Systemic inflammation and coronary microvascular endothelial dysfunction are essential pathophysiological factors in heart failure 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.

CKD in HF patients is very common condition, their dysfunction is closely linked and influence each other, so their management required multidisciplinary and personalized approaches. The diagnosis of HF and CDK relies on signs and symptoms. Several tools, such as blood-based biomarkers and echography help us to clarify and discriminate the main characteristics of these patients. Evidence in improving survival due to new drug-employment in HF, has increasingly challenged physicians to manage patients with multiple diseases, especially in patients with CKD. The difficulty is in the safe administration of these drugs in patients with HF and CKD. Knowing up to which values ​​of creatinine or renal clearance any drug can be administered is fundamental. We wanted to summarize, on this sizable and complex topic, the experiences of various prior study to get clearer ideas and a more precise reference about the assessment and management of HF and CKD.

Chronic heart failure (CHF) results when heart cannot constantly supply the body tissues with oxygen and required nutrients, and it can be categorized as heart failure (HF) with preserved ejection fraction (HFpEF), and HF with reduced ejection fraction (HFrEF). There are different causes and mechanisms of the HF pathogenesis; however, the inflammation can be regarded as one of the factors promoting both HFrEF and HFpEF. Monocytes, a subgroup of leucocytes, are known as cellular mediators in response to cardiovascular injury and are closely related to inflammatory reactions. These cells are a vital component of the immune system and are the source of macrophages, which participate in cardiac tissue repair after injury. However, the monocytes are not homogenous as thought, and thus can present different functions under different cardiovascular disease conditions. In addition, there is still an open question whether the functions of monocytes and macrophages should be regarded as a cause or a consequence in CHF development. Therefore, our aim was to summarize the current studies on the function of various monocyte subsets in CHF with a focus on the role of a certain monocyte subset in HFpEF and HFrEF patients, and the relation to inflammatory markers.

Heart failure is a prevalent cardiovascular condition with significant health implications, necessitating effective diagnostic strategies for timely intervention. This study explores the potential of continuous monitoring of non-invasive signals, specifically integrating Photoplethysmogram (PPG) and Electrocardiogram (ECG), for enhancing early detection and diagnosis of heart failure. Leveraging a dataset from the MIMIC-III database, encompassing 682 heart failure patients and 954 controls. Feature selection techniques were used to systematically select key features which were identified for their clinical relevance and significance in capturing cardiovascular dynamics and to reduce computational complexity and to decrease the chance of overfitting the ML algorithms. These features are then utilized to train and evaluate machine learning algorithms, resulting in a model with an impressive accuracy of 98%, sensitivity of 97.60%, specificity of 96.90%, and precision of 97.20%. The integrated approach outperforms single-signal strategies, showcas-ng its potential for early, precise, and non-invasive heart failure diagnosis. Furthermore, the study underscores the significance of continuous monitoring through wearables, emphasizing the benefits of integrating multiple signals for a comprehensive evaluation of cardiovascular health. The proposed approach holds promise for implementation in hardware systems to enable continuous monitoring, aiding in early detection and prevention of critical health conditions.

Background and Objectives: Ischemic and idiopathic heart failure are two different etiologies, however reactive cardiac fibrosis together with impaired vasculogenesis has been described in both of them. Implication of main proangiogenic factors as: angiogenin, agiopoietin-1 (Ang-1) and angiopoietin-2 (Ang-2) has been described mainly in experimental models of heart failure. However, differences in molecular pathways between these cardiomyopathies are still under investigation. In this short communication we aimed to evaluate and compare the expression of pro-angiogenic molecules in the heart tissue of patients with advanced chronic heart failure (CHF) of ischemic and idiopathic etiology. Methods and Results: Heart tissue from left ventricular walls was obtained at transplantation from ischemic heart disease (IHD), idiopathic cardiomyopathy (ICM) patients. Tissue samples were examined using immunohistochemistry for angiogenic molecules. Immunopositivity (I-pos) for angiopoietin-1 was mainly observed in the cardiomyocytes, while I-pos for Ang-2 and Tie-2 receptor mainly in endothelial cells. Procollagen-I (PICP), angiogenin, Ang-1, Tie-2 receptor, were similarly expressed in IHD and ICM patients. In contrast, endothelial immunopositivity for Ang-2 was higher in IHD samples compared to ICM (p=0.03). Conclusions: Ang-2 expression is different in heart tissue of ICM and ICM patients and distribution of Ang-1 and angiogenin is higher in cardiomyocytes, whereas Ang-2 higher in endothelial cells, suggesting a different pattern of angiogenic stimulation, or at least of altered endothelial integrity. This data may serve for further studies investigating angiogenesis signaling pathways and in HF of different etiology.

Heart failure is a global major healthcare problem with millions of hospitalizations annually and with a very high mortality. There is an increased interest in finding new and reliable biomarkers for the diagnostication, prognostication and therapeutical guidance of patients hospitalized for acute heart failure. There is data to sustain the role of CA 125, a worldwide used marker of ovarian cancer, in patients with heart failure. Several studies have shown links between CA 125 levels and congestion seen in acute heart failure, high mortality and readmission rates at 6 months follow up after discharge from acute heart failure and also a role of CA 125 in the guidance of heart failure therapy. There are also clinical trials that showed that several particularities of CA 125 make it even better than NTpro BNP ( a classical and more utilised marker of heart failure) in several scenarios of acute heart failure.

Aim: To investigate the effects of intensive physical exercise on retinal microvascular regulation in healthy volunteers by the adaptive optics retinal camera measurement. Methods: We included healthy volunteers (11 men and 14 women) aged 20.6± 0.9. Heart rate (HR) and systolic and diastolic blood pressure (SBP, DBP) were recorded before and after a submaximal physical exertion of continuously riding a training ergometer. The superior temporal retinal artery measurements were captured using the adaptive optics (AO) camera rtx1TM (Imagine Eyes, Orsay, France) without pupil dilatation. We compared measures of vessel diameter (VD), lumen diameter (LD), two walls (Wall 1, 2), wall-to-lumen ratio (WLR), and wall cross-sectional analysis (WCSA) before and immediately after the cessation of exercise. Results: Cardiovascular parameters: After exercise, SBP, DBP and HR changed significantly from 130.2±13.2 to 159.7±15.6 mm Hg, 81.2±6.3 to 77.1±8.2 mm Hg and 80.8±16.1 to 175.0±6.2 bpm, respectively (p < 0.002). Retinal microcirculation analysis: Before the exercise, the mean LD was 96.0±6.8, VD 118.5±8.3, WLR 0.234±0.02, WCSA 3802.8±577.6. The mean LD and Wall 1 did not change significantly after exercise but slightly decreased. The VD, Wall 2, WLR and WCSA decreased significantly (p

Malnutrition, clinically evident primarily with sarcopenia, is present in more than 50% of CHF patients and is an independent factor of morbidity and mortality. Several pathophysiological mechanisms, such as reduced appetite, metabolic imbalance and altered protein synthesis/degradation rate, due to the blood increase of hypercatabolic molecules, have been proposed to explain this phenomenon. Nutritional supplementation with proteins, amino acids and vitamins have all been used to treat malnutrition, acting through mTOR stimulation. However, the success and efficacy of these procedures are often contradictory and not conclusive. Interestingly, data on exercise training show that exercise reduces mortality and increase functional capacity, although it also increases energy expenditure and nitrogen providing substrate needs. Therefore, this paper discusses the molecular mechanisms of integrated nutritional approaches that would stimulate metabolic anabolic pathways. Pivotal in our opinion, is the relationship between exercise and Deptor, a subunit of the mTOR complex. Consequently, we propose a combination of personalized and integrate nutritional supplementation as well as exercise to treat malnutrition and related anthropometric and functional CHF-related disorders.

Heart failure (HF) is a growing issue in developed countries and most patients present with a reduced ejection fraction. This condition significantly impairs quality of life and represents a threat not only for patients, but also for the entire healthcare system due to its high management cost. In the last decade, new medical treatments and devices have been developed to reduce HF hospitalizations and improve prognosis, while reducing the overall mortality rate. Medical therapy does not achieve the same results in all patients and, whenever it fails, technology comes in handy: novel devices for the management of HF have reduced symptoms. They have also improved the treatment of fluid retention and life threatening arrhythmias. The present review article gives to the readers a comprehensive overview of the most recent and important findings that need to be considered in HF with reduced ejection fraction patients. Both novel medical treatments and devices have been presented and discussed.

Although acute heart failure (AHF) is a common disease associated with significant symptoms, morbidity and mortality, the diagnosis, risk stratification and treatment of patients with hypertensive acute heart failure (H-AHF) still remain a challenge in modern medicine. Despite great progress in diagnostic and therapeutic modalities, this disease is still accompanied by a high rate of both in-hospital (from 3.8% to 11%) and one-year mortality (from 20% to 36%). Considering the high rate of re-hospitalization (22% to 30% in the first three months), the treatment of this disease represents a major financial blow to the health system of each country. This disease is characterized by heterogeneity in precipitating factors, clinical presentation, therapeutic modalities and prognosis. Since heart decompensation usually occurs quickly (within a few hours) in patients with H-AHF, establishing a rapid diagnosis is of vital importance. In addition to establishing the diagnosis of heart failure itself, it is necessary to see the underlying cause that led to it, especially if it is de novo heart failure. Given that hypertension is a precipitating factor of AHF and in up to 11% of AHF patients, strict control of arterial blood pressure is necessary until target values are reached in order to prevent the occurrence of H-AHF, which is still accompanied by a high rate of both early and long-term mortality.

Circulating extracellular microvesicles (cEVs) are characterised by presenting surface antigens of parental cells. Since their biogenesis involves the translocation of phosphatidylserine (PS) from the inner to the outer-leaflet of the plasma membrane, exposed PS has been considered as a recognition hallmark of cEVs. However, not all cEVs externalise PS. In this study we have phenotypically and quantitatively characterised cEVs by flow cytometry with special attention to the proportions of PS in chronic heart failure patients (cHF; n=119) and reference non-HF group (n=21). PS─-cEVs were predominantly found in both groups. Parental markers showed differential pattern depending on PS exposure. Endothelium-derived and connexin 43-rich cEVs were mainly PS─-cEVs and significantly increased in cHF. On the contrary, platelet-derived cEVs were mostly PS+ and were increased in non-HF. We observed similar levels of PS+- and PS─-cEVs in non-HF subjects when analysing immune cell-derived EVs, but there was a subset-specific difference in cHF patients. Indeed, those cEVs carrying CD45+, CD29+, CD11b+ and CD15+ were mainly PS+-cEVs, while those carrying CD14+, CD3+ and CD56+ were mainly PS─-cEVs. In conclusion, endothelial and red blood cells are stressed in cHF patients as detected by a high shedding of cEVs. Despite PS+-cEVs and PS─-cEVs represent two distinct cEV populations, their release and potential function as both biomarkers and shuttles for cell communication seem unrelated to PS content.

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 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, were participated in the study from June 2020 to March 2021. Reliability coefficients and Explanatory Factor Analysis (EFA), using a Varimax rotation and the Principal Components 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 of the scale items; however, each sub-scale could not be used as an independent scale. Finally, the test-retest showed a significant strong correlation (r=0.973, p&lt;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 patient’s health conditions.

In patients with heart failure, the evaluation of left ventricular (LV) diastolic function is vital, offering crucial insights into hemodynamic impact and prognostic accuracy. Echocardiography stands as the primary imaging modality for diastolic function assessment, and using it effectively requires a profound understanding of the underlying pathology. This review covers four main topics: first, the fundamental driving forces behind each phase of normal diastolic dynamics, along with the physiological basis of two widely used echocardiographic assessment parameters, E/e' and mitral annulus early diastolic velocity (e'); second, the intricate functional relationship between the left atrium and LV in patients with varying degrees of LV diastolic dysfunction (LVDD); third, the role of stress echocardiography in diagnosing LVDD and the significance of parameter changes in this context; and fourth, the clinical utility of evaluating diastolic function from echocardiography images across diverse cardiovascular care areas.

Heart failure (HF) has become a public health problem, but exact pathophysiology is still unknown. Western diet characterised with high sugar, high fat, red meat and processed meat, eggs, fried foods and sweetened beverages, may cause oxidative stress and inflammation, leading to oxidative dysfunction and adverse effects on cardiac-ultra-structure. However, only little is known about oxidative function of the of the myocardium and how oxidative dysfunction predispose Ca-overloading resulting in to physio-pathological remodelling leading to HF. Antioxidants such as flavonoids and polyphenolics, omega-3 fatty acids, vitamins, minerals as well as essential and nonessential amino acids that are rich in Indo-Mediterranean type of diets, may have protective roles in maintaining oxidative functions of the heart. The cardiac cells use fatty acids and glucose for the metabolic functions depending upon physiological and metabolic requirements. Apart from glucotoxicity, lipotoxicity is also damaging to cardiac cells which worsen in presence of deficiency of endogenous antioxidants and lower exogenous antioxidants in the diet. There is increased production of ceramide, advanced glycation end products (AGE) and triamino-methyl-N-oxide (TMAO) due to high sugar and high fat diets, leading to oxidative dysfunction and Ca-overloading. The biological changes may begin with physiological remodelling to pathological remodelling due to oxidative damages. High fat diet in combination with inducible nitric oxide synthase (NOSi) via N-arginine methyl ester has been found to preserve ejection fraction in a mouse model of HF. It is possible that increased supplementation of High Exogenous Antioxidant Restorative Treatment (HEART) diet; polyphenolics and flavonoids, vitamins, minerals, arginine, with omega-3 fatty acids, and cessation of red meat and egg may further improve the oxidative function of cardiac cells, resulting in the prevention and improvement in the earliest of the Six Stages of HF. Cohort studies and randomised, controlled trials would be necessary for demonstration of the role of HEART diet in the management of HF.

Congestion not only represents a cardinal sign of heart failure but is also now recognized as the primary cause for hospital admissions, rehospitalizations, and mortality among patients with acute heart failure. Congestion can manifest through various heart failure phenotypes in acute settings: volume overload, volume redistribution, or both. Recognizing the congestion phenotype is paramount, as it implies different therapeutic strategies for decongestion. Complete decongestion is hardly achieved among patients with acute heart failure, as more than half still have 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 acute heart failure by highlighting insights into the pathophysiology mechanisms behind congestion and new diagnostic and management tools to achieve and maintain efficient decongestion.

Beyond plasma glucose-lowering in patients with type 2 diabetes, sodium- glucose cotransporter 2 inhibitors (SGLT2i) significantly reduced the hospitalization for heart failure (HF) and retarded the progression of chronic kidney disease (CKD). Endothelial dysfunction is not only involved in the development and progression of cardiovascular disease (CVD), and is also associated with the progression of CKD. In patients with type 2 diabetes, hyperglycemia, insulin resistance, hyperinsulinemia and dyslipidemia induce the development of endothelial dysfunction. SGLT2i have shown an improvement in endothelial dysfunction, as assessed by flow-mediated vasodila-tion, in individuals at high risk for CVD. Along with an improvement of endothelial dysfunction, SGLT2i showed improvements in oxidative stress, inflammation, mitochondrial dysfunction, glucotoxicity such as advanced glycation end products signaling and nitric oxide bioavailability. The improvements in endothelial dysfunc-tion and such endothelium-derived factors may play an important role in preventing the development of coronary artery disease, coronary microvascular dysfunction and diabetic cardiomyopathy which cause HF and in retarding CKD. The suppression of the development of HF and the progression of CKD achieved by SGLT2i might have been largely induced by the improvement of vascular endothelial function by SGLT2i.

Heart failure is a leading cause of death among people worldwide. The cost of treatment can be prohibitive, and early prediction of heart failure would reduce treatment costs to patients and hospitals. Improved prediction of readmission would also be of great help hospital, allowing them to better manage their treatment programs and budgets. This systematic review aims to summarize recent studies of predictive analytics models that have been constructed to predict heart failure and readmission. Some of these models use a statistical approach and others a machine learning approach. Electronic patient health records, including demography, physical and clinical values, and laboratory findings are used to design and build predictive models. Predictive analytics with good performance have become essential for clinicians and specialists. Choosing a suitable machine learning algorithm and data preprocessing technique will improve predictive model performance, including data imputation and class imbalance.

BackgroundHeart failure is a life-threatening disease affecting millions worldwide. Tolvaptan is the first FDA-approved orally active nonpeptide vasopressin 2 receptor antagonist to be used in hypervolemic hyponatremia, heart failure, cirrhosis, etc. In clinical trials, tolvaptan impacts short-term in increasing water excretion, and restoring Na+ and dyspnoea. Aims & ObjectivesThe objective is to analyze the outcomes of tolvaptan in existing cases of heart failure. MethodologyWe conducted a database search of the MEDLINE, Embase, and Cochrane Central Register of Controlled Trials and RCTs till 1st September 2019 were included following PRISMA guidelines after being matched with inclusion and exclusion criteria. 21 RCTs were included with 7,357 patients receiving tolvaptan and 7,273 patients being the control group. We used the MESH strings such as 'tolvaptan', 'vasopressin V2 receptor blocker', 'acute heart failure', and 'acute decompensated heart failure'. ResultsMeta-analysis showed that Tolvaptan was associated with a significant reduction in edema (RR = 1.05, 95% CI = 1.019-1.081, p=0.001) and significant body weight reduction (Control-SMD = -0.489, 95% CI =-0.637 to -0.342, p<0.001)&(Placebo-SMD = -0.425, 95% CI = -0.425 to -0.382, p<0.001) It shows significant decrease in serum sodium levels (SMD = 0.678, 95% CI = 0.609 to 0.748, p<0.001). There was no significant decrease in all-cause mortality (Control-RR = 0.855, 95% CI 0.470 to 1.555, p=0.607)(Placebo-RR= 0.972, 95% CI = 0.879-1.074, p=0.575). Results for Worsening renal function in heart failure (Placebo-RR = 0.798 95% CI 0.619 to 1.028, p=0.081)(Control-RR = 1.349, 95% CI=0.927-1.964, p=0.118). ConclusionAlthough tolvaptan may significantly reduce edema, congestive symptoms and decreased body weight, it has no impact on all-cause mortality and worsening renal function in heart failure.

Extracellular vesicles (EVs) are emerging mediators of intracellular and inter-organ communications in cardiovascular diseases (CVDs), especially in the pathogenesis of heart failure through the transference of EV-containing bioactive substances. microRNAs (miRNAs) are contained in EV cargo and are involved in the progression of heart failure. Over the past several years, a growing body of evidence has suggested that the biogenesis of miRNAs and EVs are tightly regulated, and the sorting of miRNAs into EVs is highly selective and tightly controlled. Extracellular miRNAs, in particular circulating EV-miRNAs, have shown promising potential as prognostic and diagnostic biomarkers for heart failure and as therapeutic targets. In this review, we summarize the latest progress concerning the role of EV-miRNAs in HF and their application in a therapeutic strategy development for heart failure.

Previous high throughput screening studies indicated trans-eQTLs tend to be tissue specific. In this study, I probed if this feature can be used to identify tissue-specific gene regulatory networks. eQTL data (P<5e-8) for 16,259 genes were identified and their summary association statistics were obtained from the eQTLGene database. Next, eQTLs that display both cis and trans regulatory effects were selected and the association between their corresponding genes were examined using Mendelian randomization. A total of 169 genes that exerted trans-regulatory impacts on 692 genes were identified. 90% of the genes (N=749) aggregated into a gene regulatory network significantly enriched in hemo-immune processes. The robustness of finding was confirmed through simulation. The identified network displayed the scale-free topology. This provided the reason to examine the association of the network’s hub genes with the phenome. The outcome of analyses revealed GSDMB and ORMDL3 impact several disorders of immune origin and ALDH2 overexpression contributes to obesity. This study reports trans-eQTLs can be used to identify tissue-specific gene regulatory networks and describes a workflow to achieve this purpose. The network identified in this study showed scale-free topology indicating the hub genes of a GRN could be targeted to prevent disease outcomes.

Background: Inhibition of sodium-glucose co-transporter 2 (SGLT-2) has been shown to be beneficial in the treatment of diabetic and non-diabetic patients with heart failure with reduced ejection fraction (HFrEF). The underlying mechanisms are incompletely understood. The present prospective study investigates for the first time the effect of empagliflozin on various soluble markers of inflammation in HFrEF. Methods: We included 50 inpatients with HFrEF and diabetes mellitus type 2. Half of the patients received a therapy with the SGLT-2-inhibitor empagliflozin in addition to standard medication, the other half of the patients did not receive empagliflozin and were considered as control group. Quality of life, functional status and soluble immunological parameters in serum were assessed at baseline and after 3 months. Results: Baseline characteristics of both groups revealed no significant differences. Patients on empagliflozin demonstrated a significant improvement in the Minnesota living with heart failure questionnaire (baseline 44.2 ± 20.2 vs. 24 ± 17.7; p<0.001), in distance in the 6-minute walk test (baseline 343 ± 145 m vs. 450 ± 115 m; p<0.001) and in soluble interleukin-6 level (baseline 21.7 ± 21.8 pg/ml vs. 13.7 ± 15.8 pg/ml; p=0.008). There was no significant change of these or other parameters in the control group (p>0.05 each). Conclusions: The empagliflozin-induced improvement of quality of life and functional capacity in patients with HFrEF and type 2 diabetes mellitus is accompanied by a substantial reduction of interleukin-6 levels. Thus, antiinflammatory effects may contribute to the benefits of SGLT2-inhibitors in heart failure.

Introduction: Decompensated heart failure (HF) is a complex and debilitating syndrome, which constitutes a severe emergency condition with high morbidity and mortality. The kidneys play fundamental roles in the pathophysiology of HF and, in the context of decompensations, acute kidney injury (AKI) has a bilateral cause-and-effect relationship, which can significantly worsen prognosis. However, the interaction between AKI and decompensated HF is poorly understood. Objective: This study aimed to assess the occurrence of AKI in patients hospitalized due to decompensated HF and to analyze its prognostic impact during hospitalization. Methods: Prospective single-center observational study that included patients hospitalized due to decompensated HF in a tertiary-level teaching hospital, conducted between July 2017 and January 2020. Patients who developed AKI during hospitalization were compared with those who did not develop it, until hospital discharge or death. AKI was defined as a serum creatinine increase greater than or equal to 0.3 mg/dl in 48 hours, a 1.5-fold increase in baseline creatinine in seven days or urinary volume <0.5 ml/kg/h during six hours, according to the Acute Kidney Injury Network (AKIN) criteria. The endpoints analyzed were death, need for invasive mechanical ventilation (IMV) and length of hospital stay. The Wilcoxon, Mann-Whitney and unpaired student t tests were used. Results: Ninety-nine patients were included, with a mean age of 65.4 ± 14 years, of which 47 (47.5%) were male and 52 (52.5%) were female. Reduced ejection fraction was observed in 77.8% of patients, whilst 22.2% had a diagnosis of HF with preserved EF. The decompensation clinical classifications were: dry and warm = 7 (7.1%), wet and warm = 72 (72.7%), wet and cold = 15 (15.1%) and dry and cold = 5 (5.1%). The average left ventricular ejection fraction was 38.3% ± 15. AKI ocurred in 22 patients (22.2%). Comparison between patients who evolved with and without AKI showed higher mortality (36.4% vs 10.4%, p = 0.004) and the need for IMV (54.5% vs 13%, p = 0.0001) in the first group. There was no significant difference regarding the length of in-hospital stay (22.9 ± 19 vs 18.8 ± 16 days, p = 0.26). Conclusions: The occurrence of AKI was frequent in patients with decompensated HF requiring hospitalization, affecting approximately one out of five patients. This complication was significantly associated with increased mortality and the need for IMV during hospitalization.

During the 90 days following hospitalization for acute heart failure, ejection fraction and type of discharge medications have been shown in clinical trials to have little effect on mortality. We examined the recent literature addressing brain-related etiologies of sudden death following heart failure. Two mechanisms of sudden unexpected death have been suggested to possibly result from 4 significant influences on pathophysiology in the brain. The two causes of death are severe cardiac arrhythmia, and neurogenic pulmonary edema. They are both mediated through the brainstem autonomic nuclei generally, and executed specifically through the dorsal motor nucleus of the vagus nerve. The four significant influences on pathophysiology in the brainstem autonomic nuclei are: 1) Hyper-stimulation of neurons in the solitary tract nucleus, increasing their metabolic requirements; 2) Inadequate blood flow at a vascular watershed terminus; 3) Additionally decreased blood flow following vasoconstriction related to relative hyperventilation and decreased pCO2 levels; 4) Gravitational ischemia in the brain—caused by the weight of the brain mass sitting above the brainstem. Changes in head tilt release gravitational ischemia in the brain. There is no specific head position (relative to gravity) that is considered favorable or unfavorable for an extended period of time (i.e. more than 24 hours). Even a small degree of head elevation, used in managing pulmonary congestion, may increase gravitational ischemia in the posterior fossa and brainstem. In this paper we suggest a new and important research avenue for intervening in cardiac arrhythmias, and preventing their occurrence, through the non-invasive use of head-tilting, and other head repositioning maneuvers. This could potentially help many geriatric patients with heart failure, who have decreased mobility in bed, and who tend to stay in one position longer, thereby increasing gravitational ischemia in the brain.

(1) Objectives. Patients with heart failure (HF) who experience hospitalizations for worsening HF (HFH) are at high risk of subsequent events. We aimed to evaluate the impact of an outpatient care management program that includes a clinician-to-clinician e-consultation using an integrated electronic medical record in a healthcare area with a widely dispersed population on delay time in care, hospital admissions, and mortality in a high-risk group of patients with HF and previous episodes of HFH. (2) Methods. We selected 6,444 HF patients who visited the cardiology service at least once between 2010 and 2021. Of these, 4,851 were attended in e-consult, and 2,008 in one-time in-person consultations. In 2,230 HF patients, there was documentation of a previous episode of HFH. Using an interrupted time series regression model, we analysed the impact of incorporating e-consult into the health care model in the group of patients with HFH and evaluated the elapsed time to cardiology care, heart failure (HF), cardiovascular (CV), and all-cause hospital admissions and mortality, calculating the incidence relative risk (iRR). (3) Results. In the group of patients with previous HF hospitalizations, the introduction of e-consult substantially decreased waiting times to cardiology care. The time elapsed to care after e-consult implementation was significantly reduced compared with the previous in-person period (8.6 [8.7] vs 55.4 [79.9] days, p&lt;0.001). In that group of patients, after e-consult implantation, hospital admissions for HF were reduced (iRR [CI95%]: 0,837 [0,840-0,833]), 0,900 [0,862-0,949] for CV and 0,699 [0,678-0,726] for all-cause hospitalizations. There was also lower mortality (iRR [CI95%]: 0.715 [0.657-0.798] due to HF, 0,737 [0.764-0.706] for CV and 0,687 [0.652-0,718] for all-cause). The improved outcomes after e-consultation implementation were significantly higher in the group of patients with previous HFH and were independent of the patient’s clinical characteristics managed during the in-person or e-consultation periods. (4) Conclusions. In HF patients with previous HFH, an outpatient care program that includes an e-consult significantly reduced waiting times to cardiology care and was safe, with a lower rate of hospital admissions and mortality in the first year.

Background: Limited research has explored sex-specific differences in death predictors of HF pa-tients with ischemic (iCMP) and nonischemic (niCMP) cardiomyopathy. This study assessed sex differences in niCMP and iCMP prognosis. Methods: We studied 7,487 patients with HF between February 2017 and September 2020. Clini-cal features and echocardiographic findings were collected. We used Kaplan-Meier, Cox propor-tional hazards models, and score chi-square of Cox regression to determine death predictors in women and men. Results: mean age was 64.3±14.2 years, with 4,417 (59%) males. Women with iCMP and niCMP exhibited significantly higher mean age, higher mean left ventricular ejection fraction, and smaller left ventricular diastolic diameter than men. Over 2.26 years of follow-up, 325 (14.7%) women and 420 (15.7%) men, and 211 women (24.5%) and 519 men (29.8%) died in niCMP (p=NS) and iCMP (p=0.004), respectively. Cumulative incidence of death was higher in men with iCMP (log-rank p<0.0001) but similar in niCMP. Cox regression showed chronic kidney disease, dia-betes, stroke, atrial fibrillation, age, and myocardial infarction, as main predictors of death for iCMP in women and men. Conclusion: Women exhibited a better prognosis than men in iCMP, but similar for niCMP. Nevertheless, sex was not an independent predictor of death for both CMP.

Heart failure (HF) is a disease state which has been shown to affect 1-2% of the global population, being often associated with comorbidities such as diabetes, hypertension, obesity or hyperlipidaemia which increase the prevalence of the disease, the rate of hospitalization and the mortality. Although recent advances in both pharmacological and non pharmacological approaches have led to significant improvements in clinical outcomes in patients affected by HF, residual unmet needs remain. Treatment of the disease remains unclear particularly related to poorly defined strategies in the early stages of myocardial dysfunction. Nutritional support in patients developing HF and nutraceutical supplementation have recently been shown to may contribute in the protection of the failing myocardium, though their place in the treatment of HF still needs to be better clarified. In this context, the ONUS-HF working group aimed to assess the optimal nutraceutical approach to HF in the early phases of the disease in order to counteract selected pathways which are imbalanced in the failing myocardium. In particular, we reviewed several of the most relevant pathophysiological and molecular changes occurring druing the early stages of myocardial dysfunction. These include mitochondrial and sarcoplasmic reticulum stress, insufficient nitric oxide (NO) release, cardiac stem cell mobilization and imbalanced regulation of metalloproteinases. Several candidates for nutraceutical supplementation in HF, such as CoQ10, grape seed extract, Olea Europea L- related antioxidants, SGLT2 inhibitors-rich apple extract and bergamot polyphenolic fraction have been assessed for their potential contribution to cardiomyocyte prottection. This approach should define the optimal approach for more targeted and successful strategies based on the use of nutraceuticals in HF to be confirmed by means of clinical trials exploring efficacy and safety of these compounds.

Background: The 6-minute walk test (6MWT) is a simple and low-cost method that allows assessment of functional capacity in patients with heart failure (HF). However, the prognostic role of 6MWT in HF remains uncertain. Objectives: We aimed to evaluate the 6MWT as a predictor of mid-term adverse outcomes in patients with HF with mid-range and reduced ejection fraction. Methods: Prospective single-center cohort study that included patients with HF with an ejection fraction under 50% at a specialized outpatient HF service. Patients underwent the 6MWT on admission and were compared according to the distance walked: Group I walked ≥350 meters and group II <350 meters. The primary outcome was a composite of death from any cause or hospitalization for HF decompensation in one-year follow-up. Secondary outcomes were the components of the primary outcome in an isolated analysis. Results: Sixty patients were included, 43.3% male, with a mean age of 61.1 ± 12.9 years and ejection fraction 34.3 ± 10.1%. 52 patients (86.7%) were on guideline-directed triple therapy for HF. The average distance walked in the 6MWT was 395.1 ± 98.8 meters, with 40 patients (66.7%) in group I and 20 (33.3%) in group II. The primary outcome in groups I and II were, respectively, 15,0% and 35,0% (p=0.05). One-year mortality was 5.0% vs 15.0% (p=0.18) and the hospitalization rate was 10.0% vs 20.0% (p=0.28). Conclusions: There was no association of distance <350 meters in the 6MWT with the primary outcome in patients with HF. Despite the higher occurrence of outcomes in group II, the difference was not statistically significant in this analysis. On a selective basis, the 6MWT may be a useful tool for prognostic stratification in HF, if combined with other methods.

Heart failure (HF) has several etiologies including myocardial infarction (MI) and left ventricular remodeling (LVR), but its progression remains difficult to predict in clinical practice. Systems biology analyses of LVR after MI predict molecular insights of this event such as modulation of microRNA (miRNA) that could be used as a signature of HF progression. To define a miRNA signature of LVR after MI, we use 2 systems biology approaches integrating either proteomic data generated from LV of post-MI rat induced by left coronary artery ligation or multi-omics data (proteins and non-coding RNAs) generated from plasma of post-MI patients from the REVE-2 study. The first approach predicts 13 miRNAs and 3 of these miRNAs were validated to be associated with LVR in vivo: miR-21-5p, miR-23a-3p and miR-222-3p. The second approach predicts 24 miRNAs among 1310 molecules and 6 of these miRNAs were selected to be associated with LVR in silico: miR-17-5p, miR-21-5p, miR-26b-5p, miR-222-3p, miR-335-5p and miR-375. We identified a signature of 7 microRNAs associated with LVR after MI that support the interest of integrative systems biology analyses to define a miRNA signature of HF progression.

Aim: To analyze a single center's experience with Short Bowel Syndrome/ Chronic Intestinal Failure (SBS/CIF) in adult patients treated with Home Parenteral Nutrition (HPN). Materials and methods: In the last thirty years, 13 patients with SBS/CIF were included in an HPN program. Results: Between 1992 and 2023, 13 patients were included in an HPN program. The primary underlying pathology was acute mesenteric ischemia. The median age of the starting HPN was 44 years old. Most are submitted to several surgeries of extensive intestinal resection with posterior intestinal reconstruction. Five of the 13 patients have died while on HPN for a median of 42 months. The causes of death HPN-related were catheter sepsis, endocarditis with cardiac failure, or hepatic failure. One patient died due to underlying pathology: pelvic abscesses and bleeding related to radiotherapy. Eight patients remain alive with a median time of HPN of 173 months. During the HPN support, the most frequent complications were venous catheter infection and venous territory thrombosis. None of the eight patients alive have hepatic failure. Two patients recently started teduglutide, with good tolerance, and need reduction of HPN support. All these eight patients have a satisfactory quality of life (parenteral support needs range between five to two nutrition bags per week). Conclusion: HPN remains the gold standard of SBS/CIF treatment, although Teduglutide may reduce HPN needs and HPN complications and provide a better quality of life. An HPN multidisciplinary healthcare group support is essential to ensure these patients' survival and quality of life. Keywords Short bowel Syndrome, Chronic Intestinal failure, Home Parenteral Nutrition, Teduglutide, Complications of Parenteral Support.

Background: Lung CT provides an effective modality to evaluate patients with suspected COVID-19. However, overlapping imaging findings with cardiogenic pulmonary oedema have been reported. Reports comparing lung CT features of these diseases have not been elaborated. Thus, we aimed to investigate these gaps in the knowledge regarding low-dose lung CT features of patients with COVID-19 pneumonia with those with acute heart failure (HF). Methods: This retrospective analysis enrolled hospitalized patients with COVID-19 (n=10) and acute heart failure (n=9) that exclusively underwent low-dose lung CT scans within 24-hours of admission. Clinical and lung CT characteristics were collected and analysed. Results: Ground-glass-opacities (GGO) appearance has been recorded in all subjects in HF and COVID-19 group. There was no significant statistical difference between the two groups for rounded morphology, consolidation, crazy paving pattern, lesion distribution, parenchymal band (P> 0.05). However, diffuse lesions were more frequent in HF cases (55.6% vs. 0%) than in COVID-19 pneumonia, which had predominantly multifocal pattern. Notably, CT images in HF patients were more likely to have signs of interstitial tissue thickening such as the interlobular septums, fissures and peribronchovascular interstitium (55.6% vs 0%, 88.9% vs 20% and 44.4% vs 0%,respectively), as well as cardiomegaly (77.8% vs 0%), increased artery to bronchus ratio (55.6% vs 0%), and pleural effusions (77.8% vs 0%). Conclusions: Major overlaps of lung CT imaging features existed between COVID-19 pneumonia and acute HF cases. However, signs of fluid redistribution are clues that favour HF over COVID-19 pneumonia.

Expression of miR-21 has been found to be altered in almost all types of cancers and it has been classified as an oncogenic microRNA. In addition, expression of tumor suppressor gene RECK is associated with miR-21 overexpression in high-grade cervical lesions. In the present study we analyze the role of miR-21 in RECK gene regulation in cervical cancer cells. To identify the downstream cellular target genes of upstream miR-21, we silenced endogenous miR-21 expression using siRNAs. We analyzed the expression of miR-21 and RECK, as well as functional effects on cell proliferation and migration. We found that in cervical cancer cells there was an inverse correlation between miR-21 expression and RECK mRNA and protein expression. SiRNAs to miR-21 increased luciferase reporter activity in construct plasmids containing the RECK-3′-UTR microRNA response elements MRE21-1, MRE21-2, and MRE21-3. The role of miR-21 in cell proliferation was also analyzed and cancer cells transfected with siRNAs exhibited a markedly reduced cell proliferation and migration. Our findings indicate that miR-21 post-transcriptionally down-regulates the expression of RECK to promote cell proliferation and cell migration inhibition in cervical cancer cell survival. Therefore, miR-21 and RECK may be potential therapeutic targets in gene therapy for cervical cancer.

There is a bidirectional relationship between the heart and the gut. Gut microbiome is an excellent gut-homeostasis keeper since controls the growth of potentially harmful bacteria and protects the microbiota environment. There is evidence suggesting that diet rich in fatty acid can be metabolized and converted by gut microbiome and hepatic enzymes to trimethyl-amine N-oxide (TMAO) a product that is associated with atherogenesis, platelet dysfunction, thrombotic events, coronary artery disease, stroke, heart failure and ultimately death. Heart failure, by inducing gut ischemia and congestion and consequently gut barrier dysfunction promote an intestinal leak of microbes or even of their products, facilitating their entrance into the circulation and thus stimulating the low-grade inflammation and hence the immune response. Drugs used for heart failure may alter the gut microbiome, and conversely gut microbiome may modify the pharmacokinetic properties of the drugs. Modification of lifestyle based mainly on exercise and Mediterranean diet along with the use of pre- or probiotics may be beneficial to some extent for the gut microbiome environment. The potential role of gut microbiome in heart failure development and outcomes is a fruitful area of future research.

Cardiovascular disease (CVD) is one of the contributing factors to more than one-third of human mortality and the leading cause of death worldwide. Cardiac myocyte death is a fundamental process in cardiac pathologies caused by various heart diseases, including myocardial infarction. Thus, strategies for replacing fibrotic tissue in the infarcted region with functional myocardium have long been a goal of cardiovascular research. This review focuses primarily on induced-pluripotent stem cells (iPSCs), which have emerged as perhaps the most promising source of cardiomyocytes for both therapeutic applications and drug testing. We also briefly summarize other stems- and progenitor-cell populations that have been used for regenerative myocardial therapy and attempt to generate cardiomyocytes directly from cardiac fibroblasts (i.e., transdifferentiation), which, if successful, may enable the pool of endogenous cardiac fibroblasts to be used as an in-situ source of cardiomyocytes for myocardial repair.

Advanced heart failure (AHF) presents a complex landscape with challenges spanning diagnosis, management, and patient outcomes. In response, the integration of multimodality imaging techniques has emerged as a pivotal approach. This comprehensive review delves into the profound significance of these imaging strategies within AHF scenarios. Multimodality imaging, encompassing echocardiography, cardiac magnetic resonance imaging (CMR), and cardiac computed tomography (CCT), stands as a cornerstone in the care of patients with both short- and long-term mechanical support devices. These techniques facilitate precise device selection, placement, and vigilant monitoring, ensuring patient safety and optimal device functionality. In the context of orthotopic cardiac transplant (OTC), the role of multimodality imaging remains indispensable. Echocardiography offers invaluable insights into allograft function and potential complications. Advanced methods, like speckle tracking echocardiography (STE), empower the detection of acute cell rejection. CMR and CCT further enhance diagnostic precision, especially concerning allograft rejection and cardiac allograft vasculopathy. This comprehensive imaging approach goes beyond diagnosis, shaping treatment strategies and risk assessment. By harmonizing diverse imaging modalities, clinicians gain a panoramic understanding of each patient's unique condition, facilitating well-informed decisions. Thus, this review underscores the irreplaceable role of multimodality imaging in elevating patient outcomes, refining treatment precision, and propelling advancements in the evolving landscape of advanced heart failure management.

Keywords: olfactory rehabilitation; chronic pain; fMRI;

Objectives: Evaluate hand-held echocardiography (HHE) performed and interpreted by trained Advanced Practice Providers (APPs) on hospitalized CHF patients for image quality and interpretation, by comparing against expert echocardiographer and SE findings. Background: Congestive heart failure (CHF) is associated with increased hospital admissions and mortality. While standard echocardiogram (SE) is the gold standard for cardiac assessment, it is not readily available. Hospitalized CHF patients require rapid assessment for expedited treatment. Methods: Over 6 months, five trained APPs performed HHE on hospitalized CHF patients and interpreted: a) Left ventricular (LV) size, b) LV ejection fraction (LVEF), and c) right atrial pressure (RAP). The study echocardiographer reviewed and blindly interpreted HHE images and compared with APPs and SE findings. Kappa-statistics determined the degree of agreement between APPs and study echocardiographer interpretation of HHE images and SE. Results: 80 CHF patients [age 73±14 years, 58% males; LVEF (by SE) 45±19%; 36.3% body mass indexes ≥30 kg/m2] were enrolled. HHE interpretation by APPs had good agreement for LVEF (kappa 0.79) with study echocardiographer and SE (kappa 0.74), and good agreement for RAP (kappa 0.67) with study echocardiographer. Correlation between absolute LVEF interpretation by study echocardiographer on HHE and SE was r=0.88 (p<0.0001). Conclusions: Trained APPs obtained diagnostic-quality HHE images and interpreted LV function and RAP in CHF patients, with good agreement with the study echocardiographer. LVEF by HHE correlated with LVEF by SE. Our study suggests trained APPs can use HHE to evaluate LVEF and RAP in CHF patients leading to expedited and optimized treatment.

Sodium-glucose co-transporter 2 (SGLT2) inhibitors, originally used for diabetes mellitus, are gaining more popularity for other indications owing to their positive cardiovascular and renal effects. Initially, SGLT2 inhibitors were shown to reduce heart failure (HF) hospitalization and improve cardiovascular outcomes in patients with type 2 diabetes. Later, SGLT2 inhibitors were evaluated in patients with HF with reduced ejection fraction (HFREF) and had beneficial effects independent of the presence of diabetes. Recently, reduction in cardiovascular outcomes were also observed in patients with HF with preserved ejection fraction (HFPEF). SGLT2 inhibitors also reduced renal outcomes in patients with chronic kidney disease. Overall, these drugs have an excellent safety profile with a negligible risk of genitourinary tract infections and ketoacidosis. In this review, we discuss the current data regarding SGLT2 inhibitors in special populations including acute myocardial infarction, acute HF, right ventricular (RV) failure, patients with left ventricular assist device (LVAD), and patients with type1 diabetes. We also discuss the potential mechanisms behind the cardiovascular benefits of these drugs.

Artificial Intelligence are creating a paradigm shift in health care, being phenotyping patients through clustering techniques one of the areas of interest. Objective: To develop a predictive model to classify heart failure (HF) patients according to their left ventricular ejection fraction (LVEF), by using available data in Electronic Health Records (EHR). Subjects and methods: 2854 subjects more than 25 years old with diagnose of HF and LVEF measured by echocardiography were selected to develop an algorithm to predict patients with reduced EF using supervised analysis. Performance of the algorithm developed were tested in heart failure patients from Primary Care. To select the most influencing variables, LASSO algorithm setting was used and to tackle the issue of one class exceed the other one by a large proportion we used the Synthetic Minority Oversampling Technique (SMOTE). Finally, Random Forest (RF) and XGBoost models were constructed. Results: Full XGBoost model obtained the maximized accuracy, a high negative predictive value and the highest positive predictive value. Gender, age, unstable angina, atrial fibrillation and acute myocardial infarct are the variables that most influence FE value. Applied in the EHR data set with a total 25594 patients with an ICD-code of HF and no regular follow-up in Cardiology clinics, 6170 (21.1%) were identified as those pertaining to the reduced EF group. Conclusion: The algorithm obtained is able to rescue a number of HF patients with reduced ejection fraction that can be take benefit for a protocol with strong recommendation to succeed. Furthermore, the methodology can be used for studies with data extracted from the Electronic Health Records.

Systemic amyloidosis is a multisystem illness characterized by fibrillary protein deposition, which causes dysfunction in the afflicted organ systems. Its diagnosis is frequently delayed since the disease's symptoms are unpredictable and non-specific. Its two main variants are light chain (AL) amyloidosis and transthyretin-related ATTR amyloidosis, which has both a sporadic (wildtype, ATTRwt) and hereditary (mutated, ATTRv) subtype. We discuss a case of Amyloidosis emerging in the kidneys and heart as a result of chronic inflammation caused by failure to treat TB, as well as its typical radiological characteristics, clinical presentation, imaging and instrumental evaluations, and therapeutic plan. This case report serves as a good reminder to medical personnel to ensure thorough patient follow-up in order to avoid extremely unusual and late complications resulting from treatment default.

Heart failure with reduced ejection fraction (HFrEF) is considered a major healthcare problem with frequent decompensations, high hospitalization and mortality rates. In severe heart failure (HF), the symptoms are refractory to medical treatment and require advanced therapeutic strategies. Early recognition of HF sub- and decompensation is the cornerstone of the timely treatment intensification and, therefore, improvement of the prognosis. Echocardiography is the gold standard for the assessment of systolic and diastolic functions. It allows to obtain accurate and non-invasive measurements of the ventricular function in HF. In severely compromised HF patients, advanced cardiovascular ultrasound modalities may provide a better assessment of intracardiac hemodynamic changes and subclinical congestion. Particularly, cardiovascular and lung ultrasound allow to make a more accurate diagnosis of subclinical congestion in HFrEF. The aim of this review is to summarize the advantages and limitations of currently available ultrasound modalities in the ambulatory monitoring of patients with HFrEF.

Systemic lupus erythematosus (SLE) myocarditis is presumed to be rare but associated with ad-verse outcomes. If SLE diagnosis has not previously been established, its clinical presentation is often unspecific and difficult to recognize. Furthermore, there is a lack of data in the scientific literature regarding myocarditis and its treatment in systemic immune-mediated diseases, leading to its late recognition and undertreatment. We present the case of a young woman whose first lupus manifestations included acute perimyocarditis, among other symptoms and signs that provided clues to the diagnosis of SLE. Transthoracic and speckle tracking echocardiography were helpful in detecting early abnormalities in myocardial wall thickness and contractility while waiting for cardiac magnetic resonance (CMR). Since the patient presented with acute decompensated heart failure (HF), HF treatment was promptly started in parallel with immunosuppressive therapy, with a good response. In the treatment of myocarditis with heart failure, we were guided by the echocardiographic findings, biomarkers for myocardial injury N-terminal pro b-type natriuretic peptide (NT-proBNP) and hs-troponin I, biomarkers for systemic inflammation erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP), and biomarkers for SLE disease activity (Complement C)3, C4, and anti-dsDNA levels.

Chronic renal failure (CRF) is a major public health problem worldwide. In this work, we investigated the effects of a purified Laminaria japonica polysaccharide (LJP61A) on the renal function using adenine-induced CRF mice model. Results exhibited that adenine treatment caused serious renal pathological damages and elevation of serum creatinine and blood urea nitrogen of mice. However, these changes could be significantly reversed by the administration of LJP61A in a dose-dependent manner. Additionally, LJP61A could dramatically reduce the weight loss, improve the urine biochemical index, and regulate the electrolyte disturbance of CRF mice. These results suggested that the renal functions of adenine-induced CRF mice could be improved by LJP61A, which might be developed to a potential therapeutic agent for CRF patients.

Decades of research identified numerous gene biomarkers of cardiac diseases whose restored sequence or/and expression level was hoped to recover the normal cardiac function. However, each human has unique and dynamic pathophysiological characteristics resulting from the unrepeatable combination of favoring factors such are: race, sex, age, medical history, diet, stress, exposure to toxins, habits etc. As such, no treatment fits everybody and finding personalized solutions is a top priority for medicine of 21st century. The Genomic Fabric Paradigm (GFP) provides the most theoretically possible comprehensive characterization of the transcriptome, its alterations in disease and recovery following a treatment. By attaching to each gene the independent average expression level, expression variation and expression coordination with each other gene, GFP delivers thousands times more information than the traditional analysis. This report presents the theoretical bases of the GFP and some applications to our microarray data from mouse models of post ischemic, and constant and intermittent hypoxia-induced heart failure. The GFP analyses revealed novel transcriptomic aspects of the gene expression control and networking under ischemic conditions. Through all-inclusive characterization of the transcriptome and the unrepeatable gene hierarchy in each condition, GFP is an essential avenue towards development of a truly personalized cardiogenomic therapy.

Background: The clinical impact of withdrawal of sodium-glucose cotransporter 2 inhibitor (SGLT2i) on the all-cause readmission in patients with heart failure remains unknown. Methods: Consecutive 212 patients who were hospitalized for heart failure and received SGLT2i during the index hospitalization between February 2016 and July 2022 were evaluated. Of these, 51 patients terminated SGLT2i during or after their index hospitalization. The primary outcome was defined as an all-cause readmission rates/times. Results: Over a median of 23.2 months, an all-cause readmission occurred in 38 of 51 patients (74.5%) withdrawn from SGLT2i and 93 of 161 patients (57.8%) with continuation of SGLT2i (p = 0.099). The total number of all-cause readmissions per year was 0.97 [0-1.50] in patients withdrawn from SGLT2i and 0.50 [0-1.03] in patients with continuation of SGLT2i (p = 0.030). There was no significant difference in total medical cost (62,906 [502-187,246] versus 29,236 [7,920-180,305] JPY per month, p = 0.866) between both patient groups. Conclusions: Termination of SGLT2i may be associated with incremental all-cause readmission and no benefit in reducing total medical costs.

The COVID-19 pandemic has impacted the healthcare system across the globe, leading to more than 6.9 million deaths in the past four years. Cardiac Arrest is a terminal event with associated significantly high morbidity and mortality across age groups. Multiple clinical parameters, organ dysfunction, and chronic co-morbid conditions impact mortality in COVID-19 patients with heart failure. In this retrospective, administrative dataset-based study on 148899 patients admitted to the hospital with COVID-19 and heart failure diagnosis, we reported 6703 cardiac arrests and 5783 mortality. We have used ICD 10 codes to identify the diagnosis. The primary objective of the study is to find the predictors of Cardiac Arrest among patients admitted to hospitals with COVID-19 and heart failure. Secondary objective is to calculate the percentage of cardiac Arrest and mortality across the various age groups and the correlation of hours on the mechanical ventilator and mortality. Study results have shown that the use of a mechanical ventilator has the strongest co-correlation with cardiac Arrest with an odd ratio of 14.4, followed by septic shock with an odd ratio of 5.6, tension pneumothorax with an odd ratio of 4.9 preceding the acute renal failure with an odd ratio of 2.4 and sepsis 2.3. Complete heart block had an odd ratio of 1.9, followed by ESRD with a ratio of 1.6, acute pulmonary embolism with an odd ratio of 1.5, and Type 2 MI with an odd ratio of 1.49. Chronic co-morbid condition of DM had an odd ratio of 1.3, followed by Atrial fibrillation with an odd ratio of 1.1. These results and findings emphasized that multi-organ failure has a huge impact on cardiac Arrest among COVID-19 patients with heart failure.

Introduction In sacubitril-valsartan (sacub/v), the effects of an angiotensin II receptor blocker (ARB) exerted by valsartan are strengthened by the addition of sacubitril, an inhibitor of neutral endopeptidases. PARADIGM - HF study proved this association to be superior to enalapril in reducing both all-cause death and cardiovascular mortality, as well as heart failure (HF) hospitalizations in patients with cardiac insufficiency and reduced left ventricular ejection fraction( HFREF) belonging to NYHA class II-IV. To test whether even in our experience sacub/v is associated with favorable outcomes concerning mortality and morbidity, an outpatient small population of HFREF patients was retrospectively studied, of whom one third was treated with sacub/v instead of conventional therapy with ACE -inhibitors or ARBs. Methods A retrospective cohort study was carried out to assess the effects of sacub/v in addition to beta-blocker and mineral receptor antagonist (MRA) in a group of HFREF patients in NYHA classes II-III compared with conventional therapy (comprising ACE inhibitor or ARB added to beta-blocker plus a MRA) administered in a second group of HFREF patients with comparable clinical features retrospectively enrolled as controls. In the two groups, the therapeutic regimen was established in accordance with the preferences of the treating physician. Additionally, in both groups, evidence-based drug therapy was supplemented by the adjunct of a loop diuretic, usually furosemide, at variable doses. The primary outcomes of interest were all-cause death and HF hospitalizations. Safety outcomes were symptomatic hypotension, angioedema, hyperkalemia and worsening renal function. Results Mortality at six months was 6.8% in patients under therapy with sacub/v versus 34% in those treated with conventional therapy (odds ratio[OR] = 0.14; 95% CI: 0.04-0.49). Moreover, HF hospitalizations in the observation period considered were 4.5% in sacub/v group versus 59% in the conventional therapy group (OR = 0.03; 95% CI: 0.01–0.14). Safety outcomes included in our study (angioedema, hyperkalemia, hypotension and worsening renal function) showed a comparable profile in the two groups, with evidence of good tolerability of sacub/v , except for the side - effect " hypotension" (PAS < 100 mm Hg) , found in 15.9% of patients under sacub/v versus 5.7% reported in controls (OR = 3.14; 95% CI: 0.94–10.55). Conclusions In our experience, sacub/v has yielded a strong protection against both all-cause death and HF hospitalizations at six months , in the absence of significant noxious side effects. Nevertheless, considering the retrospective character of the study and the relatively exiguous sample size, further post marketing observational studies would be desirable . In particular, studies aiming at exploring safety of the new pharmacologic principle, namely mainly focusing on hypotension and angioedema, are warranted, in order to validate further this very efficacious molecule for therapy of chronic HF, especially stable HFREF in NYHA classes II-III.

Hepatitis C virus (HCV) is a major public health threat associated with serious clinical consequences worldwide. The WHO reports an estimated 58 million people globally living with chronic hepatitis C virus (HCV) infection, with 1.5 million new cases and over 350,000 deaths annually due to HCV-related diseases. Despite the existence of multiple diagnostic methods, the accessibility of diagnosis and treatment is often hindered across the continent by limited resources, insufficient healthcare infrastructure, and low public awareness of Hepatitis C virus Hepatitis C virus infection is a major public health concern in African countries, which have the highest prevalence rates of HCV in the world (1–26%). Egypt, African country which had the highest prevalence of Hepatitis C virus infection in the world. Its national hepatitis C elimination initiative emerges as an exemplary case of success an having screened over 60 million individuals, and treated more than 4 million, thereby markedly diminishing both the prevalence and incidence of the disease. The strategies employed by Egypt offer critical insights and adaptable frameworks for other African Countries facing analogous challenges. The Aim of this Review is to highlight the triumphs and hurdles of Egypt's approach, while also providing strategic guidance for African Countries to accelerate the journey towards the eradication of hepatitis C.

Cardiac fibrosis is a severe outcome of Chagas disease (CD), caused by the protozoan Trypanosoma cruzi. Clinical evidence revealed a correlation between fibrosis levels with impaired cardiac performance in CD patients. Therefore, we sought to analyze the effect of inhibitors of TGF- (pirfenidone), p38-MAPK (losmapimod) and c-Jun (SP600125) on the modulation of collagen deposition in cardiac fibroblasts (CF) and in vivo models of T. cruzi chronic infection. Sirius Red/Fast green dye was used to quantify both collagen expression and total protein amount, assessing cytotoxicity. The compounds were also used to treat C57/Bl6 mice chronically infected with T. cruzi, Brazil strain. We identified an anti-fibrotic effect in vitro for pirfenidone (TGF-β inhibitor, IC50 114.3 μM), losmapimod (p38 inhibitor, IC50 17.6 μM) and SP600125 (c-Jun inhibitor, IC50 3.9 μM). This effect is independent of CF proliferation since these compounds do not affect T. cruzi-induced host cell multiplication as measured by BrdU incorporation. Assays of chronic infection of mice with T. cruzi have shown a reduction in heart collagen by pirfenidone. These results propose a novel approach to fibrosis therapy in CD, with the prospect of repurposing pirfenidone to prevent the onset of ECM accumulation in the heart of the patients.

In this work, we developed a highly sensitive multiplexed immunosensor for direct simultaneous detection of both N-terminal Natriuretic Peptide (NT-proBNP) and Cortisol in human artificial saliva (AS). The developed biosensor platform based on silicon nitride was composed from four gold working microelectrodes (WEs) and an integrated counter and reference electrode. Gold WEs were biofunctionalized through carboxyl diazonium (4-APA) to immobilize both anti- NT-proBNP and anti-Cortisol antibodies for simultaneous detection. The electroaddressing of the 4-APA onto the gold WE surfaces was realized by cyclic voltammetry (CV), while the interaction between antibodies and antigens in PBS was monitored by electrochemical impedance spectroscopy (EIS). The antigen detection in human AS was realized by EIS combined with the standard addition method. The immunesensor was highly sensitive and selective toward the corresponding biomarkers in both PBS and artificial human saliva as well as in the presence of other potential interfering biomarkers such as tumor necrosis factor alpha (TNF-α) and interleukin-10 (IL-10). The limit of detection (LOD) was at 0.2pg/mL for NT-proBNP within the range 0.03 to 0.9pg/mL, while the LOD for Cortisol was 0.06 ng/mL within the range 0.02 to 0.6 ng/mL for Cortisol in artificial saliva. The developed immunosensor is very promising for significant detection time reducing as it allows the simultaneous detection of various biomarkers.

Heart failure with preserved ejection fraction (HFpEF) remains a poorly characterized syndrome with many dark aspects related to different patients profile, various associated risk factors and wide aetiologies. It comprises several pathophysiological pathways related to endothelial dysfunction, myocardial fibrosis, extracellular matrix deposition and high inflammatory response. Up to now, it has been described only for clinical appearance and most common associated risk factors without an effective characterization of biological processes responsible for cardiovascular deteriorations. Recent advances in laboratory and metabolomic researches showed that HFpEF appears strictly related to specific cells and molecular mechanisms dysregulation. Some biomarkers are capable to early identify these processes adding new insights into diagnosis and risk stratification. Additionally recent advances on intermediate metabolites reflecting provide relevant information on intrinsic cellular and energetic substrate alterations. The systematic combination of clinical imaging and laboratory data may lead to a precision medicine approach providing prognostic and therapeutic advantages. Current review reports traditional and emerging biomarkers recently investigated in HFpEF setting, and it purpose a new diagnostic approach based on integrative information achieved from risk factors burden, hemodynamic dysfunction and biomarkers signature partnership.

Background: The 2021 “Universal Definition of Heart Failure (HF)” Proposed the following left ventricle ejection (LVEF) phenotype classification: ≤40%; HF with intermediate LVEF: between 41-49% and HF with preserved LVEF: ≥50%. LVEF represents the percentage of left ventricular ejected volume in each cardiac cycle and Cut-points considered statistically normal are: ≥52% in men and ≥54% in women. The prevalence HFpEF is of 35-60% among the HF phenotypes, with a facing to increase rates in relation to HFrEF and is associated with mortality rates similar to those of HFrEF. The pathophysiology of HFpEF is based on vascular and metabolic dysfunction, therefore, there is less neurohumoral stimulation compared to HFrEF. Methodology: A systematic review was performed to report of information related to Sacubitril-valsartan and the treatment of HFrEF. Terms related to “treatment” and “brazil” were used in the databases PubMed (MEDLINE) and Scientific Electronic Library Online (SCIELO). Results: Clinical trials testing drugs that modulate the neurohumoral system in patients with HFpEF failed to demonstrate benefit in the combined endpoint of reduced mortality/hospitalization due to HF compared to placebo to date. Sacubitril-valsartan is a drug with a mechanism of action surrogate the pathophysiological concept of HFpEF, it is safe and decreased endpoints of natriuretic peptides and left atrial structure in a phase II clinical study. Conclusions: The PARAGON-HF trial demonstrated that sacubitril-valsartan reduced the primary endpoint of the study when assessed the pre-specified subgroup of LVEF≤57% and improved the secondary endpoints of performance status and renal function in the population.

Researchers have asserted that, as patients rely on external powerful sources to control their disorders, in addition to their own internal powers and virtues, examining their coping mechanisms can lead to a better understanding of the initiation and progression of chronic diseases and uncover potential opportunities to balance and enhance their psycho-spiritual well-being and possibly their treatment and recovery. This review serves as a user’s manual for investigators who choose to use the CSI-SF to conduct their research on coping behaviors. The CSI-SF that measures four coping strategies based on 16 items was first assessed using the Jackson Heart Study (JHS) cohort in 2007. The reliability and construct validity of the CSI-SF was also later assessed among hemodialysis patients across 13 countries. In this study, the CSI-SF was assessed to be a reliable and valid instrument for measuring coping strategies. The CSI-SF serves the purpose of developing an inner voice that can assist with understanding how people cope with everyday life. The information gathered from administration of the CSI-SF can inform investigators about environmental cues and triggers that can also impact individual health.

Heart failure (HF) diagnosis, phenotyping, prognosis, and treatment decisions are all based on the left ventricular ejection fraction (EF). Heart failure with mid-range EF (HFmrEF) is a third EF category for heart failure with an EF between 40 and 49 percent. Comparatively, heart failure with preserved EF or reduced EF has been largely unexplored. 10–25% of patients with HF have HFmrEF. Although HFmrEF has an intermediate clinical profile, it is more similar to HF with reduced EF, particularly because these patients have a high incidence of ischaemic heart disease. Heart failure with preserved EF has a lower risk of cardiovascular events than heart failure with reduced EF, which is milder. HFmrEF and HF with preserved EF patients have a similar or higher risk of non-cardiovascular adverse events than patients with HF with reduced EF. There is still a great deal of mystery surrounding HFmrEF. The purpose of this review is to describe the major pathophysiology of HFmrEF and its similarities and differences with the other two types of EF. It is the purpose of this paper to present a comprehensive overview of the currently available evidence in support of the pathophysiology of patients with HFmrEF. Further investigation of the pathophysiology, treatment, and prognosis of this condition will be needed in the future in order to better understand it.

Patients with heart failure have difficulty in self-care management, as daily monitoring and recognizing symptoms do not readily trigger an action to avoid hospital admissions. The purpose of this study was to understand the impact of a nurse-led complex intervention on symptom recognition and fluid restriction. A latent growth model was designed to estimate self-care management and quality of life changes on patients with heart failure and assessed by a pilot study, for three months, to sixty-three patients (33 control, 30 intervention). Patients in the control group had a higher risk of hospitalisation (IRR 11.36; p<.001) and emergency admission (IRR 4.24; p<.001) at three-months follow-up. Analysis of the time scores demonstrated that the intervention group had a clear improvement in self-care behaviours (βSlope. Assign-ment_group=-.881; p<.001) and in the quality of life (βSlope. Assignment_group=1.739; p<.001). This study supports that a nurse-led program on symptom recognition and fluid restriction can have a positive impact on self-care behaviours and quality of life in patients with heart failure.

Following the era of GWAS studies, efforts are being made to identify genes underlying complex traits by merging eQTL and GWAS data and assessing the colocalization of eQTLs and GWAS signals. A problem that sometimes occurs in this context is the observation of association between several genes in a genomic region with a trait. This happens because genes in a region could be under the regulatory impact of common elements and coexpress. As such, computational approaches that rely on cis-eQTL information can not exactly pinpoint the causal gene. Here, I report an alternative solution, based on trans-eQTLs to test the association between a gene and a trait. Through the analyses applied to adjacent genes that coexpress and concordantly impact blood traits, I provide evidence that trans-eQTLs can resolve the problem of coexpression-causality without the interference of shared cis-regulatory SNPs.

Background: We aimed to evaluate whether baseline GLS and NT-proBNP and their changes after cardiac resynchronization therapy (CRT) can predict the long-term clinical outcomes and the echocardiographic-based response to CRT (defined by 15% relative reduction in left ventricular end-systolic volume). Methods: We enrolled 143 patients with stable, ischemic heart failure (HF) undergoing CRT-D implantation. NT-proBNP and echocardiogram were obtained before and 6 months after. The patients were followed-up (median: 58 months) for HF-related deaths and/or HF hospitalizations (primary endpoint) or HF-related deaths (secondary endpoint) Results: 84 patients achieved the primary and 53 the secondary endpoint, while 104 patients were considered as CRT-responders and 39 as non-responders. At baseline, event-free patients had higher absolute GLS values (p&lt;0.001) and lower NT-proBNP serum levels (p&lt;0001) than those achieving primary endpoint. A similar pattern was observed in favor of CRT-responders vs non-responders. In Cox regression analysis, lower baseline absolute GLS value (HR=0.77;95%CI, 0.51-1.91; p=0.002), higher baseline NT-proBNP levels (HR=1.55;95%CI, 1.43-2.01;p=0.002) and diabetes (HR=1.27;95%CI, 1.12-1.98;p=0.003) were associated with lower incidence of primary endpoint. Conclusions: In HF patients undergoing CRT-D, baseline GLS and NT-proBNP concentrations may serve as prognostic factors, while they may predict the echocardiographic-based response to CRT.

Aerobic exercise training (AET) has been used in the management of heart disease. AET may, totally or partially, restore the activity and/or expression of proteins that regulate calcium (Ca2+) handling, optimize intracellular Ca2+ flow, and attenuate cardiac functional impairment in failing hearts. However, the literature presents conflicting data regarding the effects of AET on Ca2+ transit and cardiac function in rats with heart failure resulting from aortic stenosis. The objective of this study was to evaluate the effects of AET on calcium handling and cardiac function in rats with heart failure due to aortic stenosis. Wistar rats were distributed into two groups: control (Sham; n= 61) and aortic stenosis (AoS; n= 44). After 18 weeks, the groups were redistributed into: non-exposed to exercise training (Sham, n = 28 and AoS, n = 22) and trained (Sham-ET, n = 33 and AoS-ET, n = 22) for 10 weeks. Treadmill exercise training was performed with a velocity equivalent to the lactate threshold. Echocardiogram, isolated papillary muscle, and isolated cardiomyocyte analyzed cardiac function. During isolated papillary muscle assay and isolated cardimyocyte was evaluated Ca2+. The expression of regulatory proteins of diastolic Ca2+ was analyzed via Western Blot. AET attenuated the diastolic dysfunction and benefited the systolic function. AoS-ET animals presented better response to post-rest contraction, and SERCA2a and L-type Ca2+ channels blocked than the AoS. Furthermore, AET was able to improve aspects of the mechanical function and the responsiveness of the myofilaments to the Ca2+ of the AoS-ET animals. AoS animals presented alteration in the protein expression of the SERCA2a and NCX, and AET restored SERCA2a and NCX levels near normal values. Therefore, AET increased SERCA2a activity, improved the cellular Ca2+ influx mechanism, and increased myofilament responsiveness to Ca2+, attenuating cardiac dysfunction at cellular, tissue, and chamber levels in animals with aortic stenosis and heart failure.

Acute-on-Chronic Liver Failure (ACLF) refers to the deterioration of liver function in individuals who already have chronic liver disease. In the setting of ACLF, liver damage leads to the failure of other organs and is associated with increased short-term mortality. Optimal medical management of patients with ACLF requires implementing complex treatment strategies, often in an intensive care unit (ICU). Failure of organs other than the liver distinguishes ACLF from other critical illnesses. Although there is growing evidence supporting the current approach of ACLF management, mortality associated with this condition remains unacceptably high. In this review, we discuss considerations for ICU care of patients with ACLF and highlight areas for further research.

Heart failure (HF) affects about 60 million people worldwide, making it one of the chronic conditions with the greatest health and economic impact. The primary objective was to assess the efficacy of lung ultrasound (LUS) in the management of HF in order to intervene early and reduce the rate of hospital readmissions. A systematic search was conducted on PubMed, Embase, Google Scholar, Web of Science, and Scopus, including clinical trials, meta-analysis, systematic reviews, and original articles from 2019/1/1-2023/12/31, about LUS for the assessment of HF, on an outpatient basis, for HF diagnosis or/and decompensation. There may be risk of bias because the effects are dependent on the persons delivering the intervention. The results were synthetized by PRISMA method. A total of 873 articles were identified of which 33 articles were selected: [n=19] focused on prognostic assessment of HF, [n=11] centred on multimodal diagnostic assessments, and [n=2] addressing therapeutic guidance for HF diagnosis. LUS exhibits advantages in the detection of sub-clinical congestion linked to prognostic significance in re-admission and mortality during out-patient follow-up, after hospital discharge, and in complex scenarios as the patients' homes or institutional long-term care facilities. However, there are considerable uncertainties in their interpretation and monitoring changes due to its lack of standardization. The need for an updated international consensus on the use of LUS seems obvious.

Introduction: Venous thromboembolism (VTE), comprising deep vein thrombosis (DVT) and pulmonary embolism (PE), is a common condition associated with high morbidity and mortality. Although patients with heart failure (HF) are known to have an increased risk of PE, there is limited evidence regarding its specific impact on patients with acute PE, both in presentation and outcomes, and its relationship with left ventricular ejection fraction (LVEF). Material and Methods: A prospective observational study was conducted at two tertiary hospitals, including patients with symptomatic acute PE between January 2012 and December 2022. The primary objective of the study was the development of a composite outcome (mortality, major bleeding, and recurrence) within the first 30 days. The secondary objective was the development of early complications in patients with HF and reduced LVEF. Results: Out of 1991 patients included with symptomatic acute PE, 7.13% had a history of HF. Patients with HF were older and had more comorbidities. The HF group showed higher mortality (11.27% vs. 4.33%, p<0.001) and major bleeding (9.86% vs. 4.54%, p=0.005). In multivariate analysis, HF was an independent risk factor for the development of the composite outcome (HR 1.93; 95% CI: 1.35-2.76). Reduced LVEF was independently associated with a higher risk of bleeding (HR 3.44; 95% CI: 1.34-8.81). Conclusion: In patients with symptomatic acute pulmonary embolism, heart failure is independently associated with a higher risk of early complications. Additionally, heart failure with reduced LVEF is an independent risk factor for major bleeding.

Background: Galectin-3 (Gal-3) is a biomarker involved in a wide range of diseases including cardiac remodeling following acute myocardial infarction (AMI). Identification of prognostic markers in patients with AMI can guide strategies towards improved survival and the quality of life. Methods: Our study included 59 patients with AMI and preserved ejection fraction. We determined the Gal-3 plasma concentration within 24 hours of chest pain onset from aortic root, femoral/radial artery, coronary sinus and cubital vein. Major adverse cardiovascular events (MACE) were evaluated at six months follow-up. Results: MACE at six months post-AMI was recorded in 20 patients (34%). The Gal-3 plasma concentration from aortic root and the femoral/radial artery were independent predictors of MACE at six months follow-up after the first AMI (OR 1.228; 95%CI: 1.011-1.491; p=0.038; OR 3.438; 95%CI: 1.275-9.265; p=0.015). ROC analysis identifies the Gal-3 plasma concentration from aortic root as a better predictor of MACE or death (cut-off &gt;10.86 ng/ml; AUC 0.858; 95%CI: 0.744-0.973; p&lt;0.001) than Gal-3 plasma concentration from femoral/radial artery (cut-off &gt;10.18 ng/ml; AUC 0.742; 95%CI: 0.596-0.888; p=0.006). Conclusion: The Gal-3 plasma concentration in patients with AMI determined during coronary angiography, especially from the aortic root, within 24 hours after chest pain onset is a valuable biomarker of prognosis at six months follow-up.

Aims: The objective of this study was to assess the cost-effectiveness of the CardioMEMS HF system in a HF Clinic in Spain by evaluating the real-time remote monitoring of pulmonary artery pressures, which has shown to reduce heart failure (HF) related hospitalizations and improve the quality of life for selected HF patients. Particularly, the study aimed to determine the value of CardioMEMS in Southern Europe, where healthcare costs are significantly lower and its effectiveness remains uncertain. Methods: This single-centre study enrolled all consecutive HF patients who had been implanted with a pulmonary artery pressure sensor (CardioMEMS-HF system, Abbott Laboratories, Abbott Park, IL, USA). The number of HF hospitalizations in the year before and the year after the sensor implantation was compared and quality-adjusted life years (QALY) gained based on a literature review of previous studies was calculated. Results: The rate of HF hospitalisations was significantly lower at 1 year compared with the year before CardioMEMS implantation (0.25 versus 1.10 events/patient-years, HR 0.22, p=0.001). At the end of first year, the usual management outperformed the CardioMEMS HF system, resulting in a net monetary value difference of 2,540€ per patient and a benefit-cost ratio of 0.38. However, by the end of the second year, the CardioMEMS system is estimated to reduce costs compared to usual management. Conclusions: Based on the results, we suggest that remote monitoring of pulmonary artery pressure with the CardioMEMS HF system represents a long-term cost-effective strategy in a healthcare setting in Southern Europe.

Although renal denervation (RDN) protects against hypertension, hypertrophy, and heart failure (HF), it is not clear whether RDN preserves ejection fraction (EF) during heart failure (HFpEF). To test this hypothesis, we simulated chronic congestive cardiopulmonary heart failure (CHF) by creating aorta-vena cava fistula (AVF) in C57BL/6J wild type (WT) mice. There are four ways to create experimental CHF: (1) myocardial infarction (MI) which is basically ligating coronary by instrumenting and injuring the heart; (2) trans-aortic constriction (TAC), although it mimics systematic hypertension but TAC again constricts aorta on top of the heart and exposes the heart; (3) acquired CHF such as by dietary factors, diabetes/salt diets etc. but it is multifactorial, and finally (4) AVF, which is the only one wherein AVF is created ~1cm below the kidney where the aorta and vena cava share the common middle-wall. By creating fistula, the red blood enters vena cava without an injury to the heart. This model mimics CHF such as during aging where with age the preload keeps increasing than the aging heart can pump out due to the weakened cardiac myocytes. This also involves the right ventricle to lung to left ventricle flow, thus creating congestion. The heart in AVF goes to transition from preserved to reduced EF (i.e., HFpEF to HFrEF). In fact, there are more models of volume overload, such as the pacing-induced and mitral valve regurgitation but these are also injurious models. Our lab is one of the original labs in creating and studying the AVF phenotype. The RDN was created by treating the cleaned bilateral renal artery. After 6 weeks, blood, heart, and renal samples were analyzed for exosome, cardiac regeneration markers and renal cortex proteinases. Cardiac function was analyzed by echocardiogram (ECHO). Fibrosis was analyzed with trichrome staining. The results suggested that there was robust increase in exosomes’ level in AVF blood, suggesting compensatory systemic response during AVF-CHF. During AVF there was no change in cardiac eNOS, Wnt1 and β-catenin, however; during RDN there was robust increase in eNOS, Wnt1 and β-catenin compared to the sham group. As expected in HFpEF there was perivascular fibrosis, hypertrophy and pEF. Interestingly, increased levels of eNOS suggested that despite fibrosis, the NO generation was higher that most likely contributed to pEF during HF. The RDN intervention revealed an increase in renal cortical caspase 8 and a decrease in caspase 9. Since caspase 8 is protective and caspase 9 is apoptotic, we suggest that RDN protects against renal stresses, and apoptosis. Our findings also suggest that RDN is cardioprotective during HFpEF via the preservation of eNOS and accompanied endocardial-endothelial function.

Objective: We aimed to clarify the differences in the association between re-admission for heart failure (HF) and left atrial (LA) overload indices by sex in heart failure and a preserved ejection fraction (HFpEF). Methods: We analysed 898 HFpEF patients hospitalized for acute decompensated HF. Blood tests and transthoracic echocardiography were performed before discharge. The primary endpoint was re-admission for HF during the first year. Results: The ratio of diastolic elastance to arterial elastance (p=0.014), a relative index of LA pressure overload, in men and LA volume index (LAVI, p=0.020) in women were significant for re-admission for HF during the first year in the multivariable Fine-Gray analysis. Stroke volume (SV)/LA volume (LAV), another index for LAV overload, was not a significant prognostic factor of re-admission for HF during this time. Conclusion: LA overload was an important prognostic factor for HF re-readmission during the first year after enrolment in patients with HFpEF, but the indices relating to LA overload differed by sex.

Heart failure with preserved ejection fraction (HFpEF) is a leading form of human cardiovascular disease and commonly associated with systemic hypertension. Unique evolved adaptations in giraffe myocardia may be a natural animal model of resistance to HFpEF. In humans, pressure-overload induced left ventricular thickening (PLVT) impairs diastolic relaxation, elevates left atrial pressures and may progress to heart failure with symptoms including exercise intolerance. In healthy giraffe, the left ventricle thickens as developmental neck lengthening widens the vertical distance between the heart and head increasing pressures needed to maintain constant brain perfusion. Yet, diastolic relaxation and exercise capacity are unimpaired, a critical adaptation for prey species such as giraffe. The proximate mechanisms underlying this unique cardiovascular physiology are not yet characterized. Developmental PLVT in giraffe emerges as a species-specific evolved adaptation which offers a roadmap for identifying innovations in therapeutic and prevention strategies for HFpEF.

fibrillation (AF) and heart failure with preserved ejection fraction (HFpEF). Join us on a journey that unravels the mysteries of molecular intricacies, delves into advanced imaging techniques, and sheds light on therapeutic pathways. Unveiling the role of cardiac amyloidosis, particularly sub-clinical isolated cardiac amyloidosis (ICA), the narrative unfolds the heightened risk of AF in the elderly. State-of-the-art imaging techniques like cardiac magnetic resonance (CMR) and molecular imaging step into the spotlight, unraveling diagnostic and prognostic nuances of AF and HFpEF. Embarking on the molecular voyage, the article navigates through next-generation sequencing and comprehensive genomic profiling, shedding light on genetic alterations shaping the AF-HFpEF landscape. This molecular compass lays the groundwork for personalized medicine, illuminating pathways to identify therapeutic bullseyes and biomarkers. In the realm of medical strategies, the discussion homes in on the promising notes struck by SGLT2 inhibitors, particularly dapagliflozin, orchestrating a reduction in AF burden. Characters like spironolactone and dronedarone make appearances, each weaving a distinct tale, revealing their potential roles in steering the ship for AF- HFpEF patients. The subplot involving obesity in HFpEF unfolds, with the LEGACY study portraying the benefits of weight reduction. The pivotal intervention of catheter ablation emerges as the hero, boasting positive outcomes in reducing hospitalization rates and overall mortality for AF-HFpEF patients. However, cautionary tales echo about its impact on left atrial function, adding layers of complexity that beckon careful consideration and monitoring. Amidst the narrative, critical discussions unfold about the limitations of current research, echoing the need to define acute heart failure, refine imaging techniques, and tailor management strategies. The narrative passionately advocates for a personalized touch in addressing AF-HFpEF, recognizing the unique blend of clinical and molecular personas. In essence, this review paints a vivid mural of AF-HFpEF, skillfully bridging the realms of molecular intricacies and the artistry of clinical management.

Especially in the last two decades, due to the developments in durable mechanical circulatory support (MCS) technology and applications, left ventricular assist (LVAD) implantation has become used in more fragile end-stage heart failure patients with higher risk. Despite advances in technology and patient care processes, right heart failure remains the leading cause of morbidity and mortality after durable LVAD implantation. It is difficult to make decisions about the type and duration of MCS during preoperative evaluation, and many clinical, hemodynamic, biochemical and echocardiographic criteria must be taken into account when evaluating the right ventricle. Complex quantitative scoring systems, including measurements of different risk factors for postimplant right ventricular failure, and composite variables, including the anatomical and functional status of the right ventricle, have been used to decide between left or biventricular assist device implantation. The successful use of artificial intelligence (AI) and machine learning (ML) in various applications in the medical field has paved the way for the idea of using it to better predict possible conditions such as right heart failure after LVAD implantation. This review aims to evaluate the current situation of risk prediction models using AI and ML technology, which have become popular in recent years, and possible future developments in predicting right heart failure after the application of durable MCS systems.

Congestive heart failure (CHF) is a major cause of morbidity and mortality with an increasing prevalence in human and canine populations. Similar to humans, overactivation of the renin-angiotensin aldosterone system is involved in the pathophysiology of CHF in dogs. Current therapeutic strategies for the management of canine CHF include the use of RAAS inhibitors, diuretics and inodilators. The present review summarizes data from our own research on the modulation of the renin-angiotensin cascade in dogs in dogs, together with new findings (including novel therapeutic targets) from the veterinary and the human literature.

Ambulatory heart rate (HR) monitors that acquire electrocardiogram (ECG) or/and photoplethysmographm (PPG) signals from the torso, wrists, or ears are notably less accurate in tasks associated with high levels of movement compared to clinical measurements. However, reliable estimation of HR can be obtained through data fusion from different sensors. These methods are especially suitable for multimodal hearable devices, where heart rate can be tracked from different modalities, including electrical ECG, optical PPG, and sounds (heart tones). Combined information from different modalities can compensate for single source limitations. In this paper, we evaluate the possible application of data fusion methods in hearables. We assess data fusion for heart rate estimation from simultaneous in-ear ECG and in-ear PPG, recorded on eight subjects while performing 5-minute sitting and walking tasks. Our findings show that data fusion methods provide a similar level of mean absolute error as the best single-source heart rate estimation but with much lower intra-subject variability, especially during walking activities. We conclude that data fusion methods provide more robust HR estimation than a single cardiovascular signal. These methods can enhance the performance of wearable devices, especially multimodal hearables, in heart rate tracking during physical activity.

Background We aimed to evaluate the effectiveness of the ALRYNGO channel-type video laryngoscope with an AI-based glottis guidance system in senior emergency medicine residents for endotracheal intubation. Methods We enrolled twenty patients would be adequate for each device (direct laryngoscope, Pentax-AWS, and ALRYNGO). Before intubation, six senior residents wore a personal protective equipment. To randomize the device in this clinical study, a sealed envelope containing a device-specific identification card was utilized. When intubation began, the person who measured the intubation time divided the total intubation time into three-time intervals. The primary outcome was the intubation time. The secondary outcomes were the glottis view using the Cormack-Lehane grade (C-L grade) and the glottis guidance performance of ALRYNGO’s artificial intelligence. Results In Pentax-AWS and ALRYNGO, all intubations were successful, but the intubation time was longer than with the direct laryngoscope. And among the three, the ALRYNGO and Pentax-AWS had the highest frequency of C-L grade I (easiest intubation) at 80%, and the direct laryngoscope had the lowest frequency of 10%. Conclusions Even if healthcare professionals without experience with the channel-type video laryngoscope improve their performance on airway mannequins after training, their intubation performance may differ when applied to actual patients.

Background: Acute heart failure (AHF) is a serious medical problem that necessitates hospitalisation and often results in death. Patients hospitalised to the emergency department (ED) should therefore receive an immediate diagnosis and treatment. Unfortunately, there is not yet a fast and accurate laboratory test for identifying AHF. The purpose of this research is to apply the principles of explainable artificial intelligence (XAI) to the analysis of hematological predictors for AHF. Methods: In this retrospective analysis, 425 patients with AHF and 430 healthy individuals served as assessments. Patients' demographic and hematological information was analyzed to determine AHF. Important risk variables for AHF diagnosis were identified using LASSO feature selection. To test the efficacy of the suggested prediction model (XGBoost), a 10-fold cross-validation procedure was implemented. The area under the receiver operating characteristic curve (AUC), F1 score, Brier score, and Positive Predictive Value (PPV) and Negative Predictive Value (NPV) were all computed to evaluate the model's efficacy. Permutation-based analysis and SHAP, were used to assess the importance and influence of the model's incorporated risk factors. Results: White blood cell (WBC), monocytes, neutrophils, neutrophil-lymphocyte ratio (NLR), red cell distribution width-standard deviation (RDW-SD), RDW-coefficient of variation (RDW-CV), and platelet distribution width (PDW) values were significantly higher than the healthy group (p&lt;0.05). On the other hand, erythrocyte, hemoglobin, basophil, lymphocyte, mean platelet volume (MPV), platelet, hematocrit, mean erythrocyte hemoglobin (MCH) and procalcitonin (PCT) values were found to be significantly lower in AHF patients compared to healthy controls (p &lt;0.05). When XGBoost was used in conjunction with LASSO to estimate AHF, the resulting model had an AUC of 87.9%, an F1 score of 87.4%, a Brier score of 0.036, and an F1 score of 87.4%. PDW, age, RDW-SD, and PLT were identified as the most crucial risk factors in differentiating AHF. Conclusions: The XGBoost model demonstrated exceptional performance in accurately estimating Acute Heart Failure, and the application of Explainable Artificial Intelligence effectively provided intuitive explanations for the model's estimations. The suggested interpretable model holds potential for the identification of patients at high risk, thereby facilitating the optimization of treatment and planning for follow-up in cases of AHF.

Patients with heart failure have difficulty in self-care management, as daily monitoring and recognizing symptoms do not readily triggers an action to avoid hospital admissions. The purpose of this study was to understand the impact of a nurse-led complex intervention on symptom recognition and fluid restriction. A latent growth model was designed to estimate self-care management and quality of life changes on patients with heart failure and assessed by a pilot study, for three months, to sixty-three patients (33 control, 30 intervention). Patients in the control group had a higher risk of hospitalisation (IRR 11.36; p<.001) and emergency admission (IRR 4.24; p<.001) at three-months follow-up. Analysis of the time scores demonstrated that the intervention group had a clear improvement in self-care behaviours (βSlope. Assignment_group=-.881; p<.001) and in the quality of life (βSlope. Assignment_group=1.739; p<.001). This study supports that a nurse-led program on symptom recognition and fluid restriction can have a positive impact on self-care behaviours and quality of life in patients with heart failure.

This review paper presents a flashback on the evolution of the disease throughout the centuries, describes in summary pathophysiologic mechanisms, discusses briefly the mechanism of action of the diuretics, presents their role in decongesting heart failure patients and unfolds the data behind ultrafiltration in the management of acutely or chronically decompensated heart failure (ADHF), focusing on all the available data and advancements in this field. Acutely decompensated heart failure (ADHF) presents a critical clinical condition characterized by worsening symptoms and signs of heart failure, necessitating prompt intervention to alleviate congestion and improve cardiac function. Diuretics have traditionally been the mainstay for managing fluid overload in ADHF. Mounting evidence suggests that due to numerous causes, such as coexisting renal failure or chronic use of the loop diuretics, an increasing rate of diuretic resistance is noticed and needs to be addressed. There has been a series of trials that combined diuretics of different categories, without the expected results. Emerging evidence suggests that ultrafiltration may offer an alternative or adjunctive approach.

Oxidative stress (OS) is reported in several chronic diseases. Extra-cellular superoxide dismutase (ec-SOD) catalyzes the dismutation of superoxide anion with a protective role on endothelial cells. In chronic kidney diseases (CKD), OS and thyroid dysfunction (low T3 syndrome) are fre-quently present, but their relationship has not been investigated. This cohort study evaluated ec-SOD activity in CKD patients during haemodialysis, divided into: “acute hemodialytic pa-tients” (AH, 1-3 months of treatment) and “chronic hemodialytic patients” (CH, treated for a longer period). We also evaluated plasmatic total antioxidant capacity (TAC) and the relation-ships with thyroid hormones. Two basal samples (“basal 1”, 3 days after the last dialysis and “basal 2”, 2 days after the last dialysis) were collected. On the same day of basal 2, a sample was collected 5 and 10 min after the standard heparin dose and at the end of the procedure. The ec-SOD values were significantly higher in CH vs AH in all determinations. Moreover, they pre-sented lower TAC values. Dividing CH patients into two subgroups according to fT3 levels (nor-mal or low) we found significantly lower ec-SOD values in the group with low fT3 at basal, 5 and 10 min samples. Finally, a significant correlation was observed between fT3 and ec-SOD in the basal 1 samples. These data, confirming OS and low T3 syndrome in CKD, suggest that low fT3 concentrations can influence ec-SOD activity and therefore contribute to possible endothelial oxi-dative damage in such a situation.

Background: Heart failure with preserved ejection fraction (HFpEF) is a major health concern. There is a growing recognition of the causal interplay between arterial stiffness and HFpEF. We recently reported that phosphate retention is a trigger for arterial stiffness. This study focuses on whether arterial stiffness due to phosphate retention could be a predictor for HFpEF. Methods: The study subjects were 158 patients (68 males and 90 females, mean age 74.8±11.2). HFpEF was defined according to the guidelines of the ESC 2019. Pulse wave velocity (PWV) and central systolic blood pressure (CSBP) were used as markers for arterial stiffness and afterload, respectively. We measured serum levels of fibroblast growth factor 23 (FGF23) as a marker of phosphate retention. Results: The serum levels of FGF23 had significant relationship with PWV. PWV had significant relationships with LV mass index, plasma BNP levels, and relative wall thickness, e’ and E/e’ (p<0.001, respectively). Multivariate logistic regression analysis revealed that PWV higher values and hypertension were significant predictors for the dependent factor (HFpEF). Conclusions: Arterial stiffness amplified LV afterload, leading to LV concentric hypertrophy and LV diastolic dysfunction. This study presents that arterial stiffness due to phosphate retention, and hypertension are important predictors of HFpEF.

Despite a large amount of research on synchronous and mutually induced kidney and heart damage, the basis of the disease is still not fully clarified. Healthy mitochondria are essential for normal kidney and heart function. Mitochondrial dysfunction occurs when the clearance or process of generation and fragmentation of mitochondria is disturbed. The kidney is the second organ after the heart in the number of mitochondria. Kidney tubules are rich in mitochondria due to the high energy requirements for absorption processes of large amounts of ultrafiltrate and dissolved substances. The place of action of oxidative stress is the influence on the balance in the production and breakdown of mitochondrial reactive oxygen species . A more precise determination of the place and role of key factors that play a role in the onset of the disease is necessary for understanding the nature of the onset of the disease and the creation of therapy in the future. The narrative review integrates results found in previously performed studies which have evaluated oxidative stress participation in renocardial syndrome type 3.

Background and Objectives: Acute Heart Failure (AHF) is a common disease and a cause of high morbidity and mortality, constituting a major health problem. The main purpose of this study was to determine the impact of multiorgan ultrasound in identifying the pulmonary hypertension (PH) in patients admitted due to AHF, predict the evolution of the disease during hospitalization and identify areas of improvement in the care of patients with AHF. Materials and Methods: Patients were evaluated with a standard exam of lung ultrasound, echocardiography, inferior vena cava (IVC) and femoral, renal, hepatic, portal venous Doppler flow patterns at admission and on the day of discharge. Results: Thirty patients were enrolled during November 2021. The mean age was seventy-nine years (Standard Deviation – SD 13,4). Seven patients (23.3%) had a renal function worsening. Regarding ultrasound findings, venous excess ultrasonography score (VExUS) score was calculated at admission and at discharge, surprisingly remaining unchanged or even worsened in most of them (21 patients, 70.0%). The area under the curve for the Lung Score was 83.9% (p = 0.008), obtaining a cutoff value of 10 that showed a sensitivity of 82.6% and a specificity of 71.4% in the identification of intermediate and high PH. It was possible to monitor significant changes between both exams on the lung score (p &lt;0.001), hepatic vein Doppler (p &lt;0.001), portal vein Doppler (p = 0.030), intra-renal vein Doppler (p = 0.025) and VExUS score (p = 0.023), remaining similar the femoral vein Doppler (p = 0.177) and IVC (p = 0.132). Conclusions: Our study results suggest that performing serial multiorgan Point-of-Care ultrasound can help us to better identify high and intermediate probability of PH patients with AHF. Currently proposed multi-organ, venous Doppler scanning protocols, such as the VExUS score, should be further studied in different populations before expanding its use in AHF patients.

Abstract Objective: To review the relevant literature on the use of atrioventricular node ablation and pacing in patients with heart failure and atrial fibrillation. Methods: A PubMed/MEDLINE and SCOPUS search was performed in order to assess the clinical outcomes of atrioventricular node ablation and pacemaker implantation, as well as the complications that may occur. Results: Several clinical trials, observational analyses and meta-analyses have shown that “pace and ablate” strategy not only improves symptoms but also can enhance cardiac performance in patients with heart failure and atrial fibrillation. Although this procedure is effective and safe, some complications may occur including worsening of heart failure, permanent fibrillation, arrhythmias and sudden death. Regarding the implantation of pacemaker, cardiac resynchronization therapy is shown to be the optimal choice compared to right ventricle apical pacing. His bundle pacing is a promising alternative to cardiac resynchronization therapy and has shown beneficial effects, while left bundle brunch pacing is an innovative modality. Conclusions: Atrioventricular node ablation and implantation of pacemaker is shown to have beneficial effects on clinical outcomes of patients with atrial fibrillation ± heart failure who do not respond or are intolerant to medical treatment. Cardiac resynchronization therapy is the treatment of choice and His bundle pacing seems to be an effective alternative way of pacing in these patients.

This strategy had a very fast and good impact on the patient’s health; the CCM improved heart failure symptoms, hemodynamics flow and cardiac functionality. Moreover, after a relatively short time, the patient comes from persistent AF to Sinus Rhythm, although he starts with a severe bi-atrial dilatation. These parameters were stable during an extended follow-up of 18 months.

Heart failure (HF) management in type 1 diabetes (T1D) is particularly challenging due to its increased prevalence and the associated risks of hospitalization and mortality, driven by diabetic cardiomyopathy. Sodium-glucose cotransporter-2 inhibitors (SGLT2-i) offer a promising avenue for treating HF, specifically the preserved ejection fraction variant most common in T1D, but their utility is hampered by the risk of euglycemic diabetic ketoacidosis (DKA). This review investigates the potential of SGLT2-i in T1D HF management, alongside the emergent Continuous Ketone Monitoring (CKM) technology as a means to mitigate DKA risk, through a comprehensive analysis of clinical trials, observational studies, and reviews. The evidence suggests SGLT2-i significantly reduce HF hospitalization and enhance cardiovascular outcomes. However, their application in T1D patients remains limited due to DKA concerns. CKM technology emerges as a crucial tool in this context, offering real-time monitoring of ketone levels, which enables the safe incorporation of SGLT2-i into treatment regimes by allowing for early detection and intervention in the development of ketosis. The synergy between SGLT2-i and CKM has the potential to revolutionize HF treatment in T1D, promising improved patient safety, quality of life, and reduced HF-related morbidity and mortality. Future research should aim at clinical trials directly assessing this integrated approach, potentially guiding new management protocols for HF in T1D.

Background. The type-2 sodium-glucose cotransporters inhibitors (SGLT2i) are a new relevant therapeutic option for patients affected by chronic heart failure with reduced ejection fraction (HFrEF). The aim of this study was to evaluate, in a real-world population from a single center, the feasibility of introducing SGLT2i and their interaction with other recommended drug classes. Methods. We evaluated the consecutive patients affected by chronic heart failure (CHF) since January 2022. At baseline clinical visit the therapy taken by the patients as well as that prescribed were accurately collected. During a 6-12 month follow-up the the changes in concomitant therapy were analyzed. Results. At baseline, among 350 patients evaluated, only 17 (5%) were already taking SGLT2i, 13 with HFrEF, 2 with CHF with mild reduced (HFmrEF) and 2 with preserved ejection fraction (HFpEF). After baseline evaluation, SGLT2i were prescribed to 220 (63%) of all the patients enrolled, among whom 178 (84%) of HFrEF patients, 25 (42%) of HFmrEF and 17 (22%) of HFpEF. After follow-up, SGLT2i therapy was highly tolerated and it was associated with a significant increased prescription of sacubitril/valsartan and a reduced use of diuretics. Finally, a significant improvement in functional status and left ventricular systolic function after SGLT2i therapy was observed. Conclusions. In this single center “real world” study, SGLT2i were prescribed in HFrEF patients most of all already in therapy with the other classes of drugs currently recommended for their treatment. Moreover, a further optimization in prescribed ther-apy was observed during a short term follow-up. These data further support the use of this thera-peutic approach in routine clinical practice.

Background A decline in cardiovascular hospitalizations was observed during the initial phases of the COVID-19 pandemic. We examine the continued effect of the pandemic on cardiovascular hospitalizations and the associated mortality rates during the first year of the pandemic in Israel. Methods We conduct a retrospective cohort study using the data of Clalit Health Services, the largest healthcare organization in Israel. We divide the Corona year into six periods (three lockdowns and three post-lockdowns) and compare the incidence rates of cardiovascular hospitalizations and their 30-day mortality during each period to the previous three years. Results The number of non-STEMI hospitalizations during the first year of the pandemic was 13.7% lower than the average of the previous three years (95% CI 11%-17%); STEMI hospitalizations were 15.7% lower (95% CI 13%-19%); and CHF hospitalizations were 23.9% lower (95%, CI 21%-27%). No significant differences in 30-day mortality rates were observed for AMI patients during most of the periods, whereas the annual 30-day all-cause mortality rate of CHF was 23% higher. Conclusions Hospitalizations for AMI and CHF were significantly lower during the first year of the pandemic relative to 2017–9. Mortality rates were higher in the case of CHF patients but not in the case of AMI patients, possibly due a change in the clinical acuity of patients arriving at the hospitals. We conclude that targeted public health messaging should be implemented, together with proactive monitoring in order to identify residual disability in patients that may have received non-optimal treatment during the pandemic.

Aims: Heart failure (HF) is frequently accompanied by atrial fibrillation (AF), a combination that worsens the outcomes of both diseases. Despite advances in the treatment of AF, it remains a serious and unsolved problem for clinicians and researchers. The aim of this study was to examine risk factors for incidents of paroxysmal and persistent AF in patients having heart failure with mid-range ejection fraction (HFmrEF). Methods. Overall, 71 patients with HFmrEF and non-valvular AF, including paroxysmal and persistent types, were enrolled in this study. As a control group, 42 HFmrEF patients without AF were also enrolled. All patients underwent detailed physical examination, including resting electrocardiography, echocardiography, and 24-hour ambulatory Holter monitoring. Levels of the inflammation markers high-sensitivity C-reactive protein (hs-CRP), interleukin-6 (IL-6), and tumor necrosis factor α (TNF-α) and the fibrotic marker transforming growth factor-β1 (TGF-β1) were measured by ELISA and expressed as odds ratios. Results: We show that paroxysmal AF was associated with higher diastolic blood pressure, whereas both paroxysmal and persistent forms of AF were associated with more frequent occurrence of hypertensive crisis episodes and greater body mass index. Progression from paroxysmal to persistent AF was associated with significant ventricular remodeling. Persistent and paroxysmal AF were associated with higher levels of inflammatory markers when compared to HFmrEF patients having no AF. In addition, TGF-1 was significantly increased in HFmrEF patients having persistent but not paroxysmal AF. Conclusions: Occurrence of AF, first paroxysmal and then persistent, in HFmrEF patients is associated with left ventricular remodeling and the appearance of systemic inflammatory and fibrotic markers. Changes in those parameters may be indicators by which to identify patients at increased risk of atrial fibrillation. Further studies are needed to determine the prognostic validity of these markers.

Based on the dynamic strength variation mechanism of concrete under complex loading conditions, two approaches were devised: numerical testing and CT scanning, guided by the principle of minimizing energy dissipation. A methodology for calculating concrete's failure area and measuring its strength was developed. The analysis delves into the mechanisms behind failure patterns and variations in concrete specimen strength, focusing on crack initiation, development, and the resultant failure surface formed by crack propagation, along with the stress distribution in concrete specimens subjected to diverse loading conditions. Through evaluating the strength and computed failure area of concrete specimens, it is evident that the loading method influences both the strength and failure area of concrete specimens. In general, a larger failure area correlates with a higher measured strength.

Mortality and readmission rates for decompensated acute heart failure (AHF) is overall increasing and risk stratification might be challenging. We sought to evaluate the prognostic role of systemic venous ultraso-nography in patients hospitalized for AHF. We prospectively recruited 74 AHF patients with a NT-proBNP level above 500 pg/mL. Then, a multiorgan ultrasound assessment (lung, inferior vena cava, Doppler of hepatic, portal, intrarenal and femoral veins) were performed at admission, discharge, and follow-up (for 90 days). An intrarenal monophasic pattern (AUC 0.923, Sn 90%, Sp 81%, PPV 43%, NPV 98%), a portal pulsatility >50% (AUC 0.749, Sn 80%, Sp 69%, PPV 30%, NPV 96%) and a VExUS score of 3 (AUC 0.885, sensitivity 80%, specificity 75%, PPV 33%, NPV 96%) predicted death during hospitalization. An IVC above 2 cm (AUC 0.758, Sn 93.l% and Sp 58.3) and the presence of an intrarenal monophasic pattern (AUC 0. 834, sensitivity 0.917, specificity 67.4%) in the follow-up visit predicted AHF related readmission. Addi-tional scans during hospitalization or calculate a VExUS score probably adds unnecessary complexity to the assessment of AHF patients. In conclusion, VExUS score does not contribute to guide therapy or the predic-tion of complications, compared to the presence of an inferior vena cava greater than 2 cm, a venous mo-nophasic intrarenal pattern or a pulsatility > 50% of the portal vein in AHF patients. Early and multidisci-plinary follow-up visit remains necessary to improve prognosis of this highly prevalent disease.

Background and Objectives: High job strain is worsening the outcome in coronary artery disease, CAD. Severe dissatisfaction on workplace, imbalance between high demands , and low rewards, are affecting the quality of life, and diminishing the duration of life, especially in CAD patients. Our study included two samples : CAD patients (experimental group), and without CAD patients, but with traditional risk factors (control group). The main objective of the study was the role played by high sensitivity C reactive protein, hs CRP, and microalbuminuria, as mediators of job strain and CAD relationship. Secondary objectives were the following: identification of the most vulnerable patients( with significant job strain) and intervention towards this category, for cardiovascular events prevention (primary or secondary). Materials and Methods: The utilized methods were the following : clinical exam; electrocardiogram; echocardiogram; non contrast enhanced computed chest tomography; laboratory findings ( lipid profile, glycemia, hs CRP, microalbuminuria); type D scale, DS 14; depression questionnaire, PHQ-9; and satisfaction with work scale, SWWS. Results: The highest values for hs CRP and microalbuminuria were noticed in patients with the lowest Likert score, for both samples CAD, and without CAD patients. The highest job strain was noticed in females. More than half of CAD patients ,with low Likert scores, revealed myocardial infarction. Conclusions: Microalbuminuria and hs CRP were statistical significant in the study as intercessors, in job strain and CAD relationship. The most vulnerable patients for vascular events were females, in both groups : CAD and “CAD waiting desk”. In CAD sample, the vascular vulnerability was also increased by high job strain.

High-flow Nasal Cannula (HFNC) oxygen therapy is gaining traction globally as a treatment for respiratory failure. There are several physiological benefits and there may be a growing patient preference for HFNC. In this narrative review, we aim to outline the basic mechanisms of HFNC, who can use it and review the literature regarding its utility both in the critical care setting, as well as in the home setting for chronic hypercapnic respiratory failure with an emphasis on Chronic Obstructive Pulmonary Disease (COPD). The role of non-pharmacological interventions like non-invasive ventilation (NIV) and HFNC in the prevention of hospital readmissions following acute exacerbations of COPD (AECOPD) is an area of increasing importance because randomised controlled trials and systematic reviews have found measures like nurse-led predischarge bundles to be clinically ineffective and to have a high cost per quality adjusted life year. This review therefore considers the evidence of NIV vs HFNC in the context of AECOPD and the application of HFNC at home in the prevention of AECOPD. We also look at applications of HFNC in specific settings, such as in the peri-operative period, emergency department, acute (mainly Critical Care) setting including in immunocompromised patients and palliative care.

Heart failure is associated with a significant mortality rate, and an elevated prevalence of this condition has been noted among hypertensive patients. The identification of predictive factors for heart failure progression in hypertensive individuals is crucial for early intervention and improved patient outcomes. In this study, we aimed to identify these predictive factors utilizing medical history data for hypertension patients. Specifically, we focused solely on utilizing medical data preceding the diagnosis of hypertension to enable patients to anticipate the onset of potential heart failure at the time of hypertension diagnosis. Age-specific and ICD system-specific predictive factors were identified utilizing the MIMIC-IV database through the application of two analytical approaches: chi-square tests and XGBoost modeling. Our findings reveal 21 overall predictive factors, encompassing conditions such as atrial fibrillation, the use of anticoagulants, kidney failure, obstructive pulmonary disease, and anemia. These factors were assessed through a comprehensive review of the existing literature. We anticipate that the results will offer valuable insights for the risk assessment of heart failure in hypertensive patients.

The decompensation trajectory check is a basic step to assess the clinical course and to plan future therapy in hospitalized patients with acute heart failure (ADHF). Due to the atypical presentation and clinical complexity, trajectory checks can be challenging in the oldest old patients with acute HF. Point of care ultrasound (POCUS) proved to be helpful in the clinical decision-making of patients with dyspnea, but no study has attempted to verify its effectiveness in predicting determinants of HF in-hospital worsening. In this single-center prospective study, we consecutively enrolled patients aged 75 or older hospitalized with acutely decompensated HF in a tertiary care hospital. All the patients underwent complete clinical examination, blood tests, and POCUS including Lung Ultrasound, Focused Cardiac Ultrasound, Pleural Effusion score (PEFs), and Inferior Vena Cava (IVC) assessment. Out of 184 patients hospitalized with ADHF enrolled in the study, sixty experienced HF in-hospital worsening. No differences were found among patients with HF worsening and controls in terms of age, gender, frailty, and left ventricular ejection fraction. By multivariable logistic analysis, total PEFs [aOR: 1.15 (CI95% 1.02– 1.33), p = 0.043], and IVC collapsibility [aOR: 0.90 (CI95% 0.83 – 0.95), p = 0.039] emerged as independent predictors of acute HF worsening after extensive adjustment for potential confounders.

In this paper, a continuous power management for a decentralized DC microgrid (DCMG) is proposed to achieve voltage regulation and power balance even under system uncertainty and voltage sensor failure. The DCMG system achieves a continuous power management through only the primary controller to reduce the computational burden of each power agent. To enhance the reliability and resilience of the DCMG system under voltage sensor failure, a DC bus voltage (DCV) sensor fault detection algorithm is proposed. In this algorithm, the DCV sensor failure is detected by comparing the measured DCV with the estimated DCV. When the power agent identifies the DCV sensor failure, it changes the operation properly according to the proposed control mode decision algorithm to maintain the stability of the DCMG system. When uncertain conditions such as the power variation of the distributed generations, sudden grid disconnection, DCV sensor failure, electricity price change, and critical battery status occur, the DCMG system is changed to transitional operation modes. These transitional operation modes are employed to transmit the power agent information to other agents without digital communication links (DCLs) and to accomplish power sharing even under such uncertain conditions. In the transitional operation modes of the DCMG system, the DCV levels are temporarily shifted to an appropriate level, enabling each power agent to detect the uncertainty conditions, and subsequently to determine its operation modes based on the DCV levels. Simulation and experimental results under different test conditions confirm the reliability and effectiveness of the proposed control scheme.

Objective: To examine variations in end-of-life care for breast cancer, heart failure, and dementia patients. Data and methods: Data from four Norwegian health registries were linked using a personal identification number. Longitudinal trends over 365 days and the type of care on the final day of life were analyzed using descriptive techniques and logistic regression analysis. Results: Patients with dementia were most commonly placed in nursing homes, while patients with heart failure and breast cancer were more frequently hospitalized. Breast cancer and heart failure patients had a higher likelihood of dying at home. The presence of general practitioners increased the probability of home-based end-of-life care for cancer patients, while non-physician healthcare workers increased the likelihood of home-based care for the other patient groups. Conclusion: Diagnoses, individual characteristics, and service availability are all associated with the place of death in end-of-life care.

Background: In this investigation, we explored the effects of pharmacological cholinergic stimulation on cardiac function and renal inflammation following acute myocardial infarction (AMI) in spontaneously hypertensive rats (SHRs). Methods: Adult male SHRs were randomized into three experimental groups: sham-operated; AMI+Veh (infarcted, treated with vehicle); and AMI+PY (infarcted, treated with the cholinesterase inhibitor pyridostigmine bromide (PY) - 40 mg/kg, once daily for seven days). Rats were euthanized 7 or 30 days post-surgery. Clinical parameters were assessed on the day before euthanasia. Subsequent to euthanasia, blood samples were collected and renal tissues were harvested for histological and gene expression analyses aimed to evaluate inflammation and injury. Results: Seven days post-surgery, the AMI+PY group demonstrated improvements in left ventricular diastolic function and autonomic regulation, and a reduction in renal macrophage infiltration compared to the AMI+Veh group. Furthermore, there was a notable downregulation of pro-inflammatory gene expression and an upregulation of anti-inflammatory gene expression. Analysis 30 days post-surgery showed that PY treatment had a sustained positive effect on renal gene expression, correlated with a decrease in biomarkers indicative of subclinical kidney injury. Conclusion: Short-term cholinergic stimulation with PY provides both cardiac and renal protection by mitigating the inflammatory response after AMI.

This study aimed to determine the correlation of colour M-mode velocity propagation in the assessment of left ventricular diastolic function among acute decompensated heart failure patients with preserved ejection fraction (HFpEF). This research is an observational analytical study using a cross–sectional study design conducted from April to June 2022. The subjects of this study were patients diagnosed with acute HFpEF and treated at Dr. Soetomo General Academic Hospital, Surabaya. Patients with heart rhythm disturbances, moderate to severe valvular heart disease, and congenital heart defects were excluded from this study. Patients were measured for diastolic function including mitral valve early mitral inflow velocity (MV E Velocity), mitral peak velocity of early filling (E’) (E' Septal and E' Lateral), left atrial volume index (LAVI), The maximal tricuspid regurgitation velocity (TR V Max), Vp, the ratio of early diastolic mitral inflow velocity to early diastolic mitral annulus velocity (E/E'), the ratio between early and late ventricular filling velocity (E/A) and E/Vp Ratio. N-terminal-pro hormone B-type natriuretic peptide (NT–ProBNP) examination was also performed on study subjects as an additional diagnosis of acute heart failure. There were 33 patients who met the inclusion and exclusion criteria and were included in our study. There were 26 patients (78.8%) with grade I diastolic dysfunction, 4 patients (12.1%) with grade II diastolic dysfunction, and 3 patients (9.1%) with grade III diastolic dysfunction. There is a strong positive correlation between Vp with parameters E' Septal (p = &lt; 0.001; r = 0.636) and E' Lateral (p = &lt; 0.001; r = 0.650). Vp is negatively correlated with the ratio E/E' (p = 0.029; r = –0.37). The PCWP estimate with E/Vp ratio had a strong correlation with the NT–Pro BNP value &gt; 300 pg/ml in acute HFpEF patients (p = &lt; 0.001; r = 0.726) compared to the PCWP estimate with E/E' (p = &lt; 0.001; r = 0.549). There is no correlation between Vp value and degree of diastolic dysfunction in patients with acute HFpEF.

Aspalathin (ASP) can protect H9c2 cardiomyocytes against high glucose (HG)-induced shifts in myocardial substrate preference, oxidative stress and apoptosis. While the protective mechanism of aspalathin remains unknown, nuclear factor (erythroid-derived 2)-like 2 (Nrf2) has emerged as a key factor for intracellular responses against oxidative stress. Therefore, we hypothesized that aspalathin protects the myocardium against hyperglycemia-induced oxidative damage by up-regulating Nrf2 expression in H9c2 cardiomyocytes and diabetic (db/db) mice. Using an oxidative stress RT2 Profiler PCR array, ASP at a dose of 1 µM was demonstrated to protect H9c2 cardiomyocytes against HG-induced oxidative stress, but silencing of Nrf2 abolished this protective response of ASP and exacerbated cardiomyocyte apoptosis. Db/db mice and their non-diabetic (db/+) littermate controls were subsequently treated daily for 6 weeks with either a low (13 mg/kg) or high (130 mg/kg) ASP dose. Compared to nondiabetic mice the db/db mice presented increased cardiac remodeling and enlarged left ventricular wall that occurred concomitant to enhanced oxidative stress. Daily treatment of mice with ASP at a dose of 130 mg/kg for 6 weeks was more effective at reversing complications than both a low dose ASP or metformin, eliciting enhanced expression of Nrf2 and its downstream antioxidant genes. These results indicate that ASP maintains cellular homeostasis and protects the myocardium against hyperglycemia-induced stress through activation of Nrf2 and its downstream target genes.

Type 2 diabetes (T2D) has a complex pathophysiology which makes modeling the disease difficult. We aimed to develop a novel model for simulating T2D in vitro, including hyperglycemia, hyperlipidemia, and variably elevated insulin levels targeting muscle cells. We investigated insulin resistance (IR), cellular respiration, mitochondrial morphometry and the associated function in different T2D -mimicking conditions in rodent skeletal (C2C12) and cardiac (H9C2) myotubes. Physiological controls included 5mM glucose with 20mM mannitol as osmotic controls. To mimic hyperglycemia, cells were exposed to 25mM glucose. Further treatments included insulin, palmitate, or both. After short-term (24h) or long-term (96h) exposure, we performed radioactive glucose uptake and mitochondrial function assays. Mitochondrial size and relative frequencies were assessed by morphometric analyses using electron micrographs. C2C12 and H9C2 cells treated short- or long-term with insulin and/or palmitate and HG showed IR. C2C12 myotubes exposed to T2D -mimicking conditions showed significantly decreased ATP-linked respiration and spare respiratory capacity, and less cytoplasmic area occupied by mitochondria, implying mitochondrial dysfunction. In contrast, H9C2 myotubes showed elevated ATP-linked and maximal respiration and increased cytoplasmic area occupied by mitochondria, indicating better adaptation to stress and compensatory lipid oxidation in a T2D environment. Both cell lines displayed elevated fractions of swollen/vacuolated mitochondria after T2D -mimicking treatments.Our stable and reproducible in vitro model of T2D rapidly induced IR, changes in ATP-linked respiration, shifts in energetic phenotypes, and mitochondrial morphology, which are comparable to the muscles of patients suffering from T2D. Thus, our model should allow studying disease mechanisms, potential new targets, and screen candidate therapeutic compounds.

Regulatory T cells are key immune cells to initiate tolerable immune responses. TGFβ is the key cytokine of regulatory T cells. TGFβ is also the master cytokine to stimulate tissue fibrosis. Systemic sclerosis is an autoimmune disease related to overt organ fibrosis. Thus, systemic sclerosis is a disease related to regulatory T cell over-representation. Besides, many end stage organ failures including heart failure, liver cirrhosis, uremia, and pulmonary fibrosis also related to tissue fibrosis. Thus, TGFβ producing regulatory T cells are also involved in the pathogenesis of these end stage organ failure. Once we know the significance of TGFβ and it induced tolerable immune reactions in the pathophysiology of end organ failure, we can develop better prevention or therapeutic strategies to combat these detrimental disorders.

Background: Sacubitril/valsartan has been shown to be superior to enalapril in reducing the risks of death and hospitalization for heart failure (HF). However the effect on cardiac performance remains unknown. We sought to evaluate the effects of sacubitril/valsartan on clinical, bioumoral and echocardiographic parameters in patients with HFrEF. Methods: Sacubitril/valsartan was administered to 205 HFrEF patients. Results: Among 230 patients (mean age 59 ± 10 years, 46% with ischemic heart disease) 205 (89%) completed the study. After a follow–up of 10.49 (2.93±18.44) months, the percentage of patients in NYHA class III changed from 40% to 17% (p<0.001). Median N–Type natriuretic peptide (Nt-proBNP) decreased from 1865 ± 2318 to 1514 ± 2205 pg/mL, (p=0.01). Furosemide dose reduced from 131.3 ± 154.5 to 120 ± 142.5 (p=0.047). Ejection fraction (from 27± 5.9% to 30 ± 7.7% (p<0.001) and E/A ratio (from 1.67 ± 1.21 to 1.42 ± 1.12 (p=0.002)) improved. Moderate to severe mitral regurgitation (from 30.1% to 17.4%; p=0.002) and tricuspid velocity decreased from 2.8 ± 0.55 m/sec to 2.64 ± 0.59 m/sec (p<0.014). CONCLUSIONS: Sacubitril/valsartan induce “hemodynamic reverse remodeling” and in association with Nt-proBNP concentrations lowering improve NYHA class despite a diuretic dose reduction.

This review aims to explore the intricate relationship between epigenetic mechanisms, stress, and affective disorders, focusing on how early life experiences and coping mechanisms contribute to susceptibility to mood disorders. Epigenetic factors play a crucial role in regulating gene expression without altering the DNA (deoxyribonucleic acid) sequence, and recent research has revealed associations between epigenetic changes and maladaptive responses to stress or psychiatric disorders. A scoping review of 33 studies employing the PRISMA-S (Preferred Reporting Items for Systematic Reviews and Meta-Analyses – Statement) guidelines investigates the role of stress-induced epigenetic mechanisms and coping strategies in affective disorders' occurrence, development, and progression. The analysis encompasses various stress factors, including childhood trauma, work-related stress, and dietary deficiencies, alongside epigenetic changes such as DNA methylation and altered gene expression. Findings indicate that specific stress-related genes frequently exhibit epigenetic changes associated with affective disorders. Moreover, the review examines coping mechanisms in patients with bipolar disorder and major depressive disorder, revealing mixed associations between coping strategies and symptom severity. While active coping is correlated with better outcomes, emotion-focused coping may exacerbate depressive or manic episodes. Overall, this review underscores the complex interplay between genetic predisposition, environmental stressors, coping mechanisms, and affective disorders. Understanding these interactions is essential for developing targeted interventions and personalized treatment strategies for individuals with mood disorders. However, further research is needed to elucidate specific genomic loci involved in affective disorders and the clinical implications of coping strategies in therapeutic settings.

Synchronous electrical cardioversion is a relatively common procedure in the emergency department (ED), often performed for unstable supraventricular tachycardia (SVT) or unstable ventricular tachycardia (VT). However, it is also used for stable cases resistant to drug therapy, which carry a risk of deterioration. In addition to the inherent risks linked with procedural sedation, there is a possibility of malignant arrhythmias or bradycardia, which could potentially result in cardiac arrest following this procedure. Here, we present a case of complete heart block unresponsive to transcutaneous pacing and positive inotropic and chronotropic drugs for 90 minutes, resulting in multiple cardiac arrests. The repositioning of the transcutaneous cardio-stimulation electrodes, one of them placed in the left latero-sternal position and the other at the level of the apex, led to immediate stabilization of the patient. Extubation of the patient was performed the following day, while full recovery and discharge within 7 days, after insertion of a permanent pacemaker.

Congenital heart disease (CHD) is a prevalent congenital disorder diagnosed with high frequency, affecting approximately 0.8% to 1.2% of all live births. Research has demonstrated that the use of pulse oximetry and clinical examination as a screening tool for CHD diagnosis has proven extremely valuable. We conducted a retrospective longitudinal study over a 3-year period that involved screening 1188 newborns admitted to the NICU during the first 72 hours of life within this timeframe. 201 newborns were diagnosed with CHD. Almost all (n=198) had a positive screening test during the 72-hour period, while 3 had a negative screening test, but were later diagnosed using echocardiography. The prevalence rate was 16.67%. A confusion matrix was constructed with 198 true positives (TP), 3 false negatives (FN), no false positives (FP), and 987 true negatives (TN). The sensitivity of the screening test was 98.51%, while the specificity 100%, with no false positives. In our study, a total of 9 deaths occurred. Using the Kaplan-Meier method, the survival probability appeared to be slightly above 0.9 (95.5%), indicating that almost all patients survived past 72 hours after being diagnosed with CHD. Pulse oximetry is an effective, low cost and easy-to-use method and a useful tool to assess and lead to the diagnosis of CHD.