Heart failure with preserved ejection fraction (HFpEF) is a complex and heterogeneous clinical condition characterized by the interplay of malnutrition and immune inflammation, especially in elderly patients. The CRP-Albumin-Lymphocyte (CALLY) index, a novel composite indicator reflecting immune inflammation and nutritional status, has not yet been validated as a prognostic tool in elderly patients with HFpEF.

This retrospective study included 320 elderly patients hospitalized at the Air Force Medical Center from October 2016 to April 2019 due to HFpEF. Patients were stratified into the all-cause mortality and the survival groups according to follow-up outcomes. Kaplan-Meier analysis and Cox regression were performed to identify risk factors associated with poor prognosis. Additionally, we constructed and evaluated a nomogram based on the CALLY index to predict survival rates.

During the follow-up period, 137 cases (42.81 %) of patients experienced all-cause mortality. Kaplan-Meier survival curves and Cox regression analysis revealed that a lower CALLY index (HR 0.811, 95 % CI 0.714-0.921, P = 0.001) was independently associated with adverse prognosis in elderly patients with HFpEF. The nomogram incorporating the CALLY index exhibited robust predictive performance for predicting 1-year, 3-year, and 5-year survival outcomes.

Our findings demonstrate that the CALLY index is an independent predictor of long-term mortality in elderly patients with HFpEF. The developed nomogram incorporating the CALLY index could effectively predict survival probabilities.

Heart failure with preserved ejection fraction (HFpEF) is an increasingly prevalent clinical syndrome with high morbidity and mortality. Although HFpEF frequently coexists with cardiometabolic diseases, the causal mechanisms and potential mediators remain poorly understood.

This study aimed to identify cardiometabolic risk factors specifically driving HFpEF and to determine their underlying circulating mediators.

We used two-sample Mendelian Randomization (MR) to analyze the effects of obesity, Type 2 diabetes, hypertension, chronic kidney disease (CKD), and dyslipidemia on HFpEF and heart failure with reduced ejection fraction (HFrEF) in large European-ancestry GWAS datasets. We then performed mediation MR to identify plasma proteins and metabolites that mediate the transition from each cardiometabolic disease to HFpEF, respectively. We applied multivariable MR to assess the impact of risk confounding on the results. Bioinformatic analyses were conducted to delineate mechanisms.

Cardiometabolic diseases had heterogeneous effects on HFpEF and HFrEF. Obesity and type 2 diabetes showed adjusted causal effects with HFpEF, hypertension showed potential relevance to HFpEF, whereas dyslipidemia and CKD did not. MR analysis identified 5 proteins that mediate obesity to HFpEF; 5 proteins that mediate type 2 diabetes to HFpEF. Further mediation MR analysis of obesity and T2D on HFrEF revealed heterogeneity in circulating mediators between metabolic HFpEF and HFrEF. Comprehensive bioinformatics analyses showed that IL1R1, together with other proteins such as TP53 and FGF19, orchestrates the inflammatory and fibrotic processes underlying HFpEF.

These findings suggest that metabolic HFpEF has distinct etiological features compared with HFrEF and is driven by complex, condition-specific mediators. IL1R1 mediates HFpEF in multiple metabolic risk states, suggesting a potential therapeutic target. Further translational studies are warranted to evaluate anti-inflammatory strategies targeting IL1R1 in HFpEF.

This study aims to investigate the prognostic impact of the presence and type of prior hospitalizations in patients with heart failure with mildly reduced ejection fraction (HFmrEF).

Data investigating the prognostic impact of the present and type of previous all-cause hospitalizations in HFmrEF is limited.

Consecutive patients hospitalized with HFmrEF at a single medical center were retrospectively included from 2016 to 2022. The prognosis of patients with a prior hospitalization < 12 months was compared to patients without. The primary endpoint was all-cause mortality at 30 months (median follow-up), the key secondary endpoint was heart failure (HF)-related rehospitalization at 30 months.

Two thousand one hundred eighty four patients with HFmrEF were included, 34.8% had a previous hospitalization < 12 months (admission to internal medicine and geriatrics: 60.8%, surgical department: 23.5%). The presence of a previous hospitalization was associated with an increased risk of all-cause mortality (38.6% vs. 27.4%; HR = 1.51; 95% CI 1.30-1.76; p = 0.01) and HF-related rehospitalization at 30 months (21.2% vs. 9.1%; HR = 2.48; 95% CI 1.96-3.14; p = 0.01), even after multivariable adjustments. However, the department of previous hospitalization (internal medicine vs. surgical) did not significantly affect the risk of 30-months all-cause mortality (37.1% vs. 43.2%; HR = 0.82, 95% CI 0.63-1.08; p = 0.16) or HF-related rehospitalization (24.0% vs. 16.8%; HR = 1.47, 95% CI 0.98-2.24; p = 0.07). Finally, the type of previous admission (i.e., elective, emergency vs. HF-related admission) (log-rank p = 0.29) did not affect the risk of 30-months all-cause mortality.

Prior hospitalizations within 12 months were independently associated with impaired long-term mortality in patients with HFmrEF, irrespective of the department or type of prior admission.

Chronic heart failure (CHF) is the outcome of various cardiac diseases. Due to the unobvious symptoms of early-stage CHF, the screening of CHF remains a challenging problem. This study focused on the dysregulated miR-4429 and evaluated its significance in the diagnosis and development of CHF, aiming to explore a novel biomarker for CHF.

A total of 103 CHF patients and 71 healthy individuals with matched clinicopathological features were enrolled. Serum miR-4429 levels were analyzed by PCR and its significance in discriminating CHF patients was evaluated by receiver operatinf curve (ROC). Cardiomyocyte was treated with H2O2 to mimic cell injury during CHF, the regulatory effect and the underlying mechanism of miR-4429 was investigated by cell transfection and cell counting kit-8 assay.

miR-4429 was significantly upregulated in CHF patients (P< 0.0001), which sensitively and specifically discriminated CHF patients from healthy individuals (AUC=0.803, 95% CI=0.735-0.872). miR-4429 was closely associated with the decreased cardiac function of CHF patients (r>0.5, P<0.0001). H2O2 induced increased miR-4429 and reduced HAPLN1 in cardiomyocytes (P<0.001). H2O2-treated cardiomyocytes showed inhibited proliferation and increased reactive oxygen species (ROS) levels, and silencing miR-4429 could alleviate cardiomyocyte injury caused by H2O2 (P<0.0001). miR-4429 negatively regulated HAPLN1, and the knockdown of HAPLN1 could reverse the protective effect of silencing miR-4429 on cardiomyocyte injury (P<0.0001).

The upregulation of miR-4429 served as a biomarker discriminating CHF patients and indicating severe disease conditions. Silencing miR-4429 could alleviate cardiomyocyte injury via negatively regulating HAPLN1.

Significant knowledge gaps remain regarding the heterogeneity of heart failure (HF) phenotypes, particularly among patients with preserved or mildly reduced left ventricular ejection fraction (HFp/mrEF). Our aim was to identify HF subtypes within the HFp/mrEF population.

K-prototypes clustering algorithm was used to identify different HF phenotypes in a cohort of 2570 patients diagnosed with heart failure with mildly reduced ejection fraction or heart failure with preserved left ventricular ejection fraction. This algorithm employs the k-means algorithm for quantitative variables and k-modes for qualitative variables.

We identified three distinct phenotypic clusters: Cluster A (n = 850, 33.1%), characterized by a predominance of women with low comorbidity burden; Cluster B (n = 830, 32.3%), mainly women with diabetes mellitus and high comorbidity; and Cluster C (n = 890, 34.5%), primarily men with a history of active smoking and respiratory comorbidities. Significant differences were observed in baseline characteristics and 1-year mortality rates across the clusters: 18% for Cluster A, 33% for Cluster B, and 26.4% for Cluster C (P < 0.001). Cluster B had the shortest median time to death (90 days), followed by Clusters C (99 days) and A (144 days) (P < 0.001). Stratified Cox regression analysis identified age, cancer, respiratory failure, and laboratory parameters as predictors of mortality.

Cluster analysis identified three distinct phenotypes within the HFp/mrEF population, highlighting significant heterogeneity in clinical profiles and prognostic implications. Women were classified into two distinct phenotypes: low-risk women and diabetic women with high mortality rates, while men had a more uniform profile with a higher prevalence of respiratory disease.

Frailty is common among heart failure (HF) patients and linked to increased risk of adverse outcomes. Contributing factors include inflammation, sarcopenia and neurohormonal issues which diminish physiological reserves and accelerate the decline of health. Managing frailty in HF requires a multidisciplinary approach to address physical, nutritional and pharmacological needs. Structured exercise and dietary support can improve physical function, while careful medication management, especially with polypharmacy, reduces frailty-related risks. Telemedicine and wearable tech facilitate continuous monitoring and timely intervention, especially for those in remote areas. Future research should develop standardised frailty assessment tools specific to HF, enhancing risk stratification and personalised care. Studies on underlying mechanisms, such as inflammation and mitochondrial dysfunction, could lead to new therapies. Addressing socioeconomic factors can also improve care equity. This review summarises the mechanisms, clinical characteristics and impact of frailty on HF, highlighting challenges in treatment and opportunities for improving patient outcomes.

Recent studies have reported blunted increases in blood pressure (BP) during static handgrip (SHG) in patients with heart failure with preserved ejection fraction (HFpEF), which may be attributed to abnormal sympathetic reactivity during exercise and/or impaired muscle metaboreflex function. However, it is unknown whether the sympathetic neural response to SHG and isolated muscle metaboreflex activation via post-exercise circulatory occlusion (PECO) are attenuated in HFpEF.

Thirty-nine patients with HFpEF and 24 age-matched non-HFpEF controls were studied in the supine position. BP, heart rate (HR), and muscle sympathetic nerve activity (MSNA) were measured during SHG at 40% of maximal voluntary contraction until fatigue followed by 2-min PECO.

Resting mean arterial pressure (MAP) was lower and peak increase (Δ) in MAP was smaller in patients with HFpEF than in controls during SHG (Δ23 ± 15 [standard deviation] vs. Δ34 ± 15 mmHg; P = 0.007) and PECO (Δ15 ± 11 vs. Δ19 ± 9 mmHg; P = 0.047). HR was greater in patients at rest but did not differ between the two groups at peak SHG. Patients had higher resting MSNA burst frequency than controls (37 ± 14 vs. 27 ± 13 bursts/min; P = 0.031); however, burst incidence was not different between the groups (P = 0.226). There were no differences in MSNA responses to SHG (Δ19 ± 15 vs. Δ18 ± 10 bursts/min at peak; P = 0.841) or PECO (Δ3 ± 12 vs. Δ5 ± 7 bursts/min; P = 0.495) between groups.

The patients with HFpEF maintained sympathetic reactivity but had an attenuated pressor response during fatiguing SHG. Additionally, muscle metaboreflex activation of vasomotor sympathetic outflow appeared to be minimal in both groups, with no significant difference between patients and controls.

Heart failure with preserved ejection fraction (HFpEF) represents a major clinical challenge with rising global prevalence. Women have a nearly double lifetime risk of developing HFpEF compared to heart failure with reduced ejection fraction (HFrEF). In HFpEF, sex differences emerge both in how traditional cardiovascular risk factors (such as hypertension, obesity, and diabetes) affect cardiac function and through distinct pathophysiological mechanisms triggered by sex-specific events like menopause and adverse pregnancy outcomes. These patterns influence not only disease development, but also therapeutic responses, necessitating sex-specific approaches to treatment. This review aims to synthesize existing knowledge regarding HFpEF in women including traditional and sex-specific risk factors, pathophysiology, presentation, and therapies, while outlining important knowledge gaps that warrant further investigation. The impact of HFpEF spans a woman's entire lifespan, requiring prevention and management strategies tailored to different life stages. While understanding of sex-based differences in HFpEF has improved, significant knowledge gaps persist. Through examination of current evidence and challenges, this review highlights promising opportunities for innovative research, therapeutic development, and clinical care approaches that could transform the management of HFpEF in women.

The value of generic quality of life (QoL) instruments in heart failure (HF) is uncertain.

In this study, the authors sought to quantify individual dimension scores and the EuroQol 5-Dimension questionnaire (EQ-5D) Level Sum Score (LSS) in patients with HF with reduced, mildly reduced, or preserved ejection fraction, the association between those scores and outcomes, and the impact of treatment with dapagliflozin on the scores.

Analyses were conducted using patient-level data from DAPA-HF and DELIVER trials. Cox proportional hazards regression models were used to assess the association between EQ-5D scores (each dimension and LSS) and clinical outcomes. Sankey diagrams were used to illustrate changes in individual patient EQ-5D dimensions from baseline to 8 months' follow-up.

Of the 11,007 patients randomized in DAPA-HF and DELIVER, 10,135 (92.1%) completed the instrument at baseline. Scores varied markedly by question with 37%, 30%, and 33% of patients reporting no, slight, or moderate or greater problem, respectively for mobility; 67%, 20%, and 13% for self-care; 40%, 33%, and 27% for usual activities; 45%, 32%, and 23% for pain/discomfort; and 57%, 27%, and 16% for anxiety/depression. Patients with higher (worse) EQ-5D-LSS were more frequently female, had more comorbidities, and had worse HF status. Compared with patients free from any problem across all dimensions (ie, an EQ-5D-LSS of 5), the HRs for the composite outcome of time to first cardiovascular death or worsening HF were 1.27 (95% CI: 1.10-1.47), 1.70 (95% CI: 1.46-1.98), and 2.31 (95% CI: 1.88-2.85) in patients with EQ-5D-LSS of 6-10, 11-15, and 16-25 points, respectively. Dapagliflozin led to greater improvement and less worsening in mobility (OR: 1.13 [95% CI: 1.04-1.23]; P = 0.004), self-care (OR: 1.13 [95% CI: 1.02-1.24]; P = 0.016), usual activities (OR: 1.11 [95% CI: 1.02-1.21]; P = 0.015), and anxiety/depression (OR: 1.10 [95% CI: 1.01-1.21]; P = 0.034) after 8 months. The number needed to treat for 1 patient to report improvement in EQ-5D-LSS was 31 (95% CI: 20-72).

The EQ-5D revealed problems not often associated (eg, pain) with HF or commonly quantified in HF (eg, anxiety/depression). Dapagliflozin improved multiple QoL dimensions, and possibly anxiety/depression. (Study to Evaluate the Effect of Dapagliflozin on the Incidence of Worsening Heart Failure or Cardiovascular Death in Patients With Chronic Heart Failure [DAPA-HF]; NCT03036124; Dapagliflozin Evaluation to Improve the Lives of Patients With Preserved Ejection Fraction Heart Failure [DELIVER]; NCT03619213).

Heart failure with preserved ejection fraction (HFpEF) and atrial fibrillation (AF) are often coexisting conditions, but their interrelationship has not yet been clarified. This study investigated the clinical characteristics and prognostic impact of AF among older patients with HFpEF hospitalized for acute HF (AHF). The study included patients 65 years of age and older who were admitted to the Emergency Department due to AHF from 1 January 2016 to 31 December 2019. Patients were divided into two groups according to the presence of AF. The primary endpoint was all-cause, in-hospital mortality. Overall, 770 patients with HFpEF were included, mean age 82 years, 53% were females. Nearly, a third (30%) of these patients had a concomitant AF and they were significantly older and had higher N-Terminal pro-B-type natriuretic peptide (NT-proBNP) values. Overall, the in-hospital mortality rate was much higher among HFpEF patients with AF compared to those without AF (11.4% vs 6.9%, respectively; p = 0.037). At multivariate analysis, AF emerged as an independent risk factor for death (OR 1.73 [1.03-2.92]; p = 0.038). Among older patients with HFpEF admitted for AHF, the coexistence of AF was associated with a nearly twofold increased risk of all-cause in-hospital mortality. Patients with HFpEF and AF describe a phenotype of older and more symptomatic patients, with higher NT-proBNP, left atrial enlargement, right ventricular dysfunction, and higher CV mortality.

Heart failure (HF) is often accompanied by a constellation of comorbidities, leading to diverse patient presentations and clinical trajectories. While traditional methods have provided valuable insights into our understanding of HF, network medicine approaches seek to leverage these complex relationships by analyzing disease at a systems level. This review introduces the concepts of network medicine and explores the use of comorbidity networks to study HF and heart disease.

Comorbidity networks are used to understand disease trajectories, predict outcomes, and uncover potential molecular mechanisms through identification of genes and pathways relevant to comorbidity. These networks have shown the importance of non-cardiovascular comorbidities to the clinical journey of patients with HF. However, the community should be aware of important limitations in developing and implementing these methods. Network approaches hold promise for unraveling the impact of comorbidities in the complex presentation and genetics of HF. Methods that consider comorbidity presence and timing have the potential to help optimize management strategies and identify pathophysiological mechanisms.

Heart failure with preserved ejection fraction (HFpEF) poses a significant clinical challenge, especially in older patients with HT. This study aimed to identify the factors influencing HFpEF occurrence in elderly patients with HT.

Elderly patients with HT were categorized into two groups: no HFpEF group and HFpEF group based on HFpEF diagnosis. Demographic, clinical, laboratory and echocardiographic data was conducted. Logistic regression analysis and joint prediction modeling were used to identify predictive factors for HFpEF.

Several factors were associated with HFpEF, including age, body mass index, duration of HT, atrial fibrillation (AF), chronic kidney disease (CKD), stroke, systolic blood pressure (SBP), serum creatinine (SCr), N-terminal pro brain natriuretic peptide (NT-proBNP), heart rate, serum sodium, low density lipoprotein cholesterol (LDL-c), triglyceride, left ventricular ejection fraction (LVEF), E/e' ratio, left atrial diameter, tricuspid regurgitation velocity, mitral regurgitation and C-reactive protein (CRP) levels. The joint prediction model shown high accuracy, with an area under the curve (AUC) of 0.840.

This study provided insights into the incidence rate and risk factors of HFpEF in elderly patients with HT. Key determinants included age, blood pressure, biomarkers, and echocardiographic parameters.

Heart failure with preserved ejection fraction (HFpEF) accounts for nearly half of all heart failure cases and has a prevalence that is expected to rise with the growing ageing population. HFpEF is associated with significant morbidity and mortality. Specific HFpEF risk factors include age, diabetes, hypertension, obesity and atrial fibrillation. Haemodynamic contributions to HFpEF include changes in left ventricular structure, diastolic and systolic dysfunction, left atrial myopathy, pulmonary hypertension, right ventricular dysfunction, chronotropic incompetence, and vascular dysfunction. Inflammation, fibrosis, impaired nitric oxide signalling, sarcomere dysfunction, and mitochondrial and metabolic defects contribute to the cellular and molecular changes observed in HFpEF. HFpEF impacts multiple organ systems beyond the heart, including the skeletal muscle, peripheral vasculature, lungs, kidneys and brain. The diagnosis of HFpEF can be made in individuals with signs and symptoms of heart failure with abnormality in natriuretic peptide levels or evidence of cardiopulmonary congestion, facilitated by the use of HFpEF risk scores and additional imaging and testing with the exclusion of HFpEF mimics. Management includes initiation of guideline-directed medical therapy and management of comorbidities. Given the significant impact of HFpEF on quality of life, future research efforts should include a particular focus on how patients can live better with this disease.

Heart failure with preserved ejection fraction (HFpEF) is a common subtype of heart failure marked by impaired left ventricular diastolic function and decreased myocardial compliance. Given the limited availability of evidence-based pharmacological treatments for HFpEF, there is a growing interest in nonpharmacological interventions as viable therapeutic alternatives. This review aims to explore the pathophysiology of HFpEF and present recent advancements in nonpharmacological management approaches, encompassing noninvasive therapies, invasive procedures and targeted treatments for comorbidities. An extensive literature review was undertaken to identify and synthesize emerging nonpharmacological treatment options for HFpEF, assessing their potential to enhance patient outcomes. Nonpharmacological strategies, such as vagus nerve stimulation, percutaneous pulmonary artery denervation, renal denervation, transcatheter insertion of atrial shunts and pericardial resection, demonstrate promising potential for alleviating HFpEF symptoms and improving patient prognosis. Moreover, addressing comorbidities, such as hypertension and diabetes, may offer additional therapeutic benefits. These cutting-edge techniques, in conjunction with well-established exercise therapies, pave the way for future research and clinical applications in the field. Nonpharmacological interventions hold promise for advancing HFpEF patient care and fostering a deeper understanding of these treatment approaches, which will facilitate new clinical applications and contribute to the development of more targeted therapies.

Coronary heart disease (CHD) and heart failure (HF) are the major causes of morbidity and mortality worldwide. Early and accurate diagnoses of CHD and HF are essential for optimal management and prognosis. However, conventional diagnostic methods such as electrocardiography, echocardiography, and cardiac biomarkers have certain limitations, such as low sensitivity, specificity, availability, and cost-effectiveness. Therefore, there is a need for simple, noninvasive, and reliable biomarkers to diagnose CHD and HF.

To investigate serum cystatin C (Cys-C), monocyte/high-density lipoprotein cholesterol ratio (MHR), and uric acid (UA) diagnostic values for CHD and HF.

We enrolled 80 patients with suspected CHD or HF who were admitted to our hospital between July 2022 and July 2023. The patients were divided into CHD (n = 20), HF (n = 20), CHD + HF (n = 20), and control groups (n = 20). The serum levels of Cys-C, MHR, and UA were measured using immunonephelometry and an enzymatic method, respectively, and the diagnostic values for CHD and HF were evaluated using receiver operating characteristic (ROC) curve analysis.

Serum levels of Cys-C, MHR, and UA were significantly higher in the CHD, HF, and CHD + HF groups than those in the control group. The serum levels of Cys-C, MHR, and UA were significantly higher in the CHD + HF group than those in the CHD or HF group. The ROC curve analysis showed that serum Cys-C, MHR, and UA had good diagnostic performance for CHD and HF, with areas under the curve ranging from 0.78 to 0.93. The optimal cutoff values of serum Cys-C, MHR, and UA for diagnosing CHD, HF, and CHD+HF were 1.2 mg/L, 0.9 × 109, and 389 µmol/L; 1.4 mg/L, 1.0 × 109, and 449 µmol/L; and 1.6 mg/L, 1.1 × 109, and 508 µmol/L, respectively.

Serum Cys-C, MHR, and UA are useful biomarkers for diagnosing CHD and HF, and CHD+HF. These can provide information for decision-making and risk stratification in patients with CHD and HF.

β-blockers are a solid pillar in the treatment of cardiovascular diseases. However, they are highly discussed regarding effectiveness for certain indications and side-effects. Even though there are up to 20 licensed compounds, only four are used for heart failure (HF) therapy. On the receptor level several key characteristics seem to influence the clinical outcome: subtype selectivity, antagonistic vs (inverse/biased) agonistic properties and -in particular- ancillary capacities. On a molecular level, divergent and novel signaling patterns are being identified and extra-cardiac effects on e.g. inflammation, metabolism and oxidative stress are highlighted. This review discusses different well-known and newly discovered characteristics that need to be considered for HF therapy and in the context of co-morbidities.

The prevalence of cardiovascular diseases markedly rises with age. Cellular senescence, a hallmark of aging, is characterized by irreversible cell cycle arrest and the manifestation of a senescence-associated secretory phenotype, which has emerged as a significant contributor to aging, mortality, and a spectrum of chronic ailments. An increasing body of preclinical and clinical research has established connections between senescence, senescence-associated secretory phenotype, and age-related cardiac and vascular pathologies. This review comprehensively outlines studies delving into the detrimental impact of senescence on various cardiovascular diseases, encompassing systemic atherosclerosis (including coronary artery disease, stroke, and peripheral arterial disease), as well as conditions such as hypertension, congestive heart failure, arrhythmias, and valvular heart diseases. In addition, we have preclinical studies demonstrating the beneficial effects of senolytics-a class of drugs designed to eliminate senescent cells selectively across diverse cardiovascular disease scenarios. Finally, we address knowledge gaps on the influence of senescence on cardiovascular systems and discuss the future trajectory of strategies targeting senescence for cardiovascular diseases.

Heart failure with preserved ejection fraction (HFpEF) accounts for over 50% of all heart failure cases nationwide and continues to rise in its prevalence. The complex, multi-organ involvement of the HFpEF clinical syndrome requires clinicians and investigators to adopt an integrative approach that considers the contribution of both cardiac and non-cardiac function to HFpEF pathophysiology. Thus, this symposium review outlines the key points from presentations covering the contributions of disease-related changes in cardiac function, arterial stiffness, peripheral vascular function, and oxygen delivery and utilization to exercise tolerance in patients with HFpEF. While many aspects of HFpEF pathophysiology remain poorly understood, there is accumulating evidence for a decline in vascular health in this patient group that may be remediable through pharmacological and lifestyle interventions and could improve outcomes and clinical status in this ever-growing patient population.

The impact of female biological sex on the development of heart failure with preserved ejection fraction (HFpEF) and its associated kidney disease and vascular endothelial dysfunction is still controversial. Whether females are protected from HFpEF and associated complications is not well established. Previous studies report conflicting prevalence between genders. We hypothesize that female mice are unprotected from HFpEF and its associated kidney disease and vascular endothelial dysfunction.

Eight-week-old female mice were divided into four groups: control groups receiving a standard diet and water for either 5 or 16 weeks, and HFpEF groups fed a high-fat diet (HFD, Rodent Diet With 60 kcal% Fat) and N [w]-nitro-l-arginine methyl ester (L-NAME - 0.5 g/L) in the drinking water for 5 or 16 weeks. Various measurements and assessments were performed, including echocardiography, metabolic and hypertensive evaluations, markers of heart and kidney injury, and assessment of vascular endothelial function.

Female mice with HFD and L-NAME developed HFpEF at 5 weeks, evidenced by increased E/E' ratio, reduced cardiac index, left ventricular mass, and unchanged ejection fraction. After 16 weeks, HFpEF worsened. Metabolic disorders, hypertension, lung wet/kidney weight increase, exercise intolerance, and cardiac/renal injury markers were observed. Vascular endothelial dysfunction was associated with ER stress and fibrosis induction.

We found that female mice are susceptible to the development of HFpEF and its associated kidney disease and vascular endothelial dysfunction. Our data support the concept that the female sex does not protect from HFpEF and its associated kidney disease and vascular endothelial dysfunction when disease risk factors are present.

Severe dysfunction in cardiac muscle intracellular Ca2+ handling is a common pathway underlying heart failure. Here we used an inducible genetic model of severe Ca2+ cycling dysfunction by the targeted temporal gene ablation of the cardiac Ca2+ ATPase, SERCA2, in otherwise normal adult mice. In this model, in vivo heart performance was minimally affected initially, even though Serca2a protein was markedly reduced. The mechanism underlying the sustained in vivo heart performance in the weeks prior to complete heart pump failure and death is not clear and is important to understand. Studies were primarily focused on understanding how in vivo diastolic function could be relatively normal under conditions of marked Serca2a deficiency. Interestingly, data show increased cardiac troponin I (cTnI) serine 23/24 phosphorylation content in hearts upon Serca2a ablation in vivo. We report that hearts isolated from the Serca2-deficient mice retained near normal heart pump functional responses to β-adrenergic stimulation. Unexpectedly, using genetic complementation models, in concert with inducible Serca2 ablation, data show that Serca2a-deficient hearts that also lacked the central β-adrenergic signaling-dependent Serca2a negative regulator, phospholamban (PLN), had severe diastolic dysfunction that could still be corrected by β-adrenergic stimulation. Notably, integrating a serines 23/24-to-alanine PKA-refractory sarcomere incorporated cTnI molecular switch complex in mice deficient in Serca2 showed blunting of β-adrenergic stimulation-mediated enhanced diastolic heart performance. Taken together, these data provide evidence of a compensatory regulatory role of the myofilaments as a critical physiological bridging mechanism to aid in preserving heart diastolic performance in failing hearts with severe Ca2+ handling deficits.

Heart failure (HF) is a common clinical condition encountered in various healthcare settings with a vast socioeconomic impact. Recent advancements in pharmacotherapy have led to the evolution of novel therapeutic agents with a decrease in hospitalization and mortality rates in HF with reduced left ventricular ejection fraction (HFrEF). Lately, the introduction of artificial intelligence (AI) to construct decision-making models for the early detection of HF has played a vital role in optimizing cardiovascular disease outcomes. In this review, we examine the newer therapies and evidence behind goal-directed medical therapy (GDMT) for managing HF. We also explore the application of AI and machine learning (ML) in HF, including early diagnosis and risk stratification for HFrEF.

Chronic ischemic heart disease (CIHD) is the leading cause of morbidity and mortality, increasing in proportion to the growth of the older population. Rehabilitative measures in patients who have undergone the myocardial revascularization, with back pain currently have insufficient evidence base. The differentiated program of medical rehabilitation (MR) at the stage of sanatorium-resort treatment is not regulated. A description of the comorbid patients' functional status will create a differentiated system of individual rehabilitation program set up.

To develop an algorithm for assessing the functional status of patients after myocardial revascularization with chronic low back pain.

The single-center cross-sectional cohort study (September 2021 - May 2022 yrs) included 50 patients after a myocardial revascularization with chronic low back pain (36 women, 14 men; median age 63.5 [55.5; 67.5] years), who were the study group and 10 patients with CIHD (5 women, 5 men; median age 65.0 [62.0; 68.0] years) who joined the control group. All patients underwent clinical (neurological and therapeutic examination), functional (clinical tests, echocardiography) and laboratory (general and biochemical blood analysis, blood cytokine levels) investigations, the functional class of impairment was defined.

There are 4 groups with combined pain syndrome (cardiogenic and vertebrogenic) in different ratios due to different functional and laboratory status among patients after the myocardial revascularization with chronic back pain. The presence of cardiogenic pain syndrome was associated with an increase in leukocyte and peripheral blood glucose levels, interleukin-6, myocardial mass enlargement, while vertebrogenic pain syndrome correlated with personal anxiety.

The evaluation of the functional status of patients according to the degree of severity of cardiogenic and vertebrogenic pain syndrome has revealed a simple method of pathogenetically based differentiation selection for individual rehabilitation program of patient development.

Patients with combined heart failure (HF) and chronic kidney disease (CKD) have been underrepresented in clinical trials. The prevalence of CKD in these patients and their clinical profile require constant evaluation. This study aimed to analyze the prevalence of CKD, its clinical profile, and patterns of use of evidence-based medical therapies in HF across CKD stages in a contemporary cohort of ambulatory patients with HF.

From October 2021 to February 2022, the CARDIOREN registry included 1107 ambulatory HF patients from 13 HF clinics in Spain.

The median age was 75 years, 63% were male, and 48% had heart failure with reduced left ventricular ejection fraction (HFrEF). A total of 654 (59.1%) had an estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2, and 122 (11%) patients with eGFR ≥ 60 mL/min/1.73 m2 had a urine albumin-creatinin ratio ≥ 30 mg/g. The most important variables associated with lower eGFR were age (R2=61%) and furosemide dose (R2=21%). The proportion of patients receiving an angiotensin-converting enzyme inhibitor (ACEI)/ angiotensin II receptor blockers (ARB), an angiotensin receptor-neprilysin inhibitor (ARNi), a sodium-glucose cotransporter 2 inhibitor (SGLT2i), or a mineralocorticoid receptor antagonist (MRA) progressively decreased with lower eGFR categories. Notably, 32% of the patients with HFrEF and an eGFR <30 mL/min/1.73 m2 received the combination of ACEI/ARB/ARNi+beta-blockers+MRA+SGLT2i.

In this contemporary HF registry, 70% of patients had kidney disease. Although this population is less likely to receive evidence-based therapies, structured and specialized follow-up approaches within HF clinics may facilitate the adoption of these life-saving drugs.

Due to hormonal variations, heart failure with preserved ejection fraction (HFpEF) remains prevalent in women and affects almost half of the heart failure (HF) patients. Given the yearly death rate of 10-30% and the unavailability of medications targeting HFpEF, the need arises for a better understanding of the fundamental mechanisms of this syndrome. This comprehensive review explores sex-specific differences in traditional risk factors; female-specific factors that may impact HFpEF development and response to therapy, including variations in hormone levels that may occur pre- and post-menopausal or during pregnancy; and disparities in comorbidities, clinical presentation, and diagnostic challenges. Lastly, the review addresses prognostic outcomes, noting that women with HFpEF have a poor quality of life but a higher survival rate. It also discusses novel biomarkers and precision medicine, emphasizing their potential to improve early detection and personalized treatment.

Cardiorenal programs have emerged to improve the management of cardiorenal disease (CRD). Evidence about the benefits of these programs is still scarce. This work aims to evaluate the performance of a novel cardiorenal program and describe the clinical profile and outcomes of patients with CRD.

We conducted a retrospective observational study of patients with CRD attended in a cardiorenal unit (CRU) from February 2021 to February 2022. Demographics and laboratory tests were collected and events (all-cause death and cardiovascular hospitalizations) were evaluated. Optimization of comorbidities and protective therapies was also assessed.

Eighty-two patients were included, with a mean age of 76.8 years [standard deviation (SD) 8.5] and 72% were men. A total of 58.5% (n = 47) had left ventricular ejection fraction <50%. The mean follow-up was 11 months (SD 4.0). Almost 54% of the patients (n = 44) required hospitalization, 30.5% for heart failure (HF) decompensation. Total hospitalizations significantly decreased after CRU inclusion: 0.70 versus 0.45 admissions/year (P < .02). Global mortality was 17.1% (n = 14). The percentage of patients with HF with reduced ejection fraction on quadruple therapy increased by 20%, and up to 60% of the patients were on three drugs. A total of 39% of the patients with HF and preserved ejection fraction started treatment with sodium-glucose co-transporter inhibitors. Hyperkalaemia required the use of potassium binders in 12.2% of the patients and treatment of secondary hyperparathyroidism was started in 42.7% and renal anaemia in 23.2%. Renal replacement therapy was initiated in 10% of the patients (n = 8).

CRD confers a considerable risk of adverse outcomes. Cardiorenal programs may improve cardiorenal syndrome management by optimizing therapies, treating comorbidities and reducing hospitalizations.

Chronic heart failure (CHF) is a set of symptoms and physical manifestations caused by the inability of the heart to perform its normal contractile function and satisfy the blood needs of all organs. This dysfunction leads to a non-physiological adaptation of all body systems, including the skeletal muscles and the diaphragm. The myopathy found in patients brings symptoms such as fatigue and intolerance to exercise, with an entity not always attributable to cardiac function. Neuromuscular incoordination is one of the symptoms related to CHF, causing an increased risk of mortality and hospitalization. The article reviews diaphragmatic adaptation in the presence of CHF and seeks to emphasize the importance of the diaphragm in understanding skeletal muscle incoordination in patients.