Circulation: Heart Failure最新文献

{"title":"Natural Language Processing to Adjudicate Heart Failure Hospitalizations in Global Clinical Trials.","authors":"Pablo M Marti-Castellote, Christopher Reeder, Brian L Claggett, Pulkit Singh, Emily S Lau, Shaan Khurshid, Puneet Batra, Steven A Lubitz, Mahnaz Maddah, Orly Vardeny, Eldrin F Lewis, Marc A Pfeffer, Pardeep S Jhund, Akshay S Desai, John J V McMurray, Patrick T Ellinor, Jennifer E Ho, Scott D Solomon, Jonathan W Cunningham","doi":"10.1161/CIRCHEARTFAILURE.124.012514","DOIUrl":"https://doi.org/10.1161/CIRCHEARTFAILURE.124.012514","url":null,"abstract":"<p><p><b>Background:</b> Medical record review by a physician clinical events committee is the gold standard for identifying cardiovascular outcomes in clinical trials, but is labor-intensive and poorly reproducible. Automated outcome adjudication by artificial intelligence (AI) could enable larger and less expensive clinical trials, but has not been validated in global studies. <b>Methods:</b> We developed a novel model for automated AI-based heart failure adjudication (\"HF-NLP\") using hospitalizations from three international clinical outcomes trials. This model was tested on potential heart failure hospitalizations from the DELIVER trial, a cardiovascular outcomes trial comparing dapagliflozin with placebo in 6063 patients with heart failure with mildly reduced or preserved ejection fraction. AI-based adjudications were compared with adjudications from a clinical events committee that followed FDA-based criteria. <b>Results:</b> AI-based adjudication agreed with the clinical events committee in 83% of events. A strategy of human review for events that the AI model deemed uncertain (16%) would have achieved 91% agreement with the clinical events committee while reducing adjudication workload by 84%. The estimated effect of dapagliflozin on heart failure hospitalization was nearly identical with AI-based adjudication (hazard ratio 0.76 [95% CI 0.66-0.88]) compared to clinical events committee adjudication (hazard ratio 0.77 [95% CI 0.67-0.89]). The AI model extracted symptoms, signs, and treatments of heart failure from each medical record in tabular format and quoted sentences documenting them. <b>Conclusions:</b> AI-based adjudication of clinical outcomes has the potential to improve the efficiency of global clinical trials while preserving accuracy and interpretability.</p>","PeriodicalId":10196,"journal":{"name":"Circulation: Heart Failure","volume":" ","pages":""},"PeriodicalIF":7.8,"publicationDate":"2024-11-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142643876","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Medical Expert System for Intelligent Telemonitoring of Chronic Heart Failure Patients: Preliminary Validation and Perspectives.","authors":"Annamaria Vianello, Martina Olivelli, Massimiliano Donati, Luca Fanucci, Alessio Bechini, Ilaria Petrucci, Stefano Masi","doi":"10.1161/CIRCHEARTFAILURE.124.012478","DOIUrl":"https://doi.org/10.1161/CIRCHEARTFAILURE.124.012478","url":null,"abstract":"","PeriodicalId":10196,"journal":{"name":"Circulation: Heart Failure","volume":" ","pages":""},"PeriodicalIF":7.8,"publicationDate":"2024-11-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142615673","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Social Determinants of Health and Disparities in Guideline-Directed Medical Therapy Optimization for Heart Failure.","authors":"Joshua A Jacobs, Iyanuoluwa Ayodele, Adam P Bress, Madeline R Sterling, Ambarish Pandey, Catherine G Derington, Alexander R Zheutlin, Kevin S Shah, Stephen J Greene, Brooke Alhanti, Rosalia Blanco, Gregg C Fonarow","doi":"10.1161/CIRCHEARTFAILURE.124.012357","DOIUrl":"https://doi.org/10.1161/CIRCHEARTFAILURE.124.012357","url":null,"abstract":"<p><strong>Background: </strong>Fewer than 20% of eligible patients with heart failure with reduced ejection fraction receive all 4 pillars of guideline-directed medical therapy. Understanding disparities by race, ethnicity, sex, and adverse social determinants of health is necessary to equitably optimize quadruple therapy.</p><p><strong>Methods: </strong>Utilizing the American Heart Association's Get With The Guidelines-Heart Failure registry, we examined associations between race and ethnicity, sex, and adverse social determinants of health (insurance type and documented social need [any barrier to accessing health care]) with quadruple therapy optimization (QTO) in patients with heart failure with reduced ejection fraction hospitalized between July 1, 2021, and September 30, 2023, with complete medication data at discharge. We calculated adjusted mean differences (AMDs) in the discharge QTO score (range, 0%-100%) reflecting the proportion of eligible use of renin-angiotensin system inhibitors, β-blockers, mineralocorticoid receptor antagonists, and sodium-glucose cotransporter-2 inhibitors and compared across demographic and adverse social determinants of health groups.</p><p><strong>Results: </strong>Among 82 637 patients (median age, 66 years; 32.5% female; 57.0% non-Hispanic White; 76.4% prior heart failure with reduced ejection fraction), the overall mean QTO score was 56.2% (SD, 25.5). After adjustment, compared with non-Hispanic White individuals, Black (AMD, 2.56 percentage points [95% CI, 2.16-2.96]) and Hispanic individuals (AMD, 0.71 percentage points [95% CI, 0.11-1.31]) had higher QTO scores. Females had higher QTO scores than males (AMD, 1.94 percentage points [95% CI, 1.58-2.31]). Patients with no insurance (AMD, -4.90 percentage points [-5.62 to -4.17]), Medicaid (AMD, -0.45 percentage points [-0.89 to -0.01]), and Medicare (AMD, -1.64 percentage points [-2.10 to -1.18]) had lower QTO scores versus private insurance. Those with an identified social need (n=24 651) had lower QTO scores than those without (AMD, -3.40 percentage points [95% CI, -4.10 to -2.71]).</p><p><strong>Conclusions: </strong>Disparities in QTO were most evident for patients with no insurance, Medicaid, Medicare, or potentially an identified social need. Future efforts should focus on reducing gaps to improve equitable guideline-directed medical therapy use.</p>","PeriodicalId":10196,"journal":{"name":"Circulation: Heart Failure","volume":" ","pages":"e012357"},"PeriodicalIF":7.8,"publicationDate":"2024-11-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142615705","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mavacamten: Real-World Experience from 22 Months of the Risk Evaluation and Mitigation Strategy (REMS) Program.","authors":"Milind Y Desai, Dewey Seto, Michael Cheung, Sonia Afsari, Niki Patel, Arnaud Bastien, Jeffrey Lockman, Michele Coiro, Matthew W Martinez","doi":"10.1161/CIRCHEARTFAILURE.124.012441","DOIUrl":"https://doi.org/10.1161/CIRCHEARTFAILURE.124.012441","url":null,"abstract":"<p><p><b>Background:</b> Mavacamten is the only cardiac myosin inhibitor approved by the US FDA for treatment of symptomatic New York Heart Association class II-III obstructive hypertrophic cardiomyopathy (HCM) patients. Under the risk evaluation and mitigation strategy (REMS) program for mavacamten, patients are required to be monitored for development of systolic heart failure, and reduction of left ventricular ejection fraction (LVEF) to <50%. We report results from the mavacamten REMS database (28-Apr-2022 to 27-Feb-2024). <b>Methods:</b> Data on healthcare providers and pharmacy certification, patient monitoring (from Patient Status Forms, based partly on echocardiograms), and screening for drug interactions prior to each dispense were collected. <b>Results:</b> Of 6,299 patients who received ≥1 dose of mavacamten, 60.0% were women; 64.6% were >60 years of age. Of 5,573 patients with submitted Patient Status Forms, 256 (4.6%) developed LVEF <50% and 71 (1.3%) experienced heart failure requiring hospitalization (HFH). On the 29,111 status forms in these patients, each representing an assessment of an echocardiogram, LVEF <50% was reported on 276 (0.9%) and HFH was reported on 86 (0.3%). Of 1,929 patients with ≥1 year of treatment, 78 (4.0%) had an LVEF reduction to <50% and 4 (0.2%) experienced LVEF <50% + HFH but later resumed treatment. Of 3,228 patients initiated on 5 mg/day mavacamten and were treated for at least 6 months, 2,391 (74.1%) remained at 5 or 10 mg/day. At 3- and 6-months following mavacamten treatment initiation, 57.2% and 70.3%, respectively, demonstrated post-Valsalva LV outflow tract gradient <30 mmHg. <b>Conclusions:</b> We describe the feasibility and experience of the first 22 months of the REMS program for prescribing mavacamten in >6,000 symptomatic obstructive HCM patients. The need for temporary interruption for LVEF <50% was low, including for patients on therapy ≥1 year, with even fewer LVEF reductions associated with HFH.</p>","PeriodicalId":10196,"journal":{"name":"Circulation: Heart Failure","volume":" ","pages":""},"PeriodicalIF":7.8,"publicationDate":"2024-11-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142615683","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comprehensive Proteomics Profiling Identifies Circulating Biomarkers to Distinguish Hypertrophic Cardiomyopathy from Other Cardiomyopathies with Left Ventricular Hypertrophy.","authors":"Keitaro Akita, Mathew S Maurer, Albree Tower-Rader, Michael A Fifer, Yuichi J Shimada","doi":"10.1161/CIRCHEARTFAILURE.124.012434","DOIUrl":"https://doi.org/10.1161/CIRCHEARTFAILURE.124.012434","url":null,"abstract":"<p><p><b>Background:</b> Distinguishing hypertrophic cardiomyopathy (HCM) from other cardiomyopathies with left ventricular hypertrophy (LVH), such as hypertensive LVH, transthyretin amyloid cardiomyopathy (ATTR-CM), and aortic stenosis (AS), is sometimes challenging. Using plasma proteomics profiling, we aimed to identify circulating biomarkers and dysregulated signaling pathways specific to HCM. <b>Methods:</b> In this multicenter case-control study, plasma proteomics profiling was performed in cases with HCM and controls with hypertensive LVH, ATTR-CM, and AS. Two-thirds of patients enrolled earlier in each disease group were defined as the training set, and the remaining one-third as the test set. Protein concentrations in HCM were compared with those in hypertensive LVH (comparison 1), ATTR-CM (comparison 2), and AS (comparison 3). Candidate proteins that meet the following 2 criteria were selected: (1) Higher abundance in HCM throughout all 3 comparisons or lower abundance in HCM throughout all 3 comparisons with univariable P<0.05 and |log₂(fold change)| >0.5 in both the training and test sets and (2) Independently associated with HCM with multivariable P<0.05 after adjusting for clinical parameters significantly different between HCM and controls. Using the selected candidate proteins, a logistic regression model to distinguish HCM from controls was developed in the training set and applied to the test set. Finally, pathway analysis was performed in each comparison using proteins with different abundance. <b>Results:</b> Overall, 4,979 proteins in 1,415 patients (HCM, n=879; hypertensive LVH, n=331; ATTR-CM, n=169; AS, n=36) were analyzed. Of those, 5 proteins were selected as candidate proteins. The logistic regression model with these 5 proteins had an area under the receiver-operating-characteristic curve of 0.86 (95% CI 0.82-0.89) in the test set. The MAPK and HIF-1 pathways were dysregulated in HCM throughout the 3 comparisons. <b>Conclusions:</b> This study identified circulating biomarkers that distinguish HCM from other cardiomyopathies with LVH independently from confounders and revealed signaling pathways associated with HCM.</p>","PeriodicalId":10196,"journal":{"name":"Circulation: Heart Failure","volume":" ","pages":""},"PeriodicalIF":7.8,"publicationDate":"2024-11-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142615678","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Stop Dreaming: Mavacamten REMS Data Are Here.","authors":"Ahmad Masri, Neal K Lakdawala","doi":"10.1161/CIRCHEARTFAILURE.124.012545","DOIUrl":"https://doi.org/10.1161/CIRCHEARTFAILURE.124.012545","url":null,"abstract":"","PeriodicalId":10196,"journal":{"name":"Circulation: Heart Failure","volume":" ","pages":""},"PeriodicalIF":7.8,"publicationDate":"2024-11-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142615726","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Inhibitors of the Interleukin-1 Receptor Accessory Protein Signaling: Another Asset in the Cardio-Immunology Toolbox.","authors":"Stefano Toldo, Guglielmo Gallone, Antonio Abbate","doi":"10.1161/CIRCHEARTFAILURE.124.012244","DOIUrl":"https://doi.org/10.1161/CIRCHEARTFAILURE.124.012244","url":null,"abstract":"","PeriodicalId":10196,"journal":{"name":"Circulation: Heart Failure","volume":" ","pages":"e012244"},"PeriodicalIF":7.8,"publicationDate":"2024-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142603409","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Renal Effects of Combination Phosphodiesterase V Inhibition and Low-Dose B-Type Natriuretic Peptide in Acute Heart Failure: A Randomized Clinical Trial.","authors":"Scott A Hubers, Sherry L Benike, Bradley K Johnson, Paul M McKie, Christopher Scott, Horng H Chen","doi":"10.1161/CIRCHEARTFAILURE.124.011761","DOIUrl":"https://doi.org/10.1161/CIRCHEARTFAILURE.124.011761","url":null,"abstract":"<p><strong>Background: </strong>Cardiorenal dysfunction with impaired cyclic GMP (cGMP) response is common in patients presenting with acute heart failure (HF). Type V phosphodiesterase (PDEV) is known to be upregulated in HF and may explain the dysfunction of renal response. The aim of this study was to determine whether B-type natriuretic peptide (BNP) alone or in combination with PDEV inhibition improves renal function and increases urinary sodium and cGMP excretion in acute HF.</p><p><strong>Methods: </strong>This open-label study included 67 patients hospitalized with acute HF and renal dysfunction. Patients were randomized to standard care, low-dose intravenous BNP (0.005 µg/kg per minute), or combination BNP/PDEV inhibition with sildenafil (25 mg q12 hours) for 48 hours. The coprimary end points were the percent change in estimated glomerular filtration rate and blood urea nitrogen from baseline to 48 hours.</p><p><strong>Results: </strong>Treatment with BNP and BNP/PDEV inhibitor significantly increased plasma cGMP at 24 hours (+25.6% [+9.8%, +84.7%] and +60.8% [+32.3%, +103.8%] for BNP and BNP/PDEV versus -13.5% [-29.1%, +14.2%] with standard care; <i>P</i>=0.001). However, there was no significant change in estimated glomerular filtration rate 0 (-10.8%, +12.7%) for standard care versus 0 (-15.3%, +11.8%) for the BNP group versus -8.8% (-14.3%, +8.3%) for the BNP/PDEV group (<i>P</i>=0.60) or blood urea nitrogen -1.4% (-10.7%, +12.0%) for standard care versus -5.9% (-14.6%, +9.4%) for the BNP group versus +6.9% (-5.3%, +18.8%) for the BNP/PDEV group (<i>P</i>=0.38) between groups. Hypotension was more common in the BNP/PDEV inhibitor group.</p><p><strong>Conclusions: </strong>BNP and combination BNP/PDEV inhibition increased plasma cGMP in patients with acute HF but did not improve renal function or urinary sodium/cGMP excretion. Our study does not support the use of intravenous low-dose BNP with or without PDEV inhibition to enhance renal function in patients admitted with acute HF.</p><p><strong>Registration: </strong>URL: https://www.clinicaltrials.gov; Unique identifier: NCT00972569.</p>","PeriodicalId":10196,"journal":{"name":"Circulation: Heart Failure","volume":" ","pages":"e011761"},"PeriodicalIF":7.8,"publicationDate":"2024-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142603338","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Myocardial Posttranscriptional Landscape in Peripartum Cardiomyopathy.","authors":"Amy Li, Bernard Fang, Mengbo Li, Yen Chin Koay, Cassandra Malecki, Benjamin Hunter, Dylan Harney, Cristobal G Dos Remedios, Mark Larance, John F O'Sullivan, Sean Lal","doi":"10.1161/CIRCHEARTFAILURE.124.011725","DOIUrl":"https://doi.org/10.1161/CIRCHEARTFAILURE.124.011725","url":null,"abstract":"<p><strong>Background: </strong>Pregnancy imposes significant cardiovascular adaptations, including progressive increases in plasma volume and cardiac output. For most women, this physiological adaptation resolves at the end of pregnancy, but some women develop pathological dilatation and ultimately heart failure late in pregnancy or in the postpartum period, manifesting as peripartum cardiomyopathy (PPCM). Despite the mortality risk of this form of heart failure, the molecular mechanisms underlying PPCM have not been extensively examined in human hearts.</p><p><strong>Methods: </strong>Protein and metabolite profiles from left ventricular tissue of end-stage PPCM patients (N=6-7) were compared with dilated cardiomyopathy (DCM; N=5-6) and nonfailing donors (N=7-18) using unbiased quantitative mass spectrometry. All samples were derived from the Sydney Heart Bank. Data are available via ProteomeXchange with identifier PXD055986. Differential protein expression and metabolite abundance and Kyoto Encyclopedia of Genes and Genomes pathway analyses were performed.</p><p><strong>Results: </strong>Proteomic analysis identified 2 proteins, SBSPON (somatomedin B and thrombospondin type 1 domain-containing protein precursor) and TNS3 (tensin 3), that were uniquely downregulated in PPCM. SBSPON, an extracellular matrix protein, and TNS3, involved in actin remodeling and cell signaling, may contribute to impaired tissue remodeling and fibrosis in PPCM. Metabolomic analysis revealed elevated levels of homogentisate and deoxycholate and reduced levels of lactate and alanine in PPCM, indicating disrupted metabolic pathways and glucose utilization. Both PPCM and DCM shared pathways related to inflammation, immune responses, and signal transduction. However, thyroid hormone signaling was notably reduced in PPCM, affecting contractility and calcium handling through altered expression of PLN (phospholamban) and Sarcoendoplasmic Reticulum Calcium ATPase (SERCA). Enhanced endoplasmic reticulum stress and altered endocytosis pathways in PPCM suggested additional mechanisms of energy metabolism disruption.</p><p><strong>Conclusions: </strong>The present study reveals unique posttranslational molecular features of the PPCM myocardium, which mediates cellular and metabolic remodeling, and holds promise as potential targets for therapeutic intervention.</p>","PeriodicalId":10196,"journal":{"name":"Circulation: Heart Failure","volume":" ","pages":"e011725"},"PeriodicalIF":7.8,"publicationDate":"2024-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142603424","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"IL1RAP Blockade With a Monoclonal Antibody Reduces Cardiac Inflammation and Preserves Heart Function in Viral and Autoimmune Myocarditis.","authors":"Diego A Lema, Gabriel Jakobsson, Abdel Daoud, David Elias, Monica V Talor, Sara Rattik, Caitríona Grönberg, Hannah Kalinoski, Elin Jaensson Gyllenbäck, Nadan Wang, David Liberg, Alexandru Schiopu, Daniela Čiháková","doi":"10.1161/CIRCHEARTFAILURE.124.011729","DOIUrl":"https://doi.org/10.1161/CIRCHEARTFAILURE.124.011729","url":null,"abstract":"<p><strong>Background: </strong>Currently, there are no therapies targeting specific pathogenic pathways in myocarditis. IL (interleukin)-1 blockade has shown promise in preclinical studies and case reports. We hypothesized that blockade of IL1RAP (IL-1 receptor accessory protein), a shared subunit of the IL-1, IL-33, and IL-36 receptors, could be more efficient than IL-1 blockade alone.</p><p><strong>Methods: </strong>We induced coxsackievirus B3 (CVB3)-mediated or experimental autoimmune myocarditis (EAM) in BALB/c mice, followed by treatment with an Fc (fragment crystallizable)-modified mIgG2a mouse anti-mouse IL1RAP monoclonal antibody (mCAN10). Myocarditis severity and immune infiltration were assessed by histology and flow cytometry. Cardiac function was measured by echocardiography. We used spatial transcriptomics (Visium 10× Genomics) to compare the gene expression landscape in the hearts of mCAN10-treated versus control mice.</p><p><strong>Results: </strong>IL1RAP blockade reduced CVB3 and EAM severity. In EAM, the treatment prevented deterioration of cardiac function, measured on day 42 post-disease induction (left ventricular ejection fraction: 56.5% versus 51.0% in isotype controls [<i>P</i>=0.002] and versus 51.4% in mice treated with anti-IL-1β antibodies alone [<i>P</i>=0.003]; n=10-11 mice per group). In the CVB3 model, mCAN10 did not impede viral clearance from the heart and significantly lowered the numbers of CD4⁺ (cluster of differentiation 4) T cells (<i>P</i>=0.025), inflammatory Ly6C⁺CCR2⁺ (lymphocyte antigen 6 complex, locus C/C-C motif chemokine receptor 2) monocytes (<i>P</i>=0.038), neutrophils (<i>P</i>=0.001) and eosinophils (<i>P</i><0.001) infiltrating the myocardium. The spatial transcriptomic analysis revealed reduced canonical IL-1 signaling and chemokine expression in cardiac immune foci in CVB3-infected mice treated with IL1RAP blockade.</p><p><strong>Conclusions: </strong>Blocking IL1RAP reduces acute CVB3 myocarditis and EAM severity and preserves cardiac function in EAM. We conclude that IL1RAP blockade is a potential therapeutic strategy in viral and autoimmune myocarditis.</p>","PeriodicalId":10196,"journal":{"name":"Circulation: Heart Failure","volume":" ","pages":"e011729"},"PeriodicalIF":7.8,"publicationDate":"2024-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142603310","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}