Neurohormonal Effects of Intravenous Dopamine in Patients with Acute Heart Failure.

Background/Objectives: Many clinical trials have shown beneficial effects of low-dose dopamine on renal function, diuresis and symptom relief, or cardiac function in hospitalized patients with acute decompensated heart failure (HF). The aim is to assess the neurohormonal effects and the effects on clinical outcomes of the addition of low-dose dopamine in furosemide treatment in patients hospitalized for acute decompensated HF. Methods: A total of 62 patients hospitalized for acute decompensation of HF, were randomly allocated to one of the following three groups: i. LDF (low-dose furosemide), ii. HDF (high-dose furosemide) and, iii. LDFD (low-dose furosemide and dopamine). Primary outcomes of the present analysis were biochemical and neurohormonal indices (i.e., urea, creatinine, hemoglobin, electrolytes, natriuretic peptides, troponin, renin, angiotensin, aldosterone, adrenaline, noradrenaline). Secondary endpoints included clinical outcomes (i.e., length of stay, in-hospital mortality, 2-month mortality and rehospitalization, and 1-year mortality and rehospitalization). Results: Urea and creatinine levels were similar for each day among the three groups (p > 0.05). The amount of urine was similar among the three groups per measurement at 2, 4, 6 and at 8 h (p > 0.05). Biochemical and neurohormonal indices as well as clinical outcomes did not differ among patients receiving different doses of furosemide, nor in patients receiving furosemide in combination with dopamine (p > 0.05). Conclusions: Although the addition of low-dose dopamine to intravenous furosemide was considered to have some theoretical advantages in maintaining renal function, no significant differences in neurohormonal effects and clinical outcomes were observed in patients hospitalized for acute decompensation of HF.

Pooled comparative analysis of transcatheter aortic valve replacement versus surgical aortic valve replacement in patients with left ventricular assist device.

A thorough literature search was conducted on patients with Left Ventricular Assist Device (LVAD) and aortic insufficiency undergoing transcatheter aortic valve replacement (TAVR). We identified all original research studies that compared the long-term outcomes of surgical transcatheter aortic valve replacement (SAVR) versus TAVR for patients with LVAD, published between 1990 and 2023. The primary endpoint was the composite of in-hospital mortality, stroke, transient ischemic attack, myocardial infarction (MI), pacemaker implantation, vascular complications and cardiac tamponade. Secondary endpoints were the median overall survival (OS), the incidence of acute kidney injury (AKI), any bleeding needing transfusions or reintervention and cost. A total of fourteen studies and 358 patients were included (TAVR: 242; SAVR: 116). The composite outcome, the incidence of AKI, the bleeding needing transfusion, along with cost were significantly higher in the SAVR group. In addition, there was no significant difference between TAVR and SAVR in terms of median OS. The median OS in the TAVR group was 18 months. Finally, the most common causes of death were progression of heart failure and pneumonia. The present meta-analysis indicates that TAVR is associated with enhanced outcomes compared to SAVR for patients with LVAD presenting aortic insufficiency. Further well-designed original studies with greater sample sizes are necessary to validate our findings.

Targeting Sodium in Heart Failure.

A dominant event determining the course of heart failure (HF) includes the disruption of the delicate sodium (Na+) and water balance leading to (Na+) and water retention and edema formation. Although incomplete decongestion adversely affects outcomes, it is unknown whether interventions directly targeting (Na+), such as strict dietary (Na+) restriction, intravenous hypertonic saline, and diuretics, reverse this effect. As a result, it is imperative to implement (Na+)-targeting interventions in selected HF patients with established congestion on top of quadruple therapy with angiotensin receptor neprilysin inhibitor, ß-adrenergic receptor blocker, mineralocorticoid receptor antagonist, and sodium glucose cotransporter 2 inhibitor, which dramatically improves outcomes. The limited effectiveness of (Na+)-targeting treatments may be partly due to the fact that the current metrics of HF severity have a limited capacity of foreseeing and averting episodes of congestion and guiding (Na+)-targeting treatments, which often leads to dysnatremias, adversely affecting outcomes. Recent evidence suggests that spot urinary sodium measurements may be used as a guide to monitor (Na+)-targeting interventions both in chronic and acute HF. Further, the classical (2)-compartment model of (Na+) storage has been displaced by the (3)-compartment model emphasizing the non-osmotic accumulation of (Na+), chiefly in the skin. 23(Na+) magnetic resonance imaging (MRI) enables the accurate and reliable quantification of tissue (Na+). Another promising approach enabling tissue (Na+) monitoring is based on wearable devices employing ion-selective electrodes for electrolyte detection, including (Na+) and (Cl-). Undoubtably, further studies using 23(Na+)-MRI technology and wearable sensors are required to learn more about the clinical significance of tissue (Na+) storage and (Na+)-related mechanisms of morbidity and mortality in HF.

Recent advances in the diagnostic methods and therapeutic strategies of transthyretin cardiac amyloidosis.

Cardiac amyloidosis is a progressive disease characterized by the buildup of amyloid fibrils in the extracellular space of the heart. It is divided in 2 main types, immunoglobulin light chain amyloidosis and transthyretin amyloidosis (ATTR), and ATTR amyloidosis is further divided in 2 subtypes, non-hereditary wild type ATTR and hereditary mutant variant amyloidosis. Incidence and prevalence of ATTR cardiac amyloidosis is increasing over the last years due to the improvements in diagnostic methods. Survival rates are improving due to the development of novel therapeutic strategies. Tafamidis is the only disease-modifying approved therapy in ATTR amyloidosis so far. However, the most recent advances in medical therapies have added more options with the potential to become part of the therapeutic armamentarium of the disease. Agents including acoramidis, eplontersen, vutrisiran, patisiran and anti-monoclonal antibody NI006 are being investigated on cardiac function in large, multicenter controlled trials which are expected to be completed within the next 2-3 years, providing promising results in patients with ATTR cardiac amyloidosis. However, further and ongoing research is required in order to improve diagnostic methods that could provide an early diagnosis, as well as survival and quality of life of these patients.

Prevention of Anthracyclines and HER2 Inhibitor-Induced Cardiotoxicity: A Systematic Review and Meta-Analysis.

BACKGROUND: This meta-analysis and systematic review aim to consolidate evidence on cardiotoxicity prevention and treatment strategies in patients receiving anthracyclines or HER2 receptor inhibitors, vital treatments for breast cancer and hematologic malignancies. By synthesizing existing research, the goal is to provide impactful insights that enhance patient care and outcomes. METHODS: Comprehensive research across PubMed, Scopus, EMBASE, and the Cochrane Central Register for Controlled Trials was conducted, selecting clinical trials focusing on cardioprotection in anthracyclines or HER2 inhibitor-treated individuals. Effect sizes were computed using OpenMeta (Analyst), with leave-out meta-analysis to assess potential small study effects. Meta-regression explored treatment duration and sample size effects. Evidence quality for primary outcomes was evaluated using ROB, Robins 2, and Newcastle-Ottawa tools. RESULTS: Twenty -three studies involving a total of 14,652 patients (13,221 adults and 1431 kids) were included in the current systematic review and meta-analysis. The risk of bias and methodological quality of the included studies suggested good and moderate quality. Patients prescribed ß-blockers demonstrated a 74% lower likelihood of exhibiting cardiotoxicity symptoms (OR 1.736). Similarly, the use of dexrazoxane was linked to a threefold decrease in cardiac abnormalities risk (OR 2.989), and ACE inhibitor administration showed half the risk compared with the control group (OR 1.956). CONCLUSIONS: Through this systematic review and meta-analysis, it was shown that there is a reduction in cardiotoxicity from either anthracyclines or HER2 inhibitors in patients receiving pharmacoprophylaxis.

Assessment of Myocardial Viability in Ischemic Cardiomyopathy With Reduced Left Ventricular Function Undergoing Coronary Artery Bypass Grafting.

BACKGROUND: We aim to provide a comprehensive review of the current state of knowledge of myocardial viability assessment in patients undergoing coronary artery bypass grafting (CABG), with a focus on the clinical markers of viability for each imaging modality. We also compare mortality between patients with viable myocardium and those without viability who undergo CABG. METHODS: A systematic database search with meta-analysis was conducted of comparative original articles (both observations and randomized controlled studies) of patients undergoing CABG with either viable or nonviable myocardium, in EMBASE, MEDLINE, Cochrane database, and Google Scholar, from inception to 2022. Imaging modalities included were dobutamine stress echocardiography (DSE), cardiac magnetic resonance (CMR), single-photon emission computed tomography (SPECT), and positron emission tomography (PET). RESULTS: A total of 17 studies incorporating a total of 2317 patients were included. Across all imaging modalities, the relative risk of death post-CABG was reduced in patients with versus without viability (random-effects model: odds ratio: 0.42; 95% confidence interval: 0.29-0.61; p < 0.001). Imaging for myocardial viability has significant clinical implications as it can affect the accuracy of the diagnosis, guide treatment decisions, and predict patient outcomes. Generally, based on local availability and expertise, either SPECT or DSE should be considered as the first step in evaluating viability, while PET or CMR would provide further evaluation of transmurality, perfusion metabolism, and extent of scar tissue. CONCLUSION: The assessment of myocardial viability is an essential component of preoperative evaluation in patients with ischemic heart disease undergoing surgical revascularization. Careful patient selection and individualized assessment of viability remain paramount.

Contemporary Use of Sodium Glucose Co-Transporter 2 Inhibitors in Hospitalized Heart Failure Patients: A "Real-World" Experience.

Background/Objectives: The aim of this study was to examine the association between in-hospital initiation of sodium glucose co-transporter 2 inhibitors (SGLT2is) and outcomes in hospitalized heart failure (HHF) patients utilizing data from a Greek center. Methods: The present work was a single-center, retrospective, observational study of consecutive HF patients hospitalized in a tertiary center. The study endpoint was all-cause mortality or HF rehospitalization. Univariate and multivariate Cox proportional-hazard models were conducted to investigate the association between SGLT2i administration at discharge and the study endpoint. Results: Sample consisted of 171 patients, 55 of whom (32.2%) received SGLT2is at discharge. Overall, mean follow-up period was 6.1 months (SD = 4.8 months). Patients who received SGLT2is at discharge had a 43% lower probability of the study endpoint compared to those who did not receive SGLT2is at discharge (HR = 0.57; 95% CI: 0.36-0.91; p = 0.018). After adjusting for age, gender, smoking, hemoglobin (Hgb), use of SGLT2is at admission, use of Angiotensin-Converting Enzyme Inhibitors (ACEI-Is)/Angiotensin Receptor Blockers (ARBs) at discharge and Sacubitril/Valsartan at discharge, the aforementioned result remained significant (HR = 0.38; 95% CI: 0.19-0.73; p = 0.004). The 55 patients who received SGLT2is at discharge were propensity score matched with the 116 patients who did not receive SGLT2is at discharge. Receiving SGLT2is at discharge continued to be significantly associated with a lower probability of the study endpoint (HR= 0.43; 95% CI: 0.20-0.89; p = 0.024). Conclusions: Initiation of SGLT2is in HHF patients may be associated with better outcomes.

Pneumococcal and Influenza Vaccination Coverage in Patients with Heart Failure: A Systematic Review.

Background/Objectives: As heart failure (HF) patients face increased vulnerability to respiratory infections, optimizing pneumococcal and influenza vaccination coverage becomes pivotal for mitigating additional health risks and reducing hospitalizations, morbidity, and mortality rates within this population. In this specific subpopulation of patients, vaccination coverage for pneumococcal and influenza holds heightened significance compared to other vaccines due to their susceptibility to respiratory infections, which can exacerbate existing cardiovascular conditions and lead to severe complications or even death. However, despite the recognized benefits, vaccination coverage among HF patients remains below expectations. The aim of the present systematic review was to assess the vaccination coverage for influenza and pneumococcus in HF patients from 2005 to 2023 and the vaccination's effects on survival and hospitalizations. Methods: The authors developed the protocol of the review in accordance with the PRISMA guidelines, and the search was performed in databases including PubMed and Scopus. After the initial search, 851 studies were found in PubMed Library and 1961 in Scopus (total of 2812 studies). Results: After the initial evaluation, 23 publications were finally included in the analysis. The total study population consisted of 6,093,497 participants. Regarding the influenza vaccine, vaccination coverage ranged from low rates of 2.5% to very high rates of 97%, while the respective pneumococcal vaccination coverage ranged from 20% to 84.6%. Most studies demonstrated a beneficial effect of vaccination on survival and hospitalizations. Conclusions: The present systematic review study showed a wide variety of vaccination coverage among patients with heart failure.

The impact of delirium on clinical and functional outcomes in hospitalized patients with acute coronary syndrome.

BACKGROUND: Delirium, which is prevalent in critical care settings, remains underexplored in acute coronary syndrome (ACS) patients in the cardiac intensive care unit (CICU). AIM: To investigate the prevalence and clinical significance of delirium in patients with ACS admitted to the CICU. STUDY DESIGN: A prospective study (n = 106, mean age 74.2 ± 5.7 years) assessed delirium using the confusion assessment method-intensive care unit (CAM-ICU) tool in 21.7% of ACS patients during their CICU stay. Baseline characteristics, geriatric conditions and clinical procedures were compared between delirious and nondelirious patients. The outcomes included in-hospital mortality, 30-day and 6-month mortality, acute adverse events and length of CICU stay and hospital stay (LOS). RESULTS: Delirious patients who were older and had a higher incidence of coronary artery disease underwent more complex procedures (e.g., pacemaker placement). Multivariate analysis identified central venous catheter insertion, urinary catheterization and benzodiazepine use as independent predictors of delirium. Delirium was correlated with prolonged LOS (p < .001) and increased in-hospital, 30-day and 6-month mortality (p < .001). CONCLUSIONS: Delirium in ACS patients in the CICU extends hospitalization and increases in-hospital, 30-day and 6-month mortality. Early recognition and targeted interventions are crucial for mitigating adverse outcomes in this high-risk population. RELEVANCE TO CLINICAL PRACTICE: This study highlights the critical impact of delirium on outcomes in hospitalized patients with ACS in the CICU. Delirium, often overlooked in ACS management, significantly extends hospitalization and increases mortality rates. Nurses and physicians must be vigilant in identifying delirium early, particularly in older ACS patients or those with comorbidities. Recognizing independent predictors such as catheterization and benzodiazepine use allows for targeted interventions to reduce delirium incidence. Integrating routine delirium assessments and preventive strategies into ACS management protocols can improve outcomes, optimize resource utilization and enhance overall patient care in the CICU setting.

Validation of Perioperative Troponin Levels for Predicting Postoperative Mortality and Long-Term Survival in Patients Undergoing Surgery for Hepatobiliary and Pancreatic Cancer.

Background: Hepatopancreato and biliary (HPB) tumors represent some of the leading cancer-related causes of death worldwide, with the majority of patients undergoing surgery in the context of a multimodal treatment strategy. Consequently, the implementation of an accurate risk stratification tool is crucial to facilitate informed consent, along with clinical decision making, and to compare surgical outcomes among different healthcare providers for either service evaluation or clinical audit. Perioperative troponin levels have been proposed as a feasible and easy-to-use tool in order to evaluate the risk of postoperative myocardial injury and 30-day mortality. The purpose of the present study is to validate the perioperative troponin levels as a prognostic factor regarding postoperative myocardial injury and 30-day mortality in Greek adult patients undergoing HPB surgery. Method: In total, 195 patients undergoing surgery performed by a single surgical team in a single tertiary hospital (2020-2022) were included. Perioperative levels of troponin before surgery and at 24 and 48 h postoperatively were assessed. Model accuracy was assessed by observed-to-expected (O:E) ratios, and area under the receiver operating characteristic curve (AUC). Survival at one year postoperatively was compared between patients with high and normal TnT levels at 24 h postoperatively. Results: Thirteen patients (6.6%) died within 30 days of surgery. TnT levels at 24 h postoperatively were associated with excellent discrimination and provided the best-performing calibration. Patients with normal TnT levels at 24 h postoperatively were associated with higher long-term survival compared to those with high TnT levels. Conclusions: TnT at 24 h postoperatively is an efficient risk assessment tool that should be implemented in the perioperative pathway of patients undergoing surgery for HPB cancer.

Latest updates on structure and recommendations of cardiac rehabilitation programs in chronic heart failure.

Chronic heart failure (HF) is a clinical syndrome with high morbidity and mortality worldwide. Cardiac rehabilitation (CR) is a medically supervised program designed to maintain or improve cardiovascular health of people living with HF, recommended by both American and European guidelines. A CR program consists of a multispecialty group including physicians, nurses, physiotherapists, trainers, nutritionists, and psychologists with the common purpose of improving functional capacity and quality of life of chronic HF patients. Physical activity, lifestyle, and psychological support are core components of a successful CR program. CR has been shown to be beneficial in all ejection fraction categories in HF and most patients, who are stable under medication, are capable of participating. An individualized exercise prescription should be developed on the basis of a baseline evaluation in all patients. The main modalities of exercise training are aerobic exercise and muscle strength training of different intensity and frequency. It is important to set the appropriate clinical outcomes from the beginning, in order to assess the effectiveness of a CR program. There are still significant limitations that prevent patients from participating in these programs and need to be solved. A significant limitation is the generally low quality of research in CR and the presence of negative trials, such as the rehabilitation after myocardial infarction trial, where comprehensive rehabilitation following myocardial infraction had no important effect on mortality, morbidity, risk factors, or health-related quality of life or activity. In the present editorial, we present all the updated knowledge and recommendations in CR programs.

Back to the basics: The need for an etiological classification of chronic heart failure.

The left ventricular (LV) ejection fraction (LVEF), despite its severe limitations, has had an epicentral role in heart failure (HF) classification, management, and risk stratification for decades. The major argument favoring the LVEF based HF classification has been that it defines groups of patients in which treatment is effective. However, this reasoning has recently collapsed, since medical treatment with neurohormonal inhibitors, has proved beneficial in most HF patients regardless of the LVEF. In addition, there has been compelling evidence, that the LVEF provides poor guidance for device treatment of chronic HF (implantation of cardioverter defibrillator, cardiac resynchronization therapy) since sudden cardiac death may occur and cardiac dyssynchronization may be disastrous in all HF patients. The same holds true for LV assist device implantation, in which the LVEF has been used as a surrogate for LV size. In this review article we update the evidence questioning the use of LVEF-based HF classification and argue that guidance of chronic HF treatment should transition to more contemporary concepts. Specifically, we propose an etiologic chronic HF classification predominantly based on epidemiological data, which will be foundational for further higher resolution phenotyping in the emerging era of precision medicine.

Heart Transplantation.

Heart transplantation (HTx) remains the last therapeutic resort for patients with advanced heart failure. The present work is a clinically focused review discussing current issues in heart transplantation. Several factors have been associated with the outcome of HTx, such as ABO and HLA compatibility, graft size, ischemic time, age, infections, and the cause of death, as well as imaging and laboratory tests. In 2018, UNOS changed the organ allocation policy for HTx. The aim of this change was to prioritize patients with a more severe clinical condition resulting in a reduction in mortality of people on the waiting list. Advanced heart failure and resistant angina are among the main indications of HTx, whereas active infection, peripheral vascular disease, malignancies, and increased body mass index (BMI) are important contraindications. The main complications of HTx include graft rejection, graft angiopathy, primary graft failure, infection, neoplasms, and retransplantation. Recent advances in the field of HTx include the first two porcine-to-human xenotransplantations, the inclusion of hepatitis C donors, donation after circulatory death, novel monitoring for acute cellular rejection and antibody-mediated rejection, and advances in donor heart preservation and transportation. Lastly, novel immunosuppression therapies such as daratumumab, belatacept, IL 6 directed therapy, and IgG endopeptidase have shown promising results.

Association between Ranolazine, Ischemic Preconditioning, and Cardioprotection in Patients Undergoing Scheduled Percutaneous Coronary Intervention.

Background and Objectives: Remote ischemic preconditioning (RIPC) has demonstrated efficacy in protecting against myocardial ischemia-reperfusion injury when applied before percutaneous coronary revascularization. Ranolazine, an anti-ischemic drug, has been utilized to minimize ischemic events in chronic angina patients. However, there is a lack of trials exploring the combined effects of ranolazine pretreatment and RIPC in patients undergoing percutaneous coronary interventions (PCIs). Materials and Methods: The present study is a prospective study which enrolled 150 patients scheduled for nonemergent percutaneous coronary revascularization. Three groups were formed: a control group undergoing only PCIs, an RIPC group with RIPC applied to either upper limb before the PCI (preconditioning group), and a group with RIPC before the PCI along with prior ranolazine treatment for stable angina (ranolazine group). Statistical analyses, including ANOVAs and Kruskal-Wallis tests, were conducted, with the Bonferroni correction for type I errors. A repeated-measures ANOVA assessed the changes in serum enzyme levels (SGOT, LDH, CRP, CPK, CK-MB, troponin I) over the follow-up. Statistical significance was set at p < 0.05. Results: The ranolazine group showed (A) significantly lower troponin I level increases compared to the control group for up to 24 h, (B) significantly lower CPK levels after 4, 10, and 24 h compared to the preconditioning group (p = 0.020, p = 0.020, and p = 0.019, respectively) and significantly lower CPK levels compared to the control group after 10 h (p = 0.050), and (C) significantly lower CK-MB levels after 10 h compared to the control group (p = 0.050). Conclusions: This study suggests that combining RIPC before scheduled coronary procedures with ranolazine pretreatment may be linked to reduced ischemia induction, as evidenced by lower myocardial enzyme levels.

Artificial Intelligence in Heart Failure: Friend or Foe?

In recent times, there have been notable changes in cardiovascular medicine, propelled by the swift advancements in artificial intelligence (AI). The present work provides an overview of the current applications and challenges of AI in the field of heart failure. It emphasizes the "garbage in, garbage out" issue, where AI systems can produce inaccurate results with skewed data. The discussion covers issues in heart failure diagnostic algorithms, particularly discrepancies between existing models. Concerns about the reliance on the left ventricular ejection fraction (LVEF) for classification and treatment are highlighted, showcasing differences in current scientific perceptions. This review also delves into challenges in implementing AI, including variable considerations and biases in training data. It underscores the limitations of current AI models in real-world scenarios and the difficulty in interpreting their predictions, contributing to limited physician trust in AI-based models. The overarching suggestion is that AI can be a valuable tool in clinicians' hands for treating heart failure patients, as far as existing medical inaccuracies have been addressed before integrating AI into these frameworks.

Conduction system pacing: how far are we from the "electrical" bypass?

Conduction system pacing is an alternative practice to conventional right ventricular apical pacing. It is a method that maintains physiologic ventricular activation, based on a correct pathophysiological basis, in which the pacing lead bypasses the lesion of the electrical fibers and the electrical impulse transmits through the intact adjacent conduction system. For this reason, it might be reasonably characterized by the term "electrical bypass" compared to the coronary artery bypass in revascularization therapy. In this review, reference is made to the sequence of events in which conventional right ventricular pacing may cause adverse outcomes. Furthermore, there is a reference to alternative strategies and pacing sites. Interest focuses on the modalities for which there are data from the literature, namely for the right ventricular (RV) septal pacing, the His bundle pacing (HBP), and the left bundle branch pacing (LBBP). A more extensive reference is about the HBP, for which there are the most updated data. We analyze the considerations that limit HBP-wide application in three axes, and we also present the data for the implantation and follow-up of these patients. The indications with their most important studies to date are then described in detail, not only in their undoubtedly positive findings but also in their weak aspects, because of which this pacing mode has not yet received a strong recommendation for implementation. Finally, there is a report on LBBP, focusing mainly on its points of differentiation from HBP.

The sympathetic nervous system in heart failure revisited.

Several attempts have been made, by the scientific community, to develop a unifying hypothesis that explains the clinical syndrome of heart failure (HF). The currently widely accepted neurohormonal model has substituted the cardiorenal and the cardiocirculatory models, which focused on salt-water retention and low cardiac output/peripheral vasoconstriction, respectively. According to the neurohormonal model, HF with eccentric left ventricular (LV) hypertrophy (LVH) (systolic HF or HF with reduced LV ejection fraction [LVEF] or HFrEF) develops and progresses because endogenous neurohormonal systems, predominantly the sympathetic nervous system (SNS) and the renin-angiotensin-aldosterone system (RAAS), exhibit prolonged activation following the initial heart injury exerting deleterious hemodynamic and direct nonhemodynamic cardiovascular effects. However, there is evidence to suggest that SNS overactivity often preexists HF development due to its association with HF risk factors, is also present in HF with preserved LVEF (diastolic HF or HFpEF), and that it is linked to immune/inflammatory factors. Furthermore, SNS activity in HF may be augmented by coexisting noncardiac morbidities and modified by genetic factors and demographics. The purpose of this paper is to provide a contemporary overview of the complex associations between SNS overactivity and the development and progression of HF, summarize the underlying mechanisms, and discuss the clinical implications as they relate to therapeutic interventions mitigating SNS overactivity.

Transcriptomic Analysis of Tight Junction Proteins Demonstrates the Aberrant Expression and Function of Zona Occludens 2 (ZO-2) Protein in Stanford Type A Aortic Dissection.

OBJECTIVE: Thoracic aortic aneurysm dissection (TAAD) represents a cardiac surgery emergency characterized by the disrupted integrity of the aortic wall and is associated with poor prognosis. In this context, the identification of biomarkers implicated in the pathobiology of TAAD is crucial. Our aim in the present original in silico study is to assess the differential gene expression profile of the tight junction proteins (TJPs) in patients with TAAD and to propose novel biomarkers for the diagnosis and prognosis of this disease. METHODS: We implemented bioinformatics methodology in order to construct the gene network of the TJPs family, identify the differentially expressed genes (DEGs) in pathologic aortic tissue excised from patients with TAAD as compared to healthy aortic tissue, and assess the related biological functions and the associated miRNA families. RESULTS: Data regarding the transcriptomic profile of selected genes were retrieved and incorporated from three microarray datasets, including 23 TAAD and 20 healthy control samples. A total of 32 TJPs were assessed. The zona occludens 2 (ZO-2) protein encoded by the gene TJP2 was significantly under-expressed in patients with TAAD compared to the control group (p = 0.009). ZO-2 was associated with fair discrimination and calibration traits in predicting the TAAD presentation. CpG islands of ZO-2 were demonstrated. No important difference was found regarding ZO-2 expression between aneurysmal non-dissected and healthy control aortic tissue. Finally, we performed gene set enrichment analysis (GSEA) and uncovered the major biological functions and miRNA families (hsa-miR-155-5p, hsa-miR-1-3p, hsa-miR-2118-5p, hsa-miR-4691-3p, and hsa-miR-1229-3p) relevant to ZO-2. CONCLUSIONS: These outcomes demonstrated the important role of ZO-2 in the pathobiology of TAAD.

Analysis of the Larissa Heart Failure Risk Score: Predictive Value in 9207 Patients Hospitalized for Heart Failure from a Single Center.

Early risk stratification is of outmost clinical importance in hospitalized patients with heart failure (HHF). We examined the predictive value of the Larissa Heart Failure Risk Score (LHFRS) in a large population of HHF patients from the Cleveland Clinic. A total of 13,309 admissions for heart failure (HF) from 9207 unique patients were extracted from the Cleveland Clinic's electronic health record system. For each admission, components of the 3-variable simple LHFRS were obtained, including hypertension history, myocardial infarction history, and red blood cell distribution width (RDW) ≥ 15%. The primary outcome was a HF readmission and/or all-cause mortality at one year, and the secondary outcome was all-cause mortality at one year of discharge. For both outcomes, all variables were statistically significant, and the Kaplan-Meier curves were well-separated and in a consistent order (Log-rank test p-value < 0.001). Higher LHFRS values were found to be strongly related to patients experiencing an event, showing a clear association of LHFRS with this study outcomes. The bootstrapped-validated area under the curve (AUC) for the logistic regression model for each outcome revealed a C-index of 0.64 both for the primary and secondary outcomes, respectively. LHFRS is a simple risk model and can be utilized as a basis for risk stratification in patients hospitalized for HF.