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Purpose of Review: The purpose of this review is to describe the evidence behind various blood and imaging-based biomarkers that can improve the identification of congestion when not clearly evident on routine examination., Recent Findings: The natriuretic peptides (NPs) BNP and NT-proBNP have been shown to closely correlate with intra-cardiac filling pressures, both at baseline and when trended following improvement in congestion. Additionally, NPs rise well before clinical congestion is apparent so can be used as a tool to help identify subclinical HF decompensation. Additional serum-based biomarkers including MR-proANP and CA-125 can be helpful in assisting with diagnostic certainty when BNP or NT-proBNP are in the "grey zone" or when factors are present which may confound NP levels. Additionally, the emerging use of ultrasound techniques may enhance our ability to fine-tune the assessment and treatment of congestion. Biomarkers, including the blood-based natriuretic peptides and markers on bedside point of care ultrasound, can be used as non-invasive indices of hemodynamic congestion. These biomarkers are particularly valuable to incorporate when the degree of a patient's congestion is not apparent on clinical exam, and they can provide important prognostic information and help guide clinical management., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Purpose of Review: This review focuses on the association between RA and heart failure, highlighting the role of inflammation and the prevalence of heart failure with preserved ejection fraction (HFpEF) in this population., Recent Findings: The incidence of heart failure in RA patients is two to three times higher than in the general population, with inflammation playing a significant role independent of traditional cardiovascular risk factors. HFpEF accounts for about half of heart failure cases and is increasingly recognized in RA patients, although it remains underdiagnosed. Atypical presentations and non-specific symptoms further complicate diagnosis. Early control of inflammation has been shown to reduce the risk of heart failure development and progression, improving both morbidity and mortality outcomes. Rheumatoid arthritis (RA) is a systemic inflammatory disease affecting approximately 1% of the population, with cardiovascular disease being the leading cause of premature death in these patients., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: There is a little evidence regarding long-term safety and efficacy for atrial shunt devices in heart failure (HF)., Methods: The REDUCE LAP-HF I (n = 44) and II (n = 621) trials (RCT-I and -II) were multicenter, randomized, sham-controlled trials of patients with HF and ejection fraction >40%. Outcome data were analyzed from RCT-I, a mechanistic trial with 5-year follow-up, and RCT-II, a pivotal trial identifying a responder group (n = 313) defined by exercise PVR <1.74 WU and no cardiac rhythm management device with 3-year follow-up., Results: At 5 years in RCT I, there were no differences in cardiovascular (CV) mortality, HF events, embolic stroke, or new-onset atrial fibrillation between groups. After 3 years in RCT II, there was no difference in the primary outcome (hierarchical composite of CV mortality, stroke, HF events, and KCCQ) between shunt and sham in the overall trial. Compared to sham, those with responder characteristics in RCT-II had a better outcome with shunt (win ratio 1.6 [95% CI 1.2-2.2], P = .006; 44% reduction in HF events [shunt 9 vs. control 16 per 100 patient-years], P = .005; and greater improvement in KCCQ overall summary score [+17.9 ± 20.0 vs. +7.6 ± 20.4], P < .001), while nonresponders had significantly more HF events. Shunt treatment at 3 years was associated with a higher rate of ischemic stroke (3.2% vs. 0%, 95% CI 2%-6.1%, P = .032) and lower incidence of worsening kidney dysfunction (10.7% vs. 19.3%, P = .041)., Conclusions: With up to 5 years of follow up, adverse events were low in patients receiving atrial shunts. In the responder group, atrial shunt treatment was associated with a significantly lower HF event rate and improved KCCQ compared to sham through 3 years of follow-up., Gov Registration: NCT02600234, NCT03088033., Competing Interests: Conflict of Interest None., (Published by Elsevier Inc.)

Background: While Reddy proposed the H2FPEF diagnostic algorithm to aid in diagnosing heart failure with preserved ejection fraction (HFpEF), certain parameters like age and obesity are not suitable for Asian population, especially given the increasing incidence of HFpEF in younger individuals. Therefore, this study aimed to develop an easy-to-use nomogram with non-invasive indices that can be used in outpatient clinics in Taiwan to quickly estimate the probability of HFpEF and help decide whether further invasive cardiopulmonary exercise test (CPET) is needed., Methods: Outpatients with unexplained dyspnea and fatigue were recruited divided into HFpEF (n = 64) and non-HFpEF (n = 34) groups based on invasive CPET and echocardiography. Multivariate logistic regression analyses identified independent noninvasive variables for developing an HFpEF nomogram. The nomogram's performance was assessed and validated using the concordance index (C-index), area under the curve (AUC), calibration curves, and decision curve analysis., Results: Multivariate logistic regression analyses identified five independent noninvasive variables for developing an HFpEF nomogram, including dyslipidemia (OR = 5.264, p = 0.010), diabetes (OR = 3.929, p = 0.050), left atrial area (OR = 1.130, p = 0.046), hemoglobin <13 g/dL (OR = 5.372, p = 0.010), and NT-proBNP ≥245 pg/mL (OR = 5.108, p = 0.027). The nomogram showed good discriminatory ability (C-index = 0.842) and calibration performance (p = 0.873) and high net benefit (0.1-0.95). Notably, the HFpEF nomogram showed better diagnostic accuracy than the H 2 FPEF score model in predicting Taiwanese HFpEF patients (AUC: 0.873 vs. 0.608, p = 0.0006)., Conclusion: The noninvasive HFpEF nomogram provides a preliminary estimation of the probability of HFpEF in Taiwanese outpatients with unexplained dyspnea and fatigue, which may help the decision-making on further invasive CPET., Competing Interests: Declaration of Competing interest All authors declare that there is no conflict of interest., (Copyright © 2024 Formosan Medical Association. Published by Elsevier B.V. All rights reserved.)

The recognition of microthrombi in the heart microcirculation has recently emerged from studies in COVID-19 decedents. The present study investigated the ultrastructure of coronary microthrombi in heart failure (HF) due to cardiomyopathies that are unrelated to COVID-19 infection. In addition, we have investigated the role of von Willebrand factor (VWF) and PECAM-1 in microthrombus formation. We used electron microscopy to investigate the occurrence of microthrombi in patients with HF due to dilated (DCM, n = 7), inflammatory (MYO, n = 6) and ischemic (ICM, n = 7) cardiomyopathy and 4 control patients. VWF and PECAM-1 was studied by quantitative immunohistochemistry and Western blot. In comparison to control, the number of microthrombi was increased 7-9 times in HF. This was associated with a 3.5-fold increase in the number of Weibel-Palade bodies (WPb) in DCM and MYO compared to control. A fivefold increase in WPb in ICM was significantly different from control, DCM and MYO. In Western blot, VWF was increased twofold in DCM and MYO, and more than threefold in ICM. The difference between ICM and DCM and MYO was statistically significant. These results were confirmed by quantitative immunohistochemistry. Compared to control, PECAM-1 was by approximatively threefold increased in all groups of patients. This is the first study to demonstrate the occurrence of microthrombi in the failing human heart. The occurrence of microthrombi is associated with increased expression of VWF and the number of WPb, being more pronounced in ICM. These changes are likely not compensated by increases in PECAM-1 expression., (© 2024. The Author(s).)

The management of right heart failure during durable left ventricular assist device (LVAD) support remains an unsolved issue so far. We had a 44-year-old male patient who was diagnosed with arrhythmogenic right ventricular cardiomyopathy and received HeartMate 3 LVAD (Abbott, USA) implantation as a bridge-to-transplant indication. The pump speed was adjusted as low as 4500 rpm to avoid the left ventricular narrowing and interventricular septal leftward shift. Riociguat was administered to decrease the afterload of the right ventricle and increase the preload of the left ventricle, in addition to the combination of neurohormonal blockers. Frequent low-flow alarm events eventually disappeared after amlodipine administration, and he was successfully returned to work. We here present a unique management in a patient with right heart failure due to arrhythmogenic right ventricular cardiomyopathy during HeartMate 3 LVAD support., Competing Interests: Declarations. Conflict of interest: There is no conflict of interest related to this manuscript., (© 2024. The Japanese Society for Artificial Organs.)

We often encounter patients with congestive heart failure refractory to conventional diuretics therapy. Kampo goreisan (Tsumura &Co. Tokyo, Japan) is receiving great concern in mediating body water balance, particularly for such a cohort. However, its detailed biological mechanism remains uncertain. Patients who received goreisan to treat congestive heart failure refractory to tolvaptan-incorporated medical therapy were prospectively included and observed for one week during the therapeutic period. The change in urine biomarkers during the first 24 h was assessed as a primary concern. Baseline factors associated with an increase in urine volume during the first 24 h were investigated as a secondary concern. A total of 18 patients were included. Median age was 81 (77, 86) and 12 (67%) were men. During the first 24 h after the initiation of goreisan, urine cyclic AMP tended to decrease, urine aquaporin-2 decreased significantly, urine osmolality decreased significantly, and urine volume tended to increase. Baseline higher common logarithm of plasma B-type natriuretic peptide was associated with any increases in urine volume during the first 24 h with an odds ratio of 73.2 (95% confidence interval 1.04-5149, p = 0.048). Baseline plasma B-type natriuretic peptide level had a positive correlation with a change in urine volume between baseline and day 1 (r = 0.533, p = 0.026). Goreisan may increase urine volume even in patients with congestive heart failure refractory to tolvaptan-incorporated medical therapy by modulating aquaporin-2 systems in the collecting duct, particularly in individuals with advanced heart failure accompanying significant congestion. Goreisan may have a regulatory effect on body fluid, rather than just forcing aquaresis., Competing Interests: Declarations Conflict of interest The authors declare that they have no conflict of interest., (© 2024. Springer Nature Japan KK, part of Springer Nature.)

Purpose: Bleeding complication is a critical risk factor for outcomes of acute heart failure patients requiring mechanical circulatory support (MCS), including percutaneous catheter-type heart pumps (Impella). The Japanese registry for Percutaneous Ventricular Assist Device (J-PVAD) is an ongoing, large-scale, real-world registry to characterize Japanese patients requiring Impella. Here we analyzed bleeding complication profiles in patients who received Impella., Methods: All consecutive Japanese patients who received Impella from October 2017 to January 2020 were enrolled. The 30-day survival and bleeding complications were analyzed., Results: A total of 1344 patients were included: 653 patients received Impella alone, 685 patients received a combination of veno-arterial extracorporeal membrane oxygenation and Impella (ECPELLA), and 6 patients had failed Impella delivery. Overall 30-day survival was 67.0%, with Impella alone at 81.9% and ECPELLA at 52.7%. Overall bleeding/hematoma adverse events with a relation or not-excluded relation to Impella was 6.92%. Among them, the rates of hematoma and bleeding from medical device access sites were 1.41% and 4.09%, respectively. There was no difference between etiologies for these events., Conclusion: This study represents the first 3-year survival and the safety profile focused on bleeding adverse events from the J-PVAD registry. The results show that the real-world frequency of bleeding adverse events for patients who received Impella was an expected range from previous reports, and future real-world studies should aim to expand this data set to improve outcomes and adverse events., Competing Interests: Declarations. Conflict of interest: This study was partially funded by the Japanese Abiomed Post-Market Surveillance Program. The authors declare no additional conflicts of interest. IRB information: “Catheter-type ventricular assist device registry study”, Graduate School of Medicine/Faculty of Medicine, Osaka University Ethics Committee, Approval #17232., (© 2024. The Japanese Society for Artificial Organs.)

Iron is an essential element for the biological processes of living organisms, including the production of crucial oxygen-carrying proteins, formation of heme enzymes, and playing roles in electron transfer and oxidation-reduction reactions. It plays a significant role in various cardiovascular functions, including bioenergetics, electrical activity, and programmed cell death. Minor deficiencies of iron have been found to have negative impact on cardiovascular function in patients with heart failure (HF). The contractility of human cardiomyocytes is impaired by iron deficiency (ID), which results in reduced mitochondrial function and lower energy production, ultimately leading to cardiac function impairment, contributing to significant morbidity and mortality in patients with HF. This review discusses iron homeostasis within the human body, as well as ID pathophysiology and its role in HF. Focusing on therapeutic approaches including iron supplementation and/or repletion in patients with ID and HF, comparing results from recent clinical trials. Intravenous (IV) iron therapy has shown promising results in treating ID in HF patients. Large, randomized trials and meta-analysis, like Ferinject Assessment in patients with ID and chronic HF, AFFIRM-AHF, IRONMAN, and HEART-FID have demonstrated the efficacy of IV iron supplementation with IV ferric carboxymaltose or IV ferric derisomaltose in reducing hospitalizations and improving quality of life in patients with Heart Failure with reduced ejection fraction (HFrEF), New York Heart Association (NYHA) II-III. However, survival and mortality have demonstrated no improvement during acute exacerbations of HF or in outpatient management. The potential benefits of IV iron across the entire HF spectrum and its interaction with other HF therapies remain areas of interest for further research., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Sodium-glucose cotransporter 2 inhibitors (SGLT2i), have shown benefits in patient with heart failure (HF), however, adherence remains a significant issue: with only 60% of patients continuing usage beyond a year. This study aims to identify patients at risk of discontinuing SGLT2i and promote its judicious use to reduce hospitalizations and improve cardiovascular outcomes. Using the Korean National Health Insurance Service database, patients diagnosed with HF and diabetes mellitus (n = 1,665,565) between 2013 and 2018 were identified. Among them, 55,694 participants prescribed SGLT2i were enrolled. The primary endpoint included 1) all-cause mortality and 2) SGLT2i-related hospitalization, encompassing incidents such as ketoacidosis, acute kidney injury, urinary tract infections, fall-related fractures, and other unplanned hospitalizations. During the follow-up period (median: 2.3 years; range: 1.2-3.6 years), 8,463 participants reached the primary endpoint (25.5 for all-cause death and 39.4 for SGLT2i-related hospitalizations per 1,000 person-years). Independent risk factors for the primary endpoint in multivariate Cox regression and propensity-score matching analyses included age of ≥ 70 years, body mass index (BMI) <18.5 kg/m2, body weight <60 kg, anemia, chronic kidney disease, and the use of diuretics. Age (hazard ratio [HR] 1.45, 95% confidence interval [CI]: 1.36-1.54), BMI (HR 1.78, 95% CI: 1.29-2.45), body weight (HR 1.17, 95% CI: 1.09-1.26) and the use of furosemide (HR 1.45, 95% CI: 1.22-1.74) (all p<0.001) were consistent independent risk factors in the propensity score-matched cohort. Having three or more risk factors was associated with an adjusted HR that was 3.04 times higher than cases with no risk factor (95% CI: 2.83-3.28, p<0.001). Old age, low weight or BMI, and the use of diuretics are risk factors that hinder the continuous use of SGLT2i in diabetic patients with HF. Close monitoring for side effects is essential when prescribing SGLT2i, particularly for those with multiple risk factors., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Kim et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Aims: Wild-type transthyretin cardiac amyloidosis (ATTRwt-CM) is an under-recognized aetiology of heart failure (HF), necessitating early detection for timely treatment. Our study aimed to differentiate patients with ATTRwt-CM from ATTRwt-negative HFpEF/HFmrEF patients by identifying and validating circulating protein biomarkers. In addition, we measured the same biomarkers in patients with cardiomyopathy due to light chain amyloidosis (AL)-CM to gain disease-specific insights., Methods and Results: In this observational study, serum concentrations of 363 protein biomarkers were measured in a discovery cohort consisting of 73 ATTRwt-CM, 55 AL-CM, and 59 ATTRwt-negative HFpEF/HFmrEF patients, using multiplex proximity extension assays. Sparse partial least squares analyses showed overlapping ATTRwt-CM and AL-CM biomarker profiles with clear visual differentiation from ATTRwt-negative patients. Pathway analyses with g:Profiler revealed significantly up-regulated proteoglycans (PG) and cell adhesion pathways in both ATTRwt-CM and AL-CM. Penalized regression analysis revealed that the proteoglycan decorin (DCN), lysosomal hydrolase alpha-L-iduronidase (IDUA) and glycosyl hydrolase galactosidase β-1 (GLB-1) most effectively distinguished ATTRwt-CM from ATTRwt-negative patients (R2 = 0.71). In a prospective validation cohort of 35 ATTRwt-CM patients and 25 ATTRwt-negative patients, DCN and IDUA significantly predicted ATTRwt-CM in the initial analysis (DCN: OR 3.3, IDUA: OR 0.4). While DCN remained significant after correcting for echocardiographic parameters, IDUA did not. DCN showed moderate discriminative ability (AUC, 0.74; 95% CI, 0.61-0.87; sensitivity, 0.91; specificity, 0.52) as did IDUA (AUC, 0.78; 95% CI, 0.65-0.91; sensitivity, 0.91; specificity, 0.61). A model combining clinical factors (AUC 0.92) outperformed DCN but not IDUA, a combination of the biomarkers was not significantly better. Neither DCN nor IDUA correlated with established disease markers., Conclusion: ATTRwt-CM has a distinctly different biomarker profile compared with HFpEF/HFmrEF, while ATTRwt-CM patients share a similar biomarker profile with AL-CM patients characterized by up-regulation of proteoglycans and cell-adhesion pathways. The biomarkers DCN and IDUA show the potential to serve as an initial screening tool for ATTTRwt-CM. Further research is needed to determine the clinical usefulness of these and other extracellular matrix components in identifying ATTRwt-CM., Competing Interests: Conflict of interest: Alwin Tubben: none. George Markousis-Mavrogenis: none. Laura M.G. Meems: none. Bart van Essen: none. Lukas Baumhove: none. Milou Berends: none. Hendrea S.A. Tingen: none. Johan Bijzet: none. Bouke P.C. Hazenberg: none. Adriaan A. Voors: The UMCG, which employs AAV, received consultancy fees or research support from Anacardio, AstraZeneca, BMS, Bayer, Boehringer Ingelheim, Cytokinetics, Corteria, EliLilly, Merck, Moderna, Novartis, NovoNordisk, Roche Diagnostics. Dirk-Jan van Veldhuisen: none. Riemer H.J.A. Slart: The UMCG, which employs RHJAS, received grant support of Pfizer and Siemens Healthineers. Hans L.A. Nienhuis: The UMCG, which employs HLAN, received consultancy fees and speaking honorarium from Pfizer and Alnylam. Peter van der Meer: PvdM is supported by a grant from the European Research Council (ERC CoG 101045236, DISSECT-HF). The UMCG, which employs PvdM, received consultancy fees and/or grants from Novartis, Pharmacosmos, Vifor Pharma, Astra Zeneca, Pfizer, Pharma Nord, BridgeBio, Novo Nordisk, Boehringer Ingelheim and Ionis., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Heart failure (HF) constitutes a substantial burden on healthcare systems worldwide, contributing to elevated rates of mortality and morbidity. Iron deficiency (ID), both with and without concurrent anemia, has been identified in up to half of all patients with CHF and is associated with an increased risk of HF exacerbations, higher rates of hospitalization, and diminished quality of life. However, data from resource-limited settings remain limited. In this study, we reviewed 108 adult Yemeni patients with HF who also had concomitant ID, defined as serum ferritin concentrations of < 100 ng/mL or 100-299 ng/mL with transferrin saturation < 20%. The prevalence of ID among HF patients was determined, and independent predictors of ID were assessed using univariate and multivariate regression analyses. Anemia was present in 64 (59.3%), ID was observed in 65 (60.2%), and both anemia and ID were concurrently present in 44 (40.7%) patients. The mean ejection fraction among the study cohort was 34.2 ± 6.3%. Multivariate regression analysis identified New York Heart Association class III (OR: 4.46; 95% CI: 1.65-12.90, p = 0.004), presence of anemia (OR: 3.95; 95% CI: 1.51-11.23, p = 0.007), and an EF < 30% (OR: 9.42; 95% CI: 1.97-54.64, p = 0.007) as independent predictors of ID. These findings highlight the potential under-recognition of ID in patients with congestive HF, suggesting the need for routine assessment of iron status in this patient population., Competing Interests: Declarations. Competing interests: The authors declare no competing interests. Ethics declarations: All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. This study was approved by Ibb University’s Ethics Committee (Code number: IBBUNI.AC.YEM.2023.117). Consent to participate/Consent to publish: All patients provided written informed consent to be involved in this study., (© 2024. The Author(s).)

Purpose of Review: Since the turn of the millennium, obesity has been on the rise worldwide, and particularly so throughout the United States. Even more concerning is the rate at which persons with severe obesity continue to trend upwards. Given the detrimental effects of obesity on cardiac structure and function, it is not surprising that obesity stands as one of the leading risk factors for developing heart failure (HF). This state-of-the-art article aims to review the updated literature on the obesity paradox to help further understand its relationship to body composition, weight loss, fitness, and exercise., Recent Findings: An intriguing phenomenon appears to exist in which obesity is associated with a better prognosis in those with HF, compared to patients with lesser body mass. Recent studies suggest, however, that weight loss induced by pharmacologic strategies might be beneficial in patients with HF with preserved ejection fraction. Despite the presence of an obesity paradox, recent data suggest that obesity could be targeted in HF, however, long-term data are currently lacking. Consequently, definitive guidelines for managing obesity, and specifically the body composition of these patients, remain amiss., Competing Interests: Declarations Ethical Approval This article does not contain any studies with human or animal subjects performed by any of the authors. Competing Interests The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Current treatment recommendations for patients with heart failure and secondary mitral regurgitation include transcatheter edge-to-edge repair and mitral-valve surgery. Data from randomized trials comparing these therapies are lacking in this patient population., Methods: In this noninferiority trial conducted in Germany, patients with heart failure and secondary mitral regurgitation who continued to have symptoms despite guideline-directed medical therapy were randomly assigned, in a 1:1 ratio, to undergo either transcatheter edge-to-edge repair (intervention group) or surgical mitral-valve repair or replacement (surgery group). The primary efficacy end point was a composite of death, hospitalization for heart failure, mitral-valve reintervention, implantation of an assist device, or stroke within 1 year after the procedure. The primary safety end point was a composite of major adverse events within 30 days after the procedure., Results: A total of 210 patients underwent randomization. The mean (±SD) age of the patients was 70.5±7.9 years, 39.9% were women, and the mean left ventricular ejection fraction was 43.0±11.7%. Within 1 year, at least one of the components of the primary efficacy end point occurred in 16 of the 96 patients with available data (16.7%) in the intervention group and in 20 of the 89 with available data (22.5%) in the surgery group (estimated mean difference, -6 percentage points; 95% confidence interval [CI], -17 to 6; P<0.001 for noninferiority). A primary safety end-point event occurred in 15 of the 101 patients with available data (14.9%) in the intervention group and in 51 of the 93 patients with available data (54.8%) in the surgery group (estimated mean difference, -40 percentage points; 95% CI, -51 to -27; P<0.001)., Conclusions: Among patients with heart failure and secondary mitral regurgitation, transcatheter edge-to-edge repair was noninferior to mitral-valve surgery with respect to a composite of death, rehospitalization for heart failure, stroke, reintervention, or implantation of an assist device in the left ventricle at 1 year. (Funded by Abbott Vascular; MATTERHORN ClinicalTrials.gov number, NCT02371512.)., (Copyright © 2024 Massachusetts Medical Society.)

Background: Whether transcatheter mitral-valve repair improves outcomes in patients with heart failure and functional mitral regurgitation is uncertain., Methods: We conducted a randomized, controlled trial involving patients with heart failure and moderate to severe functional mitral regurgitation from 30 sites in nine countries. The patients were assigned in a 1:1 ratio to either transcatheter mitral-valve repair and guideline-recommended medical therapy (device group) or medical therapy alone (control group). The three primary end points were the rate of the composite of first or recurrent hospitalization for heart failure or cardiovascular death during 24 months; the rate of first or recurrent hospitalization for heart failure during 24 months; and the change from baseline to 12 months in the score on the Kansas City Cardiomyopathy Questionnaire-Overall Summary (KCCQ-OS; scores range from 0 to 100, with higher scores indicating better health status)., Results: A total of 505 patients underwent randomization: 250 were assigned to the device group and 255 to the control group. At 24 months, the rate of first or recurrent hospitalization for heart failure or cardiovascular death was 37.0 events per 100 patient-years in the device group and 58.9 events per 100 patient-years in the control group (rate ratio, 0.64; 95% confidence interval [CI], 0.48 to 0.85; P = 0.002). The rate of first or recurrent hospitalization for heart failure was 26.9 events per 100 patient-years in the device group and 46.6 events per 100 patient-years in the control group (rate ratio, 0.59; 95% CI, 0.42 to 0.82; P = 0.002). The KCCQ-OS score increased by a mean (±SD) of 21.6±26.9 points in the device group and 8.0±24.5 points in the control group (mean difference, 10.9 points; 95% CI, 6.8 to 15.0; P<0.001). Device-specific safety events occurred in 4 patients (1.6%)., Conclusions: Among patients with heart failure with moderate to severe functional mitral regurgitation who received medical therapy, the addition of transcatheter mitral-valve repair led to a lower rate of first or recurrent hospitalization for heart failure or cardiovascular death and a lower rate of first or recurrent hospitalization for heart failure at 24 months and better health status at 12 months than medical therapy alone. (Funded by Abbott Laboratories; RESHAPE-HF2 ClinicalTrials.gov number, NCT02444338.)., (Copyright © 2024 Massachusetts Medical Society.)

Background: Congenital heart defects can lead to right ventricular (RV) pressure-overload and heart failure. Cell-based therapies, including mesenchymal stromal cells (MSCs) and c-kit positive cells (CPCs) have been studied clinically as options to restore heart function in disease states. Many studies have indicated these cells act through paracrine mechanisms to prevent apoptosis, promote cellular function, and regulate gene/protein expression. We aimed to determine the proteomic response of diseased hearts to cell therapy., Methods: We utilized a juvenile rat model of RV pressure overload created by banding the pulmonary artery (PAB). Two weeks post-banding, bone marrow-derived mesenchymal stromal cells (MSCs) and 3 populations of CPCs (nCPCs, cCPCs, ES-CPCs) were delivered to the RV free wall. RV function and cellular retention were measured for four weeks post-injection, at which point hearts were extracted and the RV was excised for liquid chromatography and tandem mass spectrometry. Resulting RV proteomes were compared and analyzed using systems biology and bioinformatics., Results: Proteomic profiling identified 1156 total proteins from the RV, of which 5.97% were significantly changed after PAB. This disease-altered proteome was responsive to cellular therapy, with 72% of the PAB-altered proteome being fully or partially reversed by MSC therapy. This was followed by nCPCs (54%), ES-CPCs (52%), and cCPCs (39%). Systems biology and bioinformatics analysis showed MSC, nCPC, or ES-CPC cell therapy is associated with a decrease in predicted adverse cardiac effects. We also observed an effect of cell therapy on the non-altered RV proteome, however, this was associated with minor predicted pathological endpoints., Conclusions: Our data indicate MSCs, ES-CPCs, and nCPCs significantly reverse the PAB-altered proteome towards a pre-disease state in our animal model. These results indicate cell-based therapies show promise in improving RV function after pressure overload through partial restoration of the disease-altered cardiac proteome., Competing Interests: Declarations Ethics approval and consent to participate This study was approved by the Institutional Review Board at Children’s Healthcare of Atlanta and Emory University for the isolation of human c-kit positive cells from patients (Protocol title: Molecular and Cellular Characterization of Cardiac Tissue in Postnatal Development; Protocol number: IRB00005500; approved on 08/15/2017). The patients or their guardians/legally authorized representatives provided written informed consent for participation in the study and the use of samples. All animal experiments were performed with the approval of the Institutional Animal Care and Use Committee of Emory University (Protocol title: Development of novel therapies for right heart failure; Protocol number: DAR-4000044-ENTRPR-N; approved on 09/12/2017) and conform to the guidelines from the NIH Guide for the Care and Use of Laboratory Animals. Consent for publication Not applicable. Competing interests The authors declare they have no competing interests., (© 2024. The Author(s).)

Introduction/background: Chronic heart failure (CHF) has important gender-specific aspects, which are worthy of note, as they influence the haemodynamic state of patients the choice of therapy, aetiology, and clinical outcomes. Women are less frequently represented in CHF studies and clinical trials than males. While some published data are conflictive, more studies tailored to this critical discourse are necessary to inform patient care and improve outcomes in patients with CHF., Objectives: The study aims to describe the rationale, design and clinical presentations, profile, and 1-year outcomes of the first 1290 CHF in the Ibadan CHF project., Materials/methods: We analyzed the differences between the genders regarding the aetiology of heart disease, comorbidities, triggers, left ventricle functional state, treatment, and all cause-mortality at 1 year., Results: A total of 1290 patients (55.8% men) were included. The men were older than the women (p<.001) and had a higher prevalence of alcohol and cigarette use, comorbidities, and worse cardiac structural abnormalities (p<.001). The are also gender differences in the pattern of aetiology of HF. HHF, DCM, and pericardial diseases are more common in men. Women have higher rates of rheumatic heart disease. Mortality rates at 6- and 12 months were higher in men., Conclusions: There is a gender difference in clinical profile and outcomes of CHF in this cohort. Males appear to have a worse clinical profile, structural cardiac abnormalities as well as worse one-year outcomes., Competing Interests: The Authors declare that no competing interest exists, (Copyright © 2024 by West African Journal of Medicine.)

Background and Objectives : Heart failure (HF) is one of the most common initial presentations of cardiovascular disease (CVD) in patients with type 2 diabetes mellitus (T2DM). There are different cardiac biomarkers related to the pathophysiological mechanisms of HF in T2DM. The current research aims to identify additional biomarkers that could improve the diagnosis and prognosis of HFpEF, which is currently assessed using NT pro-BNP levels. NT pro-BNP is a valuable tool for diagnosing heart failure but may not always correlate with clinical symptom severity or can present normal levels in certain cases, such as obesity. Biomarkers like FGF-21 and galectin-3 could provide greater insight into heart failure severity, especially in diabetic patients. The main objective of the current study is to assess the performance of NT-proBNP, FGF21, Galectin-3 and Copeptin to discriminate between advanced and mild HF. Materials and Methods : A total of 117 patients were enrolled in this study and divided into two groups: 67 patients in NYHA functional class I-II (mild HF) and 50 patients in NYHA III-IV (advanced HF). NT-pro BNP, FGF21, Galectin 3 and Copeptin serum levels were determined with the ELISA method. Receiver operating characteristic (ROC) analysis and binomial logistic regression analysis were used to measure the ability of the studied biomarkers to distinguish between advanced and mild HF patients. Results : In patients with T2DM with advanced HF, serum FGF21 level was significantly positively correlated with eGFR (ρ = 0.35, p = 0.0125) and triglycerides (ρ = 0.28, p = 0.0465) and significantly negatively correlated with serum levels of HDL cholesterol (ρ = -0.29, p = 0.0386) and with RV-RA gradient (ρ = -0.30, p = 0.0358). In patients with mild HF, serum FGF21 level was significantly negatively correlated with NT-proBNP levels (ρ = -0.37, p = 0.0022), E/e' ratio (ρ = -0.29, p = 0.0182), TR velocity (ρ = -0.24, p = 0.0470) and RV-RA gradient (ρ = -0.24, p = 0.0472). FGF21 (AUC = 0.70, 95% CI: 0.60-0.79) and NT-proBNP (AUC = 0.73, 95% CI: 0.63-0.82) demonstrated significant predictive value to discriminate T2DM patients with advanced HF from those with mild HF. Elevated values for FGF21 (≥377.50 ng/mL) or NTproBNP (≥2379 pg/mL) were significantly associated with increased odds of advanced HF after adjusting for demographic and clinical covariates. Conclusions : NTpro-BNP and FGF21 have a similar ability to discriminate T2DM patients with advanced HF from those with mild HF. Univariable and multivariable logistic models showed that, FGF21 and NTproBNP were independent predictors for advanced HF in patients with preserved and mildly reduced ejection fraction and T2DM.

Background: Healthcare policy implemented during the COVID-19 pandemic may have impacted the health of patients with heart failure. Australian data provide a unique opportunity to examine service disruption independent of significant COVID-19 burden. This study aimed to examine heart failure care during the pandemic in New South Wales (NSW)., Methods: Analysis of hospital utilisation among patients aged ≥ 18 years with a primary diagnosis of heart failure conducted using linked administrative health records from hospital admission, emergency department, non-admitted services, and mortality data collections. Health service utilisation and outcomes were compared "Pre-pandemic" (PP): 16th March 2018 - 28th August 2019 and "During pandemic" (DP): 16th March 2020 - 28th August 2021. Mortality data were available until December 2021., Results: Heart failure-related ED presentations and hospital admissions were similar between the periods (PP = 15,324 vs DP = 15,023 ED presentations, PP = 24,072 vs DP = 23,145 hospital admissions), though rates of admission from ED were lower DP (PP = 12,783/15,324 (83.4% [95% CI 82.8-84.0]) vs DP = 12,230/15,023 (81.4% [95% CI 80.8-82.0%]). There was no difference according to age, sex, rurality, or socioeconomic status. Outpatient volume reduced DP (PP = 44,447 vs DP = 35,801 occasions of service), but telehealth visits increased nearly threefold (PP = 5,978/44,447 (13.4% [95% CI 13.1-13.8%]) vs DP = 15,901/35,801 (44.4% [95% CI 43.9-44.9%]) with highest uptake among the wealthy and those in major cities. Time to heart failure-related ED presentation, hospitalisation or all-cause mortality following index admission was longer DP (PP = 273 [IQR 259, 290] days, DP = 323 [IQR 300, 342] days, HR 0.91 [95% CI 0.88, 0.95])., Conclusions: Policies implemented DP had minimal impact on volumes of inpatient heart failure care in NSW hospitals, but there were fewer admissions from ED and reduced volumes of publicly funded outpatient care. A rapid shift from patient-facing to remotely delivered care enabled compliance with restrictions and was associated with increased time to heart failure-related adverse events, but access was not afforded equally across the socio-demographic spectrum., (© 2024. The Author(s).)

Background and Aims: The efficacy and safety of early sacubitril/valsartan (Sac/Val) initiation after acute heart failure (AHF) has not been demonstrated outside North America. The present study aimed to evaluate the effect of in-hospital Sac/Val therapy initiation after an AHF episode on N-terminal pro-B-type natriuretic peptide (NT-proBNP) level in Japanese patients., Methods: This was an investigator-initiated, multicentre, prospective, randomized, open-label, blinded-endpoint pragmatic trial. After haemodynamic stabilization within 7 days after hospitalization, eligible inpatients were allocated to switch from angiotensin-converting enzyme inhibitor or angiotensin receptor blocker to Sac/Val (Sac/Val group) or to continue angiotensin-converting enzyme inhibitor or angiotensin receptor blocker (control group). The primary efficacy endpoint was the 8-week proportional change in geometric means of NT-proBNP levels., Results: A total of 400 patients were equally randomized, and 376 (median age 75 years, 31.9% women, de novo heart failure rate 55.6%, and median left ventricular ejection fraction 37%) were analysed. The per cent changes in NT-proBNP level geometric means at Weeks 4/8 were -35%/-45% (Sac/Val group) and -18%/-32% (control group), and their group ratio (Sac/Val vs. control) was 0.80 (95% confidence interval 0.68-0.94; P = .008) at Week 4 and 0.81 (95% confidence interval 0.68-0.95; P = .012) at Week 8, respectively. In the pre-specified subgroup analyses, the effects of Sac/Val were confined to patients with a left ventricular ejection fraction < 40% and were more evident in those in sinus rhythm and taking mineralocorticoid receptor antagonists. No adverse safety signal was evident., Conclusions: In-hospital Sac/Val therapy initiation in addition to contemporary recommended therapy triggered a greater NT-proBNP level reduction in Japanese patients hospitalized for AHF. These findings may expand the evidence on Sac/Val therapy in this clinical situation outside North America., Clinical Trial Registration: ClinicalTrial.gov (NCT05164653) and Japan Registry of Clinical Trials (jRCTs021210046)., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)

This study investigated sex differences in clinical characteristics and in-hospital outcomes of heart failure (HF) hospitalizations using the National Inpatient Sample data, 2016-2019. HF hospitalizations ≥ 41 years of age were included and stratified by sex. Study outcomes were in-hospital mortality, prolonged length of stay, mechanical ventilation, mechanical circulatory support, vasopressor use, and disposition other than home. Propensity score matched regression analysis was done to compare outcomes between sex. A total of 4,704,684 primary HF hospitalizations were included in the analysis. Of these, 2,447,784 (52.0%) were males and 2,256,899 (48.0%) were females. Regression analysis showed that females had significantly lower odds for mortality (aOR, 0.92, 95% CI: 0.89-0.94), mechanical ventilation (aOR, 0.89, 95% CI: 0.86-0.92), mechanical circulatory support (aOR, 0.54, 95% CI: 0.51-0.58), and vasopressor use (aOR, 0.71, 95% CI: 0.66-0.74), compared to males. However, the odds for prolonged length of stay (aOR, 1.05, 95% CI: 1.04-1.06) and disposition other than home (aOR, 1.32, 95% CI: 1.31-1.34) were significantly higher among females, compared to males. There were significant differences in outcomes between males and females hospitalized for HF. Further research is required to delineate how sex affects several aspects of HF, including epidemiology, risk factors, pathogenesis, and response to medications., (© 2024. The Author(s).)

Background: Electrolyte abnormalities (EAs) worsen the clinical course of patients with heart failure (HF). The patterns of EAs vary among patients with HF. This study investigated patterns and factors associated with EAs among patients with HF admitted to Hoima Regional Referral Hospital (HRRH) in western Uganda., Methods: This hospital-based cross-sectional study used quantitative data of 384 HF patients admitted at HRRH between 21st February and 15th May 2023. Data on sociodemographic, lifestyle, and medical characteristics were collected and presented as descriptive statistics. EAs were considered electrolyte values below or above the reference normal ranges. Bivariate and multiple logistic regression analyses were conducted to establish associations. An association with a p < 0.05 is considered statistically significant., Results: Of 384 HF patients, 342 (89.1%) had EAs. Hypocalcemia was the most common EA, 165 (43.0%). Among the patients, 69 (18.0%) were on diuretics, 185 (48.2%) were on angiotensin-converting enzyme inhibitors (ACEIs)/angiotensin receptor blockers (ARBs), and 105 (27.3%) were on calcium channel blockers (CCBs). Additionally, 264 (68.8%) had a history of hypertension, and 20 (5.2%) demonstrated good drug adherence. Patients with good drug adherence had lower odds of EAs (Adjusted Prevalence Odds Ratio [Adjusted POR] = 0.2, 95% CI: 0.1-0.7, p = 0.009). Those on diuretics had higher odds of EAs compared to those on ACEIs/ARBs and CCBs, with an Adjusted POR of 5.7 (95% CI: 1.3-15.0, p = 0.019). A history of hypertension also increased the odds of EAs (Adjusted POR = 4.0, 95% CI: 1.9-8.4, p < 0.001)., Conclusions: The prevalence of EAs in patients with HF at HRRH was high, with hypocalcemia being the most common. Patients with good drug adherence had lower odds of EAs. On the other hand, diuretic use and a history of hypertension were associated with increased odds of EAs., (© 2024. The Author(s).)

Background: Optimal medical treatment can lead to improvement in left ventricular ejection fraction (LVEF) in patients with heart failure with reduced EF (HFrEF). We investigated the characteristics, predictors, and outcomes of HFrEF according to the 1-year LVEF following angiotensin receptor-neprilysin inhibitors therapy (ARNI)., Methods and Results: Using the STRATS-HF-ARNI (Strain for Risk Assessment and Therapeutic Strategies in Patients With Heart Failure Treated With Angiotensin Receptor-Neprilysin Inhibitor) registry, we identified 1074 patients with HFrEF who took ARNI and underwent baseline and 1-year echocardiography. Patients were classified as HF with improved ejection fraction (HFimpEF) and persistent HFrEF (perHFrEF) (1-year LVEF >40% and ≤40%). The primary and secondary outcomes were all-cause and cardiac mortality from the 1-year follow-up. Among 1074 included patients, 498 (46.4%) had HFimpEF, and 576 (53.6%) had perHFrEF. Older age, male sex, and large LV end-diastolic volumes were positive predictors of perHFrEF, whereas atrial fibrillation and high systolic blood pressure were identified as inverse predictors. Patients with HFimpEF showed lower all-cause and cardiac mortality rates (both log-rank P <0.001). In the multivariable analysis, perHFrEF (hazard ratio, 2.402 [95% CI, 1.251-4.610]; P =0.008) was an independent predictor of poor outcomes. The risk of all-cause mortality decreased as the 1-year LVEF increased up to 40%; however, no additional risk reduction was observed beyond 40%. Compared with patients taking renin-angiotensin-aldosterone system inhibitors in the STRATS-AHF (Strain for Risk Assessment and Therapeutic Strategies in Patients With Acute Heart Failure) registry, those in the STRATS-HF-ARNI registry demonstrated better outcomes in both HFimpEF and perHFrEF., Conclusions: Patients with HFimpEF had better prognosis than those with perHFrEF, and ARNI treatment in HFrEF could be more beneficial than renin-angiotensin-aldosterone system inhibitors for both HFimpEF and perHFrEF., Registration: URL: https://www.who.int/clinical-trials-registry-platform; Unique identifier: KCT0008098.

Importance: Serial functional status assessments are critical to heart failure (HF) management but are often described narratively in documentation, limiting their use in quality improvement or patient selection for clinical trials., Objective: To develop and validate a deep learning natural language processing (NLP) strategy for extracting functional status assessments from unstructured clinical documentation., Design, Setting, and Participants: This diagnostic study used electronic health record data collected from January 1, 2013, through June 30, 2022, from patients diagnosed with HF seeking outpatient care within 3 large practice networks in Connecticut (Yale New Haven Hospital [YNHH], Northeast Medical Group [NMG], and Greenwich Hospital [GH]). Expert-annotated notes were used for NLP model development and validation. Data were analyzed from February to April 2024., Exposures: Development and validation of NLP models to detect explicit New York Heart Association (NYHA) classification, HF symptoms during activity or rest, and frequency of functional status assessments., Main Outcomes and Measures: Outcomes of interest were model performance metrics, including area under the receiver operating characteristic curve (AUROC), and frequency of NYHA class documentation and HF symptom descriptions in unannotated notes., Results: This study included 34 070 patients with HF (mean [SD] age 76.1 [12.6] years; 17 728 [52.0]% female). Among 3000 expert-annotated notes (2000 from YNHH and 500 each from NMG and GH), 374 notes (12.4%) mentioned NYHA class and 1190 notes (39.7%) described HF symptoms. The NYHA class detection model achieved a class-weighted AUROC of 0.99 (95% CI, 0.98-1.00) at YNHH, the development site. At the 2 validation sites, NMG and GH, the model achieved class-weighted AUROCs of 0.98 (95% CI, 0.96-1.00) and 0.98 (95% CI, 0.92-1.00), respectively. The model for detecting activity- or rest-related symptoms achieved an AUROC of 0.94 (95% CI, 0.89-0.98) at YNHH, 0.94 (95% CI, 0.91-0.97) at NMG, and 0.95 (95% CI, 0.92-0.99) at GH. Deploying the NYHA model among 182 308 unannotated notes from the 3 sites identified 23 830 (13.1%) notes with NYHA mentions, specifically 10 913 notes (6.0%) with class I, 12 034 notes (6.6%) with classes II or III, and 883 notes (0.5%) with class IV. An additional 19 730 encounters (10.8%) could be classified into functional status groups based on activity- or rest-related symptoms, resulting in a total of 43 560 medical notes (23.9%) categorized by NYHA, an 83% increase compared with explicit mentions alone., Conclusions and Relevance: In this diagnostic study of 34 070 patients with HF, the NLP approach accurately extracted a patient's NYHA symptom class and activity- or rest-related HF symptoms from clinical notes, enhancing the ability to track optimal care delivery and identify patients eligible for clinical trial participation from unstructured documentation.

Background: Heart failure is a rare manifestation of metastatic disease of the carcinoma of an unknown primary, malignancy that requires extensive work-up to identify the primary site. Initial consideration of rare etiologies in patients presented with a common clinical syndrome is challenging., Case Presentation: A 35-year-old Black woman presented with shortness of breath at rest, orthopnea, paroxysmal nocturnal dyspnea, chest pain, a blood-tinged productive cough, and fever for 2 weeks. She also had progressive body swelling, easy fatigability, loss of appetite, and abdominal pain during the same week's duration. Body imaging revealed large pleural and pericardial effusions, metastatic liver lesions, and bilateral pulmonary vascular segmental and subsegmental filling defects. Pericardial and pleural fluid cytology suggest malignant effusion. Liver lesions and core needle biopsy indicated adenocarcinoma of unknown origin, and the carcinoembryonic antigen level also increased significantly., Conclusion: Carcinoma of unknown primary origin commonly presents in an advanced stage and is often accompanied by clinical features of site metastasis. This case highlights heart failure as an unusual first manifestation of adenocarcinoma with an unknown primary origin., (© 2024. The Author(s).)

Background and Objectives : Cardiac transplantation represents the option for patients with end-stage heart failure (HF), providing the best survival rate. However, the postoperative complications of transplant patients remain a challenge for clinicians. The objective of our study was to evaluate the effect of preoperative chronic HF treatment on the occurrence of in-hospital complications. Materials and Methods : We retrospectively included a total of 50 patients who underwent cardiac transplantation between January 2011 and December 2023 from the Emergency Institute for Cardiovascular Diseases and Transplantation of Targu Mures. We correlated the preoperative chronic HF treatment with the postoperative complications by Spearmen's correlation coefficient, respectively. With logistic regression, the associations between the treatment and specific complications were determined. Results : Significant negative correlations were found between Carvedilol treatment with 2-month mortality (r = -0.30; 95% CI: -0.53--0.02; p = 0.03), Ramipril with hospital stay (r = -0.38; 95% CI: -0.60--0.12; p < 0.01) and intensive care unit (ICU) stay (r = -0.37; 95% CI: -0.59--0.11; p = 0.01), and Spironolactone usage with hospitalization duration (r = -0.28; 95% CI: -0.52--0.01; p = 0.04). Furthermore, Carvedilol treatment represented a protective factor against early acute kidney injury (AKI) (OR: 0.22; 95% CI: 0.05-0.91; p = 0.03). Spironolactone treatment was a protective factor against AGR (OR: 0.12; 95% CI: 0.02-0.66; p = 0.01) treatment, in contrast to angiotensin-converting enzyme inhibitor (ACEI) therapy (OR: 5.30; 95% CI: 1.03-27.17; p = 0.04). Conclusions : Pre-transplant Carvedilol treatment was negatively correlated with the 2-month mortality rate. Ramipril and Spironolactone therapy were negatively correlated with hospitalization duration, and Ramipril was additionally correlated with ICU stay. Moreover, Carvedilol therapy represented a protective factor against early AKI. Pre-transplant Spironolactone was associated with lower event rates of AGR, in contrast to ACEI treatment. Prospective studies with larger cohorts are needed in order to draw drastic conclusions.

Left ventricular (LV) global longitudinal strain (LVGLS) is versatile; however, it is difficult to obtain. We evaluated the potential of an artificial intelligence (AI)-generated electrocardiography score for LVGLS estimation (ECG-GLS score) to diagnose LV systolic dysfunction and predict prognosis of patients with heart failure (HF). A convolutional neural network-based deep-learning algorithm was trained to estimate the echocardiography-derived GLS (LVGLS). ECG-GLS score performance was evaluated using data from an acute HF registry at another tertiary hospital (n = 1186). In the validation cohort, the ECG-GLS score could identify patients with impaired LVGLS (≤ 12%) (area under the receiver-operating characteristic curve [AUROC], 0.82; sensitivity, 85%; specificity, 59%). The performance of ECG-GLS in identifying patients with an LV ejection fraction (LVEF) < 40% (AUROC, 0.85) was comparable to that of LVGLS (AUROC, 0.83) (p = 0.08). Five-year outcomes (all-cause death; composite of all-cause death and hospitalization for HF) occurred significantly more frequently in patients with low ECG-GLS scores. Low ECG-GLS score was a significant risk factor for these outcomes after adjustment for other clinical risk factors and LVEF. The ECG-GLS score demonstrated a meaningful correlation with the LVGLS and is effective in risk stratification for long-term prognosis after acute HF, possibly acting as a practical alternative to the LVGLS., (© 2024. The Author(s).)

Recent discoveries have identified intrapulmonary bronchopulmonary anastomoses (IBAs) as a relatively common phenomenon forming intrapulmonary right-to-left shunts. This study hypothesizes that IBAs play a significant role in the pathophysiology of heart failure. We aim to investigate the impact of these intrapulmonary right-to-left shunts on pulmonary arterial and venous pressures in heart failure patients, utilizing mixed venous oxygen saturation (SvO₂) as a key measurement. This study included 237 patients with heart failure who underwent cardiac catheterization. The relationships between SvO₂ and pulmonary artery systolic pressure (sPAP), pulmonary artery wedge pressure (PAWP), and left ventricular end-diastolic pressure (LVEDP) were examined using various statistical methods (single regression analysis, partial correlation analysis, structural equation modeling, and Bayesian estimation). All statistical methods that we performed showed that SvO₂ was significantly and negatively correlated with both sPAP and PAWP (p < 0.01, respectively). However, SvO₂ did not significantly correlate with LVEDP. These results suggest that a decrease in SvO₂ leads to an increase in PAWP and sPAP, while LVEDP is only passively influenced by PAWP. This phenomenon likely reflects the impact of an intrapulmonary right-to-left shunt caused by IBAs. The decrease in SvO₂ causes an increase in sPAP and may also cause an increase in PAWP via IBAs., (© 2024 The Author(s). Physiological Reports published by Wiley Periodicals LLC on behalf of The Physiological Society and the American Physiological Society.)

Background/aim: Connective tissue disease-associated pulmonary arterial hypertension (CTD-PAH) is a severe complication characterized by elevated pulmonary artery pressure, which can lead to right heart failure and death, if untreated. Standard treatments often fail to adequately manage symptoms, highlighting the need for novel therapeutic approaches. This study investigated the efficacy of molecular hydrogen (H 2 ) therapy in a patient with CTD-PAH., Case Report: We present the case of a 56-year-old female with CTD-PAH, diagnosed in 2013 with Sjogren's syndrome complicated by interstitial lung disease (ILD) and PAH. Despite treatment with sildenafil, bosentan, macitentan, iloprost, and corticosteroids, her condition deteriorated, resulting in severe dyspnea and cardiogenic shock in 2020. In May 2023, molecular hydrogen therapy was initiated as an adjuvant treatment. The patient received daily hydrogen capsules, which led to increased CD127+ Treg cells, reduced anti-Ro antibodies, and decreased B cell subsets. Her clinical symptoms stabilized without adverse effects., Conclusion: This case highlights the potential benefits of molecular hydrogen therapy in CTD-PAH. H 2 therapy exhibiting anti-inflammatory and immunomodulatory effects, leading to improved immune cell profiles and stabilizing clinical symptoms in a patient unresponsive to conventional treatments. Further research is needed to elucidate the mechanisms of H 2 therapy and validate its efficacy in larger cohorts. Molecular hydrogen therapy shows promise as a safe adjunctive treatment for CTD-PAH, offering a new approach for managing this challenging condition., (Copyright © 2024, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Inflammation and tissue fibrosis co-exist and are causally linked to organ dysfunction 1,2 . However, the molecular mechanisms driving immune-fibroblast cell communication in human cardiac disease remain unexplored and there are at present no approved treatments that directly target cardiac fibrosis 3,4 . Here we performed multiomic single-cell gene expression, epitope mapping and chromatin accessibility profiling in 45 healthy donor, acutely infarcted and chronically failing human hearts. We identified a disease-associated fibroblast trajectory that diverged into distinct populations reminiscent of myofibroblasts and matrifibrocytes, the latter expressing fibroblast activator protein (FAP) and periostin (POSTN). Genetic lineage tracing of FAP + fibroblasts in vivo showed that they contribute to the POSTN lineage but not the myofibroblast lineage. We assessed the applicability of experimental systems to model cardiac fibroblasts and demonstrated that three different in vivo mouse models of cardiac injury were superior compared with cultured human heart and dermal fibroblasts in recapitulating the human disease phenotype. Ligand-receptor analysis and spatial transcriptomics predicted that interactions between C-C chemokine receptor type 2 (CCR2) macrophages and fibroblasts mediated by interleukin-1β (IL-1β) signalling drove the emergence of FAP/POSTN fibroblasts within spatially defined niches. In vivo, we deleted the IL-1 receptor on fibroblasts and the IL-1β ligand in CCR2 + monocytes and macrophages, and inhibited IL-1β signalling using a monoclonal antibody, and showed reduced FAP/POSTN fibroblasts, diminished myocardial fibrosis and improved cardiac function. These findings highlight the broader therapeutic potential of targeting inflammation to treat tissue fibrosis and preserve organ function., Competing Interests: Competing interests X.L., T.Y., S.Y.S., A.F., M.F., X.Z., S.J., C.-M.L. and B.A. are or were employed by Amgen. The other authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

Background/aims: Despite the proven benefit of the guideline-directed medical therapy (GDMT), it remains underutilized in patients hospitalized with acute heart failure (HF). We aimed to evaluate the impact of the discharge checklist on GDMT installation and the prognosis of HF patients., Methods: This study was a single-center, observational study that included all patients admitted for HF from March 2021 to February 2023. The data were retrieved from electronic medical records and discharge checklists. A comparison was conducted between the checklist group and the non-checklist group. The primary endpoint was a composite of all-cause mortality or readmission for HF within 6 months., Results: The checklist was completed for 537 patients (checklist group) and not for 187 patients (non-checklist group). The proportion of patients to whom two or more components of GDMT were prescribed was significantly higher in the checklist group than in the non-checklist group (59.6% vs 42.2%, p < 0.001). The checklist group exhibited a significantly lower primary outcome compared to the non-checklist group (27.4% vs. 36.4%, HR 0.73, 95% CI 0.55-0.98, p = 0.036). The effect of the checklist was more prominent in HF with reduced ejection fraction (HR 0.51, 95% CI 0.34-0.77, p = 0.001) than in HF with mildly-reduced and preserved ejection fraction (HR 0.91, 95% CI 0.58-1.42, p = 0.676) (p for interaction = 0.06)., Conclusion: The implementation of the discharge checklist was associated with an improvement in GDMT prescription and an improved prognosis in patients with HF with reduced ejection fraction.

Background: Mechanisms of benefit with SGLT2is (sodium-glucose cotransporter-2 inhibitors) in heart failure (HF) remain incompletely characterized. Dapagliflozin alters ketone and fatty acid metabolism in HF with reduced ejection fraction though similar effects have not been observed in HF with preserved ejection fraction. We explore whether metabolic effects of SGLT2is vary across the left ventricular ejection fraction spectrum and their relationship with cardiometabolic end points in 2 randomized trials of dapagliflozin in HF., Methods: Metabolomic profiling of 61 metabolites was performed in 527 participants from DEFINE-HF (Dapagliflozin Effects on Biomarkers, Symptoms and Functional Status in Patients With HF With Reduced Ejection Fraction) and PRESERVED-HF (Dapagliflozin in PRESERVED Ejection Fraction HF; 12-week, placebo-controlled trials of dapagliflozin in HF with reduced ejection fraction and HF with preserved ejection fraction, respectively). Linear regression was used to assess changes in principal components analysis-defined metabolite factors with treatment from baseline to 12 weeks, as well as the relationship between changes in metabolite clusters and HF-related end points., Results: The mean age was 66±11 years, 43% were female, and 33% were self-identified as Black. Two principal components analysis-derived metabolite factors (which were comprised of ketone and short-/medium-chain acylcarnitines) increased with dapagliflozin compared with placebo. Ketosis (defined as 3-hydroxybutyrate >500 μM) was achieved in 4.5% with dapagliflozin versus 1.2% with placebo ( P =0.03). There were no appreciable treatment effects on amino acids, including branched-chain amino acids. Increases in several acylcarnitines were consistent across LVEF ( P interaction >0.10), whereas the ketogenic effect diminished at higher LVEF ( P interaction =0.01 for 3-hydroxybutyrate). Increases in metabolites reflecting mitochondrial dysfunction (particularly long-chain acylcarnitines) and aromatic amino acids and decreases in branched-chain amino acids were associated with worse HF-related outcomes in the overall cohort, with consistency across treatment and LVEF., Conclusions: SGLT2is demonstrate common (fatty acid) and distinct (ketogenic) metabolic signatures across the LVEF spectrum. Changes in key pathways related to fatty acid and amino acid metabolism are associated with HF-related end points and may serve as therapeutic targets across HF subtypes., Registration: URL: https://www.clinicaltrials.gov; Unique Identifiers: NCT03030235 and NCT02653482., Competing Interests: Dr Selvaraj receives research support from the National Heart, Lung, and Blood Institute (grant K23HL161348), the Doris Duke Foundation (grant 2020061), the American Heart Association (grant 935275), the Mandel Foundation, the Duke Heart Center Leadership Council, the Institute for Translational Medicine and Therapeutics, and the Foundation for Sarcoidosis Research. Dr Selvaraj has participated in advisory boards for AstraZeneca for unrelated work. Dr Sauer performs consulting and advising or receives research funding from Abbott, Boston Scientific, Biotronik, Bayer, Amgen, CSL Vifor, AstraZeneca, Acorai, Story Health, FIRE1, uLink, General Prognostics, Impulse Dynamics, Edwards Lifesciences, 35Pharma, Rivus, and Pfizer, and he owns stock as a senior advisor to ISHI, a private digital health company. Dr McGarrah has been a consultant for AstraZeneca and M3 and received research funding from Eli Lilly. Dr Newgard is a member of the Eli Lilly Global Diabetes Advisory Board. Dr Borlaug receives research support from the National Institutes of Health (NIH) and the US Department of Defense and research grant funding from AstraZeneca, Axon, GlaxoSmithKline, Medtronic, Mesoblast, Novo Nordisk, and Tenax Therapeutics. Dr Borlaug has served as a consultant for Actelion, Amgen, Aria, BD, Boehringer Ingelheim, Cytokinetics, Edwards Lifesciences, Eli Lilly, Janssen, Merck, and Novo Nordisk. Dr Borlaug and Shah are named inventors (US Patent 10,307,179) for the tools and approach for a minimally invasive pericardial modification procedure to treat heart failure. Dr Kitzman has been a consultant for AstraZeneca, Pfizer, Corvia Medical, Bayer, Boehringer Ingelheim, Novo Nordisk, Rivus, and St. Luke’s Medical Center; received grant support from Novartis, AstraZeneca, Bayer, Pfizer, Novo Nordisk, Rivus, and St. Luke’s Medical Center; and owns stock in Gilead Sciences. Dr Sanjiv Shah reports support from research grants from the NIH (U54 HL160273, R01 HL140731, and R01 HL149423), Pfizer, and AstraZeneca and consulting fees from Abbott, Alleviant, AstraZeneca, Amgen, Aria CV, Axon Therapies, Bayer, Boehringer Ingelheim, Boston Scientific, Bristol Myers Squibb, Cyclerion, Corvia, Cytokinetics, Edwards Lifesciences, Eidos, Imara, Impulse Dynamics, Intellia, Ionis, Lilly, Merck, Metabolic Flux, MyoKardia, NGM Biopharmaceuticals, Novartis, Novo Nordisk, Pfizer, Prothena, Regeneron, Rivus, Sardocor, Shifamed, Tenax, Tenaya, Ultromics, and United Therapeutics. Dr Margulies reports sponsored research funding from Amgen, Bristol Myers Squibb, and Lexicon Pharmaceuticals and advisory board activities for Amgen and Bristol Myers Squibb. Dr David Lanfear reports support from NIH grants (P50MD017351 and R01HL132154) and Illumina; consulting fees from Janssen, AstraZeneca, and Abbot Laboratories (via ACI clinical); and clinical trial participation with Lilly, Pfizer, AstraZeneca, Bayer, Illumina, and Janssen. Dr Kosiborod reports research grant support from AstraZeneca, Boehringer Ingelheim, and Pfizer; is on the consultant/advisory board of 35Pharma, Alnylam, Amgen, Applied Therapeutics, AstraZeneca, Bayer, Boehringer Ingelheim, Cytokinetics, Dexcom, Eli Lilly, Esperion Therapeutics, Imbria Pharmaceuticals, Janssen, Lexicon Pharmaceuticals, Merck (Diabetes and Cardiovascular), Novo Nordisk, Pharmacosmos, Pfizer, Sanofi, scPharmaceuticals, Structure Therapeutics, Vifor Pharma, and Youngene Therapeutics; other research support from AstraZeneca; honoraria from AstraZeneca, Boehringer Ingelheim, and Novo Nordisk; and stock options in Artera Health and Saghmos Therapeutics. Dr Svati Shah reports research funding through sponsored research agreements to Duke University from AstraZeneca, Lilly Inc, Verily Inc, and nference and is a co-inventor of unlicensed patents held by Duke University. The other authors report no conflicts.

Background: Acute decompensated heart failure (ADHF) patients with symptomatic congestion often require in-hospital admission for intravenous (IV) diuretic, impacting both patient well-being and healthcare expenses. Subcutaneous (SC) furosemide has a potential to facilitate outpatient management of ADHF patients. Thus, this study aims to assess the efficacy and safety of SC furosemide utilization, offering a potential alternative to traditional IV administration., Methods: A systematic search was conducted until April 14 2024 across scientific databases. This review included studies comparing SC furosemide with oral and IV formulations in adult HF patients., Results: This study analyzed 687 patients from 20 studies. The results demonstrate that SC furosemide can effectively manage symptomatic congestion in HF patients and results in significant cost reductions, symptom relief, and improved quality of life. Although further investigation into mortality rates is needed, SC furosemide demonstrates efficacy comparable to IV furosemide in diuresis and weight loss, with similar bioavailability and natriuretic effects. Adverse events are generally minor, predominantly related to skin irritation. Innovative strategies, such as developing isotonic alkaline solutions and improved infusion devices, are being explored to address these challenges., Conclusion: SC furosemide offers a promising alternative for managing ADHF, particularly in symptomatic HF patients with volume overload. The integration of SC furosemide into routine clinical practice and future guidelines, could optimize the management of HF, reducing hospital admission and improving patient outcomes., (© 2024. The Author(s).)

Background: Today, sodium glucose co-transporter 2 (SGLT2) inhibitors are more than diabetes drugs. They are also indicated in chronic heart failure (HF) treatment in both diabetic and non-diabetic patients, independently of the ejection fraction. Multiple mechanisms have been suggested behind the cardioprotective effects of SGLT2 inhibitors. However, the underlying mechanisms still remain largely unexplored. Here, we used a zebrafish embryo model to search for new potential players whereby SGLT2 inhibitors attenuate HF., Methods: HF in zebrafish embryos was caused exposing them to chemically induced hypoxia. As a SGLT2 inhibitor, we used empagliflozin. Its effect on hypoxia-induced HF of the embryos was evaluated using video microscopy and calculation of fractional shortening (FS) of embryos´ hearts. RT-qPCR of brain natriuretic peptide (bnp) expression was also used to examine empagliflozin´s effect on HF. Transcriptome analysis of total RNA of the embryos was performed to search for new potential mechanisms contributing to the beneficial effect of empagliflozin on HF., Results: Empagliflozin significantly attenuated hypoxia-induced HF of zebrafish embryos as shown with improved FS of the hearts and decreased bnp expression. Transcriptome analysis revealed that the improvement of HF in response to empagliflozin was accompanied with decreased matrix metalloproteinase 13a (mmp13a) expression. Treatment of hypoxia-induced embryos with MMP13 inhibitor ameliorated the impaired heart function accordingly to the effect of empagliflozin. MMP13 inhibitor was not toxic to the embryos., Conclusions: Our study shows that empagliflozin´s favorable effect on attenuating HF is mediated via MMP13. MMP13 provides a novel option when developing new therapeutics for HF treatment., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Hannu Jarvelainen reports financial support was provided by Satasairaala Central Hospital, The Wellbeing Services County of Satakunta Hannu Jarvelainen reports financial support was provided by Finnish Foundation for Cardiovascular Diseases. Hannu Jarvelainen reports financial support was provided by Turku University Foundation. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Aims: Diabetes mellitus (DM) and heart failure (HF) share vascular, skeletal and metabolic abnormalities that can reduce exercise capacity. We investigated whether exercise capacity differ in patients with type 2 DM compared to those without DM with HF of similar severity., Methods and Results: The Studies Investigating Co-morbidities Aggravating HF (SICA-HF) prospectively enrolled 615 patients with chronic HF, 259 (42.1 %) of whom had DM. We assembled a propensity score-matched cohort of 231 pairs of patients with HF with or without DM who were balanced on age, sex and variables reflecting HF severity. Patients with DM had lower median peak VO 2 (15.7 [13.0-19.1] vs. 17.3 [14.1-21.0] ml/min/kg; p = 0.005). Forearm blood flow reserve (per 1 ml/min/100 ml increase) was associated with lower exercise capacity (peak VO2 ≤ 16.6 ml/min/kg) in patients with DM (OR, 0.92; 95 % CI, (0.85-0.98; p = 0.014), but not in those without DM (OR, 0.98; 95 % CI, 0.93-1.02). A similar heterogeneity was also observed for HDL cholesterol., Conclusions: Diabetes is associated with a reduced exercise capacity in patients with HF. Most predictors of lower exercise capacity in HF are similar regardless of DM except impaired vascular function and lower HDL cholesterol which predict lower exercise capacity only in those with DM., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: [Stefan Anker reports a relationship with CSL Vifor that includes: consulting or advisory and funding grants. Stefan Anker reports a relationship with Bayer AG that includes: consulting or advisory. Stefan Anker reports a relationship with Boehringer Ingelheim GmbH that includes: consulting or advisory. Stefan Anker reports a relationship with Servier that includes: consulting or advisory. Stefan Anker reports a relationship with Abbott Vascular Inc that includes: consulting or advisory and funding grants. Stefan Anker reports a relationship with Cardiac Dimensions Inc that includes: consulting or advisory. Stefan Anker reports a relationship with Actimed Therapeutics that includes: consulting or advisory. Stefan Anker reports a relationship with AstraZeneca that includes: consulting or advisory. Stefan Anker reports a relationship with Amgen Inc that includes: consulting or advisory. Stefan Anker reports a relationship with BioVentrix Inc that includes: consulting or advisory. Stefan Anker reports a relationship with V-Wave Ltd that includes: consulting or advisory. Stefan Anker reports a relationship with Brahms that includes: consulting or advisory. Stefan Anker reports a relationship with Cordio that includes: consulting or advisory. Stefan Anker reports a relationship with Occlutech GmbH that includes: consulting or advisory. Stefan Anker reports a relationship with Cardior that includes: consulting or advisory. Stefan Anker reports a relationship with CVRx Inc that includes: consulting or advisory. Stefan Anker reports a relationship with Cytokinetics Inc that includes: consulting or advisory. Stefan Anker reports a relationship with Edwards that includes: consulting or advisory. Stefan Anker reports a relationship with Farraday Pharmaceuticals that includes: consulting or advisory. Stefan Anker reports a relationship with GSK that includes: consulting or advisory. Stefan Anker reports a relationship with HeartKinetics that includes: consulting or advisory. Stefan Anker reports a relationship with Impulse Dynamics that includes: consulting or advisory. Stefan Anker reports a relationship with Pfizer Inc that includes: consulting or advisory. Stefan Anker reports a relationship with Repairon that includes: consulting or advisory. Stefan Anker reports a relationship with Medical Sensible that includes: consulting or advisory. Stefan Anker reports a relationship with Vectorious that includes: consulting or advisory. John GF Cleland reports a relationship with British Heart Foundation that includes: board membership and funding grants. John GF Cleland reports a relationship with Pharmacosmos, Inc. that includes: consulting or advisory, funding grants, and travel reimbursement. John GF Cleland reports a relationship with CSL-Vifor that includes: funding grants. John GF Cleland reports a relationship with Abbott Vascular Inc that includes: consulting or advisory. John GF Cleland reports a relationship with Biopeutics that includes: consulting or advisory and travel reimbursement. John GF Cleland reports a relationship with Medtronic Inc that includes: board membership. John GF Cleland reports a relationship with Deputy Editor of European Heart Journal that includes: board membership. Stephan von Haehling reports a relationship with Amgen Inc that includes: funding grants. Stephan von Haehling reports a relationship with AstraZeneca that includes: consulting or advisory, funding grants, and speaking and lecture fees. Stephan von Haehling reports a relationship with Boehringer Ingelheim GmbH that includes: consulting or advisory, funding grants, and speaking and lecture fees. Stephan von Haehling reports a relationship with Pharmacosmos, Inc. that includes: consulting or advisory, funding grants, and speaking and lecture fees. Stephan von Haehling reports a relationship with IMI that includes: funding grants. Stephan von Haehling reports a relationship with German Center for Cardiovascular Research (DZHK) that includes: funding grants. Stephan von Haehling reports a relationship with BRAHMS that includes: consulting or advisory. Stephan von Haehling reports a relationship with MSD that includes: consulting or advisory. Stephan von Haehling reports a relationship with Novo Nordisk Inc that includes: consulting or advisory and speaking and lecture fees. Stephan von Haehling reports a relationship with Novartis that includes: consulting or advisory and speaking and lecture fees. Stephan von Haehling reports a relationship with Pfizer that includes: consulting or advisory. Stephan von Haehling reports a relationship with Respicardia that includes: consulting or advisory. Stephan von Haehling reports a relationship with Roche that includes: consulting or advisory. Stephan von Haehling reports a relationship with Servier that includes: consulting or advisory. Stephan von Haehling reports a relationship with Vifor that includes: consulting or advisory and speaking and lecture fees. Stephan von Haehling reports a relationship with Bayer AG that includes: speaking and lecture fees. Stephan von Haehling reports a relationship with Edwards Lifesciences Corporation that includes: speaking and lecture fees. Stephan von Haehling reports a relationship with Amomed Pharma GmbH that includes: consulting or advisory. Stephan von Haehling reports a relationship with Actimed that includes: equity or stocks. Wolfram Doehner reports a relationship with Vifor that includes: consulting or advisory and funding grants. Wolfram Doehner reports a relationship with Boehringer Ingelheim GmbH that includes: board membership, consulting or advisory, and funding grants. Wolfram Doehner reports a relationship with Aimediq that includes: consulting or advisory. Wolfram Doehner reports a relationship with AstraZeneca that includes: consulting or advisory. Wolfram Doehner reports a relationship with Bayer AG that includes: consulting or advisory. Wolfram Doehner reports a relationship with Boston Scientific Corp that includes: consulting or advisory. Wolfram Doehner reports a relationship with Medtronic that includes: consulting or advisory. Wolfram Doehner reports a relationship with Cardiomatics that includes: consulting or advisory. Wolfram Doehner reports a relationship with ICON Clinical Research LLC that includes: consulting or advisory. Wolfram Doehner reports a relationship with Pharmacosmos, Inc. that includes: travel reimbursement. Wolfram Doehner reports a relationship with IQVIA that includes: board membership. Wolfram Doehner reports a relationship with European Society of cardiology (ESC) that includes: board membership. Wolfram Doehner reports a relationship with ESC Council on Stroke that includes: board membership. Wolfram Doehner reports a relationship with Society of cachexia and wasting disorders that includes: board membership. Ewa A. Jankowska reports a relationship with Vifor Pharma that includes: board membership, consulting or advisory, and speaking and lecture fees. Ewa A. Jankowska reports a relationship with Pharmacosmos, Inc. that includes: board membership, consulting or advisory, and speaking and lecture fees. Ewa A. Jankowska reports a relationship with Novartis that includes: board membership, consulting or advisory, and speaking and lecture fees. Ewa A. Jankowska reports a relationship with Novo Nordisk that includes: board membership, consulting or advisory, and speaking and lecture fees. Ewa A. Jankowska reports a relationship with AstraZeneca that includes: board membership, consulting or advisory, and speaking and lecture fees. Ewa A. Jankowska reports a relationship with Boehringer Ingelheim that includes: board membership, consulting or advisory, and speaking and lecture fees. Ewa A. Jankowska reports a relationship with Pfizer that includes: board membership, consulting or advisory, and speaking and lecture fees. Ewa A. Jankowska reports a relationship with Zoll that includes: board membership and consulting or advisory. Ewa A. Jankowska reports a relationship with Respicardia that includes: board membership and consulting or advisory. Ewa A. Jankowska reports a relationship with Bayer that includes: board membership, consulting or advisory, and speaking and lecture fees. Ewa A. Jankowska reports a relationship with Abbott that includes: board membership, consulting or advisory, and speaking and lecture fees. Ewa A. Jankowska reports a relationship with Cardiac Dimensions Inc that includes: board membership and consulting or advisory. Ewa A. Jankowska reports a relationship with Amicus that includes: consulting or advisory. Ewa A. Jankowska reports a relationship with Swixx Biopharma that includes: speaking and lecture fees. Ewa A. Jankowska reports a relationship with Ewopharma that includes: speaking and lecture fees. Ewa A. Jankowska reports a relationship with Servier that includes: board membership and speaking and lecture fees. Ewa A. Jankowska reports a relationship with Takeda that includes: speaking and lecture fees. Ewa A. Jankowska reports a relationship with Sanofi that includes: speaking and lecture fees. Ewa A. Jankowska reports a relationship with Executive Committee of the HFA Board 2016–2022 that includes: board membership. Miroslava Valentova reports a relationship with Bayer that includes: speaking and lecture fees. Stefan Anker has patent #MR-proANP (DE 102,007,010,834 & DE 102007022367) issued to BRAHMS. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper]., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Intermittent ambulatory levosimendan administration has been shown in several small randomized controlled trials to benefit patients with advanced heart failure, preventing heart failure rehospitalization and mortality. We aim to investigate the totality of high-quality evidence regarding the efficacy and safety of intermittent levosimendan in advanced heart failure patients., Methods: Up to September 2023, we systematically reviewed the randomized controlled trials indexed in PubMed, Embase Cochrane, SCOPUS, and Web of Science. We used mean difference (MD) to estimate the continuous outcomes, and risk ratio (RR) for the dichotomous outcomes with a 95% confidence interval (CI), using the random-effects model. Ultimately, a trial sequential analysis was employed to enhance the reliability of our findings and Grading of Recommendations Assessment, Development, and Evaluation (GRADE) framework for certainty leveling., Results: Fifteen randomized controlled trials with 1181 patients were included. Intermittent levosimendan was significantly associated with an improved left ventricular ejection fraction compared with  placebo (MD 6.39 [95% CI 3.04-9.73], P = 0.002; I 2 = 75, P = 0.0005), with cumulative z-score of change after ≤ 1 week passing the monitoring boundaries, favoring the levosimendan, but did not cross the required information size. Additionally, levosimendan reduced the all-cause mortality rate (RR 0.60 [95% CI 0.40-0.90], P = 0.01; I 2 = 9, P = 0.36). However, we found no difference between levosimendan and placebo in all-cause rehospitalization rate (RR 0.75 [95% CI 0.46-1.22], P = 0.25; I 2 = 70, P = 0.04), event-free survival rate (RR 0.97 [95% CI 0.72-1.30], P = 0.84; I 2 = 63, P = 0.03), or any adverse event (RR 1 [95% CI 0.73-1.37], P = 1.00, I 2 = 0%, P = 0.70)., Conclusion: In patients with advanced heart failure, intermittent levosimendan significantly improved left ventricular ejection fraction, brain natriuretic peptide values, and all-cause mortality rate. Levosimendan use is not associated with a change in rehospitalization or event-free survival., Registration: PROSPERO identifier number (CRD42023487838)., (© 2024. The Author(s).)

Objective: To evaluate the comparative effects of dapagliflozin versus placebo in patients with heart failure (HF), focusing on functional capacity, symptoms, and safety outcomes., Background: Despite advancements in heart failure (HF) therapy, HF is still a significant cause of recurrent hospitalization and death worldwide. Dapagliflozin has demonstrated potential in lowering hospitalizations and mortality associated with heart failure; however, its impact on functional capacity, particularly the 6-min walk distance (6MWD), and the comprehensive assessment of safety outcomes in diverse HF populations, including those with preserved or reduced ejection fraction (HFpEF and HFrEF, respectively), requires further investigation., Methods: PubMed, Web of Science, Cochrane Library, and Scopus databases were comprehensively searched to identify randomized controlled trials (RCTs) investigating the efficacy of dapagliflozin in comparison with control interventions for heart failure. The primary outcome was a change in the 6MWD, KCCQ score, and safety measures included hospitalization, all-cause mortality, and adverse events., Results: In our meta-analysis of ten studies involving 12,695 patients with heart failure, dapagliflozin showed significantly improved Kansas City Cardiomyopathy Questionnaire (KCCQ) scores [risk ratio (RR) of 2.75, 95% confidence interval (CI) (1.95-3.569), p < 0.00001] and no significant differences in 6-min walk distance [6MWD; RR of 3.59, 95% CI (- 1.44 to 8.63), p = 0.16]. Dapagliflozin demonstrated a notable reduction in hospitalization for heart failure [RR of 0.76, 95% CI (0.68-0.84), p < 0.00001], significant overall reduction on the effect of any cause mortality [RR of 0.90, 95% CI (0.83-0.99), p = 0.03). There was, however, no significant effect on adverse events [RR of 0.96, 95% CI (0.98-1.03), p = 0.39)., Conclusions: Our meta-analysis of ten trials concluded that dapagliflozin significantly improved KCCQ scores in both HFrEF and HFpEF. The improvement in 6MWD was not statistically significant but trended toward dapagliflozin. Dapagliflozin also showed a mortality benefit in patients with reduced ejection fraction; however, in patients with preserved ejection fraction, the result was not statistically significant. There was also a statistically significant reduction in heart failure hospitalizations across all classes., (© 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Background: Anemia is one of the most frequent comorbidities in patients with heart failure (HF), which potentially can interfere with the effect of guideline-recommended HF medical therapy and can be associated with the use of neurohormonal blockers., Aim: The aim of this analysis was to determine the prevalence and changes of anemia status in the STRONG-HF study, its association with clinical endpoints, and possible interaction of the presence of anemia with the efficacy and safety of high-intensity HF treatment., Methods: The design and main results of the study have been previously described. Patients were randomized within 2 days prior to anticipated hospital discharge after HF worsening in a 1:1 fashion to either high-intensity care (HIC) or usual care (UC). Baseline characteristics, clinical and safety outcomes, and treatment effect of HIC vs. UC on the primary and secondary outcomes were compared in groups based on baseline anemia. In addition, dynamics of hemoglobin during the study follow-up and predictors of incident anemia at 90 days were investigated., Results: The proportion of anemia in 1077 STRONG-HF patients at enrollment was 27.2%, while at 90 days, it changed to 32.1%. The primary composite outcome occurred in 18.2% of patients without baseline anemia, and 22.5% of patients with baseline anemia (unadjusted HR 1.27; 95% CI 0.90-1.80), a difference that did not reach statistical significance. However, patients with baseline anemia had significantly less improvement of EQ-VAS questionnaire values from baseline to day 90 (adjusted LS-Mean difference -2.34 (-4.37, -0.31), P = 0.02). During the study, anemia developed in 19.4 and 14.6% in HIC and UC groups, respectively. The opposite phenomenon-recovery of anemia-occurred in 27.6 and 28.8% in HIC and UC groups (P = 0.1379). The predictors of incident anemia at 90 days were male sex, geographical region other than Europe, ischemic etiology, higher glucose, and elevated uric acid at baseline. The percentages of optimal doses of renin-angiotensin system inhibitors, beta-blockers, and mineralocorticoid receptor antagonists were not different between anemic and non-anemic patients. High-intensity care strategy did not increase rate of incident anemia at 90 days and reduced the rate of primary and secondary endpoints regardless of baseline hemoglobin., Conclusion: Hemoglobin level and status of anemia have a dynamic nature in the acute HF patients in the post-discharge period dependent on multiple factors. High-intensity HF treatment is safe and beneficial regardless of baseline hemoglobin level and presence of anemia. The improvement of quality of life is significantly lower in anemic HF patients implying specific attention to correction of this condition., (© 2024. Springer-Verlag GmbH Germany, part of Springer Nature.)

All anthracyclines, including doxorubicin (DOXO), the most common and still indispensable drug, exhibit cardiotoxicity with inherent risk of irreversible cardiomyopathy leading to heart failure with reduced ejection fraction (HFrEF). Current pharmacological strategies are clearly less effective for this type of HFrEF, hence an urgent need for new therapeutic approaches. The prerequisite for success is thorough understanding of pathophysiology of this HFrEF form, which requires an appropriate animal model of the disease. The aim of this study was to comprehensively characterise a novel model of HF with cardiorenal syndrome, i.e. DOXO-induced HFrEF with nephrotic syndrome, in which DOXO was administered to Ren-2 transgenic rats (TGR) via five intravenous injections in a cumulative dose of 10 mg/kg of body weight (BW). Our analysis included survival, echocardiography, as well as histological examination of the heart and kidneys, blood pressure, but also a broad spectrum of biomarkers to evaluate cardiac remodelling, fibrosis, apoptosis, oxidative stress and more. We have shown that the new model adequately mimics the cardiac remodelling described as "eccentric chamber atrophy" and myocardial damage typical for DOXO-related cardiotoxicity, without major damage of the peritoneum, lungs and liver. This pattern corresponds well to a clinical situation of cancer patients receiving anthracyclines, where HF develops with some delay after the anticancer therapy. Therefore, this study may serve as a comprehensive reference for all types of research on DOXO-related cardiotoxicity, proving especially useful in the search for new therapeutic strategies., (© 2024. The Author(s).)

None of the spironolactone trials in heart failure (HF) assessed the blood pressure (BP) responses to exercise, while conflicting results were reported for exercise capacity. In the HOMAGE trial, 527 patients at increased HF risk were randomized to usual treatment with or without spironolactone (25-50 mg/day). The current substudy included 113 controls and 114 patients assigned spironolactone, who all completed the incremental shuttle walk test at baseline and months 1 and 9. Quality of life (QoL) was assessed by EQ5D questionnaire. Between-group differences (spironolactone minus control [Δs]) were analyzed by repeated measures ANOVA with adjustment for baseline and, if appropriate, additionally for sex, age and body mass index. Δs in the pre-exercise systolic/diastolic BP were -8.00 mm Hg (95% CI, -11.6 to -4.43)/-0.85 mm Hg (-2.96 to 1.26) at month 1 and -9.58 mm Hg (-14.0 to -5.19)/-3.84 mm Hg (-6.22 to -1.47) at month 9. Δs in the post-exercise systolic/diastolic BP were -8.08 mm Hg (-14.2 to -2.01)/-2.07 mm Hg (-5.79 to 1.65) and -13.3 mm Hg (-19.9 to -6.75)/-4.62 mm Hg (-8.07 to -1.17), respectively. For completed shuttles, Δs at months 1 and 9 were 2.15 (-0.10 to 4.40) and 2.49 (-0.79 to 5.67), respectively. Δs in QoL were not significant. The correlations between the exercise-induced BP increases and the number of completed shuttles were similar in both groups. In conclusion, in patients at increased risk of developing HF, spironolactone reduced the pre- and post-exercise BP, but did not improve exercise capacity or QoL., (© 2024. The Author(s).)

Background: Heart failure is a major worldwide health concern and leading cause of mortality. RNAi interventions hold promise for patients resistant to conventional drugs due to their off-target effects and lack of specificity., Objectives: To examine the safety and effectiveness of RNAi therapeutics in treating heart failure., Methods: The PubMed, Embase, Scopus and Cochrane databases were searched using appropriate keyword from inception until December 31, 2023. A total of 14 studies fulfilling predefined selection criteria were included for qualitative synthesis., Results: We found that in patients with cardiac amyloidosis, patisiran and revusiran showed considerable improvements in cardiac output and left ventricular wall thickness. In animal studies, Nox2-siRNA showed effectiveness in regaining heart function. Furthermore, cardiomyocyte count and left ventricular function were improved by DUSP5 siRNA + T3 therapy and meg3 inhibition after myocardial infarction (MI). RNAi showed minimal adverse effects like peripheral neuropathy, hepatotoxicity, urinary tract infection, vaginal infection, diarrhea, abdominal pain arrhythmias, conduction disorders, and cardiotoxicity (LV wall thinning, heart failure) and improved cardiac biomarkers., Conclusion: RNAi therapeutics are novel treatment option for improving cardiac function because their high target specificity, ability to target genes that conventional drugs struggle to reach and potential for long-lasting effects. Further research on optimizing delivery methods, improving target specificity, evaluating long-term safety profiles and cost-effectiveness to fully realize their potential., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Although the use of glucagon-like peptide-1 receptor agonist (GLP-1 RA) in patients with obesity and heart failure with preserved ejection fraction (HFpEF) has demonstrated improvement in cardiovascular outcomes, the incremental benefits of GLP-1 RA for patients already on sodium-glucose cotransporter 2 inhibitors (SGLT2is) remain underexplored., Objectives: This study aimed to assess the incremental benefits of GLP-1 RA in patients with type 2 diabetes mellitus, overweight/obesity, and HFpEF receiving SGLT2i therapy., Methods: The authors conducted a retrospective cohort study using the TriNetX research database including patients ≥18 years with type 2 diabetes mellitus, body mass index ≥27 kg/m 2 , and HFpEF on SGLT2i. Two cohorts were created based on GLP-1 RA prescription. The outcomes were heart failure exacerbation, all-cause emergency department visits/hospitalizations among others over a 12-month period., Results: A total of 7,044 patients remained in each cohort after propensity score matching. There was a significantly lower risk of heart failure exacerbations, all-cause emergency department visits/hospitalizations, new-onset atrial arrhythmias, new-onset acute kidney injury, and pulmonary hypertension in the GLP-1 RA plus SGLT2i cohort compared with the SGLT2i-only cohort. The associated benefits persisted across different body mass indexes and ejection fractions as well as in patients with elevated natriuretic peptide. The risk of diabetic retinopathy was higher in the combination therapy group than with SGLT2i-only use., Conclusions: GLP-1 RA, in addition to SGLT2i, was associated with a significantly lower risk of heart failure hospitalizations in this patient population, suggesting a potential incremental benefit. This highlights the need for prospective studies to confirm the clinical benefits., Competing Interests: Funding Support and Author Disclosures Dr Bhatt is on the advisory board for Angiowave, Bayer, Boehringer Ingelheim, CellProthera, Cereno Scientific, Elsevier Practice Update Cardiology, High Enroll, Janssen, Level Ex, McKinsey, Medscape Cardiology, Merck, MyoKardia, NirvaMed, Novo Nordisk, PhaseBio, PLx Pharma, and Stasys; he is on the Board of Directors for American Heart Association New York City, Angiowave (stock options), Bristol Myers Squibb (stock), DRS.LINQ (stock options), and High Enroll (stock); he is a consultant for Broadview Ventures, GlaxoSmithKline, Hims, SFJ, Youngene; he is on the Data Monitoring Committees for Acesion Pharma, Assistance Publique-Hôpitaux de Paris, Baim Institute for Clinical Research (formerly Harvard Clinical Research Institute, for the PORTICO trial, funded by St. Jude Medical, now Abbott), Boston Scientific (Chair, PEITHO trial), Cleveland Clinic, Contego Medical (Chair, PERFORMANCE 2), Duke Clinical Research Institute, Mayo Clinic, Mount Sinai School of Medicine (for the ENVISAGE trial, funded by Daiichi Sankyo; for the ABILITY-DM trial, funded by Concept Medical; for ALLAY-HF, funded by Alleviant Medical), Novartis, Population Health Research Institute, Rutgers University (for the National Institutes of Health–funded MINT Trial); he has received honoraria from the American College of Cardiology (Senior Associate Editor, Clinical Trials and News, ACC.org; Chair, ACC Accreditation Oversight Committee), Arnold and Porter law firm (work related to Sanofi/Bristol Myers Squibb clopidogrel litigation), Baim Institute for Clinical Research (formerly Harvard Clinical Research Institute; RE-DUAL PCI clinical trial steering committee funded by Boehringer Ingelheim; AEGIS-II executive committee funded by CSL Behring), Belvoir Publications (Editor in Chief, Harvard Heart Letter), Canadian Medical and Surgical Knowledge Translation Research Group (clinical trial steering committees), CSL Behring (AHA lecture), Cowen and Company, Duke Clinical Research Institute (clinical trial steering committees, including for the PRONOUNCE trial, funded by Ferring Pharmaceuticals), HMP Global (Editor in Chief, Journal of Invasive Cardiology), Journal of the American College of Cardiology (Guest Editor, Associate Editor), K2P (Co-Chair, interdisciplinary curriculum), Level Ex, Medtelligence/ReachMD (CME steering committees), MJH Life Sciences, Oakstone CME (Course Director, Comprehensive Review of Interventional Cardiology), Piper Sandler, Population Health Research Institute (for the COMPASS operations committee, publications committee, steering committee, and USA national co-leader, funded by Bayer), WebMD (CME steering committees), Wiley (steering committee), Clinical Cardiology (Deputy Editor); he is named on a patent for sotagliflozin (assigned to Brigham and Women’s Hospital who assigned to Lexicon; neither he nor Brigham and Women's Hospital receive any income from this patent); he has received research funding for Abbott, Acesion Pharma, Afimmune, Aker Biomarine, Alnylam, Amarin, Amgen, AstraZeneca, Bayer, Beren, Boehringer Ingelheim, Boston Scientific, Bristol Myers Squibb, Cardax, CellProthera, Cereno Scientific, Chiesi, CinCor, Cleerly, CSL Behring, Eisai, Ethicon, Faraday Pharmaceuticals, Ferring Pharmaceuticals, Forest Laboratories, Fractyl, Garmin, HLS Therapeutics, Idorsia, Ironwood, Ischemix, Janssen, Javelin, Lexicon, Lilly, Medtronic, Merck, Moderna, MyoKardia, NirvaMed, Novartis, Novo Nordisk, Otsuka, Owkin, Pfizer, PhaseBio, PLx Pharma, Recardio, Regeneron, Reid Hoffman Foundation, Roche, Sanofi, Stasys, Synaptic, The Medicines Company, Youngene, and 89Bio; he has received royalties from Elsevier (Editor, Braunwald’s Heart Disease); he is Site Co-Investigator for Abbott, Biotronik, Boston Scientific, CSI, Endotronix, St. Jude Medical (now Abbott), Philips, SpectraWAVE, Svelte, and Vascular Solutions; he is trustee for American College of Cardiology; and he has done unfunded research for FlowCo. Dr Butler has been a consultant to Abbott, American Regent, Amgen, Applied Therapeutic, AskBio, Astellas, AstraZeneca, Bayer, Boehringer Ingelheim, Boston Scientific, Bristol Myers Squibb, Cardiac Dimension, Cardiocell, Cardior, CSL Bearing, CVRx, Cytokinetics, Daxor, Edwards, Element Science, Faraday, Foundry, G3P, Innolife, Impulse Dynamics, Imbria, Inventiva, Ionis, Lexicon, Lilly, LivaNova, Janssen, Medtronics, Merck, Occlutech, Owkin, Novartis, Novo Nordisk, Pfizer, Pharmacosmos, Pharmain, Prolaio, Regeneron, Renibus, Roche, Salamandra, Sanofi, SC Pharma, Secretome, Sequana, SQ Innovation, Tenex, Tricog, Ultromics, Vifor, and Zoll. Dr Kosiborod has received research grants from AstraZeneca and Boehringer Ingelheim; and has served as a consultant for Alnylam, AstraZeneca, Amgen, Applied Therapeutics, Bayer, Boehringer Ingelheim, Cytokinetics, Eli Lilly, Esperion Therapeutics, Janssen, Merck (Diabetes and Cardiovascular), Novo Nordisk, Pharmacosmos, Sanofi, and Vifor. Dr Fonarow has done consulting for Abbot, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Cytokinetics, Eli Lilly, Johnson and Johnson, Medtronic, Merck, Novartis, and Pfizer. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2024 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Heart failure with preserved ejection fraction (HFpEF) is associated with heart failure (HF) hospitalizations and death. Previous studies have shown that altered muscle composition is associated with higher risk of adverse outcome in HFpEF patients., Aim: The purpose of our study was to investigate the association between skeletal muscle composition, as measured by skeletal muscle T1-times on cardiac magnetic resonance (CMR) imaging, and adverse outcome., Methods: We measured skeletal muscle T1-times of the back muscles on standard CMR images in a prospective cohort of HFpEF patients. Cox regression models were used to test the association of skeletal muscle T1-times and adverse outcome defined as hospitalization for HF and/or cardiovascular death., Results: We included 101 patients (mean age 72±7 years, 71 % female) in our study. The median skeletal muscle T1-times were 842 ms (IQR 806-881 ms). In univariate analysis high muscle T1-time was associated with adverse outcome (HR=1.96 [95 % CI, 1.31-2.94] per every 100 ms increase; p=.001). After adjustment for age, sex, body mass index, left- and right ventricular ejection fraction, N-terminal pro-brain natriuretic peptide and myocardial native T1-times, native skeletal muscle T1-time remained an independent predictor for adverse outcome (HR=1.94 [95 % CI, 1.24-3.03] per every 100 ms increase; p=.004)., Conclusion: In patients with HFpEF, high skeletal muscle T1-times on standard CMR scans are associated with higher rates of HF hospitalizations and cardiovascular death., Condensed Abstract: Skeletal muscle abnormalities are common in patients with heart failure with preserved ejection fraction (HFpEF). The present study evaluates skeletal muscle composition, as quantified by native skeletal muscle T1-times of the back muscles on standard cardiac magnetic resonance imaging, and assessed the association with adverse outcome, defined as hospitalization for heart failure and/or cardiovascular death. In a prospective cohort of 101 patients with HFpEF, we found that high native skeletal muscle T1-times are associated with an increased risk for adverse outcome. These findings suggest that native skeletal muscle T1-time may serve as marker for improved risk prediction., Competing Interests: Declaration of competing interest The authors declare they have no conflict of interest., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background: It is unknown whether cardiac resynchronization therapy (CRT) would improve or halt the progression of heart failure (HF) in patients with mild to moderately reduced ejection fraction (HFmmrEF) and left bundle branch block (LBBB)., Objective: This study aimed to investigate the outcomes of CRT in patients with HFmmrEF and left ventricular conduction delay., Methods: A prospective, randomized clinical trial sponsored by the National Heart, Lung, and Blood Institute included 76 patients who met the study inclusion criteria (left ventricular ejection fraction [LVEF] of 36%-50% and LBBB). Patients received CRT-pacemaker and were randomized to CRT-OFF (right ventricular pacing 40 beats/min) or CRT-ON (biventricular pacing 60-150 beats/min). At a 6-month follow-up, pacing programming was changed to the opposite settings. New York Heart Association class, N-terminal pro-brain natriuretic peptide levels, and echocardiographic variables were collected at baseline, 6 months, and 12 months. The primary study end point was the left ventricular end-systolic volume (LVESV) change from baseline, and the primary randomized comparison was the comparison of 6-month to 12-month changes between randomized groups., Results: The mean age of the patients was 68.4 ± 9.8 years (male, 71%). Baseline characteristics were similar between the 2 randomized groups (all P > .05). In patients randomized to CRT-OFF first, then CRT-ON, LVESV was reduced from baseline only after CRT-ON (baseline, 116.1 ± 36.5 mL; CRT-ON, 87.6 ± 26.0 mL; P < .0001). The randomized analysis of LVEF showed a significantly better change from 6 to 12 months in the OFF-ON group (P = .003). LVEF was improved by CRT (baseline, 41.3% ±.7%; CRT-ON, 46.0% ± 8.0%; P = .002). In patients randomized to CRT-ON first, then CRT-OFF, LVESV was reduced after both CRT-ON and CRT-OFF (baseline, 109.8 ± 23.5 mL; CRT-ON, 91.7 ± 30.5 mL [P < .0001]; CRT-OFF, 99.3 ± 28.9 mL [P = .012]). However, the LVESV reduction effect became smaller between CRT-ON and CRT-OFF (P = .027). LVEF improved after both CRT-ON and CRT-OFF (baseline, 42.7% ± 4.3%; CRT-ON, 48.5% ± 8.6% [P < .001]; CRT-OFF, 45.9% ± 7.7% [P = .025])., Conclusion: CRT for patients with HFmmrEF significantly improves LVEF and ventricular remodeling after 6 months of CRT. The study provides novel evidence that early CRT benefits patients with HFmmrEF with LBBB., Competing Interests: Disclosures The authors have no conflicts of interest to disclose., (Copyright © 2024 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Background: There is a lack of data on the impact of sex on the outcomes of patients with heart failure (HF) undergoing atrial fibrillation (AF) ablation. We aimed to analyze the association of sex with outcomes of atrial fibrillation ablation in patients with heart failure., Methods: The National Readmissions Database (NRD) was analyzed from 2016 to 2019 to identify patients ≥ 18 years old with heart failure (HF) undergoing AF ablation. The outcomes of interest included peri-procedural complications, in-hospital mortality, resource utilization, and unplanned 1-year readmissions. The final cohort was divided into patients with HFrEF and HFpEF and outcomes were compared between males and females in both cohorts., Results: A total of 23,277 patients with HF underwent AF ablation between 2016 and 2019, of which 14,480 had HFrEF and 8,797 had HFpEF. Among patients with HFrEF, 61.6% were males and 38.4% were females whereas, among patients with HFpEF, 35.4% were males and 64.6% were females. On a multivariable-adjusted analysis, in patients with HFrEF, there was no difference in the odds of in-hospital mortality, peri-procedural complications, or 1-year HF-related/AF-related/all-cause readmissions between males and females. In patients with HFpEF, females had a higher risk 1-year HF-related readmissions (adjusted hazards ratio: 1.46; 95% CI: 1.13-1.87; p = 0.01), without any difference in the 1-year AF-related/all-cause readmissions, in-hospital mortality, or peri-procedural complications., Conclusion: Our results show that females with HFrEF undergoing AF ablation have similar outcomes whereas females with HFpEF have higher 1-year HF readmissions with no difference in the other outcomes, compared to males., Competing Interests: Declarations. Ethical approval: Due to the de-identified nature of the NRD dataset, the need for informed consent and Institutional Review Board approval is waived. Informed consent: Not applicable. Conflict of interest: The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objective: This study investigates the prevalence and prognostic impact of diastolic dysfunction (DD) in patients hospitalized with heart failure (HF) with mildly reduced ejection fraction (HFmrEF) in sinus rhythm., Background: Data regarding the prognostic impact of DD in patients with HFmrEF is limited., Methods: From 2016 to 2022, all patients hospitalized with HFmrEF (i.e., left ventricular ejection fraction 41-49% and signs and/or symptoms of HF) were retrospectively included at one institution. Patients with DD were compared to patients without (i.e., non-DD), further risk stratification was performed according to the severity of DD. The primary endpoint was all-cause mortality at 30 months (interquartile range (IQR) 15-61 months), key secondary endpoint was rehospitalization for worsening HF., Results: From a total of 1154 patients (median age 68 years, 68% males) hospitalized with HFmrEF, concomitant DD was present in 72% (grade I: 56%, grade II: 14%, grade III: 2%). Patients with DD were older (71 years vs. 65 years; p = 0.001) and presented with higher rates of cardiovascular comorbidities. The presence of DD was not associated with the risk of long-term all-cause mortality (adjusted HR = 0.815; 95% CI 0.612-1.085; p = 0.161) or HF-related rehospitalization (adjusted HR = 0.736; 95% CI 0.442-1.225; p = 0.238). Furthermore, the outcome did not differ in patients with more advanced stages of DD., Conclusion: DD is commonly prevalent in patients with HFmrEF, but not associated with long-term prognosis., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Secondary mitral regurgitation (MR) worsens in 10-15 % of heart failure (HF) patients receiving cardiac resynchronization therapy (CRT). Transcatheter edge-to-edge repair (TEER) with Mitra-Clip (Abbot Vascular, Santa Clara, CA, USA) therapy is associated with improved survival and decreased rates of hospitalization for HF in selected patients with secondary MR. Data on TEER outcomes in CRT-non-responders are limited. The purpose of this meta-analysis was to evaluate outcomes of mitral TEER with Mitra-Clip in CRT-non-responders., Methods: Cochrane, Scopus, MEDLINE, and EMBASE were searched for studies discussing outcomes of Mitra-Clip in CRT non-responders. Two reviewers were independently involved in screening studies and extracting relevant data. Individual study incidence rate estimates underwent logit transformation to calculate the weighted summary proportion under the random effect model., Results: A total of eight reports met the inclusion criteria (439 patients). Mitra-Clip improved MR grade to ≤2+ in 83.8 % and 86.8 % of CRT non-responders at six months and one year, respectively. Symptomatic improvement (New York Heart Association class ≤II) was also found in 71 % and 78.1 % of CRT non-responders at six months and one year, respectively. The pooled overall incidence estimates of mortality at 30 days, 6 months, 1 year, and 2 years were 3.6 %, 9.2 %, 17.8 %, and 25.9 %, respectively., Conclusion: TEER with Mitra-Clip in patients with significant secondary MR who do not respond to CRT was associated with MR improvement, alleviation of symptoms, and mortality rates similar to those in the COAPT trial., Competing Interests: Declaration of competing interest None of the authors has any conflict of interest., (Published by Elsevier Ltd.)

Heart failure continues to pose a significant burden in terms of morbidity, mortality, and healthcare costs worldwide despite the implementation of guideline-directed medical therapy. Addressing this challenge and improving clinical outcomes for this patient population remains an urgent priority. Recognizing the limitations in current medical approaches and exploring strategies to overcome these limitations are crucial steps toward improving future outcomes. Various device-based interventions, such as Cardiac Resynchronization Therapy devices and Left Ventricular Assist Devices, have demonstrated notable benefits for individuals with heart failure. Our review is aimed at summarizing the ongoing research into new device therapies for heart failure, emphasizing their potential to overcome the current challenges in treatment. By utilizing Clinicaltrials.gov, an online repository, we conducted a comprehensive search for trials investigating emerging device therapies for patients dealing with heart failure., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)