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Subjects with type 2 diabetes mellitus (T2D) are at increased risk for heart failure (HF). The cardiac-specific (FABP3) and adipose-tissue-specific (FABP4) types of the fatty acid binding proteins have been associated with both all-cause and cardiovascular (CV) mortality. The aim of this study was to explore the prognosis value of FABP3 and FABP4 in ambulatory subjects with chronic HF (CHF), with and without T2D. A prospective study involving 240 ambulatory CHF subjects was performed. Patients were followed-up for a mean of 5.78 ± 3.30 years and cause of death (if any) was recorded. Primary endpoints were defined as all-cause and CV death, and a composite endpoint that included CV death or hospitalization for HF was included as a secondary endpoint. Baseline serum samples were obtained and the serum FABP3 and FABP4 concentrations were assessed by sandwich enzyme-linked immunosorbent assay. Survival analysis was performed with multivariable Cox regressions, using Fine and Gray competing risks models when needed, to explore the prognostic value of FABP3 and FABP4 concentrations, adjusting for potential confounders. Type 2 diabetes mellitus was highly prevalent, accounting for 47.5% for total subjects with CHF. Subjects with T2D showed higher mortality rates (T2D: 69.30%; non-T2D: 50.79%, p = 0.004) and higher serum FABP3 (1829.3 (1104.9–3440.5) pg/mL vs. 1396.05 (820.3–2362.16) pg/mL, p = 0.007) and FABP4 (45.5 (27.6–79.8) ng/mL vs. 34.1 (24.09–55.3) ng/mL, p = 0.006) concentrations compared with non-T2D CHF subjects. In the whole study cohort, FABP3 was independently associated with all-cause death, and both FABP3 and FABP4 concentrations were associated with CV mortality. The predictive values of these two molecules for all-cause (FABP3: HR 1.25, 95% CI 1.09–1.44; p = 0.002. FABP4: HR 2.21, 95% CI 1.12–4.36; p = 0.023) and CV mortality (FABP3: HR 1.28, 95% CI 1.09–1.50; p = 0.002. FABP4: HR 4.19, 95% CI 2.21–7.95; p < 0.001) were only statistically significant in the subgroup of subjects with T2D. Notably, FABP4 (HR 2.07, 95% CI 1.11–3.87; p = 0.022), but not FABP3, also predicted the occurrence of the composite endpoint (death or hospitalization for HF) only in subjects with T2D. All these associations were not found in CHF subjects without T2D. Our findings support the usefulness of serum FABP3 and FABP4 concentrations as independent predictors for the occurrence of all-cause and CV mortality in ambulatory subjects with CHF with T2D. [ABSTRACT FROM AUTHOR]

Background: The Global Leadership Initiative on Malnutrition (GLIM) criteria were recently proposed to build a global consensus on the diagnostic criteria for malnutrition. This study aimed to evaluate the GLIM criteria for its prognostic significance in outpatients with heart failure (HF), and to compare them to a previous validated method, such as the Mini Nutritional Assessment (MNA). Methods: This was a post hoc observational analysis of a prospectively recruited cohort, which included 151 subjects that attended an outpatient HF clinic. At baseline, all patients completed the nutritional screening MNA short form and the nutritional assessment MNA. In a post hoc analysis, we evaluated the GLIM criteria at baseline. The outcomes were based on data from a five-year follow-up. The primary endpoint was all-cause mortality. Secondary endpoints were cardiovascular (CV) mortality and recurrent HF-related hospitalizations. We also investigated whether the GLIM criteria had better prognostic power than the MNA. Results: Abnormal nutritional status was identified in 19.8% of the patients with the GLIM criteria and in 25.1% with the MNA. In the multivariate analyses (age, sex, NYHA functional class, diabetes, and Barthel index), nutritional status assessed by the MNA, but not by the GLIM criteria, was an independent predictor of all-cause mortality, CV mortality, and recurrent HF-related hospitalizations during the five-year follow-up. Conclusions: Malnutrition assessed by MNA, but not by the GLIM criteria, was an independent predictor of all-cause mortality, CV mortality, and recurrent HF-related hospitalization in our cohort of outpatients with HF. [ABSTRACT FROM AUTHOR]

We assessed differences in long-term all-cause and cardiovascular (CV) mortality in heart failure (HF) outpatients based on the etiology of HF. Consecutive patients admitted to the HF Clinic from August 2001 to September 2019 (N = 2587) were considered for inclusion. HF etiology was divided into ischemic heart disease (IHD), dilated cardiomyopathy (DCM), hypertensive heart disease, alcoholic cardiomyopathy, drug-induced cardiomyopathy (DICM), valvular heart disease, and hypertrophic cardiomyopathy. All-cause death and CV death were the primary end points. Among 2387 patients included in the analysis (mean age 66.5 ± 12.5 years, 71.3% men), 1317 deaths were recorded (731 from CV cause) over a maximum follow-up of 18 years (median 4.1 years, interquartile range (IQR) 2–7.8). Considering IHD as the reference, only DCM had a lower risk of all-cause death (adjusted hazard ratio (aHR) 0.68, 95% confidence interval (CI) 0.56–0.83, p < 0.001), and only DICM had a higher risk of all-cause death (aHR 1.47, 95% CI 1.02–2.11, p = 0.04). However, almost all etiologies had a significantly lower risk of CV death than IHD. Among the studied HF etiologies, DCM and DICM have the lowest and highest risk of all-cause death, respectively, whereas IHD has the highest adjusted risk of CV death. [ABSTRACT FROM AUTHOR]

In recent years, there has been growing interest in the risk stratification for heart failure, and the use of multiple biomarkers to identify different pathophysiological processes associated with this condition. One such biomarker is soluble suppression of tumorigenicity-2 (sST2), which has shown some potential for integration into clinical practice. sST2 is produced by both cardiac fibroblasts and cardiomyocytes in response to myocardial stress. Other sources of sST2 are endothelial cells of the aorta and coronary arteries and immune cells such as T cells. Indeed, ST2 is also associated with inflammatory and immune processes. We aimed at reviewing the prognostic value of sST2 in both chronic and acute heart failure. In this setting, we also provide a flowchart about its potential use in clinical practice. [ABSTRACT FROM AUTHOR]

To better understand heart failure with preserved ejection fraction (HFpEF), we need to better characterize the transition from asymptomatic pre-HFpEF to symptomatic HFpEF. The current emphasis on left ventricular diastolic dysfunction must be redirected to microvascular inflammation and endothelial dysfunction that leads to cardiomyocyte remodeling and enhanced interstitial collagen deposition. A pre-HFpEF patient lacks signs or symptoms of heart failure (HF), has preserved left ventricular ejection fraction (LVEF) with incipient structural changes similar to HFpEF, and possesses elevated biomarkers of cardiac dysfunction. The transition from pre-HFpEF to symptomatic HFpEF also involves left atrial failure, pulmonary hypertension and right ventricular dysfunction, and renal failure. This review focuses on the non-left ventricular mechanisms in this transition, involving the atria, right heart cavities, kidneys, and ultimately the currently accepted driver—systemic inflammation. Impaired atrial function may decrease ventricular hemodynamics and significantly increase left atrial and pulmonary pressure, leading to HF symptoms, irrespective of left ventricle (LV) systolic function. Pulmonary hypertension and low right-ventricular function are associated with the incidence of HF. Interstitial fibrosis in the heart, large arteries, and kidneys is key to the pathophysiology of the cardiorenal syndrome continuum. By understanding each of these processes, we may be able to halt disease progression and eventually extend the time a patient remains in the asymptomatic pre-HFpEF stage. [ABSTRACT FROM AUTHOR]

Introduction: Heart failure (HF) is associated with significant alterations in body composition, including malnutrition due to insufficient intake, chronic inflammation and increased energy expenditure. Identifying the prevalence of malnutrition and the risk of sarcopenia in patients with HF is crucial to improve clinical outcomes. Material and methods: This cross-sectional, single-center, observational study involved 121 outpatients diagnosed with HF. Nutritional status was assessed using the Mini Nutritional Assessment (MNA), the Malnutrition Universal Screening Tool (MUST), and the Subjective Global Rating (SGA). Sarcopenia was screened using the SARC-F (Strength, Assistance in walking, Rise from a chair, Climb stairs, Falls) questionnaire and diagnosed based on the European Working Group in Older People (EWGSOP2) criteria and functionality with the Short Performance Battery (SPPB) test. Malnutrition was diagnosed according to the Global Leadership Initiative on Malnutrition (GLIM) criteria. Results: The study found that 10.7% had cardiac cachexia and 45.4% of deceased patients had been in this condition (p = 0.002). Moderate-to-high risk of malnutrition was identified in 37.1%, 23.9%, and 31.4% of patients according to the MNA, MUST, and SGA tests, respectively. According to the GLIM criteria, 56.2% of patients were malnourished. Additionally, 24.8% of patients had a high probability of sarcopenia, and 57.8% were not autonomous according to SPPB. Patients with less than 30% quadriceps muscle contraction were at a high risk of sarcopenia. Conclusions: There is a high prevalence of malnutrition among outpatients with HF, which is associated with worse prognosis, increased risk of sarcopenia, and greater frailty. These findings underscore the importance of early nutritional and functional assessments in this population to improve clinical outcomes. [ABSTRACT FROM AUTHOR]

Cardiac amyloidosis is an infiltrative disease that causes progressive myocardial impairment secondary to amyloid fibril deposition in the extracellular space of the myocardium. Many amyloid precursors, including transthyretin protein, are known to determine cardiac damage by aggregating and precipitating in cardiac tissue. Transthyretin cardiac amyloidosis may be either caused by rare genetic mutations of the transthyretin gene in the hereditary variant, or may arise as a consequence of age-related mechanisms in the acquired form. Although it has been labeled as a rare disease, in recent years, transthyretin cardiac amyloidosis has stood out as an emerging cause of aortic stenosis, unexplained left ventricular hypertrophy and heart failure with preserved ejection fraction, particularly in the elderly. Indeed, the integration of data deriving from both in vivo imaging techniques (whose advancement in the last years has allowed to achieve an easier and more accessible non-invasive diagnosis) and forensic studies (showing a prevalence of amyloid deposition in cardiac tissue of elderly patients up to 29%) suggests that cardiac amyloidosis is a more common disease than traditionally considered. Thanks to all the improvements in non-invasive diagnostic techniques, along with the development of efficacious therapies offering improvements in survival rates, transthyretin cardiac amyloidosis has been transformed from an incurable and infrequent condition to a relatively more diffuse and treatable disease, which physicians should take into consideration in the differential diagnostic processes in daily clinical practice. [ABSTRACT FROM AUTHOR]

Type 2 diabetes mellitus (T2DM) is a metabolic disorder that has alarmingly increased in incidence in recent decades. One of the most serious complications of T2DM is diabetic cardiomyopathy (DCM), an often underrecognized yet severe condition that is a leading cause of mortality among diabetic patients. In the early stages of DCM, patients typically show no symptoms and maintain normal systolic and diastolic left ventricle function, making early detection challenging. Currently available clinical markers are often not specific enough to detect the early stage of DCM. Conventional biomarkers of cardiac mechanical stress and injury, such as natriuretic peptides (NPs) and cardiac troponin I (cTnI), have shown limited predictive value for patients with T2DM. NPs have proven efficacy in detecting diastolic dysfunction in diabetic patients when used alongside 2D echocardiography, but their utility as biomarkers is limited to symptomatic individuals. While cTnI is a reliable indicator of general cardiac damage, it is not specific to cardiac injury caused by high glucose levels or T2DM. This underscores the need for research into biomarkers that can enable early diagnosis and management of DCM to reduce mortality rates. Promising novel biomarkers that showed good performance in detecting diastolic dysfunction or heart failure in diabetic patients include galectin-3, ST2, FGF-21, IGFBP-7, GDF-15, and TGF-β. This review summarizes the current understanding of DCM biomarkers, aiming to generate new ideas for the early recognition and treatment of DCM by exploring related pathophysiological mechanisms. [ABSTRACT FROM AUTHOR]

(1) Background: Left ventricular assist devices (LVADs) represent mechanical support in end-stage congestive heart failure and are characterized by satisfactory long-term results. Uric acid (UA) represents one of the early heart failure markers whose usefulness was postulated in clinical practice. (2) Methods: Twenty-nine male patients with a median age of 58 (51–62) years were referred for LVAD implantation due to end-stage congestive heart failure in the mean (SD) New York Heart Association (NYHA) status class 3.3 (0.6). Preoperative and postoperative right ventricular (RV) characteristics were compared with serum uric acid concentration within 12 (8–15) months following the implantation. (3) Results: Significant correlations between postoperative uric acid concentration and right ventricular dimension (r = 0.604, p = 0.005), tricuspid annulus plane systolic excursion (TAPSE) (r = −0.496, p = 0.022), left ventricular ejection fraction (r = −0.463, p = 0.046), and N-terminal pro-B-type natriuretic peptide (NT-pro-BNP) (r = 0.505, p = 0.041) were noted. (4) Conclusions: The analysis shows the association between the postoperative RV diameter and TAPSE results in LVAD patients and uric acid concentration. Serum uric acid can be regarded as a possible right ventricular dysfunction marker in LVAD patients. [ABSTRACT FROM AUTHOR]

Heart failure with preserved ejection fraction (HFpEF) represents a complex clinical syndrome, often very difficult to diagnose using the available tools. As the global burden of this disease is constantly growing, surpassing the prevalence of heart failure with reduced ejection fraction, during the last few years, efforts have focused on optimizing the diagnostic and prognostic pathways using an immense panel of circulating biomarkers. After the paradigm of HFpEF development emerged more than 10 years ago, suggesting the impact of multiple comorbidities on myocardial structure and function, several phenotypes of HFpEF have been characterized, with an attempt to find an ideal biomarker for each distinct pathophysiological pathway. Acknowledging the limitations of natriuretic peptides, hundreds of potential biomarkers have been evaluated, some of them demonstrating encouraging results. Among these, soluble suppression of tumorigenesis-2 reflecting myocardial remodeling, growth differentiation factor 15 as a marker of inflammation and albuminuria as a result of kidney dysfunction or, more recently, several circulating microRNAs have proved their incremental value. As the number of emerging biomarkers in HFpEF is rapidly expanding, in this review, we aim to explore the most promising available biomarkers linked to key pathophysiological mechanisms in HFpEF, outlining their utility for diagnosis, risk stratification and population screening, as well as their limitations. [ABSTRACT FROM AUTHOR]

Background: Heart Failure (HF) is a common chronic disease that has a high readmission rate and is associated with worsening symptoms and major financial impacts. Disease management implemented during or after an HF hospitalization has been shown to reduce hospitalization and mortality rates. Particularly for outpatients, it is necessary to provide self-care interventions. Structured nurse-led support such as timely follow-ups, including phone calls, is beneficial for improving self-care assessments. Evidence for nurse-led support has been investigated but is less than conclusive. The aim of this study is to compare the effectiveness of a nurse-led structured intervention for outpatients with chronic HF against the usual medical care in terms of self-care behaviors and occurrence of symptom exacerbation or rehospitalization. Methods and analysis: This is a cluster-randomized controlled trial. A total of 40 facilities with certified HF nurses will be allocated to two-arm clusters at a 1:1 ratio, randomly to the intervention or usual care arms. A total of 210 participants will be assigned from the hospital. Participants will be adults aged 18 years or older diagnosed with chronic HF who are classified as Stage C according to the ACCF/AHA Heart Failure staging system. In the intervention group, patients will receive structured nursing support. This begins with weekly support, including phone calls, for the first month, then transitions to monthly support thereafter. The aim is to ensure the stability of their living conditions, promote medication adherence, and encourage self-management. In the control group, patients will receive the usual care. Primary outcomes will assess the improvement or continuation of self-care behavior as measured by changes in EHFScBS (European Heart Failure Self-Care Behavior Scale) scores. Secondary outcomes include occurrence of readmission within 30 days, 3 months, 6 months, and 1 year after discharge, duration of home care until readmission, and blood levels of BNP and NT-proBNP. [ABSTRACT FROM AUTHOR]

Congestion and fluid retention are the hallmarks of decompensated heart failure and the major reason for the hospitalization of patients with heart failure. Diuretics have been used in heart failure for decades, and they remain the backbone of the contemporary management of heart failure. Loop diuretics is the preferred diuretic, and it has been given a class I recommendation by clinical guidelines for the relief of congestion symptoms. Although loop diuretics have been used virtually among all patients with acute decompensated heart failure, there is still very limited clinical evidence to guide the optimized diuretics use. This is a sharp contrast to the rapidly growing evidence of the rest of the guideline-directed medical therapy of heart failure and calls for further studies. The loop diuretics possess a unique pharmacology and pharmacokinetics that lay the ground for different strategies to increase diuretic efficiency. However, many of these approaches have not been evaluated in randomized clinical trials. In recent years, a stepped and protocolized diuretics dosing has been suggested to have superior benefits over an individual clinician-based strategy. Diuretic resistance has been a major challenge to decongestion therapy for patients with heart failure and is associated with a poor clinical prognosis. Recently, therapy options have emerged to help overcome diuretic resistance to loop diuretics and have been evaluated in randomized clinical trials. In this review, we aim to provide a comprehensive review of the pharmacology and clinical use of loop diuretics in the context of heart failure, with attention to its side effects, and adjuncts, as well as the challenges and future direction. [ABSTRACT FROM AUTHOR]

Heart failure (HF) is a syndrome characterized by signs and symptoms resulting from structural or functional cardiac abnormalities, confirmed by elevated natriuretic peptides or evidence of congestion. HF patients are classified according to left ventricular ejection fraction (LVEF). Worsening HF (WHF) is associated with increased short- and long-term mortality, re-hospitalization, and healthcare costs. The standard treatment of HF includes angiotensin-converting enzyme inhibitors, angiotensin receptor–neprilysin inhibitors, mineralocorticoid-receptor antagonists, beta-blockers, and sodium-glucose-co-transporter 2 inhibitors. To manage systolic HF by reducing mortality and hospitalizations in patients experiencing WHF, treatment with vericiguat, a direct stimulator of soluble guanylate cyclase (sGC), is indicated. This drug acts by stimulating sGC enzymes, part of the nitric oxide (NO)–sGC–cyclic guanosine monophosphate (cGMP) signaling pathway, regulating the cardiovascular system by catalyzing cGMP synthesis in response to NO. cGMP acts as a second messenger, triggering various cellular effects. Deficiencies in cGMP production, often due to low NO availability, are implicated in cardiovascular diseases. Vericiguat stimulates sGC directly, bypassing the need for a functional NO-sGC-cGMP axis, thus preventing myocardial and vascular dysfunction associated with decreased sGC activity in heart failure. Approved by the FDA in 2021, vericiguat administration should be considered, in addition to the four pillars of reduced EF (HFrEF) therapy, in symptomatic patients with LVEF < 45% following a worsening event. Cardiac rehabilitation represents an ideal setting where there is more time to implement therapy with vericiguat and incorporate a greater number of medications for the management of these patients. This review covers vericiguat's metabolism, molecular mechanisms, and drug–drug interactions. [ABSTRACT FROM AUTHOR]

Fluid restriction has long been believed to benefit patients with heart failure by counteracting the activated renin–angiotensin aldosterone system and sympathetic nervous activity. However, its effectiveness remains controversial. In this paper, we summarized the current recommendations and reviewed the scientific evidence on fluid restriction in the setting of both acute decompensated heart failure and compensated heart failure. While a recent meta-analysis demonstrated the beneficial effects of fluid restriction on both all-cause mortality and hospitalization compared to usual care, several weaknesses were identified in the assessment of the methodological quality of the meta-analysis using AMSTAR 2. Further randomized controlled trials with larger sample sizes are needed to elucidate the benefits of fluid restriction for both clinical outcomes and patient-reported outcomes in patients with heart failure. [ABSTRACT FROM AUTHOR]

Background: Major depressive disorder (MDD) plays a crucial role in the occurrence of heart failure (HF). This investigation was undertaken to explore the possible mechanism of MDD's involvement in HF pathogenesis and identify candidate biomarkers for the diagnosis of MDD with HF. Methods: GWAS data for MDD and HF were collected, and Mendelian randomization (MR) analysis was performed to investigate the causal relationship between MDD and HF. Differential expression analysis (DEA) and WGCNA were used to detect HF key genes and MDD-associated secretory proteins. Protein–protein interaction (PPI), functional enrichment, and cMAP analysis were used to reveal potential mechanisms and drugs for MDD-related HF. Then, four machine learning (ML) algorithms (including GLM, RF, SVM, and XGB) were used to screen candidate biomarkers, construct diagnostic nomograms, and predict MDD-related HF. Furthermore, the MCPcounter algorithm was used to explore immune cell infiltration in HF, and MR analysis was performed to explore the causal effect of immunophenotypes on HF. Finally, the validation of the association of MDD with reduced left ventricular ejection fraction (LVEF) and the performance assessment of diagnostic biomarkers was accomplished based on animal models mimicking MDD. Results: The MR analysis showed that the MDD was linked to an increased risk of HF (OR = 1.129, p < 0.001). DEA combined with WGCNA and secretory protein gene set identified 315 HF key genes and 332 MDD-associated secretory proteins, respectively. Through PPI and MCODE analysis, 78 genes were pinpointed as MDD-related pathogenic genes for HF. The enrichment analysis revealed that these genes were predominantly enriched in immune and inflammatory regulation. Through four ML algorithms, two hub genes (ISLR/SFRP4) were identified as candidate HF biomarkers, and a nomogram was developed. ROC analysis showed that the AUC of the nomogram was higher than 0.90 in both the HF combined dataset and two external cohorts. In addition, an immune cell infiltration analysis revealed the immune dysregulation in HF, with ISLR/SFRP4 displaying notable associations with the infiltration of B cells, CD8 T cells, and fibroblasts. More importantly, animal experiments showed that the expression levels of ISLR (r = −0.653, p < 0.001) and SFRP4 (r = −0.476, p = 0.008) were significantly negatively correlated with LVEF. Conclusions: The MR analysis indicated that MDD is a risk factor for HF at the genetic level. Bioinformatics analysis and the ML results suggest that ISLR and SFRP4 have the potential to serve as diagnostic biomarkers for HF. Animal experiments showed a negative correlation between the serum levels of ISLR/SFRP4 and LVEF, emphasizing the need for additional clinical studies to elucidate their diagnostic value. [ABSTRACT FROM AUTHOR]

Hypertension represents one of the primary and most common risk factors leading to the development of heart failure (HF) across the entire spectrum of left ventricular ejection fraction. A large body of evidence has demonstrated that adequate blood pressure (BP) control can reduce cardiovascular events, including the development of HF. Although the pathophysiological and epidemiological role of hypertension in the development of HF is well and largely known, some critical issues still deserve to be clarified, including BP targets, particularly in HF patients. Indeed, the management of hypertension in HF relies on the extrapolation of findings from high-risk hypertensive patients in the general population and not from specifically designed studies in HF populations. In patients with hypertension and HF with reduced ejection fraction (HFrEF), it is recommended to combine drugs with documented outcome benefits and BP-lowering effects. In patients with HF with preserved EF (HFpEF), a therapeutic strategy with all major antihypertensive drug classes is recommended. Besides commonly used antihypertensive drugs, different evidence suggests that other drugs recommended in HF for the beneficial effect on cardiovascular outcomes exert advantageous blood pressure-lowering actions. In this regard, type 2 sodium glucose transporter inhibitors (SGLT2i) have been shown to induce BP-lowering actions that favorably affect cardiac afterload, ventricular arterial coupling, cardiac efficiency, and cardiac reverse remodeling. More recently, it has been demonstrated that finerenone, a non-steroidal mineralocorticoid receptor antagonist, reduces new-onset HF and improves other HF outcomes in patients with chronic kidney disease and type 2 diabetes, irrespective of a history of HF. Other proposed agents, such as endothelin receptor antagonists, have provided contrasting results in the management of hypertension and HF. A novel, promising strategy could be represented by small interfering RNA, whose actions are under investigation in ongoing clinical trials. [ABSTRACT FROM AUTHOR]

Background: Cardiac troponin release is related to the cardiomyocyte loss occurring in heart failure (HF). The prognostic role of high-sensitivity cardiac troponin T (hs-cTnT) in several settings of HF is under investigation. The aim of the study is to assess the prognostic role of intrahospital hs-cTnT in patients admitted due to HF. Methods: In this observational, single center, prospective study, patients hospitalized due to HF have been enrolled. Admission, in-hospital peak, and discharge hs-cTnT have been assessed. Patients were followed up for 6 months. Cardiovascular (CV) death, HF hospitalization (HFH), and worsening HF (WHF) (i.e., urgent ambulatory visit/loop diuretics escalation) events have been assessed at 6-month follow up. Results: 253 consecutive patients have been enrolled in the study. The hs-cTnT median values at admission and discharge were 0.031 ng/mL (IQR 0.02–0.078) and 0.031 ng/mL (IQR 0.02–0.077), respectively. The risk of CV death/HFH was higher in patients with admission hs-cTnT values above the median (p = 0.02) and in patients who had an increase in hs-cTnT during hospitalization (p = 0.03). Multivariate Cox regression analysis confirmed that hs-cTnT above the median (OR: 2.06; 95% CI: 1.02–4.1; p = 0.04) and increase in hs-cTnT during hospitalization (OR:1.95; 95%CI: 1.006–3.769; p = 0.04) were predictors of CV death/HFH. In a subgroup analysis of patients with chronic HF, hs-cTnT above the median was associated with increased risk of CV death/HFH (p = 0.03), while in the subgroup of patients with HFmrEF/HFpEF, hs-cTnT above the median was associated with outpatient WHF events (p = 0.03). Conclusions: Inpatient hs-cTnT levels predict CV death/HFH in patients with HF. In particular, in the subgroup of chronic HF patients, hs-cTnT is predictive of CV death/HFH; while in patients with HFmrEF/HFpEF, hs-cTnT predicts WHF events. [ABSTRACT FROM AUTHOR]

Cardiovascular disease represents the foremost cause of mortality and morbidity worldwide, with a steadily increasing incidence due to the growth of the ageing population. Cardiac dysfunction leading to heart failure may arise from acute myocardial infarction (MI) as well as inflammatory- and cancer-related chronic cardiomyopathy. Despite pharmacological progress, effective cardiac repair represents an unmet clinical need, with heart transplantation being the only option for end-stage heart failure. The functional profiling of the biological activity of extracellular vesicles (EVs) has recently attracted increasing interest in the field of translational research for cardiac regenerative medicine. The cardioprotective and cardioactive potential of human progenitor stem/cell-derived EVs has been reported in several preclinical studies, and EVs have been suggested as promising paracrine therapy candidates for future clinical translation. Nevertheless, some compelling aspects must be properly addressed, including optimizing delivery strategies to meet patient needs and enhancing targeting specificity to the cardiac tissue. Therefore, in this review, we will discuss the most relevant aspects of the therapeutic potential of EVs released by human progenitors for cardiovascular disease, with a specific focus on the strategies that have been recently implemented to improve myocardial targeting and administration routes. [ABSTRACT FROM AUTHOR]

The associations of plasma metabolites with adverse cardiovascular (CV) outcomes are still underexplored and may be useful in CV risk stratification. We performed a systematic review and meta-analysis to establish correlations between blood metabolites and adverse CV outcomes in patients with heart failure (HF). Four cohorts were included, involving 83 metabolites and 37 metabolite ratios, measured in 1158 HF patients. Hazard ratios (HR) of 42 metabolites and 3 metabolite ratios, present in at least two studies, were combined through meta-analysis. Higher levels of histidine (HR 0.74, 95% CI [0.64; 0.86]) and tryptophan (HR 0.82 [0.71; 0.96]) seemed protective, whereas higher levels of symmetric dimethylarginine (SDMA) (HR 1.58 [1.30; 1.93]), N-methyl-1-histidine (HR 1.56 [1.27; 1.90]), SDMA/arginine (HR 1.38 [1.14; 1.68]), putrescine (HR 1.31 [1.06; 1.61]), methionine sulfoxide (HR 1.26 [1.03; 1.52]), and 5-hydroxylysine (HR 1.25 [1.05; 1.48]) were associated with a higher risk of CV events. Our findings corroborate important associations between metabolic imbalances and a higher risk of CV events in HF patients. However, the lack of standardization and data reporting hampered the comparison of a higher number of studies. In a future clinical scenario, metabolomics will greatly benefit from harmonizing sample handling, data analysis, reporting, and sharing. [ABSTRACT FROM AUTHOR]

Background: Vericiguat was developed to treat patients with heart failure (HF). Currently, limited data are available to characterize vericiguat-treated patients in real-world clinical settings. Methods: This retrospective cohort study was done using a Japanese hospital administrative database to describe the use of vericiguat in patients with HF in real-world settings. Adult patients diagnosed with HF prescribed vericiguat between 1 July 2021 and 30 September 2022 were included. Patient characteristics at the initiation of vericiguat treatment, patterns of HF medication use, and vericiguat dose titrations were assessed within the first 90 days of treatment. Results: The study included 829 patients who were initiated on vericiguat therapy. The mean age was 75.5 years and 69.0% were male. Hypertension, coronary artery disease, and diabetes mellitus were present in 91.7, 71.3, and 60.1% of patients, respectively. Most patients had previously received HF medications, with high percentages using angiotensin-receptor blocker neprilysin inhibitors (ARNI; 43.9%) and sodium-glucose cotransporter-2 inhibitors (54.4%). During the first 90 days of vericiguat treatment, 65.8% of the patients were uptitrated from their starting dose, and 32.3% had reached the maximal daily dose. The median time to reach the maximal daily dose was 34 days. The multivariable model identified that initiating vericiguat treatment in an outpatient setting and using ARNI before initiating vericiguat treatment were factors significantly associated with reaching the maximal daily dose of vericiguat at any given time, whereas older age, chronic kidney disease, hyperkalemia, and anemia were not associated. Conclusions: These findings provide early insights into the use of vericiguat, which aid in optimizing the combinations and/or sequences of HF treatment incorporating vericiguat therapy. [ABSTRACT FROM AUTHOR]

The syndrome of heart failure (HF) with preserved ejection fraction (HFpEF) makes up about half of the HF population. The HF mechanisms in these patients are varied and not fully understood. In addition, the term "diastolic HF" was switched to HFpEF because of difficulties in measuring the left ventricular (LV) diastolic performance. In the late stages, HFpEF carries a prognosis that is as bad as or worse than that of HFrEF. Hence, it is important to recognize LV diastolic impairment at an earlier stage so that the causal mechanisms, if any, can be treated to retard its progression. Despite the availability of numerous disease-modifying agents for HFrEF, there are hardly any available treatments for HFpEF. With our aging population, there will be an epidemic of HFpEF and hence this entity needs attention and respect. In this paper, we review the fundamental mechanisms of HFpEF, the physiology of LV filling and how LV diastolic function can be comprehensively measured. We also speculate how this may help with the early recognition of diastolic HF and its treatment. [ABSTRACT FROM AUTHOR]

Heart failure (HF) poses a significant world health challenge due to the increase in the aging population and advancements in cardiac care. In the pathophysiology of HF, the inflammasome has been correlated with the development, progression, and complications of HF disease. Discovering biomarkers linked to inflammasomes enhances understanding of HF diagnosis and prognosis. Directing inflammasome signaling emerges as an innovative therapeutic strategy for managing HF. The present review aims to delve into this inflammatory cascade, understanding its role in the development of HF, its potential role as biomarker, as well as the prospects of modulating inflammasomes as a therapeutic approach for HF. [ABSTRACT FROM AUTHOR]

Primary percutaneous coronary intervention (pPCI) has revolutionized the prognosis of ST-segment elevation myocardial infarction (STEMI) and is the gold standard treatment. As a result of its success, the number of pPCI centres has expanded worldwide. Despite decades of advancements, clinical outcomes in STEMI patients have plateaued. Out-of-hospital cardiac arrest and cardiogenic shock remain a major cause of high in-hospital mortality, whilst the growing burden of heart failure in long-term STEMI survivors presents a growing problem. Many elements aiming to optimize STEMI treatment are still subject to debate or lack sufficient evidence. This review provides an overview of the most contentious current issues in pPCI in STEMI patients, with an emphasis on unresolved questions and persistent challenges. [ABSTRACT FROM AUTHOR]

Cardiometabolic diseases (CMDs) are interrelated and multifactorial conditions, including arterial hypertension, type 2 diabetes, heart failure, coronary artery disease, and stroke. Due to the burden of cardiovascular morbidity and mortality associated with CMDs' increasing prevalence, there is a critical need for novel diagnostic and therapeutic strategies in their management. In clinical practice, innovative methods such as epicardial adipose tissue evaluation, ventricular–arterial coupling, and exercise tolerance studies could help to elucidate the multifaceted mechanisms associated with CMDs. Similarly, epigenetic changes involving noncoding RNAs, chromatin modulation, and cellular senescence could represent both novel biomarkers and targets for CMDs. Despite the promising data available, significant challenges remain in translating basic research findings into clinical practice, highlighting the need for further investigation into the complex pathophysiology underlying CMDs. [ABSTRACT FROM AUTHOR]

Systemic inflammation and coronary microvascular endothelial dysfunction are essential pathophysiological factors in heart failure (HF) with preserved ejection fraction (HFpEF) that support the use of statins. The pleiotropic properties of statins, such as anti-inflammatory, antihypertrophic, antifibrotic, and antioxidant effects, are generally accepted and may be beneficial in HF, especially in HFpEF. Numerous observational clinical trials have consistently shown a beneficial prognostic effect of statins in patients with HFpEF, while the results of two larger trials in patients with HFrEF have been controversial. Such differences may be related to a more pronounced impact of the pleiotropic properties of statins on the pathophysiology of HFpEF and pro-inflammatory comorbidities (arterial hypertension, diabetes mellitus, obesity, chronic kidney disease) that are more common in HFpEF. This review discusses the potential mechanisms of statin action that may be beneficial for patients with HFpEF, as well as clinical trials that have evaluated the statin effects on left ventricular diastolic function and clinical outcomes in patients with HFpEF. [ABSTRACT FROM AUTHOR]

(1) Background: Heart failure (HF) is not only a common cardiovascular disease with a poor prognosis. Its prevalence in developed countries equals 1–2% of the general population of adults, while in Poland HF, patients constitute 3.2% of the total population. Modern heart failure treatment should be focused not only on reducing the risk of death and the number of readmissions due to HF exacerbation but quality of life as well. Telemedicine has been suggested as a viable tool for enhancing HRQL. Therefore, we present the results of telemedical intervention in a group of HF patients and its effect on quality of life in chronic heart failure patients from a pilot study dedicated to reducing social inequalities in health through the use of telemedicine and e-health solutions. (2) Method: The project was a multicenter, open, non-controlled trial conducted by the University of Rzeszów, Poland. The data points were collected in the June 2023–December 2023 period from fourteen primary care units from five voivodeships, mostly considered social exclusion areas. A total of 52.7% of the patients recruited were Podkarpackie Voivodeship inhabitants. The result and discussion are presented based on the Chronic Heart Failure Questionnaire (CHFQ) and the EuroQol Visual Analogue Scale (EQVAS). (3) Results: During the program, a total of over 100,000 telemedicine examinations were conducted in the form of body weight measurement, heart rate, blood pressure tests, and 7-day Holter or 14-day event Holter assessment. Over the course of this study, coordinating the pilot program medical staff has ordered 570 changes in the patient's pharmacotherapy, confirming the positive impact on quality of life in the study group. (4) Conclusions: A comprehensive telemedical intervention can contribute to an improvement in the quality of life of patients with HF beyond what was achieved with the basic standard of care in the group of HF patients from the social exclusion region. It is now unclear if the result of the basic telemedical intervention would be constant after discontinuation of the mentioned pilot program. [ABSTRACT FROM AUTHOR]

Heart failure (HF) is a leading cause of morbidity worldwide, imposing a significant burden on deaths, hospitalizations, and health costs. Anticipating patients' deterioration is a cornerstone of HF treatment: preventing congestion and end organ damage while titrating HF therapies is the aim of the majority of clinical trials. Anyway, real-life medicine struggles with resource optimization, often reducing the chances of providing a patient-tailored follow-up. Telehealth holds the potential to drive substantial qualitative improvement in clinical practice through the development of patient-centered care, facilitating resource optimization, leading to decreased outpatient visits, hospitalizations, and lengths of hospital stays. Different technologies are rising to offer the best possible care to many subsets of patients, facing any stage of HF, and challenging extreme scenarios such as heart transplantation and ventricular assist devices. This article aims to thoroughly examine the potential advantages and obstacles presented by both existing and emerging telehealth technologies, including artificial intelligence. [ABSTRACT FROM AUTHOR]

Background: Heart failure (HF) affects around 60 million individuals worldwide. The primary aim of this study was to evaluate the efficacy of lung ultrasound (LUS) in managing HF with the goal of reducing hospital readmission rates. Methods: A systematic search was conducted on PubMed, Embase, Google Scholar, Web of Science, and Scopus, covering clinical trials, meta-analyses, systematic reviews, and original articles published between 1 January 2019 and 31 December 2023, focusing on LUS for HF assessment in out-patient settings. There is a potential for bias as the effectiveness of interventions may vary depending on the individuals administering them. Results: The PRISMA method synthesized the findings. Out of 873 articles identified, 33 were selected: 19 articles focused on prognostic assessment of HF, 11 centred on multimodal diagnostic assessments, and two addressed therapeutic guidance for HF diagnosis. LUS demonstrates advantages in detecting subclinical congestion, which holds prognostic significance for readmission and mortality during out-patient follow-up post-hospital-discharge, especially in complex scenarios, but there is a lack of standardization. Conclusions: there are considerable uncertainties in their interpretation and monitoring changes. The need for an updated international consensus on the use of LUS seems obvious. [ABSTRACT FROM AUTHOR]

Heart failure with preserved ejection fraction (HFpEF) results from a complex interplay of age, genetic, cardiac remodeling, and concomitant comorbidities including hypertension, obesity, diabetes, and chronic kidney disease (CKD). Renal failure is an important comorbidity of HFpEF, as well as a major pathophysiological mechanism for those patients at risk of developing HFpEF. Heart failure (HF) and CKD are intertwined conditions sharing common disease pathways; the so-called "kidney tamponade", explained by an increase in intracapsular pressure caused by fluid retention, is only the latest model to explain renal injury in HF. Recognizing the different phenotypes of HFpEF remains a real challenge; the pathophysiological mechanisms of renal dysfunction may differ across the HF spectrum, as well as the prognostic role. A better understanding of the role of cardiorenal interactions in patients with HF in terms of symptom status, disease progression, and prognosis remains essential in HF management. Historically, patients with HF and CKD have been scarcely represented in clinical trial populations. Current concerns affect the practical approach to HF treatment, and, in this context, physicians are frequently hesitant to prescribe and titrate both new and old treatments. Therefore, the extensive application of HF drugs in diverse HF subtypes with numerous comorbidities and different renal dysfunction etiologies remains a controversial matter of discussion. Numerous recently introduced drugs, such as sodium–glucose-linked transporter 2 inhibitors (SGLT2i), constitute a new therapeutic option for patients with HF and CKD. Because of their protective vascular and hormonal actions, the use of these agents may be safely extended to patients with renal dysfunction in the long term. The present review delves into the phenotype of patients with HFpEF and CKD from a pathophysiological perspective, proposing a treatment approach that suggests a practical stepwise algorithm for the proper application of life-saving therapies in clinical practice. [ABSTRACT FROM AUTHOR]

Congestion not only represents a cardinal sign of heart failure (HF) but is also now recognized as the primary cause of hospital admissions, rehospitalization, and mortality among patients with acute heart failure (AHF). Congestion can manifest through various HF phenotypes in acute settings: volume overload, volume redistribution, or both. Recognizing the congestion phenotype is paramount, as it implies different therapeutic strategies for decongestion. Among patients with AHF, achieving complete decongestion is challenging, as more than half still experience residual congestion at discharge. Residual congestion is one of the strongest predictors of future cardiovascular events and poor outcomes. Through this review, we try to provide a better understanding of the congestion phenomenon among patients with AHF by highlighting insights into the pathophysiological mechanisms behind congestion and new diagnostic and management tools to achieve and maintain efficient decongestion. [ABSTRACT FROM AUTHOR]

Heart failure (HF) is a complex clinical syndrome associated with significant morbidity, mortality, and healthcare costs. It is characterized by various structural and/or functional abnormalities of the heart, resulting in elevated intracardiac pressure and/or inadequate cardiac output at rest and/or during exercise. These dysfunctions can originate from a variety of conditions, including coronary artery disease, hypertension, cardiomyopathies, heart valve disorders, arrhythmias, and other lifestyle or systemic factors. Identifying the underlying cause is crucial for detecting reversible or treatable forms of HF. Recent epidemiological studies indicate that there has not been an increase in the incidence of the disease. Instead, patients seem to experience a chronic trajectory marked by frequent hospitalizations and stagnant mortality rates. Managing these patients requires a multidisciplinary approach that focuses on preventing disease progression, controlling symptoms, and preventing acute decompensations. In the outpatient setting, patient self-care plays a vital role in achieving these goals. This involves implementing necessary lifestyle changes and promptly recognizing symptoms/signs such as dyspnea, lower limb edema, or unexpected weight gain over a few days, to alert the healthcare team for evaluation of medication adjustments. Traditional methods of HF monitoring, such as symptom assessment and periodic clinic visits, may not capture subtle changes in hemodynamics. Sensor-based technologies offer a promising solution for remote monitoring of HF patients, enabling early detection of fluid overload and optimization of medical therapy. In this review, we provide an overview of the CardioMEMS device, a novel sensor-based system for pulmonary artery pressure monitoring in HF patients. We discuss the technical aspects, clinical evidence, and future directions of CardioMEMS in HF management. [ABSTRACT FROM AUTHOR]

Background and Objectives: episodes of acute decompensation in chronic heart failure (ADHF), a common health problem for the growing elderly population, pose a significant socio-economic burden on the public health systems. Limited knowledge is available on both the endothelial function in and the cardio-metabolic health profile of old adults hospitalized due to ADHF. This study aimed to investigate the connection between asymmetric dimethylarginine (ADMA)—a potent inhibitor of nitric oxide—and key health biomarkers in this category of high-risk patients. Materials and Methods: this pilot study included 83 individuals with a known ADHF history who were admitted to the ICU due to acute cardiac decompensation. Selected cardiovascular, metabolic, haemogram, renal, and liver parameters were measured at admission to the ICU. Key renal function indicators (serum creatinine, sodium, and potassium) were determined again at discharge. These parameters were compared between patients stratified by median ADMA (114 ng/mL). Results: high ADMA patients showed a significantly higher incidence of ischemic cardiomyopathy and longer length of hospital stay compared to those with low ADMA subjects. These individuals exhibited significantly higher urea at admission and creatinine at discharge, indicating poorer renal function. Moreover, their lipid profile was less favorable, with significantly elevated levels of total cholesterol and HDL. However, no significant inter-group differences were observed for the other parameters measured. Conclusions: the present findings disclose multidimensional, adverse ADMA-related changes in the health risk profile of patients with chronic heart failure hospitalized due to recurrent decompensation episodes. [ABSTRACT FROM AUTHOR]

Heart failure (HF) remains a major medical and social problem. The NT-pro-brain natriuretic peptide (NT-proBNP) and its active form, brain-type natriuretic peptide (BNP), in a simple blood test are the gold-standard biomarkers for HF diagnosis. However, even good biomarkers such as natriuretic peptides fail to predict all the risks associated with HF due to the diversity of the mechanisms involved. The pathophysiology of HF is determined by numerous factors, including oxidative stress, inflammation, neuroendocrine activation, pathological angiogenesis, changes in apoptotic pathways, fibrosis and vascular remodeling. High readmission and mortality rates prompt a search for new markers for the diagnosis, prognosis and treatment of HF. Oxidative-stress-mediated inflammation plays a crucial role in the development of subsequent changes in the failing heart and provides a new insight into this complex mechanism. Oxidative stress and inflammatory biomarkers appear to be a promising diagnostic and prognostic tool in patients with HF. This systematic review provides an overview of the current knowledge about oxidative stress and inflammation parameters as markers of HF. [ABSTRACT FROM AUTHOR]

Background: The adoption of self-care behaviors among patients with congestive heart failure (CHF) is essential for the management of their health condition. However, there is a lack of tools for estimating self-care in CHF patients. We aim to develop and validate the Greek version of the Hippocratic heart failure self-care scale (HHFSCS). Methods: The scale includes 22 items which are reviewed by a committee of experts. Individuals indicate the frequency at which they follow each self-behavior on a five-point Likert scale. Adult patients with CHF (n = 250) from a General Hospital in Athens participated in the study from June 2020 to March 2021. Reliability coefficients and an explanatory factor analysis (EFA), using a Varimax rotation and the principal component method, were used to assess the psychometric measurements. Results: The Cronbach's alpha coefficient of the HHFSCS was 0.807. The exploratory factor analysis identified two domains that accounted for 88.44% of the variance in the scale items; however, each sub-scale could not be used as an independent scale. Finally, the test–retest showed a significant and strong correlation (r = 0.973, p < 0.001). Conclusions: The HHFSCS is a reliable and valid tool for assessing self-behaviors in CHF patients. Health professionals can use it in their clinical practice to improve the management of a patient's health conditions. [ABSTRACT FROM AUTHOR]

Beta blockers (BBs) play a crucial role in enhancing the quality of life and extending the survival of patients with heart failure and reduced ejection fraction (HFrEF). Initiating the therapy at low doses and gradually titrating the dose upwards is recommended to ensure therapeutic efficacy while mitigating potential adverse effects. Vigilant monitoring for signs of drug intolerance is necessary, with dose adjustments as required. The management of older HF patients requires a case-centered approach, taking into account individual comorbidities, functional status, and frailty. Older adults, however, are often underrepresented in randomized clinical trials, leading to some uncertainty in management strategies as patients with HF in clinical practice are older than those enrolled in trials. The present article performs a scoping review of the past 25 years of published literature on BBs in older HF patients, focusing on age, outcomes, and tolerability. Twelve studies (eight randomized-controlled and four observational) encompassing 26,426 patients were reviewed. The results indicate that BBs represent a viable treatment for older HFrEF patients, offering benefits in symptom management, cardiac function, and overall outcomes. Their role in HF with preserved EF, however, remains uncertain. Further research is warranted to refine treatment strategies and address specific aspects in older adults, including proper dosing, therapeutic adherence, and tolerability. [ABSTRACT FROM AUTHOR]

Background: Acute heart failure (AHF) represents a leading cause of unscheduled hospital stays, frequent rehospitalisations, and mortality worldwide. The aim of our study was to develop a bedside prognostic tool, a multivariable predictive risk score, that is useful in daily practice, thus providing an early prognostic evaluation at admission and an accurate risk stratification after discharge in patients with AHF. Methods: This study is a subanalysis of the STADE HF study, which is a single-centre, prospective, randomised controlled trial enrolling 123 patients admitted to hospital for AHF. Here, 117 patients were included in the analysis, due to data exhaustivity. Regression analysis was performed to determine predictive variables for one-year mortality and/or rehospitalisation after discharge. Results: During the first year after discharge, 23 patients died. After modellisation, the variables considered to be of prognostic relevance in terms of mortality were (1) non-ischaemic aetiology of HF, (2) elevated creatinine levels at admission, (3) moderate/severe mitral regurgitation, and (4) prior HF hospitalisation. We designed a linear model based on these four independent predictive variables, and it showed a good ability to score and predict patient mortality with an AUC of 0.84 (95%CI: 0.76–0.92), thus denoting a high discriminative ability. A risk score equation was developed. During the first year after discharge, we observed as well that 41 patients died or were rehospitalised; hence, while searching for a model that could predict worsening health conditions (i.e., death and/or rehospitalisation), only two predictive variables were identified: non-ischaemic HF aetiology and previous HF hospitalisation (also included in the one-year mortality model). This second modellisation showed a more discrete discriminative ability with an AUC of 0.67 (95% C.I. 0.59–0.77). Conclusions: The proposed risk score and model, based on readily available predictive variables, are promising and useful tools to assess, respectively, the one-year mortality risk and the one-year mortality and/or rehospitalisations in patients hospitalised for AHF and to assist clinicians in the management of patients with HF aiming at improving their prognosis. [ABSTRACT FROM AUTHOR]

The aim of this study was to analyze the relationship between levels of sST2, NT-proBNP and oxidative stress markers in patients with reduced ejection fraction (HFrEF) due to non-ischemic cardiomyopathy. A total of 88 patients with HFrEF were divided into four groups based on left ventricular ejection fraction (≤25% and >25%) and NYHA functional class (group 1—LVEF > 25% and NYHA class I or II; group 2—LVEF > 25% and NYHA class III or IV; group III—LVEF ≤ 25% and NYHA class I or II; group IV—LVEF ≤ 25% and NYHA class III or IV). In 39 (44.32%) patients LVEF was reduced below 25%, and 22 of them (56.41%) were in NYHA functional class III/IV. Of the 49 (55.68%) patients with LVEF ≥ 25%, only 18.37% were in NYHA functional class III/IV (p < 0.001). Patients with LVEF ≥ 25% had lower levels of NT-proBNP, total oxidant status (TOS), total antioxidant capacity (TAC), and oxidative stress index (OSI). The levels of NT-proBNP but not sST-2 correlated positively with NYHA functional class (p < 0.001) and negatively with LVEF (p < 0.001). The levels of sST-2 were associated with increased TAC (p = 0.009) and uric acid (p = 0.040). These findings indicate that only NT-proBNP was related to the severity of heart failure, whereas sST2 correlated with total antioxidant capacity. Therefore, in stable patients with HFrEF due to dilated cardiomyopathy, sST2 may be an additional biomarker reflecting the redox status, but not the severity of heart failure. [ABSTRACT FROM AUTHOR]

Chronic obstructive pulmonary disease (COPD) is often part of a more complex cardiopulmonary disease, especially in older patients. The differential diagnosis of the acute exacerbation of COPD and/or heart failure (HF) in emergency settings is challenging due to their frequent coexistence and symptom overlap. Both conditions have a detrimental impact on each other's prognosis, leading to increased mortality rates. The timely diagnosis and treatment of COPD and coexisting factors like left ventricular overload or HF in inpatient and outpatient care can improve prognosis, quality of life, and long-term outcomes, helping to avoid exacerbations and hospitalization, which increase future exacerbation risk. This work aims to address existing gaps, providing management recommendations for COPD with/without HF, particularly when both conditions coexist. During virtual meetings, a panel of experts (the authors) discussed and reached a consensus on the differential and paired diagnosis of COPD and HF, providing suggestions for risk stratification, accurate diagnosis, and appropriate therapy for inpatients and outpatients. They emphasize that when COPD and HF are concomitant, both conditions should receive adequate treatment and that recommended HF treatments are not contraindicated in COPD and have favorable effects. Accurate diagnosis and therapy is crucial for effective treatment, reducing hospital readmissions and associated costs. The management considerations discussed in this study can potentially be extended to address other cardiopulmonary challenges frequently encountered by COPD patients. [ABSTRACT FROM AUTHOR]

Heart failure (HF) represents a significant global health challenge, characterized by high morbidity and mortality rates, and imposes considerable burdens on healthcare systems and patient quality of life. Traditional management strategies, primarily relying on clinical assessments and standard biomarkers like natriuretic peptides, face limitations due to the heterogeneity of HF. This review aims to delve into the evolving landscape of non-natriuretic biomarkers and the transformative potential of omics technologies, underscoring their roles in advancing HF treatment towards precision medicine. By offering novel insights into the biological underpinnings of HF, including inflammation, myocardial stress, fibrosis, and metabolic disturbances, these advancements facilitate more accurate patient phenotyping and individualized treatment strategies. The integration of non-natriuretic biomarkers and omics technologies heralds a pivotal shift in HF management, enabling a move towards tailored therapeutic interventions. This approach promises to enhance clinical outcomes by improving diagnostic accuracy, risk stratification, and monitoring therapeutic responses. However, challenges such as the variability in biomarker levels, cost-effectiveness, and the standardization of biomarker testing across different healthcare settings pose hurdles to their widespread adoption. Despite these challenges, the promise of precision medicine in HF, driven by these innovative biomarkers and technologies, offers a new horizon for improving patient care and outcomes. This review advocates for the further integration of these advancements into clinical practice, highlighting the need for ongoing research to fully realize their potential in transforming the landscape of heart failure management. [ABSTRACT FROM AUTHOR]

Developing effective anti-fibrotic therapies for heart diseases holds the potential to address unmet needs in several cardiac conditions, including heart failure with preserved ejection fraction, hypertrophic cardiomyopathy, and cardiotoxicity induced by cancer therapy. The inhibition of the primary fibrotic regulator, transforming growth factor (TGF) β, represents an efficient strategy for mitigating fibrosis in preclinical models. However, translating these findings into clinical benefits faces challenges due to potential adverse effects stemming from TGF-β's physiological actions in inflammation and tissue homeostasis. Various strategies exist for inhibiting TGF-β, each associated with a distinct risk of adverse effects. Targeting TGF-β directly or through its signaling pathway proves efficient in reducing fibrosis. However, direct TGF-β blockade may lead to uncontrolled inflammation, especially following myocardial infarction, while interference with the signaling pathway may compromise structural integrity, resulting in issues like insufficient wound healing or ventricular dilatation. Influencing TGF-β activity through interacting signaling pathways, for instance by inhibitors of the renin–angiotensin–aldosterone-system, is insufficiently potent in reducing fibrosis. Targeting activators of latent TGF-β, including ADAMTS enzymes, thrombospondin, and integrins, emerges as a potentially safer strategy to reduce TGF-β-induced fibrosis but it requires the identification of appropriate targets. Encouragement is drawn from promising agents developed for fibrosis in other organs, fueling hope for similar breakthroughs in treating cardiac fibrosis. Such advances depend on overcoming obstacles for the implementation of anti-fibrotic strategies in patients with heart disease, including fibrosis quantification. In this review, insights garnered from interventional and mechanistic studies, obtained through a non-systemic search spanning preclinical and clinical evidence, are summarized to pinpoint the most promising targets for further exploration and development. [ABSTRACT FROM AUTHOR]

The objective of this systematic review was to identify and describe information needs for individuals with heart failure (HF) throughout their patient journey. Six databases were searched (APA PsycINFO, CINAHL Ultimate, Embase, Emcare Nursing, Medline ALL, and Web of Science Core Collection) from inception to February 2023. Search strategies were developed utilizing the PICO framework. Potential studies of any methodological design were considered for inclusion through a snowball hand search. Data from the included articles were extracted by a reviewer, and the extraction accuracy was independently cross-checked by another author. Quality appraisal was assessed using the Mixed-Methods Appraisal Tool. A narrative synthesis was used to analyze all the outcomes according to the Synthesis Without Meta-analysis reporting guidelines. Twenty-five studies (15 quantitative and 10 qualitative) were included. Socioeconomic, cultural, and demographic factors influencing information needs were considered. The top three information needs for outpatients included general HF information, signs and symptoms and disease management strategies. For inpatients, medications, risk factors, and general HF were reported as the top needs. These divergent needs emphasize the importance of tailored education at different stages. Additionally, the review identified gaps in global representation, with limited studies from Africa and South America, underscoring the need for inclusive research. The findings caution against overgeneralization due to varied reporting methods. Practical implications call for culturally sensitive interventions to address nuanced HF patients' needs, while future research must prioritize standardized reporting, consider diverse patient journey timepoints, and minimize biases for enhanced reliability and applicability. [ABSTRACT FROM AUTHOR]

Background: Congestion is an essential issue in patients with heart failure (HF). Standard treatments do not usually achieve decongestion, and various strategies have been proposed to guide treatment, such as determination of natriuresis. After starting treatment with loop diuretics, we postulate that initial natriuresis might help treatment titration, decongestion, and improve prognosis. Methods: It was a prospective and observational study. Patients admitted with the diagnosis of HF decompensation were eligible. An assessment of congestion was performed during the first 48 h. Results: A total of 113 patients were included. A poor diuretic response was observed in 39.8%. After the first 48 h, patients with a greater diuretic response on admission (NaU > 80 mmol/L) showed fewer pulmonary b lines (12 vs. 15; p = 0.084), a lower IVC diameter (18 mm vs. 22 mm; p = 0.009), and lower IAP figures (11 mmHg vs. 13 mmHg; p = 0.041). Survival analysis tests demonstrated significant differences showing a higher proportion of all-cause mortality (ACM) and HF rehospitalization in the poor-diuretic-response group (log-rank test = 0.020). Conclusions: Up to 40% of the patients presented a poorer diuretic response at baseline, translating into worse outcomes. Patients with an optimal diuretic response showed significantly higher abdominal decongestion at 48 h and a better prognosis regarding ACM and/or HF rehospitalizations. [ABSTRACT FROM AUTHOR]

Worsening heart failure (WHF) is a severe and dynamic condition characterized by significant clinical and hemodynamic deterioration. It is characterized by worsening HF signs, symptoms and biomarkers, despite the achievement of an optimized medical therapy. It remains a significant challenge in cardiology, as it evolves into advanced and end-stage HF. The hyperactivation of the neurohormonal, adrenergic and renin-angiotensin-aldosterone system are well known pathophysiological pathways involved in HF. Several drugs have been developed to inhibit the latter, resulting in an improvement in life expectancy. Nevertheless, patients are exposed to a residual risk of adverse events, and the exploration of new molecular pathways and therapeutic targets is required. This review explores the current landscape of WHF, highlighting the complexities and factors contributing to this critical condition. Most recent medical advances have introduced cutting-edge pharmacological agents, such as guanylate cyclase stimulators and myosin activators. Regarding device-based therapies, invasive pulmonary pressure measurement and cardiac contractility modulation have emerged as promising tools to increase the quality of life and reduce hospitalizations due to HF exacerbations. Recent innovations in terms of WHF management emphasize the need for a multifaceted and patient-centric approach to address the complex HF syndrome. [ABSTRACT FROM AUTHOR]

Background: Heart failure is an epidemiologically relevant disease because of the aging population and widespread lifestyles that promote it. In addition to the acute event, it is possible for the disease to become chronic with periodic flare-ups. It is essential to study pathology from a diagnostic and prognostic point of view and to identify parameters for effective monitoring. In addition, heart failure is associated with multiple comorbidities, including cognitive impairment, which is monitored clinically but not through specific biomarkers in these patients. The purpose of this review is to gather the most recent scientific evidence on a few possible biomarkers previously identified for monitoring heart failure and associated cognitive impairment. Methods: We surveyed studies inherent to a set of previously identified markers, evaluating English-language articles from the past five years conducted in adult heart failure patient populations. We used the databases PubMed, Web of Sciences, and Cochrane Library for search studies, and we considered articles published in journals with an impact factor greater than five in the publication year. Results: Among the biomarkers evaluated, a concordant indication for serial measurements for heart failure monitoring emerged only for interleukin-6. For the other markers, there is still little evidence available, which is interesting but sometimes conflicting. Interesting studies have also emerged for biomarkers of cognitive decline assessed in patients with heart failure, confirming the hypotheses of the increasingly studied heart-brain correlation. Conclusion: Certainly, further studies in large populations are needed to identify effective biomarkers for monitoring heart failure and associated cognitive impairment. [ABSTRACT FROM AUTHOR]

Background: The pathophysiologic heterogeneity of heart failure (HF) necessitates a more detailed identification of diagnostic biomarkers that can reflect its diverse pathogenic pathways. Methods: We conducted weighted gene and multiscale embedded gene co-expression network analysis on differentially expressed genes obtained from HF and non-HF specimens. We employed a machine learning integration framework and protein–protein interaction network to identify diagnostic biomarkers. Additionally, we integrated gene set variation analysis, gene set enrichment analysis (GSEA), and transcription factor (TF)-target analysis to unravel the biomarker-dominant pathways. Leveraging single-sample GSEA and molecular docking, we predicted immune cells and therapeutic drugs related to biomarkers. Quantitative polymerase chain reaction validated the expressions of biomarkers in the plasma of HF patients. A two-sample Mendelian randomization analysis was implemented to investigate the causal impact of biomarkers on HF. Results: We first identified COL14A1, OGN, MFAP4, and SFRP4 as candidate biomarkers with robust diagnostic performance. We revealed that regulating biomarkers in HF pathogenesis involves TFs (BNC2, MEOX2) and pathways (cell adhesion molecules, chemokine signaling pathway, cytokine–cytokine receptor interaction, oxidative phosphorylation). Moreover, we observed the elevated infiltration of effector memory CD4+ T cells in HF, which was highly related to biomarkers and could impact immune pathways. Captopril, aldosterone antagonist, cyclopenthiazide, estradiol, tolazoline, and genistein were predicted as therapeutic drugs alleviating HF via interactions with biomarkers. In vitro study confirmed the up-regulation of OGN as a plasma biomarker of HF. Mendelian randomization analysis suggested that genetic predisposition toward higher plasma OGN promoted the risk of HF. Conclusions: We propose OGN as a diagnostic biomarker for HF, which may advance our understanding of the diagnosis and pathogenesis of HF. [ABSTRACT FROM AUTHOR]

Self-management interventions (SMIs) may enhance heart failure (HF) outcomes and address challenges associated with disease management. This study aims to review randomized evidence and identify knowledge gaps in SMIs for adult HF patients. Within the COMPAR-EU project, from 2010 to 2018, we conducted searches in the databases MEDLINE, CINAHL, Embase, Cochrane, and PsycINFO. We performed a descriptive analysis using predefined categories and developed an evidence map of randomized controlled trials (RCTs). We found 282 RCTs examining SMIs for HF patients, comparing two to four interventions, primarily targeting individual patients (97%) globally (34 countries, only 31% from an European country). These interventions involved support techniques such as information sharing (95%) and self-monitoring (62%), often through a mix of in-person and remote sessions (43%). Commonly assessed outcomes included quality of life, hospital admissions, mortality, exercise capacity, and self-efficacy. Few studies have focused on lower socio-economic or minority groups. Nurses (68%) and physicians (30%) were the primary providers, and most studies were at low risk of bias in generating a random sequence for participant allocation; however, the reporting was noticeably unclear of methods used to conceal the allocation process. Our analysis has revealed prevalent support techniques and delivery methods while highlighting methodological challenges. These findings provide valuable insights for researchers, clinicians, and policymakers striving to optimize SMIs for individuals living with HF. [ABSTRACT FROM AUTHOR]

Heart failure (HF) with preserved ejection fraction (HFpEF) is an increasingly frequent form and is estimated to be the dominant form of HF. On the other hand, HFpEF is a syndrome with systemic involvement, and it is characterized by multiple cardiac and extracardiac pathophysiological alterations. The increasing prevalence is currently reaching epidemic levels, thereby making HFpEF one of the greatest challenges facing cardiovascular medicine today. Compared to HF with reduced ejection fraction (HFrEF), the medical attitude in the case of HFpEF was a relaxed one towards the disease, despite the fact that it is much more complex, with many problems related to the identification of physiopathogenetic mechanisms and optimal methods of treatment. The current medical challenge is to develop effective therapeutic strategies, because patients suffering from HFpEF have symptoms and quality of life comparable to those with reduced ejection fraction, but the specific medication for HFrEF is ineffective in this situation; for this, we must first understand the pathological mechanisms in detail and correlate them with the clinical presentation. Another important aspect of HFpEF is the diversity of patients that can be identified under the umbrella of this syndrome. Thus, before being able to test and develop effective therapies, we must succeed in grouping patients into several categories, called phenotypes, depending on the pathological pathways and clinical features. This narrative review critiques issues related to the definition, etiology, clinical features, and pathophysiology of HFpEF. We tried to describe in as much detail as possible the clinical and biological phenotypes recognized in the literature in order to better understand the current therapeutic approach and the reason for the limited effectiveness. We have also highlighted possible pathological pathways that can be targeted by the latest research in this field. [ABSTRACT FROM AUTHOR]

Atrial fibrillation (AF) is the most common arrhythmia in patients affected by cardiomyopathies. Reports estimate a prevalence of 27% in patients with hypertrophic cardiomyopathy (HCM) and 40% in patients with cardiac amyloidosis (CA). The presence of AF typically results in progressive functional decline, an increased frequency of hospitalizations for heart failure, and a higher thromboembolic risk. Medical management using mainly beta-blockers or amiodarone has produced variable outcomes and a high rate of recurrence. Catheter ablation reduces symptom burden and complications despite a moderate rate of recurrence. Recent evidence suggests that an early rhythm control strategy may lead to more favorable short- and long-term outcomes. In this review, we summarize contemporary data on the management of AF in patients with cardiomyopathy (HCM and CA) with particular reference to the timing and outcomes of ablation procedures. [ABSTRACT FROM AUTHOR]

Limited data concerning the diagnostic and prognostic value of blood-derived biomarkers in heart failure with mildly reduced ejection fraction (HFmrEF) is available. This study investigates the diagnostic and prognostic value of aminoterminal prohormone of brain natriuretic peptide (NT-proBNP) in patients with HFmrEF, stratified by the estimated glomerular filtration rate (eGFR). Consecutive patients with HFmrEF were retrospectively included at one institution from 2016 to 2022. First, the diagnostic value of NT-proBNP for acute decompensated heart failure (ADHF) was tested. Thereafter, the prognostic value of NT-proBNP levels was tested for 30-months all-cause mortality in patients with ADHF. From a total of 755 patients hospitalized with HFmrEF, the rate of ADHF was 42%. Patients with ADHF revealed higher NT-proBNP levels compared to patients without (median 5394 pg/mL vs. 1655 pg/mL; p = 0.001). NT-proBNP was able to discriminate ADHF with an area under the curve (AUC) of 0.777 (p = 0.001), with the highest AUC in patients with eGFR ≥ 60 mL/min (AUC = 0.800; p = 0.001), and no diagnostic value was seen in eGFR < 30 mL/min (AUC = 0.576; p = 0.210). Patients with NT-proBNP levels > 3946 pg/mL were associated with higher rates of all-cause mortality at 30 months (57.7% vs. 34.4%; HR = 2.036; 95% CI 1.423–2.912; p = 0.001), even after multivariable adjustment (HR = 1.712; 95% CI 1.166–2.512; p = 0.006). In conclusion, increasing NT-proBNP levels predicted the risk of ADHF and all-cause mortality in patients with HFmrEF and preserved renal function; however, NT-proBNP levels were not predictive in patients with HFmrEF and eGFR < 30 mL/min. [ABSTRACT FROM AUTHOR]