data and outcome measures were assessed pre- and post-CR, including weight, body mass index (BMI), 5x-sit-to-stand (5xStS), timed-up-and-go (TUG), 6-minute walk test (6MWT), Ferrans and Powers Quality of Life (F&P QOL), waist circumference, BERG balance, and Patient Health Questionnaire-9 (PHQ-9). Independent and paired t-tests were performed with statistical significance set at p < 0.05. Results: At baseline, compared to patients with HFrEF, patients with HFpEF were older with a significantly lower 6MWT distance (350.6 m vs. 299.6 m), lower BERG balance scores (52/56 vs. 49/56, respectively), and a 5xSTS score indicating a fall risk (16.9 ± 6.5). Following CR, both groups had significant improvements in all functional and self-reported outcome measures (p < 0.001), with no significant differences between HF subtypes. Patients with HFpEF also had a significant improvement in waist circumference. Conclusions: Compared to patients with HFrEF, patients with HFpEF presented with similar or greater impairments and had similar or greater improvements following CR. These results underscore the effectiveness of CR for HFpEF management and the need for insurance coverage. Full article

Heart failure (HF) remains a global health burden with high morbidity and mortality, despite significant pharmacological advances. Vitamin D deficiency (VDD) is commonly observed in HF patients and may exacerbate disease progression through various pathophysiological mechanisms, including activation of the renin–angiotensin–aldosterone system, inflammation, oxidative stress, and impaired calcium homeostasis. While vitamin D (VD) supplementation may positively influence surrogate markers in selected patient groups—particularly those with reduced ejection fraction or severe vitamin D deficiency—its effect on primary endpoints such as mortality or HF-related hospitalization varies significantly across studies and patient populations. As a result, while VD supplementation may benefit VD-deficient HF patients, current evidence does not support routine administration across the whole HF population. It is still a matter of debate whether VDD belongs to prognostic markers of worse outcomes in HF or is instead their potential cause. Therefore, the clinical utility of VD in HF management remains underexplored. This review aims to assess the evidence regarding vitamin D status and its supplementation in the context of HF, with a focus on different HF phenotypes: reduced (HFrEF), mildly reduced (HFmrEF), and preserved ejection fraction (HFpEF). The aim is to synthesize findings from novel observational studies, randomized controlled trials, and meta-analyses that shed light onto this intricate relationship and may be valuable in everyday clinical practice. Full article

Background/Objectives: This study aims to investigate the potential etiopathogenesis of HFpEF development and identify possible different phenotypes of HFpEF in patients with chronic obstructive pulmonary disease (COPD) and systemic sclerosis-associated interstitial lung diseases (SS-ILDs). It could help clinicians improve early HFpEF personalized detection and management. Methods: This study included 150 patients with chronic lung diseases (CLDs), such as COPD and SS-ILD, who were outside of exacerbation, had no history of chronic heart failure (CHF), and had a left ventricular ejection fraction (LV EF) of ≥50%. The functional status of the lungs, heart, endothelial dysfunction, and acid–base balance was assessed. The results obtained were compared in groups of patients with CLD depending on the presence or absence of HF with preserved ejection fraction (HFpEF). The diagnosis of HFpEF was established based on the HFA-PEFF Score classification. Nonparametric statistical methods were used. Results: In patients with CLD, indicators such as age, longitudinal size of the right atrium, mid-regional pro-atrial natriuretic peptide (MR-proANP), and highly sensitive cardiac troponin T (hsTnT) were higher than in the group of patients without HFpEF. In patients with COPD and HFpEF, statistically significant changes were found in the volume of the left atrium. In patients with SS-ILD and HFpEF, statistically significant differenceswere found in SBP before and after the 6 min walk test (6MWT), the Borg scale before 6MWT, MR-proANP, and the longitudinal dimension of the right atrium. Conclusions: The results of our study allow us to identify two different mechanisms of HFpEF development: In patients with COPD, the predominant factor in the development of HFpEF was hypoxia, while in patients with SS-ILD, myocardial dysfunction with remodeling developed against the background of secondary pulmonary hypertension, highlighting the importance of phenotype-specific evaluation. These findings suggest potential approaches for personalized risk stratification and the development of targeted management strategies for patients with HFpEF. Full article

Background/Objectives: Heart failure (HF) with preserved ejection fraction (HFpEF) poses a diagnostic challenge, as it lacks a definitive hallmark beyond preserved left ventricular (LV)EF. This retrospective study aims to analyze the demographic and clinical characteristics of HFpEF patients within a real-world hospital cohort, with a particular focus on obesity and associated comorbidities. Methods: A total of 4019 patients who underwent echocardiography in 2020–2021 at a university hospital were screened for HFpEF. After stringent manual verification, 219 patients fulfilled the European Society of Cardiology (ESC) criteria for HFpEF. Demographic, clinical, and comorbidity data were analyzed and stratified by body mass index (BMI) categories and sex distribution. Results: Among the 219 HFpEF patients, 71.3% were classified as pre-obese or obese. Hypertension (93.6%), atrial fibrillation (74.3%), and obesity were common in the cohort, while sex distribution was balanced. Edema was more prevalent among obese patients, though HFpEF severity, as reflected by New York Heart Association (NYHA) classification and natriuretic peptide levels, did not differ significantly across BMI groups. Medical treatment patterns varied with BMI, with obese patients more frequently receiving diuretics, sodium-glucose cotransporter-2 inhibitors (SGLT-2i), and angiotensin receptor blockers (ARB). No significant differences were observed between male and female patients in terms of HFpEF severity markers. Conclusions: Obesity is a predominant feature in HFpEF and is associated with a high burden of comorbidities. However, sex does not appear to influence HFpEF severity in this cohort. These findings underscore the need for targeted therapeutic strategies in obese HFpEF patients. Full article

Background/Objectives: This study aimed to investigate the prognostic value of the red cell distribution width-to-estimated glomerular filtration rate (RGR) ratio in patients hospitalized with chronic heart failure (CHF) and its potential interaction with NT-proBNP levels. By integrating anemia and renal dysfunction markers, the RGR may provide enhanced predictive insights regarding extended length of hospital stay (ELOS) > 7 days, in-hospital mortality, and 6-month all-cause mortality across specific CHF phenotypes. Methods: In this retrospective, single-center pilot observational study, 627 CHF admissions (January 2022–August 2024) were analyzed. Patients were classified according to the ESC guidelines into heart failure with reduced (HFrEF), mildly reduced (HFmrEF), or preserved ejection fraction (HFpEF). The RGR was calculated as red cell distribution width standard deviation (RDW-SD) divided by estimated glomerular filtration rate (eGFR). Predictive accuracy was evaluated using logistic regression, receiver operating characteristic (ROC) analyses, and stepwise Cox proportional hazard regression. Results: RGR was significantly higher in HFrEF than in HFpEF (p = 0.042) and predicted ELOS only in HFpEF (AUC = 0.619). In contrast, for in-hospital mortality, RGR achieved excellent discrimination in HFrEF (AUC = 0.945), outperforming RDW and NT-proBNP. In HFmrEF, RDW exhibited the highest predictive power (AUC = 0.826), whereas in HFpEF, NT-proBNP was the strongest predictor (AUC = 0.958), although RGR preserved good discrimination (AUC = 0.746). Across the entire cohort and HF phenotypes, RGR consistently emerged as a significant predictor in univariable analysis. In multivariable models, it improved the significance prognosis especially alongside NT-proBNP in the entire cohort and HFrEF. For 6-month all-cause mortality, RGR surpassed RDW in prediction in all HF phenotypes. Conclusions: The RGR independently predicts prolonged hospitalization, in-hospital, and 6-month mortality in CHF—often outperforming RDW and eGFR and being comparable to NT-proBNP, especially in HFrEF. These findings suggest that RGR may serve as a valuable risk stratification tool in CHF management. Full article

Heart failure (HF) is a leading cause of morbidity and mortality worldwide, representing a complex clinical syndrome in which the heart’s ability to pump blood efficiently is impaired. HF can be subclassified into heart failure with reduced ejection fraction (HFrEF) and heart failure with preserved ejection fraction (HFpEF), each with distinct pathophysiological mechanisms and varying levels of severity. The progression of HF is significantly driven by cardiac fibrosis, a pathological process in which the extracellular matrix undergoes abnormal and uncontrolled remodelling. Cardiac fibrosis is characterized by excessive matrix protein deposition and the activation of myofibroblasts, increasing the stiffness of the heart, thus disrupting its normal structure and function and promoting lethal arrythmia. MicroRNAs, long non-coding RNAs, and circular RNAs, collectively known as non-coding RNAs (ncRNAs), have recently gained significant attention due to a growing body of evidence suggesting their involvement in cardiac remodelling such as fibrosis. ncRNAs can be found in the peripheral blood, indicating their potential as biomarkers for assessing HF severity. In this review, we critically examine recent advancements and findings related to the use of ncRNAs as biomarkers of HF and discuss their implication in fibrosis development. Full article

Obesity is a current pandemic that sets all affected individuals at risk of heart failure (HF), and the majority of them will develop the clinical syndrome of HF with preserved ejection fraction (HFpEF). The diagnosis of HFpEF is challenging as it is based on the detection of subtle functional and structural remodeling of the heart that leads to diastolic dysfunction with increased left ventricular (LV) filling pressures and raised natriuretic peptides (NPs). The accurate diagnosis of HFpEF is even more challenging in patients who are obese, since the echocardiographic imaging quality may be suboptimal, the parameters for the evaluation of cardiac structure are indexed to the body surface area (BSA) and thus may underestimate the severity of the remodeling, and the NPs in patients who are obese have a lower normal threshold. Moreover, patients who are obese are prone to atrial fibrillation (AF) and pulmonary hypertension (PH), making the evaluation of diastolic dysfunction more strenuous. The current review aims to offer insights on the accurate diagnosis of HFpEF in patients who are obese in different clinical scenarios—patients who are obese in different clinical scenarios—such as in sinus rhythm, in atrial fibrillation, and in the case of pulmonary hypertension—by applying multimodality imaging and clinical diagnostic algorithms. Full article

Sodium-glucose cotransporter-2 inhibitors (SGLT2i), initially developed as antihyperglycemic agents, have revolutionized heart failure (HF) management, offering substantial benefits across all stages and phenotypes of the disease. Regardless of left ventricular ejection fraction (LVEF), these agents have proven efficacy in both chronic and acute HF presentations. This review explores SGLT2i applications spanning the HF continuum, from early stages (Stage A) in at-risk individuals to the mitigation of progression in advanced HF (Stage D). Evidence from numerous trials has shown that SGLT2i significantly lower rates of HF hospitalization, improve renal function, and decreases cardiovascular mortality, highlighting their multifaced mechanisms of action in HF care. This review also highlights the potential mechanisms by which SGLT2i exert their beneficial effects on the cardiovascular and renal systems, each contributing to early and sustained clinical improvements. However, the integration of SGLT2i into guideline-directed medical therapy poses practical challenges, including initiation timing, dosing, and monitoring, which are addressed to support effective treatment adaptation across patient populations. Ultimately, this review provides a comprehensive assessment of SGLT2i as a foundational therapy in HF, emphasizing their role as an intervention across multiple stages aimed at improving outcomes across the entire HF spectrum. Full article