Journal of Cardiac Failure最新文献

{"title":"","authors":"","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":15204,"journal":{"name":"Journal of Cardiac Failure","volume":"32 2","pages":"Pages 533-537"},"PeriodicalIF":8.2,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146679485","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impact Of End-stage Renal Disease On Outcomes In Heart Failure Patients Undergoing Left Ventricular Assist Device Placement: A Nationwide Readmission Study","authors":"Nadhem Abdallah ,&nbsp;Momen Alsayed ,&nbsp;Meriam Abdallah","doi":"10.1016/j.cardfail.2025.11.011","DOIUrl":"10.1016/j.cardfail.2025.11.011","url":null,"abstract":"<div><h3>Background</h3><div>Patients with chronic kidney disease, particularly those diagnosed with end-stage renal disease (ESRD), face an elevated risk of adverse outcomes, especially during cardiac procedures. However, the impact of ESRD on outcomes in patients with heart failure undergoing left ventricular assist device (LVAD) implantation remains underexplored.</div></div><div><h3>Methods</h3><div>Utilizing the 2016-2020 Nationwide Readmission Database, we analyzed data to evaluate heart failure patients who underwent LVAD implantation. Outcomes were compared between individuals with and without ESRD. The primary endpoint was inpatient mortality. Secondary endpoints included 90-day all-cause readmission rates, incidence of cardiogenic shock, length of stay (LOS), and total hospitalization charges (THC). Multivariate linear and logistic regression models were applied to account for confounders.</div></div><div><h3>Results</h3><div>Among 4,920 heart failure patients receiving an LVAD, 2.4% were identified as having ESRD. The presence of ESRD was associated with significantly higher odds of inpatient mortality (adjusted odds ratio [aOR] 1.91, 95% confidence interval [CI] 1.05-3.5), extended LOS (73 days vs. 33 days, p &lt; 0.001), and increased THC ($1,873,835 vs. $896,426, p &lt; 0.001) compared to non-ESRD patients. No significant differences were observed in 90-day all-cause readmission rates (aOR 1.61, 95% CI 0.74-3.5) or rates of cardiogenic shock (aOR 2.84, 95% CI 0.88-9.1) between the two groups.</div></div><div><h3>Conclusion</h3><div>In heart failure patients undergoing LVAD placement, the presence of ESRD was linked to heightened inpatient mortality, prolonged hospital stays, and greater healthcare costs, underscoring the need for tailored interventions to improve outcomes in this vulnerable population.</div></div>","PeriodicalId":15204,"journal":{"name":"Journal of Cardiac Failure","volume":"32 1","pages":"Page 173"},"PeriodicalIF":8.2,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145950117","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical Outcomes Of Patients With Elevated Pulmonary Artery Pressures Following Heartmate 3 Left Ventricular Assist Device Implantation: An Analysis Of The Euromacs Registry","authors":"William Baker ,&nbsp;Gaik Nersesian ,&nbsp;Timothy Moore ,&nbsp;Zeina Zedeon ,&nbsp;Balaphanidhar Mogga ,&nbsp;Katrina Etts ,&nbsp;Theo de By ,&nbsp;Evgenij Potapov ,&nbsp;David Baran ,&nbsp;Abhishek Jaiswal","doi":"10.1016/j.cardfail.2025.11.012","DOIUrl":"10.1016/j.cardfail.2025.11.012","url":null,"abstract":"<div><h3>Purpose</h3><div>The effect of pulmonary hemodynamics on outcomes after the implantation of the HeartMate 3 left ventricular assist device (HM3-LVAD) is still not fully understood, although some studies indicate positive results. We conducted an analysis using the EUROMACS international database, which includes many patients from various sites across Europe.</div></div><div><h3>Methods</h3><div>We identified adults who underwent HM3-LVAD implantation from the EUROMACS Database of the European Association of Cardiothoracic Surgery from January 2018 through April 2024. We excluded those with previous cardiac surgery, undergoing concomitant cardiac procedures, on an IABP or ECMO, and those with missing hemodynamic data. Based on the pre-transplant hemodynamic profile, patients were categorized into: Group 1 with a mean pulmonary artery PA pressure (mPAP) &lt; 20 mmHg and a pulmonary vascular resistance (PVR) &lt; 2 WU; Group 2 with a mPAP &gt; 20 mmHg and a PVR &lt; 2 WU; and Group 3 with a PVR &gt; 2 WU. We compared 1- and 2-year mortality rates, major bleeding, and right ventricular (RV) failure after adjusting for factors in the HM3 Survival Risk Score.</div></div><div><h3>Results</h3><div>632 individuals were identified: 47 (7.4%) in group 1, 144 (22.8%) in group 2, and 441 (69.8%) in group 3. Groups differed in age, gender, body mass index, race, and pre-LVAD use of some medications. Post-implant 1-year and 2-year death rates were 14.1% (n=89) and 18.7% (n=118), respectively while 16.0% (n=103) experienced a major bleed. After adjusting for factors in the HM3 Risk Score, no differences were seen in the odds of 1-year death when group 1 (Odds Ratio [OR] 1.09, 95% confidence interval [CI] 0.46-2.59) and group 2 (OR 0.61, 95% CI 0.61-1.86) were compared with group 3 (<strong>Figure</strong>). Similar results were seen for 2-year mortality (group 1 vs. group 3, p = 0.561; group 2 vs group 3, p = 0.330) and major bleeding (group 1 vs. group 3, p = 0.476; group 2 vs group 3, p = 0.958) with no difference between the groups. While, compared with group 3, group 1 increased the odds of late (&gt;14 days) RV failure, no other differences in late or early (14 days) failure were seen.</div></div><div><h3>Conclusions</h3><div>In this retrospective study, elevated PA pressure and/or resistance did not affect the mortality and bleeding rates up to 2 years after HM3-LVAD implantation in adults enrolled in the EUROMACS database.</div></div>","PeriodicalId":15204,"journal":{"name":"Journal of Cardiac Failure","volume":"32 1","pages":"Pages 173-174"},"PeriodicalIF":8.2,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145950118","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Trends In The Incidence, Mortality, And Cost Of Heart Transplant Hospitalizations In The United States; Analysis Of A 7-year Recent National Inpatient Sample Data (2016-2022)","authors":"Bekure Siraw ,&nbsp;Yordanos Tafesse ,&nbsp;Amha Weldehana ,&nbsp;Juveriya Yasmeen ,&nbsp;Yonas Gebrecherkos ,&nbsp;Shahin Isha ,&nbsp;Mouaz Oudih ,&nbsp;Mohammed Haroun ,&nbsp;Didien Meyahnwi ,&nbsp;Hemraj Paudel ,&nbsp;Sushil Sharma","doi":"10.1016/j.cardfail.2025.11.027","DOIUrl":"10.1016/j.cardfail.2025.11.027","url":null,"abstract":"<div><h3>Introduction</h3><div>Heart transplantation remains the gold standard for the treatment of end-stage heart failure, with continuous advancements in surgical techniques and post-transplant care. However, the burden of heart transplant hospitalizations, including associated mortality rates, length of stay, and hospitalization costs, remains a critical area of study. Understanding these trends over time can provide valuable insights into the evolving landscape of heart transplant care in the United States.</div></div><div><h3>Objective</h3><div>The objective of this study is to assess the trends in the incidence, mortality, hospitalization cost, and length of stay for heart transplant admissions in the United States from 2016 to 2022.</div></div><div><h3>Methods</h3><div>In this descriptive study, we utilized data from the National Inpatient Sample (NIS) spanning from 2016 to 2022. We included patients who underwent heart transplants, identified through ICD-10 PCS codes. Quarterly trends were assessed for the mean number of transplants, the mean mortality rate, the median length of hospital stay (in days), and the median cost of hospitalization (in USD). The cost of hospitalization was adjusted for inflation using the corresponding average quarterly consumer price indices provided by the United States Bureau of Labor Statistics.</div></div><div><h3>Results</h3><div>A total of 20,905 heart transplant-related admissions were recorded over the study period. The mean age of the study population was 49.1 years (SD = 19.4), with 70.8% of the patients being male. The racial and ethnic composition was 58% White, 22% Black, and 11.5% Hispanic. Additionally, 99.4% of the admissions occurred at urban teaching hospitals. The annual number of heart transplants showed a modest increase, rising from 2,701 in 2016 to 3,361 in 2022. The annual mortality rate, however, remained relatively stable across the study period. The median hospitalization cost significantly increased from $670,147 (IQR = $761,238) in 2016 to $1,156,591 (IQR = $1,149,662) in 2022. The length of hospital stay also exhibited a steady upward trend, with a median of 25 days (IQR = 40) in 2016, increasing to 37 days (IQR = 40) in 2022.</div></div><div><h3>Conclusions</h3><div>Our analysis reveals a steady increase in heart transplant hospitalizations, with a notable rise in hospitalization costs and LOS, while the mortality rate remains stable.</div></div>","PeriodicalId":15204,"journal":{"name":"Journal of Cardiac Failure","volume":"32 1","pages":"Page 181"},"PeriodicalIF":8.2,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145950215","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Machine Learning And Predicting Heart Failure Readmissions In A Safety-net Hospital Integrating Housing Instability And Environmental Justice","authors":"Melvin R. Echols,&nbsp;Muhammed Idris","doi":"10.1016/j.cardfail.2025.11.046","DOIUrl":"10.1016/j.cardfail.2025.11.046","url":null,"abstract":"<div><h3>Background</h3><div>Environmental factors and housing instability (HI) may affect heart failure (HF) readmissions, which are a substantial clinical and economic burden. National prediction models attempt to address this issue, but they often ignore local factors like social drivers of health (SDOH). Standardized models rarely account for how housing instability affects medication adherence, post-discharge care, and HF treatment.</div></div><div><h3>Hypothesis</h3><div>We tested whether adding an extended definition of the HI variable and the Environmental Justice Index (EJI) to machine learning (ML)-based prediction models improves 30-, 60-, and 90-day HF readmission estimates at a large urban safety-net hospital. We expected that locally calibrated SDOH-integrated models would outperform clinical variable-based techniques.</div></div><div><h3>Methods</h3><div>This retrospective cohort analysis included 5,989 persons hospitalized with HF at Grady Memorial Hospital in Atlanta, GA, between January 2018 and December 2021. Comparing a Traditional Clinical Model (TCM) to an “expanded” Social Determinants Model (SDM) with HI status defined as having had HI within the past twelve months vs. the categorical definition of the TCM on admission. Logistic Regression, Random Forest, XGBoost, Neural Network, and SVM trained (70%) and validated (30%) to predict HF readmissions across 30, 60, and 90 days. Area under the ROC curve (AUC), accuracy, sensitivity, specificity, Brier score, and related metrics examined model discrimination and calibration.</div></div><div><h3>Results</h3><div>HI patients (10.5% of the cohort) showed higher readmission rates (32.96% vs. 12.33% at 30 days, 46.34% vs. 20.52% at 90 days; p&lt;0.001). At all-time points, ML models with HI and the EJI demonstrated higher discriminative capacity over traditional models, with lower Brier’s score (XGBoost 0.7788 at 90 days). Ensemble-based approaches (Random Forest, XGBoost) of the SDM outperformed logistic regression and SVM, showing the predictive power of local SDOH variables and the extent of variable definition.</div></div><div><h3>Conclusions</h3><div>Extending the definition of HI to challenges up to twelve months and integrating the EJI enhanced HF readmission in an urban safety-net hospital. ML models' discrimination of 30-, 60-, and 90-day outcomes increased with local social context, highlighting the value of institution-specific SDOH data. This personalized approach could reduce HF readmissions, especially in vulnerable populations.</div></div>","PeriodicalId":15204,"journal":{"name":"Journal of Cardiac Failure","volume":"32 1","pages":"Page 190"},"PeriodicalIF":8.2,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145950321","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comparative Effectiveness And Safety Of Soluble Guanylate Cyclase Stimulator Monotherapy Versus Combination With Endothelin Receptor Antagonists In Pulmonary Arterial Hypertension: A Multi-center Real-world Cohort Study","authors":"Olayiwola Bolaji ,&nbsp;Mohammed Nor ,&nbsp;Mubarak Yusuf ,&nbsp;Sultana Jahan ,&nbsp;Olanrewaju Adabale ,&nbsp;Sula Mazimba","doi":"10.1016/j.cardfail.2025.11.057","DOIUrl":"10.1016/j.cardfail.2025.11.057","url":null,"abstract":"<div><h3>Background</h3><div>Pulmonary arterial hypertension (PAH) remains a progressive disease with high morbidity despite therapeutic advances. While guidelines recommend combination therapy, data comparing soluble guanylate cyclase stimulators (sGCs) alone versus in combination with endothelin receptor antagonists (ERAs) are limited.</div></div><div><h3>Methods</h3><div>Using the TriNetX Research Network, we conducted a propensity score-matched cohort study of PAH patients receiving either sGC monotherapy (riociguat/vericiguat) or sGC+ERA combination therapy (with bosentan/ambrisentan/macitentan) between 2015-2023. After 1:1 propensity matching (n=1,267 per group), we compared 5-year outcomes including mortality, major adverse cardiac events (MACE), and other clinical endpoints.</div></div><div><h3>Results</h3><div>The sGC+ERA group demonstrated significantly higher MACE incidence (7.3% vs 4.5%; p=0.005) and lower MACE-free survival rates (86.5% vs 91.6%). All-cause mortality appeared higher in the combination therapy group (27.0% vs 22.7%, p=0.013), but this difference was not significant in time-to-event analysis. The combination therapy group showed higher rates of BNP elevation (HR: 1.36, p=0.047) and hypotension (HR: 1.30, p=0.010). However, after accounting for competing risks, mortality differences diminished (23.8% vs 21.9%, p=0.319). Multivariable Cox regression revealed a protective effect of combination therapy (adjusted HR: 0.85, p=0.022) after controlling for demographics, comorbidities, and clinical parameters.</div></div><div><h3>Conclusions</h3><div>In this real-world analysis, sGC+ERA combination therapy was associated with higher risks of MACE and hypotension compared to sGC monotherapy. However, after accounting for competing risks and patient characteristics, combination therapy showed potential mortality benefits. These findings emphasize the complex risk-benefit profile of combination therapy and underscore the importance of individualized treatment approaches in PAH management, with careful consideration of patient-specific factors to optimize outcomes.</div></div>","PeriodicalId":15204,"journal":{"name":"Journal of Cardiac Failure","volume":"32 1","pages":"Page 195"},"PeriodicalIF":8.2,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145950344","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Feasibility Of A Novel Implantable Device To Provide Heart Failure Therapy And Left Atrial Pressure Monitoring In A Chronic Animal Study","authors":"Shuchen Ge,&nbsp;Hui Yu,&nbsp;Haiyang Xu,&nbsp;Bo Li,&nbsp;Eva Yu,&nbsp;Kun Liu,&nbsp;Tao Zhang,&nbsp;Jing Zhang,&nbsp;Min Jiang,&nbsp;Qingyi Sun,&nbsp;Li Wang","doi":"10.1016/j.cardfail.2025.11.060","DOIUrl":"10.1016/j.cardfail.2025.11.060","url":null,"abstract":"<div><h3>Introduction</h3><div>Pulmonary Artery Pressure Monitoring has been shown to reduce rehospitalization in HF patients. Interatrial Shunting (IS) is in clinical studies for similar purposes. However, none of the currently available devices provide both at the same time.</div></div><div><h3>Hypothesis</h3><div>A novel implantable system has been developed to provide IS and LAP monitoring. It consists of an implant device, a delivery system, and an external Monitoring Unit (MU). The MU works with the device’s MEMS pressure sensor to provide the measured LAP. This study aims to assess the feasibility of the system and accuracy of measured LAP in a chronic canine study.</div></div><div><h3>Methods</h3><div>The device was implanted in 10 healthy dogs (Labrador, 30-35 Kg), with 4 observed for 1 month and 6 for 3 months. Procedure success, safety outcome, shunt patency (via TEE) and pressure accuracy were evaluated. To achieve various pressure levels, phenylephrine (0.05-2.00 mg) was injected during implant and at the end of each follow up (FU) before termination. Waveforms of PCWP from Swan Ganz and LAP from the device were recorded for more than 10 seconds by PowerLab (PLC01) and MU respectively. Correlation and agreement between LAP and PCWP were assessed with Pearson’s correlation analysis and Bland-Altman plots.</div></div><div><h3>Results</h3><div>The implant was successful in all dogs with shunt patent at 1 or 3 months. No device related adverse event was observed. Pressure points were obtained for each dog, with a total of 42 pairs of pressure measurements ranging from 0 to 22 mmHg from all dogs. <strong>Fig. 1a</strong> shows an example of the device encapsulation by a thin layer of endothelium at 3 months. Simultaneous pressure waveform recordings, correlation and Bland-Altman plot are shown in <strong>Fig.1b-d</strong>. The PCWP and LAP measurements correlated well (<strong><em>R²</em>=0.87</strong>), with an average difference of 0.33±1.80 mmHg. In the Bland-Altman plot, 40 of 42 pairs fell inside the 95% limit of agreement, indicating good agreement between PCWP measured by Swan-Ganz and LAP by the device.</div></div><div><h3>Conclusions</h3><div>This preliminary chronic animal study demonstrated the feasibility of this implantable device and the accuracy of device-based LAP as compared to PCWP. Further studies are warranted. This novel device with interatrial shunting therapy and hemodynamic monitoring has the potential to provide clinicians with more options for managing HF patients.</div></div>","PeriodicalId":15204,"journal":{"name":"Journal of Cardiac Failure","volume":"32 1","pages":"Page 197"},"PeriodicalIF":8.2,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145950347","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Temporal Trends In Gender, Racial, And Geographic Disparities Of Heart Failure And Pulmonary Embolism-related Mortality Among Adults In The United States: A Retrospective Analysis","authors":"Suhayya Batool ,&nbsp;Daniya Naveed ,&nbsp;Ahmed Sanan ,&nbsp;Rutaba Siddiqui ,&nbsp;Abdul Hannan ,&nbsp;Qura Tul Ain","doi":"10.1016/j.cardfail.2025.11.050","DOIUrl":"10.1016/j.cardfail.2025.11.050","url":null,"abstract":"<div><h3>Background</h3><div>Heart Failure (HF) and Pulmonary Embolism (PE)-related mortality rates are increasing annually in the United States. This study aims to analyze mortality trends of HF and PE-related deaths in the adult population of the United States (1999-2000).</div></div><div><h3>Methods</h3><div>The study analyzed HF and PE-related mortality rates from 1999 to 2020 using death certificate data from the Centers for Disease Control and Prevention Wide-Ranging OnLine Data for Epidemiologic Research (CDC WONDER). The Age-Adjusted Mortality Rates (AAMR), per 100 000 people, Annual Percent Changes (APCs) and corresponding Confidence Intervals (CIs) were calculated. Data was further stratified by year, sex, race, and geographic region (state and census regions).</div></div><div><h3>Results</h3><div>This study examines 60,072 deaths related to HF and PE among U.S. adults aged 25-85+ years from 1999 to 2020. The age-adjusted mortality rate (AAMR) increased from 1.1 (95% CI: 1.05-1.15) in 1999 to 1.88 (95% CI: 1.83-1.93) in 2020, with a particularly sharp rise from 2018 to 2020 with an APC of 12.14%. The total number of deaths increased from 1,980 in 1999 to a peak of 5,026 in 2020. Mortality was higher among females accounting for 56.07% than males with just 43.93% of total deaths, although men exhibited higher AAMRs 1.35 than that of females of 1.2, AAMRs among men increased from 1.15 in 1999 to 2.14 in 2020 with an APC of 7.21%, while females' AAMR had a significant rise from 1.3 in 2018 to 1.66 in 2020 having an APC of 12.16%. Racial disparities were evident, with non-Hispanic Black individuals having the highest AAMR of 2.10, followed by non-Hispanic Whites with AAMR of 1.24, non-Hispanic American Indian or Alaska Natives had AAMR of 1.13, Hispanics with 0.41 AAMR, and non-Hispanic Asian or Pacific Islanders had an AAMR of 0.38 The AAMR for non-Hispanic Black individuals rose significantly after 2016 all the way to 2020 with a staggering APC of 11.48%. Geographic differences were also notable, with the Southern region accounting for the highest proportion of deaths,37.50% of the total deaths where Wyoming recorded the highest AAMR of 2.05, while Hawaii had the lowest of 0.65. States like Texas and California contributed the highest total deaths with an AAMR of 1.55 and AAMR of 1.12 respectively.</div></div><div><h3>Conclusion</h3><div>Heart failure and pulmonary embolism-related AAMR inclined in the US from 1999 to 2020, with an obvious rise seen in the last year of our study period. This trend was seen more in men, NH black Africans, and southern regions of the country. Further prospective research with larger sample sizes and controlling for potential confounding factors is critical to better elucidate these correlations.</div></div>","PeriodicalId":15204,"journal":{"name":"Journal of Cardiac Failure","volume":"32 1","pages":"Page 192"},"PeriodicalIF":8.2,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145950368","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"CRRL 101, A Novel Bispecific Biologic Targeting The Glucagon-like Peptide-1 (glp-1) Receptor And Guanylyl Cyclase A (gca) Receptor, Demonstrates Beneficial Cardiometabolic Effects In Vitro","authors":"Jasraj Singh,&nbsp;Fadi Adel,&nbsp;Xiaoyu Ma,&nbsp;Ye Zheng,&nbsp;Shuchong Pan,&nbsp;JC Malsawmzuali,&nbsp;Dante Moroni,&nbsp;Horng Chen","doi":"10.1016/j.cardfail.2025.11.005","DOIUrl":"10.1016/j.cardfail.2025.11.005","url":null,"abstract":"<div><h3>Introduction</h3><div>The increasing prevalence of cardiometabolic diseases which, via insulin resistance, cellular apoptosis, and myocardial fibrosis, lead to heart failure with preserved ejection fraction.</div></div><div><h3>Hypothesis</h3><div>Our novel bispecific biologic (CRRL 101) mitigates these processes by targeting both the GLP-1 and GCA pathways.</div></div><div><h3>Methods</h3><div>We evaluated CRRL 101 (10 µM) in vitro using transfected human embryonic kidney (HEK) cells, INS-1 rat pancreatic beta cells, human cardiac fibroblasts (HCF), AC16 human cardiomyocytes, and human preadipocytes-visceral(HPA-vis). Data was analyzed using GraphPad Prism 9.4.1 and are presented as mean ± SEM.</div></div><div><h3>Results</h3><div>In HEK cells, CRRL 101 markedly increased cyclic guanosine monophosphate (cGMP) levels (8.9 pmol/mL ± 5.1 vs 457.2 pmol/mL ± 64.9 relative activity 100) in GCA-expressing HEK, with no effect in guanylyl cyclase B (GCB) receptor-expressing HEK cells (3.57 pmol/mL ± 0.53 vs 5.12 pmol/mL ±1.86 relative activity 1.4). Demonstrating its effect via the GLP-1 signaling pathway, it also increased cAMP levels at all doses in a 20 mM glucose medium (16.7 pmol/mL ± 1.47 vs 24.87 pmol/mL ± 2.53 p=0.0041, 22.95 pmol/mL ± 3.95 p=0.0042, and 23.19 pmol/mL ± 1.51 p=0.0036) in INS-1 cells, and doubled insulin secretion independent of the glucose environment (3.8 ng/mL ± 0.74 vs 7.1 ng/mL in 2.8 mM glucose p = 0.0019 and 4.4 ng/mL ± 0.44 vs 9.5 ng/mL ± 0.34 in 20 mM glucose p &lt; 0.0001). In HCF cells, CRRL 101 attenuated alpha smooth muscle actin (α-SMA) activation by both insulin and transforming growth factor beta 1 (TGF-β1). In AC16 cells, CRRL 101 exhibited dose-dependent inhibition of insulin mediated apoptosis and a similar inhibition of TGF-β1 and insulin-mediated collagen secretion (85.11 µg/mL ± 15.32 vs 55.93 µg/mL ± 13.15 p=0.09; and 86.27 µg/mL ± 14.10 vs 48.20µg/mL ± 12.03 p=0.0331, respectively). Finally, CRRL 101 demonstrated marked adipose browning in HPA-vis (Figure 1).</div></div><div><h3>Conclusion</h3><div>CRRL 101 is a GCA-selective and GLP-1 chimeric bispecific biologic with favorable insulinergic, anti-apoptotic, anti-fibrotic, and pro-adipose browning effects uniquely mediated through its activity at the GLP-1 and GCA receptors. Further in vivo studies are in progress to explore its therapeutic potential.</div></div>","PeriodicalId":15204,"journal":{"name":"Journal of Cardiac Failure","volume":"32 1","pages":"Page 171"},"PeriodicalIF":8.2,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145950423","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Time-to-Diuretics in Acute Heart Failure Management: Striking the Balance Between Speed and Accuracy","authors":"SIAMACK ALAM-SHOUSHTARI ,&nbsp;NATHANIEL M. HAWKINS ,&nbsp;ROBERT MCKELVIE ,&nbsp;STEPHANIE POON ,&nbsp;GEORGE HONOS ,&nbsp;SHELLEY ZIEROTH ,&nbsp;JUSTIN EZEKOWITZ ,&nbsp;SEAN A. VIRANI ,&nbsp;NIMA MOGHADDAM MD FRCPC.","doi":"10.1016/j.cardfail.2025.07.011","DOIUrl":"10.1016/j.cardfail.2025.07.011","url":null,"abstract":"","PeriodicalId":15204,"journal":{"name":"Journal of Cardiac Failure","volume":"32 1","pages":"Pages 157-159"},"PeriodicalIF":8.2,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144816746","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}