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Introduction: Pulmonary transit time (PTT) is the time it takes blood to pass from the right ventricle to the left ventricle via the pulmonary circulation, making it a potentially useful marker for heart failure. We assessed the association of PTT with diastolic dysfunction (DD) and mitral valve regurgitation (MVR). Methods: We evaluated routine stress perfusion cardiovascular magnetic resonance (CMR) scans in 83 patients including assessment of PTT with simultaneously available echocardiographic assessment. Relevant DD and MVR were defined as exceeding Grade I (impaired relaxation and mild regurgitation). PTT was determined from CMR rest perfusion scans. Normalized PTT (nPTT), adjusted for heart rate, was calculated using Bazett's formula. Results: Higher PTT and nPTT values were associated with higher grade DD and MVR. The diagnostic accuracy for the prediction of DD as quantified by the area under the ROC curve (AUC) was 0.73 (CI 0.61–0.85; p = 0.001) for PTT and 0.81 (CI 0.71–0.89; p < 0.001) for nPTT. For MVR, the diagnostic performance amounted to an AUC of 0.80 (CI 0.68–0.92; p < 0.001) for PTT and 0.78 (CI 0.65–0.90; p < 0.001) for nPTT. PTT values < 8 s rule out the presence of DD and MVR with a probability of 70% (negative predictive value 78%). Conclusion: CMR‐derived PTT is a readily obtainable hemodynamic parameter. It is elevated in patients with DD and moderate to severe MVR. Low PTT values make the presence of DD and MVR—as assessed by echocardiography—unlikely. [ABSTRACT FROM AUTHOR]

AbstractObjectiveMethodResultConclusionThis meta-analysis to assess the effectiveness of telerehabilitation for heart failure compared to either usual medical care or centre-based rehabilitation on 6-minutes walking distance (6MWD) and peak oxygen uptake (VO2 peak). At the same time, we wanted to explore the effects of different telerehabilitation strategies on exercise capacity in heart failure patients.We conducted a search in five databases, namely PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure (CNKI), and CBM. The search was conducted up until 4th, 2024. The quality of the included studies was assessed using the Revised Cochrane Risk-of-bias Tool for Randomised Trials. Statistical analysis was performed using Review Manager 5.4. The study included a total of 11 articles.We included 11 randomised controlled trials that incorporated 13 different rehabilitation strategies. We found that a randomised controlled trial providing tele-rehabilitation was more effective than usual care in improving patients’ 6MWD (p<0.00001; MD 18.43, 95%CI 14.63, 22.21), as well as VO2 peak (p<0.0001; MD1.23, 95%CI 0.67, 1.78).The review suggests that remote rehabilitation enhances exercise capacity and cardiopulmonary function in heart failure patients who have been discharged. In the future, such rehabilitation measures could be an effective alternative to hospital-based rehabilitation. [ABSTRACT FROM AUTHOR]

ABSTRACT Aims Methods and results Conclusion Biomarkers associated with asymptomatic ventricular dysfunction might improve risk stratification and identify pathways leading to heart failure (HF). We explored the association between proteomic biomarkers and left ventricular hypertrophy (LVH), diastolic dysfunction (DD) and incident HF in three population‐based cohorts.A chip was used to measure 92 protein biomarkers in blood samples from >1500 Malmö Preventive Project (MPP) participants, of whom 514 had LVH (34%), 462 had DD (32.4%) and, over a median follow‐up of 13 (11–14) years, 130 developed HF (7.7%). Findings were confirmed in the STANISLAS (n > 1500, 238 participants with LVH, 76 with DD) and HOMAGE case‐control (562 cases of incident HF, 871 controls) cohorts. In multivariable logistic or Cox regression analyses adjusted for age, sex and cardiovascular risk factors, N‐terminal pro‐B‐type natriuretic peptide (NT‐proBNP) was associated with LVH, DD and incident HF in all cohorts: MPP (LVH odds ratio [OR] [95% confidence interval] 1.48 [1.28–1.71]; DD OR 1.71 [1.53–1.92]; HF HR 1.98 [1.66–2.36]); STANISLAS (LVH OR 1.20 [1.02–1.41]; DD OR 1.46 [1.12–1.90]); HOMAGE (HF HR 1.85 [1.62–2.12]). Galectin‐4, growth differentiation factor 15 and suppression of tumorigenicity‐2 were associated with incident HF in MPP and HOMAGE. A pathway enrichment analysis suggested that inflammation and viral infection were related to incident HF.In conclusion, our study reinforces the role of NT‐proBNP as a key biomarker for asymptomatic cardiac dysfunction and incident HF, consistent with its established use in clinical practice. This underscores the value of NT‐proBNP for identifying patients at high risk for HF, and provides insights into pathways leading to HF and potential therapeutic targets. [ABSTRACT FROM AUTHOR]

Aims Methods and results Conclusions Data from US have shown a reversal in the improvement of heart failure (HF)‐related mortality over the last ~10 years. It is unknown whether these trends generalize to European universal healthcare systems. We assessed temporal trends in (i) HF‐related mortality in the overall national population; and (ii) all‐cause mortality following an incident HF diagnosis, overall and stratified by ejection fraction (EF), in Sweden between 1997 and 2022.Annual mortality rates with a HF diagnosis as underlying cause were extracted from the Cause of Death Register. All‐cause mortality following incident HF was assessed in two HF cohorts derived from the National Patient Register (NPR) and the Swedish HF Registry (SwedeHF). Temporal trends were presented as average annual percentage change (AAPC). Between 1997 and 2022, age‐adjusted HF‐related mortality in the general population declined from 33.4 to 23.8 per 100 000 individuals (AAPC −2.15%, p < 0.001). In the HF cohort from NPR (n = 423 092), all‐cause mortality at 1, 3, and 5 years following a first diagnosis of HF was 25%, 46%, and 58%, respectively, in 2022; 1‐year mortality declined (AAPC −1.10%, p < 0.001) over time regardless of age or sex. In SwedeHF (n = 63 753), the decline in 1‐year mortality was less steep with increasing EF (AAPC −2.64%, p < 0.001; −2.30%, p = 0.062; and −2.16%, p = 0.032 in EF <40%, 40–49%, and ≥50%, respectively).Heart failure‐related mortality has declined over the last ~25 years in Sweden. All‐cause mortality in patients with HF has also declined, more in HF with reduced than preserved EF, mirroring the different availability of life‐saving treatments across the EF spectrum. [ABSTRACT FROM AUTHOR]

ABSTRACT Aims Design Methods Results Conclusions Reporting Method Patient or Public Contribution This study aims to describe disease‐specific self‐care behaviours in patients with heart failure (HF), diabetes mellitus (DM) and chronic obstructive pulmonary disease (COPD) in various combinations; to compare these self‐care behaviours within patient groups; and to evaluate differences across these groups.Cross‐sectional study.A total sample of 1079 older patients was recruited from outpatient clinics and home settings. Eligible patients were aged ≥ 65 years and had a diagnosis of HF and/or DM, and/or COPD, along with at least one additional chronic condition. Data were collected using validated tools: the Self‐Care of Heart Failure Index, Self‐Care of Diabetes Inventory and Self‐Care of Chronic Obstructive Pulmonary Disease Inventory. Descriptive statistics were used to analyse disease‐specific self‐care behaviours. Group comparisons were performed using Student's t‐test and univariate, followed by multivariate analyses of variance.The analysis focused on a subset of 223 patients who had a combination of at least two chronic conditions between HF, DM and/or COPD. The mean age of participants was 77.3 (SD 7.5) years, with a majority being female (53.4%). Self‐care maintenance, monitoring and management for HF and COPD were found to be inadequate across all patient groups. Adequate self‐care was only observed in DM management among those with HF and DM and in DM maintenance for those with DM and COPD treated with insulin. Significant differences in all self‐care dimensions were observed across groups, particularly in patients managing all three conditions (HF, DM and COPD).The findings provide valuable insights into the complexities of self‐care in patients with multiple chronic conditions, underscoring the need for tailored, integrated and patient‐centred interventions. Healthcare strategies should focus on enhancing patient education and developing personalised approaches to improve health outcomes and quality of life in this population.All the authors have adhered to the EQUATOR guidelines STROBE Statement.A convenience sample of patients was recruited in outpatient clinics and their homes. Data were collected between March 2017 and August 2022, by face‐to‐face during routine outpatient visits or directly at the patient's home. [ABSTRACT FROM AUTHOR]

Introduction Objectives Methods Results Conclusion There is a paucity of data evaluating early initiation of sodium‐glucose cotransporter‐2 inhibitors (SGLT2i) in patients with diabetes following acute coronary syndrome (ACS) and coronary artery bypass graft surgery (CABG).To describe the efficacy and safety of SGLT2i initiated early after CABG in patients with type 2 diabetes who experienced ACS.This is a retrospective cohort study of patients with type 2 diabetes (T2DM) who experienced ACS and subsequent CABG with follow up at 3 and 12 months. Patients who filled a SGLT2i prescription within 14 days of discharge were allocated to the SGLT2i group and those who did not were included in the no SGLT2i group. The primary efficacy end point was first occurrence of a 4‐point Major Adverse Cardiovascular Event (MACE), and the primary safety end point was a composite of hypoglycemia, hypotension, diabetic ketoacidosis, acute kidney injury, and urinary tract infection. Secondary end points included a comparative analysis of the primary outcome, 30‐day readmission rates, and subgroup analyses of key populations.A total of 1629 patients were included: 226 received a SGLT2i within 14 days of discharge and 1403 did not. At 12 months, 8.9% and 15.3% of patients experienced MACE in the SGLT2i and no SGLT2i groups, respectively (adjusted Hazard Ratio [aHR] 0.65, 95% confidence interval [CI] 0.41–1.04). The primary safety outcome occurred in 12.0% of the SGLT2i group and 19.1% of the no SGLT2i group at 12 months (aHR 0.68, 95% CI 0.45–1.01).Early initiation of SGLT2i use was not associated with a reduction in MACE in patients with T2DM who experienced ACS and underwent subsequent CABG surgery. However, no apparent safety concerns were identified. Adequately powered trials are required to confirm this finding. [ABSTRACT FROM AUTHOR]

The article discusses the role of incretin hormones, specifically glucagon-like peptide-1 receptor agonists (GLP-1RAs), in treating kidney and liver diseases in individuals with type 2 diabetes and obesity. GLP-1RAs have shown benefits in reducing albuminuria, preserving kidney function, alleviating liver steatosis, and reducing inflammation in the liver. Clinical trials have demonstrated the potential of GLP-1RAs in managing chronic kidney disease and metabolic dysfunction-associated steatotic liver disease. Further research is needed to optimize the application of GLP-1RAs and evaluate their long-term effects across diverse populations. [Extracted from the article]

Aims Methods and results Conclusion Clinical practice guidelines are commonly written by professional societies in high‐income countries (HIC) with limited anticipation of implementation obstacles in other environments. We used heart failure (HF) guidelines as a paradigm to examine this concern, by conducting a survey to understand clinicians' ability to implement HF guidelines and their perceptions of the current HF guideline applicability in low‐ and middle‐income countries (LMIC).An online survey of physicians in the database of the Translational Medicine Academy who treat HF patients was offered by email from 5 October to 27 November 2023, inquiring of participants' demographic information, experience, and views of HF guidelines as related to their practice. Of 2622 participating clinicians, 1592 partially completed, and an additional 1030 fully completed the survey. Participants were from 138 countries; 668 practiced in HIC, and 1954 in LMIC. Those from LMIC regarded HF guidelines to be less applicable in their country than did those from HIC (p = 0.0002). Of all those responding, 75.3% indicated that it was somewhat or mostly true that the HF guidelines were mostly applicable to HIC. Those from LMIC, but not HIC indicated that the greatest implementation obstacle was that the guidelines were for HIC (51.3% vs. 43.1%; p = 0.0387). A significantly higher proportion of respondents from LMIC indicated that resources for caring for their patients were somewhat or mostly limiting in most cases, than did those in HIC (41.6% vs. 32.5%, p = 0.0068).This survey examined the widely‐held thought that HF guidelines are broadly applicable to all regions of the world, concluding that such a perception is incorrect. Clinicians from LMIC view the absence of consideration of local resource limitations as the greatest obstacle for guideline implementation. The results regarding HF guidelines likely also have implications for other guidelines and resultant patient outcomes. [ABSTRACT FROM AUTHOR]

Aims Methods and results Conclusions Concerns exist that intravenous (IV) iron might increase the risk of infections. The IRONMAN trial provided an opportunity to investigate whether giving IV ferric derisomaltose (FDI) to patients with heart failure and iron deficiency alters the rate of hospitalization or death due to infections.IRONMAN was a randomized trial of IV FDI versus usual care in patients with symptomatic heart failure, left ventricular ejection fraction (LVEF) ≤45%, and transferrin saturation (TSAT) <20% or ferritin <100 μg/L. Infection was a pre‐specified, blindly‐adjudicated, safety endpoint. The primary analysis of interest was infection as the main reason for hospitalization or death, using first and recurrent events analyses. The composite primary event of interest tended to be lower in those randomized to FDI when analysed as first (hazard ratio [HR] 0.79, 95% confidence interval [CI] 0.62–1.01, p = 0.055) or recurrent event (rate ratio 0.85, 95% CI 0.64–1.13, p = 0.089). The composite results were driven by fewer hospitalizations for infection (HR 0.76, 95% CI 0.49–0.98, p = 0.032), with 5% fewer patients (absolute reduction) experiencing such an event if assigned to FDI. Similar trends were observed for recurrent events (HR 0.82, 95% CI 0.62–1.10). Further analyses suggested that the reduction in hospitalizations due to infection with FDI was restricted to patients with TSAT <20%.In patients with heart failure and a reduced LVEF, correction of iron deficiency is not associated with an increased risk of hospitalization or death from infection, and may reduce such events, especially when TSAT is <20%.Clinical Trial Registration: ClinicalTrials.gov, NCT02642562. [ABSTRACT FROM AUTHOR]

The article discusses the 25in25 initiative, a project aimed at reducing mortality due to heart failure by 25% in the next 25 years. The initiative focuses on early diagnosis, treatment, and prevention of heart failure, with the goal of saving over 10,000 lives annually. By collaborating with various organizations and implementing a Fast-Track Communities approach, the initiative seeks to make heart failure a national priority and improve outcomes for patients with heart failure. The project is currently in a pilot phase in the UK, with plans to expand nationally and internationally in the future. [Extracted from the article]

ABSTRACT Background Aims Design Methods Results Conclusion Reporting Method Relevance to Clinical Practice Patient or Public Contribution Although heart failure (HF) symptoms affect patients' quality of life (QoL), improving patients' QoL requires certain self‐care behaviours. However, the specific role of self‐care behaviours in the relationship between HF symptoms and QoL has not been clarified.To evaluate the status of symptom clusters, self‐care behaviours and QoL in HF patients, and to analyse and test the moderating effect of self‐care behaviours between symptom clusters and QoL.This study is a cross‐sectional study.A total of 320 HF patients who treated in the three hospitals in Chengdu, China, from December 2022 to July 2023 were selected as the research subjects. The patients were evaluated using The General Information Questionnaire, Memorial Symptom Assessment Scale Heart Failure, Self‐Care of Heart Failure Index and Minnesota Living with Heart Failure Questionnaire. The statistical analysis methods were exploratory factor analysis, Pearson correlation analysis, hierarchical regression analysis and simple slope analysis.There were five symptom clusters in HF patients: emotional symptom cluster (sadness, anxiety, irritability, feeling nervous), digestive symptom cluster (lack of appetite, dry mouth, weight loss, nausea, abdominal distension), ischemic symptom cluster (dizziness, chest pain, palpitations, fatigue), dyspnoea symptom cluster (difficulty breathing when lying flat, waking up breathless at night, sleep difficulty) and congestion symptom cluster (cough, shortness of breath, oedema). There was a significant correlation between HF symptom group, self‐care behaviours and QoL (p < 0.05). Both self‐care maintenance (β = −0.262, p < 0.001) and self‐care management (β = −0.258, p < 0.001) had a moderating effect between symptom clusters and QoL.There are a variety of symptom clusters in HF patients. Improving the self‐care behaviours ability of HF patients is conducive to reducing the impact of HF symptom clusters on QoL.The study used the STROBE checklist for reporting.Medical staff should focus on the impact of HF symptom clusters and self‐care behaviours on QoL, and formulate corresponding interventions for HF symptom clusters and self‐care behaviours to improve the QoL of patients.The head nurse of the cardiovascular department actively assisted us in collecting questionnaires from HF patients, and all HF patients surveyed participated in this study seriously. [ABSTRACT FROM AUTHOR]

Malnutrition and insulin resistance are linked to complications like delirium, yet their impact on elderly heart failure patients remains underexplored. This study investigates how nutritional status and the triglyceride-glucose (TyG) index influence delirium in this population. We conducted a retrospective study involving patients aged 75 and older with decompensated heart failure. Delirium was assessed using the Confusion Assessment Method (CAM), and nutritional status was evaluated with the Mini Nutritional Assessment Scale-Short Form (MNA-SF). The TyG index was calculated as: TyG index = ln [triglycerides (mg/dL) × fasting glucose (mg/dL) / 2]. The study included 412 patients (mean age 84.30 ± 5.16 years; 56.31% male), with 24.03% experiencing delirium during hospitalization. After adjusting for confounders, a higher TyG index was significantly associated with increased delirium risk (OR = 1.549, 95% CI: 1.102–2.178, P = 0.012), while a higher MNA-SF score correlated with reduced risk (OR = 0.793, 95% CI: 0.662–0.949, P = 0.011). Kaplan-Meier analysis showed significant differences in cumulative survival based on nutritional status and TyG index (Log-Rank test: χ²= 65.604, P < 0.001). Mediation analysis indicated that nutritional status partially mediated the relationship between the TyG index and delirium, and vice versa. Malnutrition and elevated TyG index levels increase delirium risk in elderly heart failure patients, underscoring the need for effective nutritional management and metabolic regulation. [ABSTRACT FROM AUTHOR]

Background/Objectives: Frailty is a common condition among older adults and is associated with an increased risk of adverse health outcomes, including mortality, disability, dysmobility, falls, and hospitalization. In patients with atrial fibrillation (AF), these risks are further exacerbated. However, evidence linking AF and frailty, particularly in the South American context, is limited. This study aimed to assess frailty and other geriatric conditions in older outpatients with atrial fibrillation in a resource-limited setting in Lima, Peru. Methods: In this cross-sectional study, we included adults aged 60 years and older diagnosed with atrial fibrillation who were attending outpatient check-ups. Patients who were hospitalized, receiving chemotherapy induction, or presenting with acute infections or exacerbations were excluded. Standardized questionnaires were used to assess frailty, cognitive impairment, and functional dependence. Statistical analysis was performed using R Studio version 4.3.1, with a significance level set at p < 0.05. Results: Among the 200 patients who agreed to participate (mean age 74.76 ± 8.42 years, 41% females), 28.5% exhibited frailty, and 46.5% were classified as prefrail. Frailty and prefrailty were significantly associated with older age (p<0.01), female gender (p = 0.01), illiteracy (p<0.01), heart failure (p<0.01), falls (p<0.05), cognitive impairment (p<0.01), and functional dependence (p<0.01). Multivariate analysis revealed significant associations between frailty and cognitive impairment (p<0.05), frailty and functional dependence (p<0.05), and cognitive impairment and functional dependence (p<0.05). Conclusions: One-third of older outpatients with atrial fibrillation were identified as frail, while half were classified as prefrail. In this population, frailty frequently coexists with cognitive impairment and functional dependence, highlighting the need for timely screening and the implementation of evidence-based interventions for individuals with atrial fibrillation in resource-limited settings. [ABSTRACT FROM AUTHOR]

Background: Heart failure is a serious chronic medical condition that negatively impacts daily living. Living with heart failure can be challenging due to the physical symptoms, unpredictable nature of the disease, and lifestyle changes required. The objective of this study was to explore and describe the experiences of people living with heart failure and how it affects their health-related quality of life in Ethiopia. Methods: A qualitative descriptive design was employed to explore the experience of people living with heart failure, guided by the Theory of Symptom Management. A purposive sample of 14 participants was recruited from the cardiac outpatient clinics at two tertiary-level public hospitals in Ethiopia. Data were collected using a semi-structured interview. The recorded interviews were transcribed verbatim in Amharic, translated into English, and entered NVivo statistical software for analysis. An inductive-deductive hybrid thematic analysis method was used to analyse the data. Results: Three themes were identified deductively, while an additional three themes emerged inductively:—"Journey from diagnosis to daily life with heart failure"; "Symptom experience"; "Impact of heart failure on health-related quality of life"; "Perception of health-related quality of life and influencing factors"; "Symptom management and coping strategies"; and "Challenges faced in the journey of living with heart failure". Fatigue, and depression were the most frequently reported symptoms. Participants described how their condition affected their overall physical functioning. Participants utilized consistent follow up-care, adhered to their medications, ensured adequate rest, made dietary modifications, sought social support and engaged in spiritual activities to manage their symptoms and cope with their condition. Challenges they faced included financial difficulties, unavailability of medications, and a lack of continuity of care. Conclusion: People living with heart failure in Ethiopia experience various symptoms. The impact of heart failure on various aspects of their lives, combined with the challenges they face while living with heart failure, significantly affect their health-related quality of life. Health care providers caring for these people need to understand their experiences and the impact on their daily life. Effective multimodal interventions are needed to reduce the impact of heart failure and improve health-related quality of life in this population. [ABSTRACT FROM AUTHOR]

Background: Hypertension (HTN) and diabetes mellitus (DM) are two common comorbidities of heart failure with reduced ejection fraction (HFrEF), each of which can cause right ventricular (RV) dysfunction. The aim of this study was to investigate the impact of DM on RV dysfunction and ventricular interdependence in hypertensive HFrEF patients via cardiac magnetic resonance imaging (MRI) feature tracking. Methods: This study included 249 patients with HFrEF: 77 HFrEF controls, 97 with hypertensive HFrEF (HTN-HFrEF [DM-]) and 75 with hypertensive HFrEF and comorbid DM (HTN-HFrEF [DM+]). The cardiac MRI-derived biventricular global radial (GRS), circumferential (GCS) and longitudinal (GLS) peak strains were obtained and compared among the groups. Multivariable linear regression and mediation analyses were used to evaluate the effects of DM and left ventricular (LV) strain on RV strain. Results: The biventricular GLS and GLS of segments 8, 9 and 14 of the interventricular septum (IVS) decreased gradually from the HFrEF control group to the HTN-HFrEF (DM−) group to the HTN-HFrEF (DM+) group (all P < 0.05). Patients with DM had even lower biventricular GCS and IVS strains in all directions in specific segments than did those without DM and the HFrEF controls (all P < 0.05). DM was independently associated with impaired RVGLS and RVGCS (both P < 0.05) in hypertensive HFrEF patients. The difference in RVGLS between the hypertensive HFrEF subgroups was partly mediated by LVGLS [β = 0.80, 95% CI (0.39–1.31)], and that of RVGCS was partly mediated by LVGCS [β = 0.28, 95% CI (0.01–0.62)]. Conclusions: In hypertensive HFrEF patients, comorbid DM may have aggravated RV dysfunction and was an independent determinant of impaired RV strain. RV dysfunction might be directly affected by DM and partially mediated by LV strain through unfavorable ventricular independence. [ABSTRACT FROM AUTHOR]

During the disease trajectory, patients with advanced heart failure are often hospitalised with a high probability of admission to the intensive care setting. Using a case study, this article explores the care given to a patient with decompensated heart failure in an intensive care unit (ICU). It will discuss the significance of holistic assessment and effective symptom management, in particular the research related to breathlessness management. The importance of effective communication within the ICU multidisciplinary team, including with the patient/family will be explored, as the ICU environment can often lead to communication breakdown, patients being unable to voice their wishes and over-medicalisation. The effectiveness of early involvement of the palliative care team in ICU will be examined, including the use of tools such advance care planning and a treatment escalation plan and whether use of these can enable a better patient and family experience at the end of life. The role of palliative care champions will be discussed. [ABSTRACT FROM AUTHOR]

Heart failure (HF) is a prevalent cardiovascular disease with significant morbidity and mortality rates worldwide. Due to the intricate structure of the heart, diverse cell types, and the complex pathogenesis of HF, further in‐depth investigation into the underlying mechanisms is required. The elucidation of the heterogeneity of cardiomyocytes and the intercellular communication network is particularly important. Traditional high‐throughput sequencing methods provide an average measure of gene expression, failing to capture the "heterogeneity" between cells and impacting the accuracy of gene function knowledge. In contrast, single‐cell sequencing techniques allow for the amplification of the entire genome or transcriptome at the individual cell level, facilitating the examination of gene structure and expression with unparalleled precision. This approach offers valuable insights into disease mechanisms, enabling the identification of changes in cellular components and gene expressions during hypertrophy associated with HF. Moreover, it reveals distinct cell populations and their unique roles in the HF microenvironment, providing a comprehensive understanding of the cellular landscape that underpins HF pathogenesis. This review focuses on the insights provided by single‐cell sequencing techniques into the mechanisms underlying HF and discusses the challenges encountered in current cardiovascular research. [ABSTRACT FROM AUTHOR]

Aims Methods and results Conclusion The CASTLE‐HTx trial showed the benefit of atrial fibrillation (AF) ablation compared to medical therapy in decreasing mortality, need for left ventricular assist device implantation or heart transplantation (HTx) in patients with end‐stage heart failure (HF). Herein we describe the effects of catheter ablation on AF burden, arrhythmia recurrences, and ventricular function in end‐stage HF.The CASTLE‐HTx protocol randomized 194 patients in end‐stage HF with AF to catheter ablation and medical therapy or medical therapy alone. AF burden, left ventricular ejection fraction (LVEF), and type of AF were assessed at baseline and at each follow‐up visit. Overall, 97 patients received ablation; 66 patients (68%) underwent pulmonary vein isolation (PVI) and 31 patients (32%) were treated with PVI and additional ablation. Electroanatomic mapping showed the extent of left atrial low voltage (cardiomyopathy) >10% in 31 (31.9%) patients. At 12 months post‐ablation, persistent AF was present in 31/89 patients (34.8%), which was significantly less frequent compared to baseline (p = 0.0001). Median AF burden reduction was 36.3 (interquartile range 13.6–63.3) percentage points at 12 months and LVEF improved from 29.2 ± 6.2% to 39.1 ± 8.3% (p < 0.001) following ablation. AF burden reduction <50% was significantly associated with LVEF improvement ≥5% at 12 months after ablation (p = 0.017).Atrial fibrillation ablation in end‐stage HF leads to a substantial decrease in AF burden, a regression from persistent to paroxysmal AF and notably improved LVEF. Favourable ablation outcomes were observed in patients regardless of the presence or absence of signs indicating left atrial cardiomyopathy. [ABSTRACT FROM AUTHOR]

Background: Tetanus is a clinical rarity due to the successful globally adopted childhood vaccination programme. The rising elderly population in the United Kingdom creates a subset of individuals whom are prone to develop Tetanus as they preceded this vaccination drive. Case summary: A 76 year old Caucasian lady presented with a soil contaminated laceration injury on her knee following a fall. Though she received urgent assessment and wound care, the relevance of the injury in the backdrop of her age was not appreciated and her tetanus post exposure prophylaxis was overlooked. She readmitted seeking further management 1 week later with an infected wound with Trismus and clinical features favoring Generalized tetanus. During her stay she developed Takotsubo-cardiomyopathy with congestive cardiac failure and required prolonged care in the intensive unit with mechanical ventilation and rehabilitation before being discharged home. Conclusion: First contact physicians should have a greater appreciation of the types of injuries and at-risk individuals who are more prone to develop tetanus upon exposure to ensure early and appropriate identification. There should be greater situational awareness with regard to the elderly in view of their heightened risk of development of tetanus specially those born before the vaccination drive. Knowledge regarding post exposure prophylaxis measures for tetanus should be regularly updated using local guidance to ensure awareness, so as to despite its rarity Tetanus remains an adequately appreciated disease. [ABSTRACT FROM AUTHOR]

Background: The association between plasma free fatty acid (FFA) and the outcomes in the heart failure (HF) patients remains unclear. Methods: A cohort study among HF patients was performed. Plasma FFA was analyzed as both a continuous and a categorical variable (grouped by tertiles) to assess its association with composite cardiovascular (CV) death and HF hospitalization (CV death & HHP), CV death alone, and all-cause mortality (ACM) using Cox regression models. Subgroup analyses of HF patients with preserved ejection fraction (HFpEF) and mildly reduced/reduced ejection fraction (HFmrEF/HFrEF) were performed. This work also assessed the effectiveness of combining FFA and NT-pro BNP biomarkers for risk stratification by calculating the concordance index (C-index). Results: Among the 4,109 HF patients, FFA levels exceeding 0.4–0.42 mmol/L were associated with increased risks of the three outcomes. Patients in the highest FFA tertile faced greater risks than those in the lowest tertile. Adjusted hazard ratios were 1.32 (95% CI: 1.11–1.58) for CV death & HHP, 1.45 (95% CI: 1.16–1.82) for CV death, and 1.39 (95% CI: 1.15–1.68) for ACM, with a maximum follow-up of 8 years (median: 25 months). Subgroup analyses revealed that elevated FFA levels consistently predicted worse outcomes in both HFmrEF/HFrEF and HFpEF patients. The C-index for predicting outcomes was significantly greater when NT-pro BNP and FFA were combined than when NT-pro BNP was used alone (P < 0.01). Conclusion: Increased plasma FFA concentrations were independently associated with greater risks of CV death & HHP, CV death, and ACM among HF patients, irrespective of the ejection fraction. The combination of FFA and NT-pro BNP biomarkers significantly improved risk stratification in HF patients. [ABSTRACT FROM AUTHOR]

Introduction: Cardiac amyloidosis is a rarely reported and potentially fatal variant of the systemic disease. Its early diagnosis could potentially lead to significantly improved clinical outcomes. Case presentation: A 56-year-old female presented with dyspnea and palpitations. Her physical exam and non-invasive evaluation with cardiac magnetic resonance imaging (CMRI) revealed restrictive cardiomyopathy, and the bone marrow biopsy results showed systemic amyloidosis. Discussion: The diagnosis of cardiac amyloidosis is not always straightforward, and delay can cause the progression of the disease and an increased risk of morbidity and mortality. Electrocardiograms, echocardiograms, cardiac magnetic resonance imaging, and histopathologic evaluation are the main methods for diagnosing cardiac amyloidosis. The treatment consists of controlling heart failure symptoms and disease-modifying interventions, including medical and surgical therapeutic methods. Clinical learning point (conclusion): Cardiac involvement is the main cause of death in systemic amyloidosis. Early suspicion, diagnosis, and treatment are crucial in improving patients' survival. CMRI can play an essential role in the diagnosis of cardiac Amyloidosis. A graphical abstract is provided for visual summary. [ABSTRACT FROM AUTHOR]

Background : Altered metabolism plays a role in the pathophysiology of cardiac diseases, such as atrial fibrillation (AF) and heart failure (HF). We aimed to identify novel plasma metabolites and proteins associating with cardiac disease. Methods: Mendelian randomisation (MR) was used to assess the association of 174 metabolites measured in up to 86,507 participants with AF, HF, dilated cardiomyopathy (DCM), and non-ischemic cardiomyopathy (NICM). Subsequently, we sourced data on 1567 plasma proteins and performed cis MR to identify proteins affecting the identified metabolites as well as the cardiac diseases. Proteins were prioritised on cardiac expression and druggability, and mapped to biological pathways. Results: We identified 35 metabolites associating with cardiac disease. AF was affected by seventeen metabolites, HF by nineteen, DCM by four, and NCIM by taurine. HF was particularly enriched for phosphatidylcholines (p = 0.029) and DCM for acylcarnitines (p = 0.001). Metabolite involvement with AF was more uniform, spanning for example phosphatidylcholines, amino acids, and acylcarnitines. We identified 38 druggable proteins expressed in cardiac tissue, with a directionally concordant effect on metabolites and cardiac disease. We recapitulated known associations, for example between the drug target of digoxin (AT1B2), taurine and NICM risk. Additionally, we identified numerous novel findings, such as higher RET values associating with phosphatidylcholines and decreasing AF and HF. RET is targeted by drugs such as regorafenib which has known cardiotoxic side-effects. Pathway analysis implicated involvement of GDF15 signalling through RET, and ghrelin regulation of energy homeostasis in cardiac pathogenesis. Conclusions: This study identified 35 plasma metabolites involved with cardiac diseases and linked these to 38 druggable proteins, providing actionable leads for drug development. [ABSTRACT FROM AUTHOR]

Background: Scheie syndrome, an attenuated subtype of mucopolysaccharidosis type I, is a rare storage disease that causes progressive glycosaminoglycans (GAGs) accumulation. Cardiovascular disorders determine the prognosis, and cardiac valve abnormalities are the most common cause. The patients are usually young so mechanical valve replacement is often performed, but because of the features of this disease, the surgical treatment is very risky. Recently, transcatheter aortic valve implantation (TAVI) has been reported as an alternative choice for aortic stenosis, but optimal choice is still unclear. Here, we introduce a patient that underwent TAVI and refer to the histological finding of a biological valve extracted in relation to GAGs accumulation. Case presentation: A 54-year-old woman with Scheie syndrome underwent valve surgeries three times throughout her whole life. At age 41, she received a mitral valve replacement with a mechanical valve for mitral stenosis. She promptly developed severe diastolic dysfunction and low output syndrome after the release of aortic clamping, thus requiring temporary mechanical circulatory support4. At age 51, she suffered from heart failure due to severe aortic stenosis and underwent TAVI because conventional aortic valve replacement (AVR) was deemed too risky. Three years later, her heart failure relapsed, and an echocardiogram unexpectedly revealed thickened bioprosthetic valve leaflets and a significant pressure gradient across the valve, consistent with early structural valve deterioration. AVR was performed via median sternotomy with a mechanical valve. As with the first operation, she presented refractory heart failure requiring mechanical circulatory support and was meticulously managed. However, she steadily showed worsening of multiple organ systems and died 9 days after the operation. Pathological autopsy and histological examination revealed accumulation of tissue with GAGs on the leaflets of the bioprosthetic valve of TAVI, which may have been the cause of early structural valve deterioration. Conclusion: For patients with Scheie syndrome, a biological valve can be compromised by the accumulation of GAGs, thereby causing early SVD. These findings may support valve selection for these high-risk patients. [ABSTRACT FROM AUTHOR]

Aims Methods and results Conclusion Long‐term fine particulate matter (PM2.5) exposure has been linked to incident heart failure (HF), but the impacts of its constituents remain unknown. We aimed to investigate the associations of PM2.5 constituents with incident HF, and further evaluate the modification effects of genetic susceptibility.PM2.5 and its constituents, including elemental carbon (EC), organic matter (OM), ammonium (NH4+), nitrate (NO3−), and sulfate (SO42−), were estimated using the European Monitoring and Evaluation Programme model applied to the UK (EMEP4UK) driven by Weather and Research Forecast model meteorology. A polygenic risk score (PRS) was calculated to represent genetic susceptibility to HF. We employed Cox models to evaluate the associations of PM2.5 constituents with incident HF. Quantile‐based g‐computation model was used to identify the main contributor of PM2.5 constituents. Among 411 807 individuals in the UK Biobank, 7554 participants developed HF during a median follow‐up of 12.05 years. The adjusted hazard ratios of HF for each interquartile range increase in PM2.5, EC, OM, NH4+, NO3−, and SO42− were 1.50 (1.46–1.54), 1.31 (1.27–1.34), 1.12 (1.09–1.15), 1.42 (1.41–1.44), 1.26 (1.23–1.29), and 1.25 (1.24–1.26), respectively. EC (43%) played the most important role, followed by NH4+ and SO42−. Moreover, synergistic additive interactions accounted for 9–16% of the HF events in individuals exposed to both PM2.5, NH4+, NO3−, and SO42− and PRS.Long‐term exposure to PM2.5 constituents may elevate HF risk, and EC was the major contributor. Additive effects of PM2.5 constituents and PRS on HF risk were revealed. [ABSTRACT FROM AUTHOR]

Aims Methods and results Conclusion Resting heart rate (HR) is a strong risk marker in patients with heart failure (HF), but the clinical implications of visit‐to‐visit changes in HR (ΔHR) are less well established. We aimed to explore the association between ΔHR and subsequent outcomes in a pooled dataset of two well‐characterized cohorts of patients with HF across the full range of left ventricular ejection fraction (LVEF).PARADIGM‐HF and PARAGON‐HF were randomized trials testing sacubitril/valsartan versus enalapril or valsartan, respectively, in patients with HF and LVEF ≤40% (PARADIGM‐HF) or LVEF ≥45% (PARAGON‐HF). We analysed the association between ΔHR from the preceding visit with the primary endpoint of HF hospitalization (HFH) or cardiovascular death using covariate‐adjusted Cox proportional hazards models. A total of 13 194 patients (mean age 67 ± 11 years, 67% men, mean LVEF 40 ± 15%) were included. Over a median follow‐up of 2.5 years, 3114 patients experienced a first HFH or cardiovascular death event (10.4 events per 100 patient‐years). An increase in HR from the preceding visit, compared with no change, was associated with a higher risk (hazard ratio 1.12; 95% confidence interval [CI] 1.10–1.15; p < 0.001 per 5 bpm increase). Conversely, a drop in HR was associated with a lower risk (hazard ratio 0.97; 95% CI 0.94–1.00; p = 0.044 per 5 bpm drop). The prognostic implications of ΔHR were consistent across the range of LVEF and observed regardless of β‐blocker use or presence of a permanent pacemaker. Visit‐to‐visit increases in HR were especially prognostic in patients without atrial fibrillation (pinteraction = 0.006).Across a broad spectrum of patients with chronic HF, increases in HR from a preceding visit independently predicted clinical outcomes. The detection of notable increases in HR between outpatient visits may help identify patients at heightened risk of adverse events.Clinical Trial Registration; ClinicalTrials.gov NCT01035255 (PARADIGM‐HF), NCT01920711 (PARAGON‐HF). [ABSTRACT FROM AUTHOR]

Background: Gastrojejunostomy junction perforation is a rare yet critical complication associated with enteral tube placement, presenting unique challenges in patients with a history of Roux-en-Y gastric bypass surgery. Case presentation: A 63-year-old white female with a complex medical history, including heart failure, atrial fibrillation, stage 4 chronic kidney disease, and prior Roux-en-Y gastric bypass surgery in 2015, experienced a significant decline in her health. She was discharged to a skilled nursing facility after a fall but deteriorated rapidly in the 2 weeks before admission. She presented with symptoms of failure to thrive, abdominal/back pain, inability to eat or drink, constipation, and stool incontinence. Lab tests showed anemia, electrolyte imbalances, and acute kidney injury. Imaging confirmed Roux-en-Y gastric bypass anatomy and a small hiatal hernia. Despite treatment attempts, her condition worsened. Nutrition discussions led to a temporary Dobhoff tube placement, considering her Roux-en-Y gastric bypass history, with plans for a gastrostomy tube. However, Dobhoff tube placement posed challenges, and imaging later revealed perforation near the gastrojejunostomy junction. After consulting with the family, the decision was made to transition the patient to comfort care due to her overall condition. Yearly education of staff about Roux-en-Y gastric bypass anatomy and updated Dobhoff placement protocol was implemented with physician oversight. Further imaging protocol in a patient who had had a Roux-en-Y gastric bypass was updated to include fluoroscopic guidance when endoscopic placement was unavailable. Conclusions: This case highlights the intricacies of managing patients with Roux-en-Y gastric bypass history and underscores the need for meticulous planning and consideration of anatomical variations when performing procedures involving the gastrointestinal tract and the importance of involving multiple healthcare disciplines in complex decision-making and preventive measures to enhance patient safety in similar cases. [ABSTRACT FROM AUTHOR]

ABSTRACT Bradycardia, atrial tachyarrhythmia, heart failure, residual shunts, and pulmonary hypertension (PH) are significant problems after congenital heart disease surgery. We performed His‐bundle pacing (HBP) for drug‐resistant PH with bradycardia in a woman post‐total anomalous pulmonary venous return repair complicated by bradycardia, hypertension, PH, residual atrial shunts, and heart failure. Significant improvement in PH post‐HBP was achieved without exacerbation of left ventricular function. We successfully closed the atrial shunts 12 months after HBP. [ABSTRACT FROM AUTHOR]

Background and Purpose Experimental Approach Key Results Conclusion and Implications Opioid analgesics can alleviate ischaemia/reperfusion (I/R) injury in chronic heart failure. However, the underlying mechanisms and targets remain unknown. Here, we investigate if caveolin‐3 (Cav3) interacts with μ opioid receptors and if Cav3–μ receptor interactions play a role in morphine‐induced cardioprotection in failing hearts.Cav3 and μ receptor proteins in human and rat heart tissue were determined by western blot, immunofluorescence and co‐immunoprecipitation. Methyl‐β‐cyclodextrin (MβCD), a destroyer of caveolae, and AAV‐Cav3 shRNA were used to reduce Cav3 expression in failing rat hearts. CTOP, a specific μ antagonist, was administrated before morphine preconditioning in perfused failing heart models of myocardial I/R injury.Levels of Cav3 and μ receptor proteins were significantly higher in human and rat myocardial tissues with heart failure than in control tissues. Cav3 and μ receptor expression levels were positively correlated with disease severity. The signal of the cardiac Cav3 protein was colocalized with μ receptor in both the human and rat heart sections. Disruption of caveolae in the failing heart by either MβCD or AAV‐Cav3 shRNA significantly inhibits morphine‐induced phosphorylation of ERK1/2 and cardioprotection. Administration of CTOP substantially reduced Cav3 expression and morphine‐induced cardioprotective effect in heart failure.Our data suggest that up‐regulation of the Cav3/μ receptor complex is critical for morphine protection of the failing heart against I/R injury by regulating the ERK1/2 pathway. The activated Cav3/μ receptor complex is an understudied therapeutic target for opioid treatment of heart failure and ischaemic insult. [ABSTRACT FROM AUTHOR]

Inflammation is thought to be an important mechanism for the development and progression of obesity-related heart failure with preserved ejection fraction (HFpEF). In the STEP-HFpEF Program, once-weekly 2.4 mg semaglutide improved heart failure–related symptoms, physical limitations, and exercise function, reduced the levels of C-reactive protein (CRP), a biomarker of inflammation, and reduced body weight in participants with obesity-related HFpEF. However, neither the prevalence nor the clinical characteristics of patients who have various magnitudes of inflammation in the context of obesity-related HFpEF have been well described. Furthermore, whether the beneficial effects of semaglutide on the various HF efficacy endpoints in the STEP-HFpEF Program are modified by the baseline levels of inflammation has not been fully established. Finally, the relationship between weight reduction and changes in CRP across the STEP-HFpEF Program have not been fully defined. This study sought to: 1) evaluate baseline characteristics and clinical features of patients with obesity-related HFpEF that have various levels of inflammation in the STEP-HFpEF Program; 2) determine if the effects of weekly semaglutide 2.4 mg vs placebo across all key outcomes are influenced by baseline levels of inflammation assessed by CRP levels; and 3) determine the relationship between change in CRP and weight loss in the STEP-HFpEF Program. This was a secondary analysis of pooled data from 2 international, double-blind, placebo-controlled, randomized trials (STEP-HFpEF and STEP-HFpEF DM). The outcomes were change in the dual primary endpoints (health status [measured by the Kansas City Cardiomyopathy Questionnaire—Clinical Summary Score (KCCQ-CSS)] and body weight) from baseline to 52 weeks according to baseline CRP levels. Additional efficacy endpoints included change in 6-minute walk distance (6MWD), a hierarchical composite endpoint that included death, heart failure events, and differences in the change in the KCCQ-CSS and 6MWD, and levels of CRP in semaglutide- vs placebo-treated patients. Patients were stratified into 3 categories based on baseline CRP levels (<2, ≥2 to <10, and ≥10 mg/L). In total, 1,145 patients were randomized, of which 71% of patients had evidence of inflammation (CRP ≥2 mg/L). At baseline, those with higher levels of inflammation were younger, were more likely to be female, and had higher body mass index, worse health status (KCCQ-CSS), and shorter 6MWD. Semaglutide vs placebo led to reductions in HF-related symptoms and physical limitations as well as body weight, and to improvements in 6MWD and the hierarchical composite endpoint that were consistent across baseline CRP categories (all P interaction nonsignificant). Semaglutide also reduced CRP to a greater extent than placebo regardless of baseline CRP levels (P interaction = 0.32). Change in CRP from baseline to 52 weeks was similar regardless of the magnitude of weight loss (P interaction = 0.91). Inflammation is highly prevalent in obesity-related HFpEF. Semaglutide consistently improved HF-related symptoms, physical limitations, and exercise function, and reduced body weight across the categories of baseline CRP. Semaglutide also reduced inflammation, regardless of either baseline CRP or magnitude of weight loss during the trials. (Research Study to Investigate How Well Semaglutide Works in People Living With Heart Failure and Obesity [STEP-HFpEF; NCT04788511 ]; Research Study to Look at How Well Semaglutide Works in People Living With Heart Failure, Obesity and Type 2 Diabetes [STEP HFpEF DM; NCT04916470 ]) [ABSTRACT FROM AUTHOR]

Obesity is a key factor in the development and progression of both heart failure with preserved ejection fraction (HFpEF) and atrial fibrillation (AF). In the STEP-HFpEF Program (comprising the STEP-HFpEF [Research Study to Investigate How Well Semaglutide Works in People Living With Heart Failure and Obesity] and STEP-HFpEF DM [Research Study to Look at How Well Semaglutide Works in People Living With Heart Failure, Obesity and Type 2 Diabetes] trials), once-weekly semaglutide 2.4 mg improved HF-related symptoms, physical limitations, and exercise function and reduced body weight in patients with obesity-related HFpEF. Whether the effects of semaglutide in this patient group differ in participants with and without AF (and across various AF types) has not been fully examined. The goals of this study were: 1) to evaluate baseline characteristics and clinical features of patients with obesity-related HFpEF with and without a history of AF; and 2) to determine if the efficacy of semaglutide across all key trial outcomes are influenced by baseline history of AF (and AF types) in the STEP-HFpEF Program. This was a secondary analysis of pooled data from the STEP-HFpEF and STEP-HFpEF DM trials. Patients with heart failure, left ventricular ejection fraction ≥45%, body mass index ≥30 kg/m2, and Kansas City Cardiomyopathy Questionnaire–Clinical Summary Score (KCCQ-CSS) <90 points were randomized 1:1 to receive once-weekly semaglutide 2.4 mg or matching placebo for 52 weeks. Dual primary endpoints (change in KCCQ-CSS and percent change in body weight), confirmatory secondary endpoints (change in 6-minute walk distance; hierarchical composite endpoint comprising all-cause death, HF events, thresholds of change in KCCQ-CSS, and 6-minute walk distance; and C-reactive protein [CRP]), and exploratory endpoint (change in N-terminal pro–B-type natriuretic peptide [NT-proBNP]) were examined according to investigator-reported history of AF (yes/no). Responder analyses examined the proportions of patients who experienced a ≥5-, ≥10, ≥15, and ≥20-point improvement in KCCQ-CSS per history of AF. Of the 1,145 participants, 518 (45%) had a history of AF (40% paroxysmal, 24% persistent AF, and 35% permanent AF) and 627 (55%) did not. Participants with (vs without) AF were older, more often male, had higher NT-proBNP levels, included a higher proportion of those with NYHA functional class III symptoms, and used more antithrombotic therapies, beta-blockers, and diuretics. Semaglutide led to larger improvements in KCCQ-CSS (11.5 points [95% CI: 8.3-14.8] vs 4.3 points [95% CI: 1.3-7.2]; P interaction = 0.001) and the hierarchal composite endpoint (win ratio of 2.25 [95% CI: 1.79-2.83] vs 1.30 [95% CI: 1.06-1.59]; P interaction < 0.001) in participants with AF vs without AF, respectively. The proportions of patients receiving semaglutide vs those receiving placebo experiencing ≥5-, ≥10-, ≥15-, and ≥20-point improvement in KCCQ-CSS were also higher in those with (vs without) AF (all P interaction values <0.05). Semaglutide consistently reduced CRP, NT-proBNP, and body weight regardless of AF status (all P interaction values not significant). There were fewer serious adverse events and serious cardiac disorders in participants treated with semaglutide vs placebo irrespective of AF history. In the STEP-HFpEF Program, AF was observed in nearly one-half of patients with obesity-related HFpEF and was associated with several features of more advanced HF. Treatment with semaglutide led to significant improvements in HF-related symptoms, physical limitations, and exercise function, as well as reductions in weight, CRP, and NT-proBNP in people with and without AF and across AF types. The magnitude of semaglutide-mediated improvements in HF-related symptoms and physical limitations was more pronounced in those with AF vs without AF at baseline. (Research Study to Investigate How Well Semaglutide Works in People Living With Heart Failure and Obesity [STEP-HFpEF; NCT04788511 ]; Research Study to Look at How Well Semaglutide Works in People Living With Heart Failure, Obesity and Type 2 Diabetes [STEP-HFpEF DM; NCT04916470 ]) [ABSTRACT FROM AUTHOR]

Obesity is associated with adverse cardiac remodeling and is a key driver for the development and progression of heart failure (HF). Once-weekly semaglutide (2.4 mg) has been shown to improve HF-related symptoms and physical limitations, body weight, and exercise function in patients with obesity-related heart failure with preserved ejection fraction (HFpEF), but the effects of semaglutide on cardiac structure and function in this population remain unknown. In this echocardiography substudy of the STEP-HFpEF Program, we evaluated treatment effects of once-weekly semaglutide (2.4 mg) vs placebo on cardiac structure and function. Echocardiography at randomization and 52 weeks was performed in 491 of 1,145 participants (43%) in the STEP-HFpEF Program (pooled STEP-HFpEF [Semaglutide Treatment Effect in People with Obesity and HFpEF] and STEP-HFpEF DM [Semaglutide Treatment Effect in People with Obesity, HFpEF, and Type 2 Diabetes] trials). The prespecified primary outcome was change in left atrial (LA) volume, with changes in other echocardiography parameters evaluated as secondary outcomes. Treatment effects of semaglutide vs placebo were assessed using analysis of covariance stratified by trial and body mass index, with adjustment for baseline parameter values. Overall, baseline clinical and echocardiographic characteristics were balanced among those receiving semaglutide (n = 253) and placebo (n = 238). Between baseline and 52 weeks, semaglutide attenuated progression of LA remodeling (estimated mean difference [EMD] in LA volume, −6.13 mL; 95% CI: −9.85 to −2.41 mL; P = 0.0013) and right ventricular (RV) enlargement (EMD in RV end-diastolic area: −1.99 cm2; 95% CI: −3.60 to −0.38 cm2; P = 0.016; EMD in RV end-systolic area: −1.41 cm2; 95% CI: −2.42 to −0.40] cm2; P = 0.0064) compared with placebo. Semaglutide additionally improved E-wave velocity (EMD: −5.63 cm/s; 95% CI: −9.42 to −1.84 cm/s; P = 0.0037), E/A (early/late mitral inflow velocity) ratio (EMD: −0.14; 95% CI: −0.24 to −0.04; P = 0.0075), and E/e′ (early mitral inflow velocity/early diastolic mitral annular velocity) average (EMD: −0.79; 95% CI: −1.60 to 0.01; P = 0.05). These associations were not modified by diabetes or atrial fibrillation status. Semaglutide did not significantly affect left ventricular dimensions, mass, or systolic function. Greater weight loss with semaglutide was associated with greater reduction in LA volume (P interaction = 0.033) but not with changes in E-wave velocity, E/e′ average, or RV end-diastolic area. In the STEP-HFpEF Program echocardiography substudy, semaglutide appeared to improve adverse cardiac remodeling compared with placebo, further suggesting that treatment with semaglutide may be disease modifying among patients with obesity-related HFpEF. (Research Study to Investigate How Well Semaglutide Works in People Living With Heart Failure and Obesity [STEP-HFpEF]; NCT04788511 ; Research Study to Look at How Well Semaglutide Works in People Living With Heart Failure, Obesity and Type 2 Diabetes [STEP-HFpEF DM]; NCT04916470) [ABSTRACT FROM AUTHOR]

People with type 2 diabetes (T2D) and chronic kidney disease (CKD) are at high risk for heart failure (HF) and premature death from cardiovascular (CV) causes. The FLOW (Research Study To See How Semaglutide Works Compared to Placebo in People With Type 2 Diabetes and Chronic Kidney Disease), which enrolled participants with T2D and CKD, demonstrated that semaglutide, a glucagon-like peptide-1 receptor agonist, reduced the incidence of the primary composite outcome (persistent ≥50% decline in estimated glomerular filtration rate, persistent estimated glomerular filtration rate <15 mL/min/1.73 m2, kidney replacement therapy, and kidney or CV death) by 24%. This prespecified analysis examined the effects of semaglutide on HF outcomes in this high-risk population. Participants were randomized (1:1) to once-weekly subcutaneous semaglutide 1 mg or placebo. The prespecified main outcome was a composite of HF events (new onset or worsening of HF leading to an unscheduled hospital admission or an urgent visit, with initiation of or intensified diuretic/vasoactive therapy) or CV death. HF data were collected by the investigator. CV death was adjudicated by an independent committee. A total of 3,533 randomized participants were followed for a median of 3.4 years. HF was present at baseline in 342 participants (19.4%) in the semaglutide group and 336 (19.0%) in the placebo group. In the overall trial population, semaglutide increased time to first HF events or CV death (HR: 0.73; 95% CI: 0.62-0.87; P = 0.0005), HF events alone (HR: 0.73; 95% CI: 0.58-0.92; P = 0.0068), and CV death alone (HR: 0.71; 95% CI: 0.56-0.89; P = 0.0036). The risk reduction for the composite HF outcome was similar in those with (HR: 0.73; 95% CI: 0.54-0.98; P = 0.0338) and without (HR: 0.72; 95% CI: 0.58-0.89; P = 0.0028) HF at baseline. The risk of HF outcomes (HF events or CV death) was generally higher in participants categorized as NYHA functional class III and those with the HF reduced ejection fraction subtype, regardless of treatment. Semaglutide substantially reduced the risk of time to first composite outcome of HF events or CV death, as well as HF events and CV death alone, in a high-risk population with T2D and CKD. These effects were consistent regardless of history of HF. (A Research Study To See How Semaglutide Works Compared to Placebo in People With Type 2 Diabetes and Chronic Kidney Disease [FLOW]; NCT03819153) [ABSTRACT FROM AUTHOR]

Obesity is an ongoing pandemic and is associated with the development of heart failure (HF), and especially HF with preserved ejection fraction. The definition of obesity is currently based on anthropometric measurements but neglects the location and molecular properties of excess fat. Important depots associated with HF development are subcutaneous adipose tissue and visceral adipose tissue, both located in the abdominal region, and epicardial adipose tissue (EAT) surrounding the myocardium. However, mechanisms linking these different adipose tissue depots to HF development are incompletely understood. EAT in particular is of great interest because of its close proximity to the heart. In this review, we therefore focus on the characteristics of different adipose tissue depots and their response to obesity. In addition, we evaluate how different mechanisms associated with EAT expansion potentially contribute to HF and in particular HF with preserved ejection fraction development. • Obesity is a major contributor to the development of HFpEF, but pathophysiological mechanisms remain elusive. • Fat localization is an important consideration because subcutaneous, visceral, and epicardial adipose tissue respond differently in obesity. • Epicardial adipose tissue potentially contributes to HFpEF development through proinflammatory paracrine effects, lipid infiltration, and pericardial constraint. • Targeting unique properties of different adipose tissues is a potential approach to reduce incident HFpEF. [ABSTRACT FROM AUTHOR]

To examine temporal changes in patient characteristics, the incidence rate of surgical intervention, and the three-year mortality rate for patients undergoing surgical intervention for mitral valve stenosis (MS) from 2001 to 2021 in Denmark. Utilizing Danish nationwide registries, we identified all adult patients undergoing first-time surgical intervention for MS (2001–2021). Temporal changes in the incidence rate of surgical intervention across calendar periods were investigated (2001–2005, 2006–2010, 2011–2015, and 2016–2021). Using Kaplan-Meier estimates, we computed temporal changes in three-year all-cause mortality across calendar periods. With multivariable Cox regression analysis, we assessed the adjusted rates of mortality. We included 256 patients (median age 60.3 years, 31.3% males). A stepwise decrease in the burden of chronic heart failure was identified (2001–2005: 54%, and 2016–2021: 20%, p-value < 0.001 for trend), while the burden of atrial fibrillation seemed stable (2001–2005: 51%, and 2016–2021: 46%, p-value = 0.27 for trend). The proportion of patients with rheumatic MS was 64% in 2001–2005 and 33% in 2016–2021, p-value < 0.001 for trend. 28 patients (10.9%) had mitral valve surgery prior to the first-time surgical intervention for MS. A stepwise decrease in the incidence rate of surgical intervention was observed: 3.3 cases per million person-years in 2001–2005 and 2.2 in 2016–2021. The incidence of patients diagnosed with first-time MS remained stable over calendar periods (2001–2005: 54.5 incidences per million person-years, and 2016–2021: 41.9, p-value = 0.46 for trend). The in-hospital mortality was 8.6% and the three-year mortality after surgical discharge was 9.0%, and we found no difference over calendar periods in either crude estimates or adjusted analysis. From nationwide data across three decades, we identified that the incidence of surgical interventiondecreased significantly within the past 20 years, while all-cause mortality remained stable. The burden of heart failure decreased, while the burden of atrial fibrillation remained stable over the study period. [ABSTRACT FROM AUTHOR]

Explainability of convolutional neural networks (CNNs) is integral for their adoption into radiological practice. Commonly used attribution methods localize image areas important for CNN prediction but do not characterize relevant imaging features underlying these areas, acting as a barrier to the adoption of CNNs for clinical use. We therefore propose Semantic Exploration and Explainability using a Style-based Generative Adversarial Autoencoder Network (SEE-GAAN), an explainability framework that uses latent space manipulation to generate a sequence of synthetic images that semantically visualizes how clinical and CNN features manifest within medical images. Visual analysis of changes in these sequences then facilitates the interpretation of features, thereby improving explainability. SEE-GAAN was first developed on a cohort of 26,664 chest radiographs across 15,409 patients from our institution. SEE-GAAN sequences were then generated across several clinical features and CNN predictions of NT-pro B-type natriuretic peptide (BNPP) as a proxy for acute heart failure. Radiological interpretations indicated SEE-GAAN sequences captured relevant changes in anatomical and pathological morphology associated with clinical and CNN predictions and clarified ambiguous areas highlighted by commonly used attribution methods. Our study demonstrates SEE-GAAN can facilitate our understanding of clinical features for imaging biomarker exploration and improve CNN transparency over commonly used explainability methods. [ABSTRACT FROM AUTHOR]

Muscle wasting is a serious complication in heart failure patients. Oxidative stress and inflammation are implicated in the pathogenesis of muscle wasting. Oxidative stress leads to the formation of toxic lipid peroxidation products, such as 4-hydroxy-2-nonenal (HNE), which covalently bind with proteins and DNA and activate atrophic pathways. Whether the formation of lipid peroxidation products and metabolic pathways that remove these toxic products are affected during heart failure-associated skeletal muscle wasting has never been studied. Male C57BL/6J mice were subjected to sham and transverse aortic constriction (TAC) surgeries for 4, 8 or 14 weeks. Different skeletal muscle beds were weighed, and the total cross-sectional area of the gastrocnemius muscle was measured via immunohistochemistry. Muscle function and muscle stiffness were measured by a grip strength meter and atomic force microscope, respectively. Atrophic and inflammatory marker levels were measured via qRT‒PCR. The levels of acrolein and HNE-protein adducts, aldehyde-removing enzymes, the histidyl dipeptide-synthesizing enzyme carnosine synthase (CARNS), and amino acid transporters in the gastrocnemius muscle were measured via Western blotting and qRT‒PCR. Histidyl dipeptides and histidyl dipeptide aldehyde conjugates in the Gastrocnemius and soleus muscles were analyzed by LC/MS–MS. Body weight, gastrocnemius muscle and soleus muscle weights and the total cross-sectional area of the gastrocnemius muscle were decreased after 14 weeks of TAC. Heart weight, cardiac function, grip strength and muscle stiffness were decreased in the TAC-operated mice. Expression of the atrophic and inflammatory markers Atrogin1 and TNF-α, respectively, was increased ~ 1.5–2fold in the gastrocnemius muscle after 14 weeks of TAC (p < 0.05 and p = 0.004 vs sham). The formation of HNE and acrolein protein adducts was increased, and the expression of the aldehyde-removing enzyme aldehyde dehydrogenase (ALDH2) was decreased in the gastrocnemius muscle of TAC mice. Carnosine (sham: 5.76 ± 1.3 vs TAC: 4.72 ± 0.7 nmol/mg tissue, p = 0.04) and total histidyl dipeptide levels (carnosine and anserine; sham: 11.97 ± 1.5 vs TAC: 10.13 ± 1.4 nmol/mg tissue, p < 0.05) were decreased in the gastrocnemius muscle of TAC mice. Depletion of histidyl dipeptides diminished the aldehyde removal capacity of the atrophic gastrocnemius muscle. Furthermore, CARNS and TAUT protein expression were decreased in the atrophic gastrocnemius muscle. Our data reveals that reduced expression of ALDH2 and depletion of histidyl dipeptides in the gastrocnemius muscle during heart failure leads to the accumulation of toxic aldehydes and might contribute to muscle wasting. [ABSTRACT FROM AUTHOR]

Background Methods Results Conclusions Impella 5.5 is a temporary left ventricular assist device utilized to support patients with cardiogenic shock and those undergoing high‐risk cardiac interventions.From October 2019 to January 2023, 226 patients received Impella 5.5 support at Cleveland Clinic main campus. Patients were stratified by Society for Cardiovascular Angiography and Interventions (SCAI) shock stages. Immediate post‐Impella 5.5 trajectories were compared across groups. Trajectories were defined as mortality on Impella 5.5, transition to advanced heart failure therapies (durable left ventricular assist device/heart transplantation), or survival to Impella 5.5 removal without advanced therapies.Overall, 148 (65%) patients with cardiogenic shock and 78 (35%) undergoing high‐risk cardiac interventions received Impella 5.5 support. SCAI stage was A in 63 (28%), B in 10 (4.4%), C in 29 (13%), D in 104 (46%), and E in 20 (8.8%). Mortality on Impella 5.5 was highest in SCAI stage E (A: 3.2%, B: 10%, C: 14%, D: 27%, E: 35%; p < 0.01). Transition to advanced therapies (durable left ventricular assist device or heart transplantation) was highest in SCAI stages C‐D (A: 1.6%, B: 0.0%, C: 45%, D: 36%, E: 20%; p < 0.01). Survival to Impella removal without advanced therapies was highest in SCAI stages A‐B (A: 95%, B: 90%, C: 41%, D: 38%, E: 45%; p < 0.01).Stratification by presentation acuity in candidates for Impella 5.5 insertion may help identify which patients may and may not benefit from this escalation of tailored temporary mechanical circulatory support. [ABSTRACT FROM AUTHOR]

The article discusses the use of hierarchical endpoints analyzed using the win-ratio method in deprescribing trials for older adults with multimorbidity. Deprescribing, the process of discontinuing drugs when harms outweigh benefits, has shown potential to improve quality of life and reduce medication burden. The win-ratio method integrates patient priorities into composite outcomes, enhancing statistical power and accounting for competing risks like mortality. This approach can advance deprescribing research by focusing on patient-centered outcomes and improving study design for clinical trials. [Extracted from the article]

Azilsartan is an angiotensin II receptor blocker used for treating adult hypertension. It significantly improves cardiovascular outcomes in patients with high‐risk hypertension, heart failure, and diabetic nephropathy. A single‐center, randomized, open‐label, single‐dose, dual‐cycle, dual‐crossover clinical trial was conducted to evaluate the bioequivalence of azilsartan under fasting and postprandial conditions in 60 Chinese healthy volunteers. Thirty healthy subjects were enrolled in each test group, with random cross‐administration for fasting and postprandial tests. The concentration of azilsartan in human plasma was evaluated using liquid chromatography‐tandem mass spectrometry after a single oral administration of test and reference preparations, each at a dose of 20 mg (1 tablet). Pharmacokinetic parameters were determined using WinNonlin8.2 software, and bioequivalence was evaluated using SAS 9.4 software. The geometric mean ratios and 90% confidence intervals for maximum concentration, area under the plasma concentration‐time curve from time 0 to the time of last measurable concentration, and area under the plasma concentration‐time curve from time 0 to infinity of the test and reference preparations in the fasting and postprandial test groups were in the range of 80%‐125%. The incidence of adverse events in the fasting and postprandial test groups was 30% (9/30) and 33.3% (10/30), respectively. No serious adverse events or unexpected adverse drug reactions were observed. In conclusion, the test and reference preparations of azilsartan tablets demonstrate bioequivalence and good safety in healthy Chinese subjects under fasting and postprandial conditions. [ABSTRACT FROM AUTHOR]

Since there is no specific recommendation of sodium‐glucose cotransporter‐2 (SGLT‐2) inhibitors in acute myocardial infarction (MI), this systematic review and meta‐analysis was performed to address this lack of evidence. Scopus, Embase, PubMed, Web of Sciences, and Cochrane Library were searched from inception until May 30, 2024. We used both random and fixed‐effects models for data analyses. Odds ratio (OR) and standard means difference (SMD) were performed for binary and continuous variables, respectively. Nine studies including five randomized clinical trials (RCTs) and four observational studies including 15,595 individuals with acute MI were entered. Overall, SGLT‐2 inhibitors are significantly associated with a reduction of hospitalization for heart failure (OR, 0.78; 95% CI, 0.63 to 0.97; P =  .02; I2 = 0%) and all‐cause mortality (OR, 0.55; 95% CI, 0.38 to 0.81; P =  .002; I2 = 0%) based on the RCTs and observational studies, respectively. SGLT‐2 inhibitors also significantly improved the left ventricular ejection fraction (SMD, 0.36; 95% CI, 0.02 to 0.70; P =  .04; I2 = 62%) among RCTs. Further evaluation of these drugs also revealed an acceptable safety profile without any major adverse events. In conclusion, although SGLT‐2 inhibitors may have some clinical benefits among acute MI individuals, further RCTs are still needed to provide robust evidence regarding the use of SGLT‐2 inhibitors in this setting. [ABSTRACT FROM AUTHOR]

Background: Cardiac resynchronization therapy is an essential treatment for heart failure patients. Candidates typically have cardiomyopathy accompanied by delayed electrical activation in the left ventricular lateral wall, causing uncoordinated contractions and worsening heart failure. Heart failure severity can be assessed with functional tests: the cardiopulmonary test, which is a maximal exercise test, remains the gold standard, but the 6 min walk test has emerged as an easier, faster, and more comfortable alternative to be used by clinicians to adjust treatment protocols for cardiovascular and pulmonary conditions. Methods: This is a prospective observational study that included 69 patients from a single healthcare facility, and the purpose was to determine if the 6 min walk test results could be associated with changes in various electrocardiographic, clinical, functional, and demographic parameters. All the parameters and the 6 min walk distance were recorded at four key time moments: before the procedure and after 6, 9, and 12 months. The electrocardiographic parameters were obtained from the patients' electrocardiograms recorded in the four key moments and included variables such as QRS area, duration, percentage of biventricular pacing, and many others, while the functional variables included the monitored intraprocedural systolic blood pressure and the end-systolic left ventricular volume. We also aimed to check if clinical conditions such as diabetes and chronic kidney disease and demographic variables such as age or sex have any impact. Results and Conclusions: All this research was performed in order to identify which parameters hold a predictive value and can serve as future criteria for better patient selection and for defining a proper resynchronization outcome. The study shows that parameters such as diabetes and QRS duration have an impact over the 6 min walk distance. Also, newer variables such as the QRS area and the R/S ratio may represent a direction worth studying in order to predict the outcomes of cardiac resynchronization therapy. [ABSTRACT FROM AUTHOR]

Background: Percutaneous left atrial appendage closure (LAAC) reduces the incidence of stroke/bleeding events in patients with non-valvular atrial fibrillation, high risk of stroke, and contraindication in continuing anticoagulation therapy. Of them, patients with heart failure may remain at high risk of these events after LAAC. Method: Patients who underwent LAAC and were listed for the multi-center, prospectively collected OCEAN-LAAC registry, were eligible. Of them, individuals without baseline plasma B-type natriuretic peptide (BNP) levels and those dependent on hemodialysis were excluded. The prognostic impact of baseline plasma BNP levels on the incidence of death or stroke/bleeding events after LAAC was evaluated. Results: A total of 937 patients (median 78 years, 596 men) were included. The LAAC device was successfully implanted in 934 (98%) patients. Over the 366 (251, 436) days after the LAAC, 148 patients encountered a primary outcome. The common logarithm of baseline plasma BNP was independently associated with the primary outcome with an adjusted hazard ratio of 1.46 (95% confidence interval 1.06–2.18, p = 0.043). A calculated cutoff of 2.12 (equivalent to 133 pg/mL of plasma BNP level) significantly stratified the cumulative incidence of the primary outcome (29% vs. 21% for 2 years, p = 0.004). Conclusions: Using prospectively collected large-scale multi-center Japanese registry data, we demonstrated that a baseline higher plasma BNP level was independently associated with a higher incidence of stroke/bleeding events and mortality after LAAC. Further studies are warranted to understand the optimal therapeutic strategy for LAAC candidates with elevated baseline plasma BNP levels. [ABSTRACT FROM AUTHOR]

Natriuretic peptides (NPs) are polypeptide hormones involved in the homeostasis of the cardiovascular system. They are produced by cardiomyocytes and regulate circulating blood volume and sodium concentration. Clinically, measurements of brain natriuretic peptide (BNP) and N-terminal pro-BNP (NT-proBNP) are recommended by international guidelines as evidence is accumulating on their usefulness. They have a high negative predictive value, and in the setting of low NPs, a diagnosis of heart failure (HF) can be safely excluded in both emergency (BNP < 100 pg/mL, NT-proBNP < 300 pg/mL) and outpatient settings (BNP < 35 pg/mL and NT-proBNP < 125 pg/mL). Moreover, the 2023 consensus from the European Society of Cardiology suggests threshold values for inclusion diagnosis. These values are also associated with increased risks of major cardiovascular events, cardiovascular mortality, and all-cause mortality whether measured in inpatient or outpatient settings. Among patients without known HF, but at high risk of developing it (e.g., in the setting of diabetes mellitus, hypertension, or atherosclerotic cardiovascular disease), NPs may be useful in stratifying cardiovascular risk, optimizing therapy, and reducing the risk of developing overt HF. In the diabetes setting, risk stratification with the use of these peptides can guide the physician to a more informed and appropriate therapeutic choice as recommended by guidelines. Notably, NP levels should be carefully interpreted in light of certain conditions that may affect their reliability, such as chronic kidney disease and obesity, as well as demographic variables, including age and sex. In conclusion, NPs are useful in the diagnosis and prognosis of HF, but they also offer advantages in the primary prevention setting. [ABSTRACT FROM AUTHOR]

Background/Objectives: Heart failure worsens the prognosis of patients with infective endocarditis (IE) and is mainly caused by severe valvular regurgitation. The aim of our investigation is to describe the clinical, epidemiological, microbiological, and echocardiographic characteristics of patients with native left-sided infective endocarditis (NLSIE) with severe valvular regurgitation; to describe the prognosis according to the therapeutic approach; and to determine the prognostic factors of in-hospital mortality. Methods: We prospectively recruited all episodes of possible or definite NLSIE diagnosed at three tertiary hospitals between 2005 and 2022. Patients were divided into two groups: patients with severe valvular regurgitation at the time of admission or during hospitalization and patients without severe valvular regurgitation. We analyzed up to 85 variables concerning epidemiological, clinical, analytical, microbiological, and echocardiographic data. Results: We recovered 874 patients with NLSIE, 564 (65%) of them with severe valvular regurgitation. There were no differences in mortality among patients with and without severe regurgitation (30.2% vs. 26.5%, p = 0.223). However, mortality increased when patients with severe regurgitation developed heart failure (33% vs. 11.4%, p < 0.001). Independent factors related to heart failure were age (OR 1.02 [1.01–1.034], p = 0.001), anemia (OR 1.2 [1.18–3.31], p = 0.01), atrial fibrillation (OR 2.3 [1.08–4.89], p = 0.03), S. viridans-related IE (OR 0.47 [0.3–0.73], p = 0.001), and mitroaortic severe regurgitation (OR 2.4 [1.15–5.02], p = 0.019). Conclusions: Severe valvular regurgitation is very frequent among patients with NLSIE, but it does not worsen the prognosis of patients unless complicated with heart failure. [ABSTRACT FROM AUTHOR]

Background: Heart failure deaths have increased in recent years in the United States and are projected to continue to increase in the future. Rates of liver disease and cirrhosis have similarly increased in the United States. Patients with cirrhosis are at an elevated risk of heart failure with a worsened prognosis. As such, investigations of the epidemiology of these comorbid conditions are important. Methods: We obtained data on heart failure deaths among people with cirrhosis in the United States from 1999 to 2020 from the Centers for Disease Control Wide-ranging Online Data for Epidemiologic Research multiple cause of death database. Rates were analyzed for the population as a whole and for demographic subgroups. Results: From 1999 to 2020, there were 7424 cirrhosis-related heart failure deaths. Rates were higher among Black (AAMR ratio = 1.288, 95% CI: 1.282–1.295) and Asian people (AAMR ratio = 3.310, 95% CI: 3.297–3.323) compared to White people. Rates were also higher in rural areas than in urban areas (AAMR ratio = 1.266, 95% CI: 1.261–1.271). Rates increased over time across demographic subgroups. Conclusions: People with cirrhosis are at an elevated risk of heart failure death compared to the general population. Rates were particularly elevated in Asian people, Black people, males, and people living in rural areas. These data indicate a significant and previously underappreciated disease burden. Clinicians taking care of cirrhosis patients should be aware of the risk of heart failure and should collaborate with cardiac specialists as needed. [ABSTRACT FROM AUTHOR]

Correlation between echocardiographic and pathoanatomic variables and their prognostic value in murine cardiomyopathy models remain unknown. Using echocardiography, morphometrics, and survival monitoring, we characterized transgenic (TG) mice with dilated cardiomyopathy due to cardiac overexpression of β2‐adrenoceptors focusing on predicting heart failure (HF) risk and HF mortality. In 12‐month‐old non‐TG and TG mice, echocardiography was performed to determine left ventricular (LV) dimensions (d), wall thickness (h), and fractional shortening (FS). Animals were monitored for 3 months for survival. Organ weights and pathological events indicating left HF were determined. TG mice (n = 76) had reduced FS and enlarged LV, and 79% died of HF or likely arrhythmias during the follow‐up period while all non‐TG mice (n = 26) survived. These mice with left HF also had pulmonary congestion and hypertrophy/dilatation of the right ventricle (RV). Weights of lungs, RV, and atria were intercorrelated (r = 0.79–0.83) and also negatively correlated with FS × (h/d) index (r = −0.502 to −0.609). By FS × (h/d) tertiles, TG mice of low tertiles were identified with the highest mortality (96%) largely due to HF (76%). In conclusion, in aged cardiomyopathy mice a good correlation existed between echocardiographic and pathoanatomic variables. Echocardiography‐derived LV function and remodeling were useful in identifying a subgroup of TG mice with a high risk of HF and HF fatality. [ABSTRACT FROM AUTHOR]

This study investigates the role of gut microbiota in cardiovascular diseases, with an additional focus on pro-atherogenic metabolites. We use advanced network analysis and machine learning techniques to identify key microbial features linked to coronary artery disease (CAD) and heart failure with reduced ejection fraction (HFrEF). This cross-sectional study included 189 participants divided into three groups: coronary artery disease (n = 93), heart failure with reduced ejection fraction (n = 43), and controls (n = 53). Assessments included physical exams, echocardiography, dietary surveys, blood analysis, and fecal analysis. Gut microbiota composition was analyzed using next-generation sequencing (NGS) and quantitative polymerase chain reaction (qPCR). Statistical analysis methods for testing hypotheses and correlations, alpha and beta-diversity analyses, co-occurrence networks, and machine learning were conducted using Python libraries or R packages with multiple comparisons corrected using the Benjamini–Hochberg procedure. Significant gut microbiota alterations were observed, with higher Bacillota/Bacteroidota ratios in CAD and HFrEF groups compared to controls (p < 0.001). Significant differences were observed in α-diversity indices (Pielou, Chao1, Faith) between disease groups and controls (p < 0.001). β-diversity analyses also revealed distinct microbial profiles (p = 0.0015). Interestingly, trimethylamine N-oxide (TMAO) levels were lower in CAD and HFrEF groups compared to controls (p < 0.05), while indoxyl sulfate (IS) levels were comparable between the study groups. Co-occurrence network analysis and machine learning identified key microbial features linked to these conditions, highlighting complex interactions within the gut microbiota associated with cardiovascular disease. [ABSTRACT FROM AUTHOR]